S26A4_HUMAN
ID S26A4_HUMAN Reviewed; 780 AA.
AC O43511; B7Z266; O43170;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Pendrin;
DE AltName: Full=Sodium-independent chloride/iodide transporter;
DE AltName: Full=Solute carrier family 26 member 4;
GN Name=SLC26A4; Synonyms=PDS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PDS CYS-667.
RC TISSUE=Thyroid;
RX PubMed=9398842; DOI=10.1038/ng1297-411;
RA Everett L.A., Glaser B., Beck J.C., Idol J.R., Buchs A., Heyman M.,
RA Adawi F., Hazani E., Nassir E., Baxevanis A.D., Sheffield V.C., Green E.D.;
RT "Pendred syndrome is caused by mutations in a putative sulphate transporter
RT gene (PDS).";
RL Nat. Genet. 17:411-422(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [4]
RP FUNCTION.
RX PubMed=10192399; DOI=10.1038/7783;
RA Scott D.A., Wang R., Kreman T.M., Sheffield V.C., Karnishki L.P.;
RT "The Pendred syndrome gene encodes a chloride-iodide transport protein.";
RL Nat. Genet. 21:440-443(1999).
RN [5]
RP VARIANTS PDS PHE-138; ALA-139; VAL-209; PRO-236; HIS-271; HIS-409; PRO-416;
RP TRP-445; TYR-565 AND ARG-723.
RX PubMed=9618166; DOI=10.1093/hmg/7.7.1099;
RA van Hauwe P., Everett L.A., Coucke P., Scott D.A., Kraft M.L.,
RA Ris-Stalpers C., Bolder C., Otten B., de Vijlder J.J.M., Dietrich N.L.,
RA Ramesh A., Srisailapathy S.C.R., Parving A., Cremers C.W.R.J.,
RA Willems P.J., Smith R.J.H., Green E.D., van Camp G.;
RT "Two frequent missense mutations in Pendred syndrome.";
RL Hum. Mol. Genet. 7:1099-1104(1998).
RN [6]
RP VARIANTS PDS PHE-138; PRO-236; GLY-384; HIS-409; MET-410; PRO-416; HIS-530;
RP CYS-556 AND GLU-672.
RX PubMed=9618167; DOI=10.1093/hmg/7.7.1105;
RA Coyle B., Reardon W., Herbrick J.-A., Tsui L.-C., Gausden E., Lee J.,
RA Coffey R., Grueters A., Grossman A., Phelps P.D., Luxon L.,
RA Kendall-Taylor P., Scherer S.W., Trembath R.C.;
RT "Molecular analysis of the PDS gene in Pendred syndrome (sensorineural
RT hearing loss and goitre).";
RL Hum. Mol. Genet. 7:1105-1112(1998).
RN [7]
RP VARIANTS DFNB4 LEU-490 AND SER-497.
RX PubMed=9500541; DOI=10.1038/ng0398-215;
RA Li X.C., Everett L.A., Lalwani A.K., Desmukh D., Friedman T.B., Green E.D.,
RA Wilcox E.R.;
RT "A mutation in PDS causes non-syndromic recessive deafness.";
RL Nat. Genet. 18:215-217(1998).
RN [8]
RP VARIANTS DFNB4 VAL-209; GLU-369; VAL-372; MET-721 AND ARG-723.
RX PubMed=10190331; DOI=10.1007/s004390050933;
RA Usami S., Abe S., Weston M.D., Shinkawa H., Van Camp G., Kimberling W.J.;
RT "Non-syndromic hearing loss associated with enlarged vestibular aqueduct is
RT caused by PDS mutations.";
RL Hum. Genet. 104:188-192(1999).
RN [9]
RP VARIANT PDS TRP-445.
RX PubMed=10602116;
RX DOI=10.1002/(sici)1096-8628(20000103)90:1<38::aid-ajmg8>3.0.co;2-r;
RA Masmoudi S., Charfedine I., Hmani M., Grati M., Ghorbel A.M.,
RA Elgaied-Boulila A., Drira M., Hardelin J.-P., Ayadi M.;
RT "Pendred syndrome: phenotypic variability in two families carrying the same
RT PDS missense mutation.";
RL Am. J. Med. Genet. 90:38-44(2000).
RN [10]
RP VARIANT PDS ASN-508.
RX PubMed=10718825; DOI=10.1046/j.1365-2265.2000.00930.x;
RA Bogazzi F., Raggi F., Ultimieri F., Campomori A., Cosci C., Berrettini S.,
RA Neri E., La Rocca R., Ronca G., Martino E., Bartalena L.;
RT "A novel mutation in the pendrin gene associated with Pendred's syndrome.";
RL Clin. Endocrinol. (Oxf.) 52:279-285(2000).
RN [11]
RP VARIANT PDS ILE-193.
RX PubMed=10878664; DOI=10.1038/sj.ejhg.5200489;
RA Adato A., Raskin L., Petit C., Bonne-Tamir B.;
RT "Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF
RT and PDS mutations, low prevalence of GJB2 35delG mutation and indication
RT for a new DFNB locus.";
RL Eur. J. Hum. Genet. 8:437-442(2000).
RN [12]
RP VARIANTS DFNB4 PHE-117; VAL-209; PRO-236; MET-410; PRO-416; TRP-445 AND
RP ARG-446.
RX PubMed=10700480; DOI=10.1093/qjmed/93.2.99;
RA Reardon W., O'Mahoney C.F., Trembath R., Jan H., Phelps P.D.;
RT "Enlarged vestibular aqueduct: a radiological marker of Pendred syndrome,
RT and mutation of the PDS gene.";
RL QJM 93:99-104(2000).
RN [13]
RP VARIANTS PDS PHE-138 AND PRO-411.
