BEST1_HUMAN
ID BEST1_HUMAN Reviewed; 585 AA.
AC O76090; A8K0W6; B7Z3J8; B7Z736; O75904; Q53YQ9; Q8IUR9; Q8IZ80;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Bestrophin-1;
DE AltName: Full=TU15B;
DE AltName: Full=Vitelliform macular dystrophy protein 2;
GN Name=BEST1; Synonyms=VMD2;
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 [GENOMIC DNA], AND VARIANTS VMD2.
RX PubMed=9700209; DOI=10.1093/hmg/7.9.1517;
RA Marquardt A., Stoehr H., Passmore L.A., Kraemer F., Rivera A.,
RA Weber B.H.F.;
RT "Mutations in a novel gene, VMD2, encoding a protein of unknown properties
RT cause juvenile-onset vitelliform macular dystrophy (Best's disease).";
RL Hum. Mol. Genet. 7:1517-1525(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VMD2 PRO-6; HIS-85;
RP CYS-93; ASN-227 AND GLU-299.
RX PubMed=9662395; DOI=10.1038/915;
RA Petrukhin K., Koisti M.J., Bakall B., Li W., Xie G., Marknell T.,
RA Sandgren O., Forsman K., Holmgren G., Andreasson S., Vujic M.,
RA Bergen A.A.B., McGarty-Dugan V., Figueroa D., Austin C.P., Metzker M.L.,
RA Caskey C.T., Wadelius C.;
RT "Identification of the gene responsible for Best macular dystrophy.";
RL Nat. Genet. 19:241-247(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TOPOLOGY.
RX PubMed=12907679; DOI=10.1074/jbc.m306150200;
RA Tsunenari T., Sun H., Williams J., Cahill H., Smallwood P., Yau K.-W.,
RA Nathans J.;
RT "Structure-function analysis of the bestrophin family of anion channels.";
RL J. Biol. Chem. 278:41114-41125(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANT
RP VAL-357.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 52-585 (ISOFORM 1).
RC TISSUE=Amygdala, Subthalamic nucleus, and Synovium;
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 [7]
RP FUNCTION.
RX PubMed=11904445; DOI=10.1073/pnas.052692999;
RA Sun H., Tsunenari T., Yau K.-W., Nathans J.;
RT "The vitelliform macular dystrophy protein defines a new family of chloride
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4008-4013(2002).
RN [8]
RP FUNCTION, AND CHARACTERIZATION OF VARIANTS VMD2 HIS-85; CYS-92 AND CYS-93.
RX PubMed=18400985; DOI=10.1152/ajpcell.00398.2007;
RA Qu Z., Hartzell H.C.;
RT "Bestrophin Cl- channels are highly permeable to HCO3-.";
RL Am. J. Physiol. 294:C1371-C1377(2008).
RN [9]
RP SUBCELLULAR LOCATION, VARIANTS RP50 VAL-140; THR-205; CYS-227 AND ASN-228,
RP CHARACTERIZATION OF VARIANTS RP50 VAL-140; THR-205 AND ASN-228, AND
RP CHARACTERIZATION OF VARIANT ARB ASN-312.
RX PubMed=19853238; DOI=10.1016/j.ajhg.2009.09.015;
RA Davidson A.E., Millar I.D., Urquhart J.E., Burgess-Mullan R., Shweikh Y.,
RA Parry N., O'Sullivan J., Maher G.J., McKibbin M., Downes S.M., Lotery A.J.,
RA Jacobson S.G., Brown P.D., Black G.C., Manson F.D.;
RT "Missense mutations in a retinal pigment epithelium protein, bestrophin-1,
RT cause retinitis pigmentosa.";
RL Am. J. Hum. Genet. 85:581-592(2009).
RN [10]
RP VARIANTS VMD2 HIS-13; CYS-93; CYS-218; ASP-300; GLU-301 AND ILE-307.
RX PubMed=10331951; DOI=10.1006/geno.1999.5808;
RA Caldwell G.M., Kakuk L.E., Griesinger I.B., Simpson S.A., Nowak N.J.,
RA Small K.W., Maumenee I.H., Rosenfeld P.J., Sieving P.A., Shows T.B.,
RA Ayyagari R.;
RT "Bestrophin gene mutations in patients with Best vitelliform macular
RT dystrophy.";
RL Genomics 58:98-101(1999).
RN [11]
RP VARIANTS VMD2 VAL-10; VAL-82; CYS-92; HIS-96; SER-135; CYS-218; SER-218 AND
RP LYS-293.
RX PubMed=10394929; DOI=10.1007/s004390050972;
RA Bakall B., Marknell T., Ingvast S., Koisti M.J., Sandgren O., Li W.,
RA Bergen A.A.B., Andreasson S., Rosenberg T., Petrukhin K., Wadelius C.;
RT "The mutation spectrum of the bestrophin protein -- functional
RT implications.";
RL Hum. Genet. 104:383-389(1999).
RN [12]
RP VARIANTS VMD2 LYS-146; SER-297 AND ASP-300, AND VARIANTS GLN-119; ILE-216;
RP ALA-525; LYS-557; ALA-561 AND PHE-567.
RX PubMed=10453731; DOI=10.1007/s004390050986;
RA Allikmets R., Seddon J.M., Bernstein P.S., Hutchinson A., Atkinson A.,
RA Sharma S., Gerrard B., Li W., Metzker M.L., Wadelius C., Caskey C.T.,
RA Dean M., Petrukhin K.;
RT "Evaluation of the Best disease gene in patients with age-related macular
RT degeneration and other maculopathies.";
RL Hum. Genet. 104:449-453(1999).
RN [13]
RP VARIANT VMD2 TRP-221.
RX PubMed=10682987; DOI=10.1016/s0002-9394(99)00327-x;
RA Palomba G., Rozzo C., Angius A., Pierrottet C.O., Orzalesi N., Pirastu M.;
RT "A novel spontaneous missense mutation in VMD2 gene is a cause of a Best
RT macular dystrophy sporadic case.";
RL Am. J. Ophthalmol. 129:260-262(2000).
