TT21B_HUMAN
ID TT21B_HUMAN Reviewed; 1316 AA.
AC Q7Z4L5; A8MUZ3; Q3LIE4; Q53T84; Q6P4A1; Q6PIF5; Q8NCN3; Q96MA4; Q9HAK8;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Tetratricopeptide repeat protein 21B {ECO:0000305};
DE Short=TPR repeat protein 21B;
DE AltName: Full=Intraflagellar transport 139 homolog {ECO:0000305};
GN Name=TTC21B {ECO:0000312|HGNC:HGNC:25660};
GN Synonyms=IFT139 {ECO:0000303|PubMed:25860617, ECO:0000303|PubMed:27932497},
GN KIAA1992; ORFNames=Nbla10696;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS MET-201
RP AND ALA-276.
RC TISSUE=Neuroblastoma;
RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA Hirato J., Nakagawara A.;
RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT genesis and biology of neuroblastoma.";
RL Cancer Lett. 197:63-68(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS MET-201
RP AND ALA-276.
RC TISSUE=Adrenal cortex, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-701 AND 1029-1316 (ISOFORM 1),
RP AND VARIANTS MET-201 AND ALA-276.
RC TISSUE=Embryo, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 464-1316 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12056414; DOI=10.1093/dnares/9.2.47;
RA Ohara O., Nagase T., Mitsui G., Kohga H., Kikuno R., Hiraoka S.,
RA Takahashi Y., Kitajima S., Saga Y., Koseki H.;
RT "Characterization of size-fractionated cDNA libraries generated by the in
RT vitro recombination-assisted method.";
RL DNA Res. 9:47-57(2002).
RN [6]
RP IDENTIFICATION IN THE IFT-A COMPLEX.
RX PubMed=20889716; DOI=10.1101/gad.1966210;
RA Mukhopadhyay S., Wen X., Chih B., Nelson C.D., Lane W.S., Scales S.J.,
RA Jackson P.K.;
RT "TULP3 bridges the IFT-A complex and membrane phosphoinositides to promote
RT trafficking of G protein-coupled receptors into primary cilia.";
RL Genes Dev. 24:2180-2193(2010).
RN [7]
RP INVOLVEMENT IN CILIOPATHIES, VARIANTS NPHP12 ARG-150; LEU-209; SER-231;
RP ARG-566 AND CYS-1167, VARIANTS SRTD4 SER-231; TYR-755 AND PRO-795, VARIANTS
RP JBTS11 ASN-591; CYS-867 AND VAL-1186, VARIANTS TYR-60; ARG-66; GLU-157;
RP LEU-222; SER-231; ASN-242; CYS-255; VAL-280; SER-327; CYS-347; GLY-411;
RP ARG-412; GLU-424; CYS-616; VAL-624; ARG-645; THR-724; LEU-753; VAL-844;
RP HIS-867; ARG-869; GLN-939; TRP-939; VAL-1002; VAL-1011; CYS-1035; ASN-1041;
RP ARG-1103; SER-1208; HIS-1284 AND GLY-1311, CHARACTERIZATION OF VARIANTS
RP NPHP12 ARG-150; LEU-209; SER-231; ARG-566 AND CYS-1167, CHARACTERIZATION OF
RP VARIANTS SRTD4 SER-231; TYR-755 AND PRO-795, CHARACTERIZATION OF VARIANTS
RP JBTS11 ASN-591; CYS-867 AND VAL-1186, AND CHARACTERIZATION OF VARIANTS
RP TYR-60; GLU-157; LEU-222; SER-231; CYS-255; VAL-280; SER-327; CYS-347;
RP GLY-411; LEU-753; VAL-844; HIS-867; ARG-869; GLN-939; TRP-939; VAL-1002;
RP ARG-1103; ASN-1041 AND SER-1208.