RX PubMed=11375792; DOI=10.1530/eje.0.1440585;
RA Gonzalez Trevino O., Karamanoglu Arseven O., Ceballos C.J., Vives V.I.,
RA Ramirez R.C., Gomez V.V., Medeiros-Neto G., Kopp P.;
RT "Clinical and molecular analysis of three Mexican families with Pendred's
RT syndrome.";
RL Eur. J. Endocrinol. 144:585-593(2001).
RN [14]
RP VARIANTS PDS GLN-29; CYS-105; ASP-106; PHE-138; VAL-209; PRO-236; LEU-335;
RP PRO-416; ASP-480; HIS-530; ALA-653 AND GLU-672, AND VARIANT SER-597.
RX PubMed=11317356; DOI=10.1002/humu.1116;
RA Campbell C., Cucci R.A., Prasad S., Green G.E., Edeal J.B., Galer C.E.,
RA Karniski L.P., Sheffield V.C., Smith R.J.H.;
RT "Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel
RT mutations and possible genotype-phenotype correlations.";
RL Hum. Mutat. 17:403-411(2001).
RN [15]
RP VARIANTS PDS TRP-445; HIS-556 AND MET-721, AND VARIANTS DFNB4 ILE-132 AND
RP MET-410.
RX PubMed=11748854; DOI=10.1002/humu.1238;
RA Lopez-Bigas N., Melchionda S., de Cid R., Grifa A., Zelante L., Govea N.,
RA Arbones M.L., Gasparini P., Estivill X.;
RT "Identification of five new mutations of PDS/SLC26A4 in Mediterranean
RT families with hearing impairment.";
RL Hum. Mutat. 18:548-548(2001).
RN [16]
RP ERRATUM OF PUBMED:11748854.
RX PubMed=12112665; DOI=10.1002/humu.9043;
RA Lopez-Bigas N., Melchionda S., de Cid R., Grifa A., Zelante L., Govea N.,
RA Arbones M.L., Gasparini P., Estivill X.;
RL Hum. Mutat. 20:77-78(2002).
RN [17]
RP CHARACTERIZATION OF VARIANTS PDS ARG-102; PHE-117; PHE-138; VAL-209;
RP PRO-236; MET-410; ARG-446; CYS-556 AND GLU-672.
RX PubMed=11932316; DOI=10.1210/jcem.87.4.8435;
RA Taylor J.P., Metcalfe R.A., Watson P.F., Weetman A.P., Trembath R.C.;
RT "Mutations of the PDS gene, encoding pendrin, are associated with protein
RT mislocalization and loss of iodide efflux: implications for thyroid
RT dysfunction in Pendred syndrome.";
RL J. Clin. Endocrinol. Metab. 87:1778-1784(2002).
RN [18]
RP VARIANTS PDS ARG-28; THR-133; HIS-409 AND MET-410, AND VARIANT SER-597.
RX PubMed=11919333; DOI=10.1203/00006450-200204000-00013;
RA Fugazzola L., Cerutti N., Mannavola D., Crino A., Cassio A., Gasparoni P.,
RA Vannucchi G., Beck-Peccoz P.;
RT "Differential diagnosis between Pendred and pseudo-Pendred syndromes:
RT clinical, radiologic, and molecular studies.";
RL Pediatr. Res. 51:479-484(2002).
RN [19]
RP VARIANTS PDS ASP-239 AND ARG-723.
RX PubMed=12974744; DOI=10.1034/j.1399-0004.2003.00144.x;
RA Tekin M., Akcayoez D., Comak E., Bogoclu G., Duman T., Fitoz S., Ilhan I.,
RA Akar N.;
RT "Screening the SLC26A4 gene in probands with deafness and goiter (Pendred
RT syndrome) ascertained from a large group of students of the schools for the
RT deaf in Turkey.";
RL Clin. Genet. 64:371-374(2003).
RN [20]
RP VARIANTS DFNB4 SER-123; VAL-147 AND PHE-666.
RX PubMed=14508505; DOI=10.1038/sj.ejhg.5201073;
RA Tsukamoto K., Suzuki H., Harada D., Namba A., Abe S., Usami S.;
RT "Distribution and frequencies of PDS (SLC26A4) mutations in Pendred
RT syndrome and nonsyndromic hearing loss associated with enlarged vestibular
RT aqueduct: a unique spectrum of mutations in Japanese.";
RL Eur. J. Hum. Genet. 11:916-922(2003).
RN [21]
RP VARIANTS PDS THR-133; PHE-138; GLY-384 AND HIS-530.
RX PubMed=12788906; DOI=10.1210/jc.2002-021334;
RA Borck G., Roth C., Martine U., Wildhardt G., Pohlenz J.;
RT "Mutations in the PDS gene in German families with Pendred's syndrome:
RT V138F is a founder mutation.";
RL J. Clin. Endocrinol. Metab. 88:2916-2921(2003).
RN [22]
RP VARIANTS DFNB4 ARG-28; LEU-90; ASP-239; PRO-252; TYR-392; PRO-409; MET-410;
RP LYS-457; GLN-676; MET-721 AND ARG-723, AND VARIANT PHE-455.
RX PubMed=12676893; DOI=10.1136/jmg.40.4.242;
RA Park H.-J., Shaukat S., Liu X.-Z., Hahn S.H., Naz S., Ghosh M., Kim H.-N.,
RA Moon S.-K., Abe S., Tukamoto K., Riazuddin S., Kabra M., Erdenetungalag R.,
RA Radnaabazar J., Khan S., Pandya A., Usami S., Nance W.E., Wilcox E.R.,
RA Riazuddin S., Griffith A.J.;
RT "Origins and frequencies of SLC26A4 (PDS) mutations in east and south
RT Asians: global implications for the epidemiology of deafness.";
RL J. Med. Genet. 40:242-248(2003).