RN [14]
RP VARIANT VAL-222.
RX PubMed=10766140; DOI=10.1001/archopht.118.4.538;
RA Lotery A.J., Namperumalsamy P., Jacobson S.G., Weleber R.G., Fishman G.A.,
RA Musarella M.A., Hoyt C.S., Heon E., Levin A., Jan J., Lam B., Carr R.E.,
RA Franklin A., Radha S., Andorf J.L., Sheffield V.C., Stone E.M.;
RT "Mutation analysis of 3 genes in patients with Leber congenital
RT amaurosis.";
RL Arch. Ophthalmol. 118:538-543(2000).
RN [15]
RP VARIANTS AGE-RELATED MACULAR DEGENERATION CYS-105 AND ILE-275, AND VARIANTS
RP VMD2 THR-201; ILE-207; PRO-224; THR-243; LEU-276; HIS-296; GLY-302;
RP VAL-302; ASP-306; GLY-306 AND ALA-307.
RX PubMed=10798642;
RA Lotery A.J., Munier F.L., Fishman G.A., Weleber R.G., Jacobson S.G.,
RA Affatigato L.M., Nichols B.E., Schorderet D.F., Sheffield V.C., Stone E.M.;
RT "Allelic variation in the VMD2 gene in best disease and age-related macular
RT degeneration.";
RL Invest. Ophthalmol. Vis. Sci. 41:1291-1296(2000).
RN [16]
RP VARIANTS VMD2 PHE-16; CYS-17; ASN-73; HIS-92; CYS-218; HIS-218; LEU-235 AND
RP SER-296.
RX PubMed=11241846; DOI=10.1002/humu.9;
RA Marchant D., Gogat K., Boutboul S., Pequignot M., Sternberg C., Dureau P.,
RA Roche O., Uteza Y., Hache J.C., Puech B., Puech V., Dumur V., Mouillon M.,
RA Munier F.L., Schorderet D.F., Marsac C., Dufier J.-L., Abitbol M.;
RT "Identification of novel VMD2 gene mutations in patients with Best
RT vitelliform macular dystrophy.";
RL Hum. Mutat. 17:235-235(2001).
RN [17]
RP VARIANT VMD2 ALA-89.
RX PubMed=11449320; DOI=10.1076/opge.22.2.107.2226;
RA Eksandh L., Bakall B., Bauer B., Wadelius C., Andreasson S.;
RT "Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala)
RT in the VMD2 gene.";
RL Ophthalmic Genet. 22:107-115(2001).
RN [18]
RP VARIANT VMD2 THR-295.
RX PubMed=12187431; DOI=10.1076/opge.23.2.129.2213;
RA Yanagi Y., Sekine H., Mori M.;
RT "Identification of a novel VMD2 mutation in Japanese patients with Best
RT disease.";
RL Ophthalmic Genet. 23:129-133(2002).
RN [19]
RP VARIANTS VMD2 HIS-302; GLU-303 AND SER-308.
RX PubMed=12324875; DOI=10.1076/opge.23.3.167.7880;
RA Marchant D., Gogat K., Dureau P., Sainton K., Sternberg C., Gadin S.,
RA Dollfus H., Brasseur G., Hache J.C., Dumur V., Puech V., Munier F.L.,
RA Schorderet D.F., Marsac C., Menasche M., Dufier J.-L., Abitbol M.;
RT "Use of denaturing HPLC and automated sequencing to screen the VMD2 gene
RT for mutations associated with Best's vitelliform macular dystrophy.";
RL Ophthalmic Genet. 23:167-174(2002).
RN [20]
RP VARIANTS VMD2 ILE-11; ARG-26; HIS-29; PRO-41; ARG-102; HIS-104; ASN-241;
RP VAL-294 AND SER-298.
RX PubMed=14517959; DOI=10.1002/humu.9189;
RA Kraemer F., Mohr N., Kellner U., Rudolph G., Weber B.H.F.;
RT "Ten novel mutations in VMD2 associated with Best macular dystrophy
RT (BMD).";
RL Hum. Mutat. 22:418-418(2003).
RN [21]
RP VARIANTS VMD2 SER-297 AND ASP-300.
RX PubMed=13129869; DOI=10.1016/s0161-6420(03)00575-x;
RA Seddon J.M., Sharma S., Chong S., Hutchinson A., Allikmets R.,
RA Adelman R.A.;
RT "Phenotype and genotype correlations in two best families.";
RL Ophthalmology 110:1724-1731(2003).
RN [22]
RP VARIANT VMD2 LEU-113.
RX PubMed=15176385;
RA Li Y., Wang G.L., Dong B.;
RT "Gene Symbol: VMD2. Disease: Best vitelliform macular dystrophy (VMD2).";
RL Hum. Genet. 114:608-608(2004).
RN [23]
RP VARIANTS VRCP MET-86; CYS-236 AND MET-239.
RX PubMed=15452077; DOI=10.1167/iovs.04-0550;
RA Yardley J., Leroy B.P., Hart-Holden N., Lafaut B.A., Loeys B.,
RA Messiaen L.M., Perveen R., Reddy M.A., Bhattacharya S.S., Traboulsi E.,
RA Baralle D., De Laey J.-J., Puech B., Kestelyn P., Moore A.T.,
RA Manson F.D.C., Black G.C.M.;
RT "Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal
RT dominant vitreoretinochoroidopathy (ADVIRC).";
RL Invest. Ophthalmol. Vis. Sci. 45:3683-3689(2004).
RN [24]
RP VARIANTS ARB PRO-41; HIS-141; ALA-152; ASN-312; MET-317 AND THR-325, AND
RP CHARACTERIZATION OF VARIANTS ARB HIS-141 AND ALA-152.
RX PubMed=18179881; DOI=10.1016/j.ajhg.2007.08.004;
RA Burgess R., Millar I.D., Leroy B.P., Urquhart J.E., Fearon I.M.,
RA De Baere E., Brown P.D., Robson A.G., Wright G.A., Kestelyn P.,
RA Holder G.E., Webster A.R., Manson F.D.C., Black G.C.M.;
RT "Biallelic mutation of BEST1 causes a distinct retinopathy in humans.";
RL Am. J. Hum. Genet. 82:19-31(2008).