RX PubMed=21258341; DOI=10.1038/ng.756;
RA Davis E.E., Zhang Q., Liu Q., Diplas B.H., Davey L.M., Hartley J.,
RA Stoetzel C., Szymanska K., Ramaswami G., Logan C.V., Muzny D.M.,
RA Young A.C., Wheeler D.A., Cruz P., Morgan M., Lewis L.R., Cherukuri P.,
RA Maskeri B., Hansen N.F., Mullikin J.C., Blakesley R.W., Bouffard G.G.,
RA Gyapay G., Rieger S., Tonshoff B., Kern I., Soliman N.A., Neuhaus T.J.,
RA Swoboda K.J., Kayserili H., Gallagher T.E., Lewis R.A., Bergmann C.,
RA Otto E.A., Saunier S., Scambler P.J., Beales P.L., Gleeson J.G.,
RA Maher E.R., Attie-Bitach T., Dollfus H., Johnson C.A., Green E.D.,
RA Gibbs R.A., Hildebrandt F., Pierce E.A., Katsanis N.;
RT "TTC21B contributes both causal and modifying alleles across the ciliopathy
RT spectrum.";
RL Nat. Genet. 43:189-196(2011).
RN [8]
RP INTERACTION WITH TTC25.
RX PubMed=25860617; DOI=10.1371/journal.pone.0124378;
RA Xu Y., Cao J., Huang S., Feng D., Zhang W., Zhu X., Yan X.;
RT "Characterization of tetratricopeptide repeat-containing proteins critical
RT for cilia formation and function.";
RL PLoS ONE 10:E0124378-E0124378(2015).
RN [9]
RP IDENTIFICATION IN THE IFT-A COMPLEX, AND FUNCTION.
RX PubMed=27932497; DOI=10.1091/mbc.e16-11-0813;
RA Hirano T., Katoh Y., Nakayama K.;
RT "Intraflagellar transport-A complex mediates ciliary entry and retrograde
RT trafficking of ciliary G protein-coupled receptors.";
RL Mol. Biol. Cell 28:429-439(2017).
RN [10]
RP VARIANT JBTS11 THR-1011.
RX PubMed=22425360; DOI=10.1016/j.ajhg.2012.02.011;
RA Srour M., Schwartzentruber J., Hamdan F.F., Ospina L.H., Patry L.,
RA Labuda D., Massicotte C., Dobrzeniecka S., Capo-Chichi J.M.,
RA Papillon-Cavanagh S., Samuels M.E., Boycott K.M., Shevell M.I.,
RA Laframboise R., Desilets V., Maranda B., Rouleau G.A., Majewski J.,
RA Michaud J.L.;
RT "Mutations in C5ORF42 cause Joubert syndrome in the French Canadian
RT population.";
RL Am. J. Hum. Genet. 90:693-700(2012).
RN [11]
RP VARIANT HIS-867.
RX PubMed=27666822; DOI=10.1038/srep34232;
RA Duran I., Taylor S.P., Zhang W., Martin J., Forlenza K.N., Spiro R.P.,
RA Nickerson D.A., Bamshad M., Cohn D.H., Krakow D.;
RT "Destabilization of the IFT-B cilia core complex due to mutations in IFT81
RT causes a spectrum of short-rib polydactyly syndrome.";
RL Sci. Rep. 6:34232-34232(2016).
CC -!- FUNCTION: Component of the IFT complex A (IFT-A), a complex required
CC for retrograde ciliary transport and entry into cilia of G protein-
CC coupled receptors (GPCRs). Essential for retrograde trafficking of IFT-
CC 1, IFT-B and GPCRs (PubMed:27932497). Negatively modulates the SHH
CC signal transduction (By similarity). {ECO:0000250|UniProtKB:Q0HA38,
CC ECO:0000269|PubMed:27932497}.
CC -!- SUBUNIT: Component of the IFT complex A (IFT-A) complex
CC (PubMed:20889716, PubMed:27932497). IFT-A complex is divided into a
CC core subcomplex composed of IFT122:IFT140:WDR19 which is associated
CC with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B
CC (PubMed:27932497). Interacts directy with WDR35 and TTC21B
CC (PubMed:27932497). Interacts with TTC25 (PubMed:25860617).
CC {ECO:0000269|PubMed:20889716, ECO:0000269|PubMed:25860617,
CC ECO:0000269|PubMed:27932497}.