RN [23]
RP VARIANTS PDS/DFNB4 GLY-24; GLN-29; CYS-78; VAL-104; CYS-105; ASP-106;
RP PHE-138; ALA-139; VAL-209; PRO-236; HIS-271; LEU-335; GLY-384; HIS-409;
RP MET-410; PRO-416; ARG-421; ALA-429 DEL; TRP-445; ASP-480; HIS-530; CYS-556;
RP TYR-565; ALA-653; GLU-672; SER-683 AND ARG-723, AND VARIANTS TYR-324 AND
RP SER-597.
RX PubMed=14679580; DOI=10.1002/ajmg.a.20272;
RA Prasad S., Koelln K.A., Cucci R.A., Trembath R.C., Van Camp G.,
RA Smith R.J.H.;
RT "Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing
RT high-performance liquid chromatography and the identification of eleven
RT novel mutations.";
RL Am. J. Med. Genet. A 124:1-9(2004).
RN [24]
RP VARIANTS PDS GLN-29; CYS-78; PRO-137; PHE-138; ILE-193; VAL-209; PRO-236;
RP ASN-391; HIS-409; MET-410; PRO-416; TRP-445; HIS-530; ILE-552; PRO-694;
RP MET-721 AND ASN-724, AND VARIANT SER-597.
RX PubMed=15355436; DOI=10.1111/j.1399-0004.2004.00296.x;
RA Blons H., Feldmann D., Duval V., Messaz O., Denoyelle F., Loundon N.,
RA Sergout-Allaoui A., Houang M., Duriez F., Lacombe D., Delobel B., Leman J.,
RA Catros H., Journel H., Drouin-Garraud V., Obstoy M.-F., Toutain A.,
RA Oden S., Toublanc J.E., Couderc R., Petit C., Garabedian E.-N., Marlin S.;
RT "Screening of SLC26A4 (PDS) gene in Pendred's syndrome: a large spectrum of
RT mutations in France and phenotypic heterogeneity.";
RL Clin. Genet. 66:333-340(2004).
RN [25]
RP VARIANT PDS PRO-416.
RX PubMed=15531480; DOI=10.1210/jc.2004-1013;
RA Napiontek U., Borck G., Mueller-Forell W., Pfarr N., Bohnert A.,
RA Keilmann A., Pohlenz J.;
RT "Intrafamilial variability of the deafness and goiter phenotype in Pendred
RT syndrome caused by a T416P mutation in the SLC26A4 gene.";
RL J. Clin. Endocrinol. Metab. 89:5347-5351(2004).
RN [26]
RP VARIANTS PDS ARG-514 AND SER-530, AND VARIANTS GLY-609 AND CYS-776.
RX PubMed=15689455; DOI=10.1136/jmg.2004.024208;
RA Pryor S.P., Madeo A.C., Reynolds J.C., Sarlis N.J., Arnos K.S., Nance W.E.,
RA Yang Y., Zalewski C.K., Brewer C.C., Butman J.A., Griffith A.J.;
RT "SLC26A4/PDS genotype-phenotype correlation in hearing loss with
RT enlargement of the vestibular aqueduct (EVA): evidence that Pendred
RT syndrome and non-syndromic EVA are distinct clinical and genetic
RT entities.";
RL J. Med. Genet. 42:159-165(2005).
RN [27]
RP VARIANT CYS-776, AND CHARACTERIZATION OF VARIANT CYS-776.
RX PubMed=16684826; DOI=10.1210/jc.2006-0142;
RA Pfarr N., Borck G., Turk A., Napiontek U., Keilmann A., Mueller-Forell W.,
RA Kopp P., Pohlenz J.;
RT "Goitrous congenital hypothyroidism and hearing impairment associated with
RT mutations in the TPO and SLC26A4/PDS genes.";
RL J. Clin. Endocrinol. Metab. 91:2678-2681(2006).
RN [28]
RP VARIANT MET-99.
RX PubMed=17146393; DOI=10.1097/01.mlg.0000244389.68568.a7;
RA Propst E.J., Blaser S., Stockley T.L., Harrison R.V., Gordon K.A.,
RA Papsin B.C.;
RT "Temporal bone imaging in GJB2 deafness.";
RL Laryngoscope 116:2178-2186(2006).
RN [29]
RP VARIANTS PDS PHE-138; VAL-209; PRO-236; GLY-384; MET-402; PRO-416; TRP-445;
RP ARG-514; HIS-530; TYR-565 AND THR-775, VARIANTS DFNB4 LEU-335; MET-402;
RP SER-530 AND THR-775, AND VARIANTS SER-597; GLY-609 AND CYS-776.
RX PubMed=19204907; DOI=10.1002/humu.20884;
RA Choi B.Y., Stewart A.K., Madeo A.C., Pryor S.P., Lenhard S., Kittles R.,
RA Eisenman D., Kim H.J., Niparko J., Thomsen J., Arnos K.S., Nance W.E.,
RA King K.A., Zalewski C.K., Brewer C.C., Shawker T., Reynolds J.C.,
RA Butman J.A., Karniski L.P., Alper S.L., Griffith A.J.;
RT "Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss
RT and enlargement of the vestibular aqueduct: genotype-phenotype correlation
RT or coincidental polymorphisms?";
RL Hum. Mutat. 30:599-608(2009).
RN [30]
RP VARIANT DFNB4 ILE-281, AND VARIANTS VAL-6; ALA-144; THR-185 AND SER-597.
RX PubMed=20597900; DOI=10.1111/j.1469-1809.2010.00581.x;
RA Pourova R., Janousek P., Jurovcik M., Dvorakova M., Malikova M.,
RA Raskova D., Bendova O., Leonardi E., Murgia A., Kabelka Z., Astl J.,
RA Seeman P.;
RT "Spectrum and frequency of SLC26A4 mutations among Czech patients with
RT early hearing loss with and without enlarged vestibular aqueduct (EVA).";
RL Ann. Hum. Genet. 74:299-307(2010).