RN [25]
RP VARIANTS VMD2 CYS-218 AND MET-242.
RX PubMed=18766995; DOI=10.1080/13816810802087394;
RA Atchaneeyasakul L.O., Jinda W., Sakolsatayadorn N., Trinavarat A.,
RA Ruangvoravate N., Thanasombatskul N., Thongnoppakhun W., Limwongse C.;
RT "Mutation analysis of the VMD2 gene in Thai families with Best macular
RT dystrophy.";
RL Ophthalmic Genet. 29:139-144(2008).
RN [26]
RP VARIANTS VMD2 THR-3; PRO-6; VAL-82; ASN-227; VAL-243; ALA-299 AND
RP 302-ASP--ASP-304 DEL.
RX PubMed=19357557; DOI=10.1097/iae.0b013e31819d4fda;
RA Boon C.J.F., Theelen T., Hoefsloot E.H., van Schooneveld M.J.,
RA Keunen J.E.E., Cremers F.P.M., Klevering B.J., Hoyng C.B.;
RT "Clinical and molecular genetic analysis of Best vitelliform macular
RT dystrophy.";
RL Retina 29:835-847(2009).
RN [27]
RP CHARACTERIZATION OF VARIANTS ARB PRO-41; VAL-140; HIS-141; ALA-152;
RP VAL-195; TRP-202; ASN-312; MET-317 AND THR-325, AND CHARACTERIZATION OF
RP VARIANTS VMD2 HIS-85 AND ARG-237.
RX PubMed=21330666; DOI=10.1167/iovs.10-6707;
RA Davidson A.E., Millar I.D., Burgess-Mullan R., Maher G.J., Urquhart J.E.,
RA Brown P.D., Black G.C., Manson F.D.;
RT "Functional characterization of bestrophin-1 missense mutations associated
RT with autosomal recessive bestrophinopathy.";
RL Invest. Ophthalmol. Vis. Sci. 52:3730-3736(2011).
RN [28]
RP VARIANT ARB HIS-141, CHARACTERIZATION OF VARIANT ARB HIS-141, SUBCELLULAR
RP LOCATION, AND OLIGOMERIZATION.
RX PubMed=26200502; DOI=10.1167/iovs.15-16910;
RA Johnson A.A., Bachman L.A., Gilles B.J., Cross S.D., Stelzig K.E.,
RA Resch Z.T., Marmorstein L.Y., Pulido J.S., Marmorstein A.D.;
RT "Autosomal recessive bestrophinopathy is not associated with the loss of
RT bestrophin-1 anion channel function in a patient with a novel BEST1
RT mutation.";
RL Invest. Ophthalmol. Vis. Sci. 56:4619-4630(2015).
RN [29]
RP VARIANTS ARB PRO-40 AND VAL-195, AND CHARACTERIZATION OF VARIANTS ARB
RP PRO-40; CYS-93 AND VAL-195.
RX PubMed=26720466; DOI=10.1167/iovs.15-18168;
RA Lee C.S., Jun I., Choi S.I., Lee J.H., Lee M.G., Lee S.C., Kim E.K.;
RT "A novel BEST1 mutation in autosomal recessive bestrophinopathy.";
RL Invest. Ophthalmol. Vis. Sci. 56:8141-8150(2015).
CC -!- FUNCTION: Forms calcium-sensitive chloride channels. Highly permeable
CC to bicarbonate. {ECO:0000269|PubMed:11904445,
CC ECO:0000269|PubMed:12907679, ECO:0000269|PubMed:18400985}.
CC -!- SUBUNIT: Homooligomer (tetramer or pentamer) (PubMed:26200502). May
CC interact with PPP2CB and PPP2R1B (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:26200502}.
CC -!- INTERACTION:
CC O76090; O76090: BEST1; NbExp=2; IntAct=EBI-11693370, EBI-11693370;
CC O76090-4; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-18631885, EBI-12070086;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19853238,
CC ECO:0000269|PubMed:26200502}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19853238}. Basolateral cell membrane
CC {ECO:0000269|PubMed:19853238, ECO:0000269|PubMed:26200502}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O76090-1; Sequence=Displayed;
CC Name=3;
CC IsoId=O76090-3; Sequence=VSP_008973, VSP_008974;
CC Name=4;
CC IsoId=O76090-4; Sequence=VSP_008973, VSP_008975;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the basolateral membrane
CC of the retinal pigment epithelium.
CC -!- PTM: Phosphorylated by PP2A. {ECO:0000250}.
CC -!- DISEASE: Macular dystrophy, vitelliform, 2 (VMD2) [MIM:153700]: An
CC autosomal dominant form of macular degeneration that usually begins in
CC childhood or adolescence. VMD2 is characterized by typical 'egg-yolk'
CC macular lesions due to abnormal accumulation of lipofuscin within and
CC beneath the retinal pigment epithelium cells. Progression of the
CC disease leads to destruction of the retinal pigment epithelium and
CC vision loss. {ECO:0000269|PubMed:10331951, ECO:0000269|PubMed:10394929,
CC ECO:0000269|PubMed:10453731, ECO:0000269|PubMed:10682987,
CC ECO:0000269|PubMed:10798642, ECO:0000269|PubMed:11241846,
CC ECO:0000269|PubMed:11449320, ECO:0000269|PubMed:12187431,
CC ECO:0000269|PubMed:12324875, ECO:0000269|PubMed:13129869,
CC ECO:0000269|PubMed:14517959, ECO:0000269|PubMed:15176385,
CC ECO:0000269|PubMed:18400985, ECO:0000269|PubMed:18766995,
CC ECO:0000269|PubMed:19357557, ECO:0000269|PubMed:21330666,
CC ECO:0000269|PubMed:9662395, ECO:0000269|PubMed:9700209}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Retinitis pigmentosa 50 (RP50) [MIM:613194]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:19853238}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Bestrophinopathy, autosomal recessive (ARB) [MIM:611809]: A
CC retinopathy characterized by loss of central vision, an absent electro-
CC oculogram light rise, and electroretinogram anomalies.
CC {ECO:0000269|PubMed:18179881, ECO:0000269|PubMed:19853238,
CC ECO:0000269|PubMed:21330666, ECO:0000269|PubMed:26200502,
CC ECO:0000269|PubMed:26720466}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Vitreoretinochoroidopathy (VRCP) [MIM:193220]: An autosomal
CC dominant ocular disorder characterized by vitreoretinochoroidal
CC dystrophy. The clinical presentation is variable. VRCP may be
CC associated with cataract, nanophthalmos, microcornea, shallow anterior
CC chamber, and glaucoma. {ECO:0000269|PubMed:15452077}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the bestrophin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAH12234.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAH13472.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Mutations of the BEST1 gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/vmd2mut.htm";
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DR EMBL; AF073500; AAC64926.1; -; Genomic_DNA.
DR EMBL; AF073491; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073492; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073493; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073494; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073495; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073496; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073497; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073498; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF073499; AAC64926.1; JOINED; Genomic_DNA.
DR EMBL; AF057169; AAC64343.1; -; mRNA.
DR EMBL; AF057170; AAC64344.1; -; mRNA.
DR EMBL; AF073501; AAC33766.1; -; mRNA.
DR EMBL; AY515704; AAR99654.1; -; mRNA.
DR EMBL; CH471076; EAW73982.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW73985.1; -; Genomic_DNA.
DR EMBL; BC015220; AAH15220.1; -; mRNA.
DR EMBL; BC041664; AAH41664.1; -; mRNA.
DR EMBL; AK289681; BAF82370.1; -; mRNA.
DR EMBL; AK295998; BAH12234.1; ALT_INIT; mRNA.
DR EMBL; AK301392; BAH13472.1; ALT_INIT; mRNA.
DR CCDS; CCDS31580.1; -. [O76090-1]
DR CCDS; CCDS44623.1; -. [O76090-3]
DR RefSeq; NP_001132915.1; NM_001139443.1. [O76090-3]
DR RefSeq; NP_001287715.1; NM_001300786.1. [O76090-4]
DR RefSeq; NP_001287716.1; NM_001300787.1.
DR RefSeq; NP_004174.1; NM_004183.3. [O76090-1]
DR RefSeq; XP_005274272.1; XM_005274215.3.
DR RefSeq; XP_016873718.1; XM_017018229.1.
DR AlphaFoldDB; O76090; -.
DR SMR; O76090; -.
DR BioGRID; 113279; 12.
DR IntAct; O76090; 4.
DR STRING; 9606.ENSP00000399709; -.
DR TCDB; 1.A.46.1.1; the anion channel-forming bestrophin (bestrophin) family.
DR iPTMnet; O76090; -.
DR PhosphoSitePlus; O76090; -.
DR BioMuta; BEST1; -.
DR MassIVE; O76090; -.
DR PaxDb; O76090; -.
DR PeptideAtlas; O76090; -.
DR PRIDE; O76090; -.
DR ProteomicsDB; 50408; -. [O76090-1]
DR ProteomicsDB; 50409; -. [O76090-3]
DR ProteomicsDB; 50410; -. [O76090-4]
DR Antibodypedia; 28370; 283 antibodies from 29 providers.
DR DNASU; 7439; -.
DR Ensembl; ENST00000378043.9; ENSP00000367282.4; ENSG00000167995.17. [O76090-1]
DR Ensembl; ENST00000449131.6; ENSP00000399709.2; ENSG00000167995.17. [O76090-3]
DR GeneID; 7439; -.
DR KEGG; hsa:7439; -.
DR MANE-Select; ENST00000378043.9; ENSP00000367282.4; NM_004183.4; NP_004174.1.
DR UCSC; uc001nsr.3; human. [O76090-1]
DR CTD; 7439; -.
DR DisGeNET; 7439; -.
DR GeneCards; BEST1; -.
DR GeneReviews; BEST1; -.
DR HGNC; HGNC:12703; BEST1.
DR HPA; ENSG00000167995; Tissue enhanced (bone marrow, brain).
DR MalaCards; BEST1; -.
DR MIM; 153700; phenotype.
DR MIM; 193220; phenotype.
DR MIM; 607854; gene.
DR MIM; 611809; phenotype.
DR MIM; 613194; phenotype.
DR neXtProt; NX_O76090; -.
DR OpenTargets; ENSG00000167995; -.
DR Orphanet; 99000; Adult-onset foveomacular vitelliform dystrophy.
DR Orphanet; 3086; Autosomal dominant vitreoretinochoroidopathy.
DR Orphanet; 139455; Autosomal recessive bestrophinopathy.
DR Orphanet; 1243; Best vitelliform macular dystrophy.
DR Orphanet; 263347; MRCS syndrome.
DR Orphanet; 35612; Nanophthalmos.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA162377454; -.
DR VEuPathDB; HostDB:ENSG00000167995; -.
DR eggNOG; KOG3547; Eukaryota.
DR GeneTree; ENSGT00940000158650; -.
DR HOGENOM; CLU_018069_5_0_1; -.
DR InParanoid; O76090; -.
DR OMA; IHCVPPA; -.
DR OrthoDB; 279144at2759; -.
DR PhylomeDB; O76090; -.
DR TreeFam; TF315803; -.
DR PathwayCommons; O76090; -.
DR Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR SignaLink; O76090; -.
DR SIGNOR; O76090; -.
DR BioGRID-ORCS; 7439; 15 hits in 1065 CRISPR screens.
DR ChiTaRS; BEST1; human.
DR GeneWiki; Bestrophin_1; -.
DR GenomeRNAi; 7439; -.
DR Pharos; O76090; Tbio.
DR PRO; PR:O76090; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O76090; protein.
DR Bgee; ENSG00000167995; Expressed in pigmented layer of retina and 144 other tissues.
DR ExpressionAtlas; O76090; baseline and differential.