RN [31]
RP VARIANT DFNB4 LYS-558.
RX PubMed=20108392;
RA Alasti F., Peeters N., Wuyts W., Sanati M.H., Van Camp G.;
RT "Novel human pathological mutations. Gene symbol: SLC26A4. Disease:
RT Deafness, non-syndromic, autosomal recessive.";
RL Hum. Genet. 127:116-116(2010).
RN [32]
RP VARIANTS DFNB4 THR-185 AND LEU-335, VARIANTS LEU-335; GLY-384; TRP-445;
RP SER-597; CYS-775 AND CYS-776, AND CHARACTERIZATION OF VARIANT DFNB4
RP THR-185.
RX PubMed=24051746; DOI=10.1001/jamaoto.2013.4185;
RA Chattaraj P., Reimold F.R., Muskett J.A., Shmukler B.E., Chien W.W.,
RA Madeo A.C., Pryor S.P., Zalewski C.K., Butman J.A., Brewer C.C.,
RA Kenna M.A., Alper S.L., Griffith A.J.;
RT "Use of SLC26A4 mutation testing for unilateral enlargement of the
RT vestibular aqueduct.";
RL JAMA Otolaryngol. Head Neck Surg. 139:907-913(2013).
RN [33]
RP VARIANT PHE-455.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
RN [34]
RP VARIANTS DFNB4 PRO-227 AND CYS-556.
RX PubMed=28281779; DOI=10.1089/gtmb.2016.0328;
RA Wang R., Han S., Khan A., Zhang X.;
RT "Molecular Analysis of Twelve Pakistani Families with Nonsyndromic or
RT Syndromic Hearing Loss.";
RL Genet. Test. Mol. Biomarkers 21:316-321(2017).
CC -!- FUNCTION: Sodium-independent transporter of chloride and iodide.
CC {ECO:0000269|PubMed:10192399}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cell membrane; Multi-pass membrane protein.
CC Note=Localizes to the apical brush border of cells in the cortical
CC collecting ducts of the kidney. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43511-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43511-2; Sequence=VSP_056688;
CC -!- TISSUE SPECIFICITY: High expression in adult thyroid, lower expression
CC in adult and fetal kidney and fetal brain. Not expressed in other
CC tissues.
CC -!- DISEASE: Pendred syndrome (PDS) [MIM:274600]: An autosomal recessive
CC disorder characterized by congenital sensorineural hearing loss in
CC association with thyroid goiter. The disorder may account for up to 10%
CC of the cases of hereditary deafness. The deafness is most often
CC associated with a Mondini cochlear defect. Deafness occurs early,
CC starting at birth or during the first years of life. It is bilateral,
CC sometimes asymmetrical, fluctuant and often progressive. Thyroid
CC perturbations, such as thyroid goiter and/or hypothyroidism appear most
CC commonly during adolescence, but they can be congenital or appear
CC later. {ECO:0000269|PubMed:10602116, ECO:0000269|PubMed:10718825,
CC ECO:0000269|PubMed:10878664, ECO:0000269|PubMed:11317356,
CC ECO:0000269|PubMed:11375792, ECO:0000269|PubMed:11748854,
CC ECO:0000269|PubMed:11919333, ECO:0000269|PubMed:11932316,
CC ECO:0000269|PubMed:12788906, ECO:0000269|PubMed:12974744,
CC ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436,
CC ECO:0000269|PubMed:15531480, ECO:0000269|PubMed:15689455,
CC ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:9398842,
CC ECO:0000269|PubMed:9618166, ECO:0000269|PubMed:9618167}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Deafness, autosomal recessive, 4 (DFNB4) [MIM:600791]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. DFNB4 is associated with an enlarged vestibular aqueduct.
CC {ECO:0000269|PubMed:10190331, ECO:0000269|PubMed:10700480,
CC ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:12676893,
CC ECO:0000269|PubMed:14508505, ECO:0000269|PubMed:14679580,
CC ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:20108392,
CC ECO:0000269|PubMed:20597900, ECO:0000269|PubMed:24051746,
CC ECO:0000269|PubMed:28281779, ECO:0000269|PubMed:9500541}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page;
CC URL="https://hereditaryhearingloss.org/recessive-genes";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Pendrin entry;
CC URL="https://en.wikipedia.org/wiki/Pendrin";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A missing sense - Issue 133
CC of November 2011;
CC URL="https://web.expasy.org/spotlight/back_issues/133";
CC ---------------------------------------------------------------------------
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CC ---------------------------------------------------------------------------
DR EMBL; AF030880; AAC51873.1; -; mRNA.
DR EMBL; AK294388; BAH11752.1; -; mRNA.
DR EMBL; AC002467; AAB88773.2; -; Genomic_DNA.
DR EMBL; AC078937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS5746.1; -. [O43511-1]
DR RefSeq; NP_000432.1; NM_000441.1. [O43511-1]
DR RefSeq; XP_005250482.1; XM_005250425.2. [O43511-1]
DR AlphaFoldDB; O43511; -.
DR SMR; O43511; -.
DR BioGRID; 111198; 104.
DR STRING; 9606.ENSP00000265715; -.
DR BindingDB; O43511; -.
DR ChEMBL; CHEMBL4523138; -.
DR DrugBank; DB05382; Iodine.
DR TCDB; 2.A.53.2.17; the sulfate permease (sulp) family.
DR iPTMnet; O43511; -.
DR PhosphoSitePlus; O43511; -.
DR BioMuta; SLC26A4; -.
DR jPOST; O43511; -.
DR MassIVE; O43511; -.
DR PaxDb; O43511; -.
DR PeptideAtlas; O43511; -.
DR PRIDE; O43511; -.
DR ProteomicsDB; 49001; -. [O43511-1]
DR ProteomicsDB; 6414; -.