DR Genevisible; O76090; HS.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:HGNC-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0005254; F:chloride channel activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005229; F:intracellular calcium activated chloride channel activity; TAS:Reactome.
DR GO; GO:0006821; P:chloride transport; IDA:MGI.
DR GO; GO:0050908; P:detection of light stimulus involved in visual perception; IEA:Ensembl.
DR GO; GO:0034220; P:ion transmembrane transport; TAS:Reactome.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0030321; P:transepithelial chloride transport; IDA:HGNC-UCL.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR InterPro; IPR033041; Best1.
DR InterPro; IPR000615; Bestrophin.
DR InterPro; IPR021134; Bestrophin/UPF0187.
DR PANTHER; PTHR10736; PTHR10736; 1.
DR PANTHER; PTHR10736:SF4; PTHR10736:SF4; 1.
DR Pfam; PF01062; Bestrophin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Chloride; Chloride channel;
KW Disease variant; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Retinitis pigmentosa; Sensory transduction;
KW Transmembrane; Transmembrane helix; Transport; Vision.
FT CHAIN 1..585
FT /note="Bestrophin-1"
FT /id="PRO_0000143114"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..70
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..178
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 200..228
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 229..249
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..270
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 271..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 292..585
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..60
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008973"
FT VAR_SEQ 290..316
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008975"
FT VAR_SEQ 581..585
FT /note="DEAHS -> SVLHLNQGHCIALCPTPASLALSLPFLHNFLGFHHCQSTLDLR
FT PALAWGIYLATFTGILGKCSGPFLTSPWYHPEDFLGPGEGR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008974"
FT VARIANT 3
FT /note="I -> T (in VMD2)"
FT /evidence="ECO:0000269|PubMed:19357557"
FT /id="VAR_058273"
FT VARIANT 6
FT /note="T -> P (in VMD2; dbSNP:rs28940275)"
FT /evidence="ECO:0000269|PubMed:19357557,
FT ECO:0000269|PubMed:9662395"
FT /id="VAR_000830"
FT VARIANT 6
FT /note="T -> R (in VMD2; dbSNP:rs281865204)"
FT /id="VAR_017366"
FT VARIANT 9
FT /note="V -> A (in VMD2; dbSNP:rs281865205)"
FT /id="VAR_000831"
FT VARIANT 9
FT /note="V -> M (in VMD2; dbSNP:rs28940276)"
FT /id="VAR_000832"
FT VARIANT 10
FT /note="A -> T (in VMD2; dbSNP:rs281865206)"
FT /id="VAR_000833"
FT VARIANT 10
FT /note="A -> V (in VMD2; dbSNP:rs281865207)"
FT /evidence="ECO:0000269|PubMed:10394929"
FT /id="VAR_010468"
FT VARIANT 11
FT /note="N -> I (in VMD2; dbSNP:rs281865208)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_017367"
FT VARIANT 13
FT /note="R -> H (in VMD2; dbSNP:rs281865209)"
FT /evidence="ECO:0000269|PubMed:10331951"
FT /id="VAR_010469"
FT VARIANT 16
FT /note="S -> F (in VMD2; dbSNP:rs281865210)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010470"
FT VARIANT 17
FT /note="F -> C (in VMD2; dbSNP:rs281865211)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010471"
FT VARIANT 21
FT /note="L -> V (in VMD2; dbSNP:rs281865212)"
FT /id="VAR_000834"
FT VARIANT 24
FT /note="W -> C (in VMD2; dbSNP:rs281865213)"
FT /id="VAR_000835"
FT VARIANT 25
FT /note="R -> Q (in VMD2; dbSNP:rs281865215)"
FT /id="VAR_000836"
FT VARIANT 25
FT /note="R -> W (in VMD2; dbSNP:rs281865214)"
FT /id="VAR_000837"
FT VARIANT 26
FT /note="G -> R (in VMD2)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_017368"
FT VARIANT 27
FT /note="S -> R (in VMD2; dbSNP:rs281865216)"
FT /id="VAR_000838"
FT VARIANT 29
FT /note="Y -> H (in VMD2; dbSNP:rs281865217)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_017369"
FT VARIANT 30
FT /note="K -> R (in VMD2; dbSNP:rs281865218)"
FT /id="VAR_017370"
FT VARIANT 40
FT /note="L -> P (in ARB; unknown pathological significance;
FT no effect on subcellular location in transfected HEK293T
FT cells; loss of chloride conductance)"
FT /evidence="ECO:0000269|PubMed:26720466"
FT /id="VAR_075346"
FT VARIANT 41
FT /note="L -> P (in VMD2 and ARB; no effect on subcellular
FT location in transfected MDCK.2 cells; possible decrease in
FT protein stability; reduced chloride conductance;
FT dbSNP:rs121918288)"
FT /evidence="ECO:0000269|PubMed:14517959,
FT ECO:0000269|PubMed:18179881, ECO:0000269|PubMed:21330666"
FT /id="VAR_017371"
FT VARIANT 47
FT /note="R -> H (in VMD2; dbSNP:rs28940278)"
FT /id="VAR_017372"
FT VARIANT 58
FT /note="Q -> L (in VMD2; dbSNP:rs281865529)"
FT /id="VAR_000839"
FT VARIANT 67
FT /note="L -> V"
FT /id="VAR_000840"
FT VARIANT 73
FT /note="I -> N (in VMD2; dbSNP:rs1591280714)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010472"
FT VARIANT 80
FT /note="F -> L (in VMD2; dbSNP:rs281865221)"
FT /id="VAR_017373"
FT VARIANT 82
FT /note="L -> V (in VMD2; dbSNP:rs281865530)"
FT /evidence="ECO:0000269|PubMed:10394929,
FT ECO:0000269|PubMed:19357557"
FT /id="VAR_010473"
FT VARIANT 85
FT /note="Y -> H (in VMD2; decreased chloride and bicarbonate
FT conductance; dbSNP:rs28940274)"
FT /evidence="ECO:0000269|PubMed:18400985,
FT ECO:0000269|PubMed:21330666, ECO:0000269|PubMed:9662395"
FT /id="VAR_000841"
FT VARIANT 86
FT /note="V -> M (in VRCP; dbSNP:rs121918289)"
FT /evidence="ECO:0000269|PubMed:15452077"
FT /id="VAR_058274"
FT VARIANT 89
FT /note="V -> A (in VMD2)"
FT /evidence="ECO:0000269|PubMed:11449320"
FT /id="VAR_017374"
FT VARIANT 91
FT /note="T -> I (in VMD2; dbSNP:rs281865223)"
FT /id="VAR_017375"
FT VARIANT 92
FT /note="R -> C (in VMD2; loss of cloride and bicarbonate
FT conductance; dbSNP:rs281865224)"
FT /evidence="ECO:0000269|PubMed:10394929,
FT ECO:0000269|PubMed:18400985"
FT /id="VAR_010474"
FT VARIANT 92
FT /note="R -> H (in VMD2; dbSNP:rs281865225)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010475"
FT VARIANT 92
FT /note="R -> S (in VMD2; dbSNP:rs281865224)"
FT /id="VAR_000842"
FT VARIANT 93
FT /note="W -> C (in VMD2; no effect on subcellular location
FT in transfected HEK293T cells; loss of cloride and
FT bicarbonate conductance; dbSNP:rs28940273)"
FT /evidence="ECO:0000269|PubMed:10331951,
FT ECO:0000269|PubMed:18400985, ECO:0000269|PubMed:26720466,
FT ECO:0000269|PubMed:9662395"
FT /id="VAR_000843"
FT VARIANT 96
FT /note="Q -> H (in VMD2; dbSNP:rs281865226)"
FT /evidence="ECO:0000269|PubMed:10394929"
FT /id="VAR_010476"
FT VARIANT 99
FT /note="N -> K (in VMD2; dbSNP:rs281865227)"
FT /id="VAR_000844"
FT VARIANT 100
FT /note="L -> R (in VMD2; dbSNP:rs281865228)"
FT /id="VAR_000845"
FT VARIANT 101
FT /note="P -> T (in VMD2; dbSNP:rs281865229)"
FT /id="VAR_017376"
FT VARIANT 102
FT /note="W -> R (in VMD2; dbSNP:rs281865230)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_017377"
FT VARIANT 104
FT /note="D -> E (in VMD2; dbSNP:rs281865232)"
FT /id="VAR_000846"
FT VARIANT 104
FT /note="D -> H (in VMD2; dbSNP:rs281865231)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_017378"
FT VARIANT 105
FT /note="R -> C (in age-related macular degeneration;
FT dbSNP:rs281865273)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025731"
FT VARIANT 113
FT /note="F -> L (in VMD2; dbSNP:rs1445469923)"
FT /evidence="ECO:0000269|PubMed:15176385"
FT /id="VAR_025732"
FT VARIANT 119
FT /note="E -> Q (in a sporadic case of concentric annular
FT macular dystrophy; dbSNP:rs1805142)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010477"
FT VARIANT 133
FT /note="N -> K (in VMD2; dbSNP:rs281865233)"
FT /id="VAR_017379"
FT VARIANT 135
FT /note="G -> S (in VMD2; dbSNP:rs281865234)"
FT /evidence="ECO:0000269|PubMed:10394929"
FT /id="VAR_010478"
FT VARIANT 140
FT /note="L -> R (in VMD2; dbSNP:rs281865235)"
FT /id="VAR_017380"
FT VARIANT 140
FT /note="L -> V (in RP50 and ARB; possible decrease in
FT protein stability; causes protein mislocalization to the
FT cytoplasm and reduction of channel activity;
FT dbSNP:rs267606678)"
FT /evidence="ECO:0000269|PubMed:19853238,
FT ECO:0000269|PubMed:21330666"
FT /id="VAR_063169"
FT VARIANT 141
FT /note="R -> H (in VMD2 and ARB; no effect on subcellular
FT location in induced pluripotent stem cell-derived retinal
FT pigment epithelial cells; loss of cell membrane
FT localization in transfected MDCK.2 cells; possible decrease
FT in protein stability; reduced chloride conductance;
FT dbSNP:rs121918284)"
FT /evidence="ECO:0000269|PubMed:18179881,
FT ECO:0000269|PubMed:21330666, ECO:0000269|PubMed:26200502"
FT /id="VAR_000847"
FT VARIANT 146
FT /note="A -> K (in VMD2; sporadic; requires 2 nucleotide
FT substitutions; dbSNP:rs1800995)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010479"
FT VARIANT 152
FT /note="P -> A (in ARB; no effect on protein stability; loss
FT of cell membrane localization in transfected MDCK.2 cells;
FT reduced whole-cell conductance; dbSNP:rs1417478879)"
FT /evidence="ECO:0000269|PubMed:18179881,
FT ECO:0000269|PubMed:21330666"
FT /id="VAR_043493"
FT VARIANT 195
FT /note="A -> V (in ARB and VMD2; no effect on subcellular
FT location in transfected MDCK.2 and HEK293T cells; possible
FT decrease in protein stability; reduced chloride
FT conductance; dbSNP:rs200277476)"
FT /evidence="ECO:0000269|PubMed:21330666,
FT ECO:0000269|PubMed:26720466"
FT /id="VAR_017381"
FT VARIANT 201