DR Antibodypedia; 31372; 169 antibodies from 25 providers.
DR DNASU; 5172; -.
DR Ensembl; ENST00000644269.2; ENSP00000494017.1; ENSG00000091137.14. [O43511-1]
DR GeneID; 5172; -.
DR KEGG; hsa:5172; -.
DR MANE-Select; ENST00000644269.2; ENSP00000494017.1; NM_000441.2; NP_000432.1.
DR UCSC; uc003vep.4; human. [O43511-1]
DR CTD; 5172; -.
DR DisGeNET; 5172; -.
DR GeneCards; SLC26A4; -.
DR GeneReviews; SLC26A4; -.
DR HGNC; HGNC:8818; SLC26A4.
DR HPA; ENSG00000091137; Tissue enriched (thyroid).
DR MalaCards; SLC26A4; -.
DR MIM; 274600; phenotype.
DR MIM; 600791; phenotype.
DR MIM; 605646; gene.
DR neXtProt; NX_O43511; -.
DR OpenTargets; ENSG00000091137; -.
DR Orphanet; 95713; Athyreosis.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 705; Pendred syndrome.
DR Orphanet; 95720; Thyroid hypoplasia.
DR PharmGKB; PA35506; -.
DR VEuPathDB; HostDB:ENSG00000091137; -.
DR eggNOG; KOG0236; Eukaryota.
DR GeneTree; ENSGT01050000244807; -.
DR HOGENOM; CLU_003182_9_4_1; -.
DR InParanoid; O43511; -.
DR OMA; KMEQCGF; -.
DR OrthoDB; 690428at2759; -.
DR PhylomeDB; O43511; -.
DR TreeFam; TF313784; -.
DR PathwayCommons; O43511; -.
DR Reactome; R-HSA-427601; Multifunctional anion exchangers.
DR Reactome; R-HSA-5619046; Defective SLC26A4 causes Pendred syndrome (PDS).
DR SignaLink; O43511; -.
DR SIGNOR; O43511; -.
DR BioGRID-ORCS; 5172; 13 hits in 1068 CRISPR screens.
DR GeneWiki; Pendrin; -.
DR GenomeRNAi; 5172; -.
DR Pharos; O43511; Tbio.
DR PRO; PR:O43511; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O43511; protein.
DR Bgee; ENSG00000091137; Expressed in palpebral conjunctiva and 122 other tissues.
DR ExpressionAtlas; O43511; baseline and differential.
DR Genevisible; O43511; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015301; F:anion:anion antiporter activity; IBA:GO_Central.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015111; F:iodide transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0019531; F:oxalate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0008271; F:secondary active sulfate transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0015116; F:sulfate transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015698; P:inorganic anion transport; TAS:ProtInc.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0006885; P:regulation of pH; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR GO; GO:0008272; P:sulfate transport; TAS:ProtInc.
DR Gene3D; 3.30.750.24; -; 1.
DR InterPro; IPR030285; Pendrin.
DR InterPro; IPR018045; S04_transporter_CS.
DR InterPro; IPR011547; SLC26A/SulP_dom.
DR InterPro; IPR001902; SLC26A/SulP_fam.
DR InterPro; IPR002645; STAS_dom.
DR InterPro; IPR036513; STAS_dom_sf.
DR PANTHER; PTHR11814; PTHR11814; 1.
DR PANTHER; PTHR11814:SF33; PTHR11814:SF33; 1.
DR Pfam; PF01740; STAS; 1.
DR Pfam; PF00916; Sulfate_transp; 1.
DR SUPFAM; SSF52091; SSF52091; 1.
DR TIGRFAMs; TIGR00815; sulP; 1.
DR PROSITE; PS01130; SLC26A; 1.
DR PROSITE; PS50801; STAS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Chloride; Deafness; Disease variant;
KW Membrane; Non-syndromic deafness; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..780
FT /note="Pendrin"
FT /id="PRO_0000080164"
FT TOPO_DOM 1..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..156
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 157..191
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 213..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 219..239
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 240..263
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 264..284
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 285..295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 296..316
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 317..344
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 366..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 406..421
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 422..442
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 443..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 470..486
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 487..507
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 508..780
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 535..729
FT /note="STAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00198"
FT VAR_SEQ 1..431
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056688"
FT VARIANT 6
FT /note="G -> V (in dbSNP:rs111033423)"
FT /evidence="ECO:0000269|PubMed:20597900"
FT /id="VAR_064988"
FT VARIANT 24
FT /note="R -> G (in Pendred syndrome/deafness individuals;
FT dbSNP:rs1268256689)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_021638"
FT VARIANT 28
FT /note="S -> R (in PDS and DFNB4; dbSNP:rs539699299)"
FT /evidence="ECO:0000269|PubMed:11919333,
FT ECO:0000269|PubMed:12676893"
FT /id="VAR_021639"
FT VARIANT 29