FT /note="I -> T (in VMD2; dbSNP:rs199529046)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025733"
FT VARIANT 202
FT /note="R -> W (in ARB; possible decrease in protein
FT stability; loss of cell membrane localization in
FT transfected MDCK.2 cells; reduced chloride conductance;
FT dbSNP:rs765998048)"
FT /evidence="ECO:0000269|PubMed:21330666"
FT /id="VAR_075347"
FT VARIANT 205
FT /note="I -> T (in RP50; reduced channel activity;
FT dbSNP:rs267606680)"
FT /evidence="ECO:0000269|PubMed:19853238"
FT /id="VAR_063170"
FT VARIANT 207
FT /note="L -> I (in VMD2; benign variant; dbSNP:rs74653691)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025734"
FT VARIANT 209
FT /note="S -> N (in VMD2; dbSNP:rs281865237)"
FT /id="VAR_000848"
FT VARIANT 216
FT /note="T -> I (in a sporadic case of age-related macular
FT degeneration; dbSNP:rs281865275)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010480"
FT VARIANT 218
FT /note="R -> C (in VMD2; dbSNP:rs281865238)"
FT /evidence="ECO:0000269|PubMed:10331951,
FT ECO:0000269|PubMed:10394929, ECO:0000269|PubMed:11241846,
FT ECO:0000269|PubMed:18766995"
FT /id="VAR_000849"
FT VARIANT 218
FT /note="R -> H (in VMD2; dbSNP:rs281865239)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010481"
FT VARIANT 218
FT /note="R -> Q (in VMD2)"
FT /id="VAR_000850"
FT VARIANT 218
FT /note="R -> S (in VMD2; dbSNP:rs281865238)"
FT /evidence="ECO:0000269|PubMed:10394929"
FT /id="VAR_000851"
FT VARIANT 221
FT /note="C -> W (in VMD2; dbSNP:rs281865240)"
FT /evidence="ECO:0000269|PubMed:10682987"
FT /id="VAR_025735"
FT VARIANT 222
FT /note="G -> V (in a family affected by Leber congenital
FT amaurosis/VMD2; dbSNP:rs281865241)"
FT /evidence="ECO:0000269|PubMed:10766140"
FT /id="VAR_025736"
FT VARIANT 224
FT /note="L -> M (in VMD2; dbSNP:rs281865242)"
FT /id="VAR_000852"
FT VARIANT 224
FT /note="L -> P (in VMD2; dbSNP:rs281865243)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025737"
FT VARIANT 227
FT /note="Y -> C (in RP50; dbSNP:rs267606677)"
FT /evidence="ECO:0000269|PubMed:19853238"
FT /id="VAR_000853"
FT VARIANT 227
FT /note="Y -> N (in VMD2; dbSNP:rs28941469)"
FT /evidence="ECO:0000269|PubMed:19357557,
FT ECO:0000269|PubMed:9662395"
FT /id="VAR_000854"
FT VARIANT 228
FT /note="D -> N (in RP50; causes protein mislocalization to
FT the cytoplasm; dbSNP:rs267606676)"
FT /evidence="ECO:0000269|PubMed:19853238"
FT /id="VAR_063171"
FT VARIANT 231
FT /note="S -> R (in VMD2; dbSNP:rs281865244)"
FT /id="VAR_000855"
FT VARIANT 235
FT /note="V -> L (in VMD2; dbSNP:rs281865245)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010482"
FT VARIANT 235
FT /note="V -> M (in VMD2; dbSNP:rs281865245)"
FT /id="VAR_000856"
FT VARIANT 236
FT /note="Y -> C (in VRCP; dbSNP:rs121918291)"
FT /evidence="ECO:0000269|PubMed:15452077"
FT /id="VAR_058275"
FT VARIANT 237
FT /note="T -> R (in VMD2; dbSNP:rs281865246)"
FT /evidence="ECO:0000269|PubMed:21330666"
FT /id="VAR_000857"
FT VARIANT 239
FT /note="V -> M (in VRCP; dbSNP:rs121918290)"
FT /evidence="ECO:0000269|PubMed:15452077"
FT /id="VAR_058276"
FT VARIANT 241
FT /note="T -> N (in VMD2; dbSNP:rs281865247)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_025738"
FT VARIANT 242
FT /note="V -> M (in VMD2; late-onset of visual disturbance)"
FT /evidence="ECO:0000269|PubMed:18766995"
FT /id="VAR_058277"
FT VARIANT 243
FT /note="A -> T (in VMD2; dbSNP:rs137853905)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025739"
FT VARIANT 243
FT /note="A -> V (in VMD2; dbSNP:rs28940570)"
FT /evidence="ECO:0000269|PubMed:19357557"
FT /id="VAR_000858"
FT VARIANT 275
FT /note="V -> I (in age-related macular degeneration;
FT dbSNP:rs281865276)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025740"
FT VARIANT 276
FT /note="F -> L (in VMD2; dbSNP:rs281865248)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025741"
FT VARIANT 293
FT /note="Q -> K (in VMD2; dbSNP:rs281865250)"
FT /evidence="ECO:0000269|PubMed:10394929"
FT /id="VAR_010483"
FT VARIANT 294
FT /note="L -> V (in VMD2; dbSNP:rs281865251)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_025742"
FT VARIANT 295
FT /note="I -> T (in VMD2; dbSNP:rs281865253)"
FT /evidence="ECO:0000269|PubMed:12187431"
FT /id="VAR_025743"
FT VARIANT 295
FT /note="Missing (in VMD2)"
FT /id="VAR_000859"
FT VARIANT 296
FT /note="N -> H (in VMD2; dbSNP:rs281865254)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025744"
FT VARIANT 296
FT /note="N -> S (in VMD2; dbSNP:rs281865255)"
FT /evidence="ECO:0000269|PubMed:11241846"
FT /id="VAR_010484"
FT VARIANT 297
FT /note="P -> A (in VMD2; dbSNP:rs1805143)"
FT /id="VAR_000860"
FT VARIANT 297
FT /note="P -> S (in VMD2; dbSNP:rs1805143)"
FT /evidence="ECO:0000269|PubMed:10453731,