FT /note="E -> Q (in PDS; dbSNP:rs111033205)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436"
FT /id="VAR_021640"
FT VARIANT 78
FT /note="Y -> C (in PDS)"
FT /evidence="ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436"
FT /id="VAR_021641"
FT VARIANT 90
FT /note="S -> L (in DFNB4; dbSNP:rs370588279)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021642"
FT VARIANT 99
FT /note="T -> M (in dbSNP:rs141142414)"
FT /evidence="ECO:0000269|PubMed:17146393"
FT /id="VAR_064989"
FT VARIANT 102
FT /note="G -> R (in PDS; fails to localize to cell membrane;
FT abolishes iodide transport; dbSNP:rs1219724284)"
FT /evidence="ECO:0000269|PubMed:11932316"
FT /id="VAR_021643"
FT VARIANT 104
FT /note="A -> V (in Pendred syndrome/deafness individuals;
FT dbSNP:rs1203167658)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_021644"
FT VARIANT 105
FT /note="Y -> C (in PDS; dbSNP:rs1442599990)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580"
FT /id="VAR_021645"
FT VARIANT 106
FT /note="A -> D (in PDS)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580"
FT /id="VAR_021646"
FT VARIANT 117
FT /note="L -> F (in DFNB4 and PDS; does not affect protein
FT localization to cell membrane; does not affect iodide
FT transport; dbSNP:rs145254330)"
FT /evidence="ECO:0000269|PubMed:10700480,
FT ECO:0000269|PubMed:11932316"
FT /id="VAR_021647"
FT VARIANT 123
FT /note="P -> S (in DFNB4; dbSNP:rs984967571)"
FT /evidence="ECO:0000269|PubMed:14508505"
FT /id="VAR_027238"
FT VARIANT 132
FT /note="T -> I (in DFNB4; dbSNP:rs1554354370)"
FT /evidence="ECO:0000269|PubMed:11748854"
FT /id="VAR_021648"
FT VARIANT 133
FT /note="S -> T (in PDS; dbSNP:rs121908365)"
FT /evidence="ECO:0000269|PubMed:11919333,
FT ECO:0000269|PubMed:12788906"
FT /id="VAR_021649"
FT VARIANT 137
FT /note="S -> P (in PDS; dbSNP:rs1554354382)"
FT /evidence="ECO:0000269|PubMed:15355436"
FT /id="VAR_021650"
FT VARIANT 138
FT /note="V -> F (in PDS; fails to localize to cell membrane;
FT abolishes iodide transport; dbSNP:rs111033199)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:11375792, ECO:0000269|PubMed:11932316,
FT ECO:0000269|PubMed:12788906, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:9618166, ECO:0000269|PubMed:9618167"
FT /id="VAR_021651"
FT VARIANT 139
FT /note="G -> A (in PDS)"
FT /evidence="ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:9618166"
FT /id="VAR_021652"
FT VARIANT 144
FT /note="V -> A (found at heterozygosity in a patient with
FT non-syndromic deafness; uncertain pathological
FT significance; dbSNP:rs772023020)"
FT /evidence="ECO:0000269|PubMed:20597900"
FT /id="VAR_064990"
FT VARIANT 147
FT /note="M -> V (in DFNB4; dbSNP:rs760413427)"
FT /evidence="ECO:0000269|PubMed:14508505"
FT /id="VAR_027239"
FT VARIANT 185
FT /note="R -> T (in DFNB4; also found at heterozygosity in a
FT patient with non-syndromic deafness; uncertain pathological
FT significance; may affect subcellular location at the plasma
FT membrane; dbSNP:rs542620119)"
FT /evidence="ECO:0000269|PubMed:20597900"
FT /id="VAR_064991"
FT VARIANT 193
FT /note="T -> I (in PDS; dbSNP:rs111033348)"
FT /evidence="ECO:0000269|PubMed:10878664,
FT ECO:0000269|PubMed:15355436"
FT /id="VAR_011623"
FT VARIANT 209
FT /note="G -> V (in DFNB4 and PDS; severely reduces iodide
FT transport without affecting protein localization to cell
FT membrane; dbSNP:rs111033303)"
FT /evidence="ECO:0000269|PubMed:10190331,
FT ECO:0000269|PubMed:10700480, ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:11932316, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:9618166"
FT /id="VAR_007440"
FT VARIANT 227
FT /note="A -> P (in DFNB4)"
FT /evidence="ECO:0000269|PubMed:28281779"
FT /id="VAR_079503"
FT VARIANT 236
FT /note="L -> P (in PDS and DFNB4; common mutation; fails to
FT localize to cell membrane; abolishes iodide transport;
FT dbSNP:rs80338848)"
FT /evidence="ECO:0000269|PubMed:10700480,
FT ECO:0000269|PubMed:11317356, ECO:0000269|PubMed:11932316,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436,
FT ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:9618166,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_007441"
FT VARIANT 239
FT /note="V -> D (in PDS and DFNB4; dbSNP:rs111033256)"
FT /evidence="ECO:0000269|PubMed:12676893,
FT ECO:0000269|PubMed:12974744"
FT /id="VAR_021653"
FT VARIANT 252
FT /note="S -> P (in DFNB4; dbSNP:rs1315422549)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021654"
FT VARIANT 271
FT /note="D -> H (in PDS)"
FT /evidence="ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:9618166"
FT /id="VAR_021655"
FT VARIANT 281
FT /note="V -> I (in DFNB4; dbSNP:rs727505080)"
FT /evidence="ECO:0000269|PubMed:20597900"
FT /id="VAR_064992"
FT VARIANT 301
FT /note="P -> L (in dbSNP:rs34373141)"
FT /id="VAR_053663"
FT VARIANT 324
FT /note="N -> Y (in dbSNP:rs36039758)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_053664"