FT ECO:0000269|PubMed:13129869"
FT /id="VAR_010485"
FT VARIANT 298
FT /note="F -> S (in VMD2; dbSNP:rs281865257)"
FT /evidence="ECO:0000269|PubMed:14517959"
FT /id="VAR_025745"
FT VARIANT 299
FT /note="G -> A (in VMD2)"
FT /evidence="ECO:0000269|PubMed:19357557"
FT /id="VAR_058313"
FT VARIANT 299
FT /note="G -> E (in VMD2; dbSNP:rs28941468)"
FT /evidence="ECO:0000269|PubMed:9662395"
FT /id="VAR_000861"
FT VARIANT 300
FT /note="E -> D (in VMD2; dbSNP:rs1805144)"
FT /evidence="ECO:0000269|PubMed:10331951,
FT ECO:0000269|PubMed:10453731, ECO:0000269|PubMed:13129869"
FT /id="VAR_010486"
FT VARIANT 300
FT /note="E -> K (in VMD2; dbSNP:rs281865258)"
FT /id="VAR_000862"
FT VARIANT 301
FT /note="D -> E (in VMD2; dbSNP:rs281865261)"
FT /evidence="ECO:0000269|PubMed:10331951"
FT /id="VAR_000863"
FT VARIANT 301
FT /note="D -> N (in VMD2; dbSNP:rs281865259)"
FT /id="VAR_000864"
FT VARIANT 302..304
FT /note="Missing (in VMD2)"
FT /evidence="ECO:0000269|PubMed:19357557"
FT /id="VAR_058278"
FT VARIANT 302
FT /note="D -> G (in VMD2; dbSNP:rs281865263)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025746"
FT VARIANT 302
FT /note="D -> H (in VMD2; dbSNP:rs281865262)"
FT /evidence="ECO:0000269|PubMed:12324875"
FT /id="VAR_025747"
FT VARIANT 302
FT /note="D -> V (in VMD2; dbSNP:rs281865263)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025748"
FT VARIANT 303
FT /note="D -> E (in VMD2; dbSNP:rs281865264)"
FT /evidence="ECO:0000269|PubMed:12324875"
FT /id="VAR_025749"
FT VARIANT 305
FT /note="F -> S (in VMD2; dbSNP:rs281865265)"
FT /id="VAR_000865"
FT VARIANT 306
FT /note="E -> D (in VMD2; dbSNP:rs281865267)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025750"
FT VARIANT 306
FT /note="E -> G (in VMD2; dbSNP:rs281865266)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025751"
FT VARIANT 307
FT /note="T -> A (in VMD2; dbSNP:rs281865268)"
FT /evidence="ECO:0000269|PubMed:10798642"
FT /id="VAR_025752"
FT VARIANT 307
FT /note="T -> I (in VMD2; dbSNP:rs281865269)"
FT /evidence="ECO:0000269|PubMed:10331951"
FT /id="VAR_010487"
FT VARIANT 308
FT /note="N -> S (in VMD2; dbSNP:rs281865270)"
FT /evidence="ECO:0000269|PubMed:12324875"
FT /id="VAR_025753"
FT VARIANT 310
FT /note="I -> T (in VMD2; dbSNP:rs281865271)"
FT /id="VAR_000866"
FT VARIANT 311
FT /note="V -> G (in VMD2)"
FT /id="VAR_000867"
FT VARIANT 312
FT /note="D -> N (in VMD2 and ARB; no effect on protein
FT stability; loss of cell membrane localization in
FT transfected MDCK.2 cells; reduced chloride conductance;
FT dbSNP:rs281865277)"
FT /evidence="ECO:0000269|PubMed:18179881,
FT ECO:0000269|PubMed:19853238, ECO:0000269|PubMed:21330666"
FT /id="VAR_000868"
FT VARIANT 317
FT /note="V -> M (in ARB; no effect on protein stability; loss
FT of cell membrane localization in transfected MDCK.2 cells;
FT reduced chloride conductance; dbSNP:rs121918287)"
FT /evidence="ECO:0000269|PubMed:18179881,
FT ECO:0000269|PubMed:21330666"
FT /id="VAR_043494"
FT VARIANT 325
FT /note="M -> T (in ARB; possible decrease in protein
FT stability; loss of cell membrane localization in
FT transfected MDCK.2 cells; reduced chloride conductance;
FT dbSNP:rs368387447)"
FT /evidence="ECO:0000269|PubMed:18179881,
FT ECO:0000269|PubMed:21330666"
FT /id="VAR_043495"
FT VARIANT 357
FT /note="A -> V (in dbSNP:rs17854138)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043496"
FT VARIANT 525
FT /note="E -> A (in dbSNP:rs200582915)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010488"
FT VARIANT 557
FT /note="E -> K (in dbSNP:rs147192139)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010489"
FT VARIANT 561
FT /note="T -> A (in dbSNP:rs281865283)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010490"
FT VARIANT 567
FT /note="L -> F (in a sporadic case of age-related macular
FT degeneration; unknown pathological significance;
FT dbSNP:rs148060787)"
FT /evidence="ECO:0000269|PubMed:10453731"
FT /id="VAR_010491"
FT VARIANT 578
FT /note="E -> V (in dbSNP:rs1800010)"
FT /id="VAR_009278"
SQ SEQUENCE 585 AA; 67684 MW; D0629AAF65BA1ACD CRC64;
MTITYTSQVA NARLGSFSRL LLCWRGSIYK LLYGEFLIFL LCYYIIRFIY RLALTEEQQL
MFEKLTLYCD SYIQLIPISF VLGFYVTLVV TRWWNQYENL PWPDRLMSLV SGFVEGKDEQ
GRLLRRTLIR YANLGNVLIL RSVSTAVYKR FPSAQHLVQA GFMTPAEHKQ LEKLSLPHNM
FWVPWVWFAN LSMKAWLGGR IRDPILLQSL LNEMNTLRTQ CGHLYAYDWI SIPLVYTQVV
TVAVYSFFLT CLVGRQFLNP AKAYPGHELD LVVPVFTFLQ FFFYVGWLKV AEQLINPFGE
DDDDFETNWI VDRNLQVSLL AVDEMHQDLP RMEPDMYWNK PEPQPPYTAA SAQFRRASFM
GSTFNISLNK EEMEFQPNQE DEEDAHAGII GRFLGLQSHD HHPPRANSRT KLLWPKRESL
LHEGLPKNHK AAKQNVRGQE DNKAWKLKAV DAFKSAPLYQ RPGYYSAPQT PLSPTPMFFP
LEPSAPSKLH SVTGIDTKDK SLKTVSSGAK KSFELLSESD GALMEHPEVS QVRRKTVEFN
LTDMPEIPEN HLKEPLEQSP TNIHTTLKDH MDPYWALENR DEAHS