FT VARIANT 335
FT /note="F -> L (in PDS and DFNB4; dbSNP:rs111033212)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:24051746"
FT /id="VAR_021656"
FT VARIANT 369
FT /note="K -> E (in DFNB4; dbSNP:rs121908361)"
FT /evidence="ECO:0000269|PubMed:10190331"
FT /id="VAR_007442"
FT VARIANT 372
FT /note="A -> V (in DFNB4; dbSNP:rs121908364)"
FT /evidence="ECO:0000269|PubMed:10190331"
FT /id="VAR_007443"
FT VARIANT 384
FT /note="E -> G (in PDS; also found at heterozygosity in a
FT patient with hearing loss and unilateral enlargement of the
FT vestibular aqueduct; uncertain pathological significance;
FT dbSNP:rs111033244)"
FT /evidence="ECO:0000269|PubMed:12788906,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:24051746, ECO:0000269|PubMed:9618167"
FT /id="VAR_007444"
FT VARIANT 391
FT /note="S -> N (in PDS)"
FT /evidence="ECO:0000269|PubMed:15355436"
FT /id="VAR_021657"
FT VARIANT 392
FT /note="N -> Y (in DFNB4; dbSNP:rs201562855)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021658"
FT VARIANT 402
FT /note="V -> M (in PDS and DFNB4; dbSNP:rs397516414)"
FT /evidence="ECO:0000269|PubMed:19204907"
FT /id="VAR_058580"
FT VARIANT 409
FT /note="R -> H (in PDS; dbSNP:rs111033305)"
FT /evidence="ECO:0000269|PubMed:11919333,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436,
FT ECO:0000269|PubMed:9618166, ECO:0000269|PubMed:9618167"
FT /id="VAR_021659"
FT VARIANT 409
FT /note="R -> P (in DFNB4; dbSNP:rs111033305)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021660"
FT VARIANT 410
FT /note="T -> M (in DFNB4 and PDS; fails to localize to cell
FT membrane; abolishes iodide transport; dbSNP:rs111033220)"
FT /evidence="ECO:0000269|PubMed:10700480,
FT ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:11919333,
FT ECO:0000269|PubMed:11932316, ECO:0000269|PubMed:12676893,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_021661"
FT VARIANT 411
FT /note="A -> P (in PDS; dbSNP:rs1293971731)"
FT /evidence="ECO:0000269|PubMed:11375792"
FT /id="VAR_021662"
FT VARIANT 416
FT /note="T -> P (in PDS and DFNB4; common mutation;
FT dbSNP:rs28939086)"
FT /evidence="ECO:0000269|PubMed:10700480,
FT ECO:0000269|PubMed:11317356, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:15531480,
FT ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:9618166,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_007445"
FT VARIANT 421
FT /note="Q -> R (in Pendred syndrome/deafness individuals;
FT dbSNP:rs201660407)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_021663"
FT VARIANT 429
FT /note="Missing (in Pendred syndrome/deafness individuals)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_021664"
FT VARIANT 445
FT /note="L -> W (in PDS and DFNB4; also found at
FT heterozygosity in a patient with hearing loss and
FT unilateral enlargement of the vestibular aqueduct;
FT uncertain pathological significance; dbSNP:rs111033307)"
FT /evidence="ECO:0000269|PubMed:10602116,
FT ECO:0000269|PubMed:10700480, ECO:0000269|PubMed:11748854,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436,
FT ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:24051746,
FT ECO:0000269|PubMed:9618166"
FT /id="VAR_011624"
FT VARIANT 446
FT /note="Q -> R (in DFNB4 and PDS; fails to localize to cell
FT membrane; abolishes iodide transport; dbSNP:rs768471577)"
FT /evidence="ECO:0000269|PubMed:10700480,
FT ECO:0000269|PubMed:11932316"
FT /id="VAR_021665"
FT VARIANT 455
FT /note="I -> F (in dbSNP:rs375576481)"
FT /evidence="ECO:0000269|PubMed:12676893,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_021666"
FT VARIANT 457
FT /note="N -> K (in DFNB4; dbSNP:rs1554359670)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021667"
FT VARIANT 480
FT /note="V -> D (in PDS; retains residual transport
FT function)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580"
FT /id="VAR_021668"
FT VARIANT 490
FT /note="I -> L (in DFNB4; dbSNP:rs200511789)"
FT /evidence="ECO:0000269|PubMed:9500541"
FT /id="VAR_021669"
FT VARIANT 497
FT /note="G -> S (in DFNB4; dbSNP:rs111033308)"
FT /evidence="ECO:0000269|PubMed:9500541"
FT /id="VAR_007446"
FT VARIANT 508
FT /note="T -> N (in PDS)"
FT /evidence="ECO:0000269|PubMed:10718825"
FT /id="VAR_027240"
FT VARIANT 514
FT /note="Q -> R (in PDS; dbSNP:rs111033316)"
FT /evidence="ECO:0000269|PubMed:15689455,
FT ECO:0000269|PubMed:19204907"
FT /id="VAR_027241"
FT VARIANT 530
FT /note="Y -> H (in PDS; dbSNP:rs111033254)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:12788906, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_021670"
FT VARIANT 530
FT /note="Y -> S (in PDS and DFNB4; dbSNP:rs747636919)"
FT /evidence="ECO:0000269|PubMed:15689455,
FT ECO:0000269|PubMed:19204907"
FT /id="VAR_027242"
FT VARIANT 552
FT /note="S -> I (in PDS)"
FT /evidence="ECO:0000269|PubMed:15355436"
FT /id="VAR_021671"
FT VARIANT 556
FT /note="Y -> C (in PDS and DFNB4; partially affects protein
FT localization to cell membrane; abolishes iodide transport;
FT dbSNP:rs763006761)"
FT /evidence="ECO:0000269|PubMed:11932316,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:28281779,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_021672"
FT VARIANT 556
FT /note="Y -> H (in PDS)"
FT /evidence="ECO:0000269|PubMed:11748854"
FT /id="VAR_021673"
FT VARIANT 558
FT /note="N -> K (in DFNB4)"
FT /evidence="ECO:0000269|PubMed:20108392"
FT /id="VAR_064993"
FT VARIANT 565
FT /note="C -> Y (in PDS; dbSNP:rs111033257)"
FT /evidence="ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:9618166"
FT /id="VAR_021674"
FT VARIANT 597
FT /note="L -> S (found at heterozygosity in a patient with
FT hearing loss and unilateral enlargement of the vestibular
FT aqueduct; uncertain pathological significance;
FT dbSNP:rs55638457)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:11919333, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:20597900, ECO:0000269|PubMed:24051746"
FT /id="VAR_021675"
FT VARIANT 609
FT /note="V -> G (in dbSNP:rs17154335)"
FT /evidence="ECO:0000269|PubMed:15689455,
FT ECO:0000269|PubMed:19204907"
FT /id="VAR_027243"
FT VARIANT 653
FT /note="V -> A (in PDS; retains residual transport function;
FT dbSNP:rs1554361015)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:14679580"
FT /id="VAR_021676"
FT VARIANT 666
FT /note="S -> F (in DFNB4; dbSNP:rs1584337274)"
FT /evidence="ECO:0000269|PubMed:14508505"
FT /id="VAR_027244"
FT VARIANT 667
FT /note="F -> C (in PDS; dbSNP:rs121908360)"
FT /evidence="ECO:0000269|PubMed:9398842"
FT /id="VAR_007447"
FT VARIANT 672
FT /note="G -> E (in PDS; partially affects protein
FT localization to cell membrane; abolishes iodide transport;
FT dbSNP:rs111033309)"
FT /evidence="ECO:0000269|PubMed:11317356,
FT ECO:0000269|PubMed:11932316, ECO:0000269|PubMed:14679580,
FT ECO:0000269|PubMed:9618167"
FT /id="VAR_021677"
FT VARIANT 676
FT /note="L -> Q (in DFNB4; dbSNP:rs111033318)"
FT /evidence="ECO:0000269|PubMed:12676893"
FT /id="VAR_021678"
FT VARIANT 683
FT /note="F -> S (in Pendred syndrome/deafness individuals;
FT dbSNP:rs1060499808)"
FT /evidence="ECO:0000269|PubMed:14679580"
FT /id="VAR_021679"
FT VARIANT 687
FT /note="D -> Y (in dbSNP:rs35548413)"
FT /id="VAR_053665"
FT VARIANT 694
FT /note="S -> P (in PDS; dbSNP:rs981410021)"
FT /evidence="ECO:0000269|PubMed:15355436"
FT /id="VAR_021680"
FT VARIANT 721
FT /note="T -> M (in DFNB4 and PDS; dbSNP:rs121908363)"
FT /evidence="ECO:0000269|PubMed:10190331,
FT ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:12676893,
FT ECO:0000269|PubMed:15355436"
FT /id="VAR_007448"
FT VARIANT 723
FT /note="H -> R (in DFNB4 and PDS; common mutation in Korea
FT and Japan; dbSNP:rs121908362)"
FT /evidence="ECO:0000269|PubMed:10190331,
FT ECO:0000269|PubMed:12676893, ECO:0000269|PubMed:12974744,
FT ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:9618166"
FT /id="VAR_007449"
FT VARIANT 724
FT /note="D -> N (in PDS; dbSNP:rs994170964)"
FT /evidence="ECO:0000269|PubMed:15355436"
FT /id="VAR_021681"
FT VARIANT 740
FT /note="G -> S (in dbSNP:rs17154353)"
FT /id="VAR_027245"
FT VARIANT 775
FT /note="M -> C (found at heterozygosity in a patient with
FT hearing loss and unilateral enlargement of the vestibular
FT aqueduct; requires 2 nucleotide substitutions; uncertain
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:24051746"
FT /id="VAR_080402"
FT VARIANT 775
FT /note="M -> T (in PDS and DFNB4; dbSNP:rs1562845849)"
FT /evidence="ECO:0000269|PubMed:19204907"
FT /id="VAR_058581"
FT VARIANT 776
FT /note="R -> C (found at heterozygosity in a patient with
FT hearing loss and unilateral enlargement of the vestibular
FT aqueduct; unknown pathological significance; retains its
FT ability to transport iodide in vitro; dbSNP:rs111033255)"
FT /evidence="ECO:0000269|PubMed:15689455,
FT ECO:0000269|PubMed:16684826, ECO:0000269|PubMed:19204907,
FT ECO:0000269|PubMed:24051746"
FT /id="VAR_027246"
SQ SEQUENCE 780 AA; 85723 MW; 3AEF5D720B155CE0 CRC64;
MAAPGGRSEP PQLPEYSCSY MVSRPVYSEL AFQQQHERRL QERKTLRESL AKCCSCSRKR
AFGVLKTLVP ILEWLPKYRV KEWLLSDVIS GVSTGLVATL QGMAYALLAA VPVGYGLYSA
FFPILTYFIF GTSRHISVGP FPVVSLMVGS VVLSMAPDEH FLVSSSNGTV LNTTMIDTAA
RDTARVLIAS ALTLLVGIIQ LIFGGLQIGF IVRYLADPLV GGFTTAAAFQ VLVSQLKIVL
NVSTKNYNGV LSIIYTLVEI FQNIGDTNLA DFTAGLLTIV VCMAVKELND RFRHKIPVPI
PIEVIVTIIA TAISYGANLE KNYNAGIVKS IPRGFLPPEL PPVSLFSEML AASFSIAVVA
YAIAVSVGKV YATKYDYTID GNQEFIAFGI SNIFSGFFSC FVATTALSRT AVQESTGGKT
QVAGIISAAI VMIAILALGK LLEPLQKSVL AAVVIANLKG MFMQLCDIPR LWRQNKIDAV
IWVFTCIVSI ILGLDLGLLA GLIFGLLTVV LRVQFPSWNG LGSIPSTDIY KSTKNYKNIE
EPQGVKILRF SSPIFYGNVD GFKKCIKSTV GFDAIRVYNK RLKALRKIQK LIKSGQLRAT
KNGIISDAVS TNNAFEPDED IEDLEELDIP TKEIEIQVDW NSELPVKVNV PKVPIHSLVL
DCGAISFLDV VGVRSLRVIV KEFQRIDVNV YFASLQDYVI EKLEQCGFFD DNIRKDTFFL
TVHDAILYLQ NQVKSQEGQG SILETITLIQ DCKDTLELIE TELTEEELDV QDEAMRTLAS