CC -!- INTERACTION:
CC Q7Z4L5; Q9HBG6-3: IFT122; NbExp=2; IntAct=EBI-2851301, EBI-26854447;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme
CC {ECO:0000250|UniProtKB:Q0HA38}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z4L5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z4L5-2; Sequence=VSP_026306, VSP_026307;
CC -!- DISEASE: Note=Ciliary dysfunction leads to a broad spectrum of
CC disorders, collectively termed ciliopathies. Overlapping clinical
CC features include retinal degeneration, renal cystic disease, skeletal
CC abnormalities, fibrosis of various organ, and a complex range of
CC anatomical and functional defects of the central and peripheral nervous
CC system. The ciliopathy range of diseases includes Meckel-Gruber
CC syndrome, Bardet-Biedl syndrome, Joubert syndrome, nephronophtisis,
CC Senior-Loken syndrome, and Jeune asphyxiating thoracic dystrophy among
CC others. TTC21B is causally associated with diverse ciliopathies. It
CC also acts as a modifier gene across the ciliopathy spectrum,
CC interacting in trans with mutations in other ciliopathy-causing genes
CC and contributing to disease manifestation and severity.
CC {ECO:0000269|PubMed:21258341}.
CC -!- DISEASE: Nephronophthisis 12 (NPHP12) [MIM:613820]: An autosomal
CC recessive disorder resulting in end-stage renal disease. It is a
CC progressive tubulo-interstitial kidney disorder histologically
CC characterized by modifications of the tubules with thickening of the
CC basement membrane, interstitial fibrosis and, in the advanced stages,
CC medullary cysts. Some patients manifest extra-renal features including
CC retinal, skeletal and central nervous system defects.
CC {ECO:0000269|PubMed:21258341}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Short-rib thoracic dysplasia 4 with or without polydactyly
CC (SRTD4) [MIM:613819]: A form of short-rib thoracic dysplasia, a group
CC of autosomal recessive ciliopathies that are characterized by a
CC constricted thoracic cage, short ribs, shortened tubular bones, and a
CC 'trident' appearance of the acetabular roof. Polydactyly is variably
CC present. Non-skeletal involvement can include cleft lip/palate as well
CC as anomalies of major organs such as the brain, eye, heart, kidneys,
CC liver, pancreas, intestines, and genitalia. Some forms of the disease
CC are lethal in the neonatal period due to respiratory insufficiency
CC secondary to a severely restricted thoracic cage, whereas others are
CC compatible with life. Disease spectrum encompasses Ellis-van Creveld
CC syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-
CC Saldino syndrome, and short rib-polydactyly syndrome.
CC {ECO:0000269|PubMed:21258341}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Joubert syndrome 11 (JBTS11) [MIM:613820]: A disorder
CC presenting with cerebellar ataxia, oculomotor apraxia, hypotonia,
CC neonatal breathing abnormalities and psychomotor delay.
CC Neuroradiologically, it is characterized by cerebellar vermian
CC hypoplasia/aplasia, thickened and reoriented superior cerebellar
CC peduncles, and an abnormally large interpeduncular fossa, giving the
CC appearance of a molar tooth on transaxial slices (molar tooth sign).
CC Additional variable features include retinal dystrophy and renal
CC disease. {ECO:0000269|PubMed:21258341, ECO:0000269|PubMed:22425360}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the TTC21 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14750.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAB13836.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB073395; BAE45724.1; -; mRNA.
DR EMBL; AC010127; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC011241; AAY14750.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC035767; AAH35767.1; -; mRNA.
DR EMBL; BC055424; AAH55424.1; -; mRNA.
DR EMBL; BC063579; AAH63579.1; -; mRNA.
DR EMBL; AK021519; BAB13836.1; ALT_INIT; mRNA.
DR EMBL; AK057268; BAB71404.1; -; mRNA.
DR EMBL; AB082523; BAC02701.1; -; mRNA.
DR CCDS; CCDS33315.1; -. [Q7Z4L5-1]
DR RefSeq; NP_079029.3; NM_024753.4. [Q7Z4L5-1]
DR AlphaFoldDB; Q7Z4L5; -.
DR BioGRID; 122904; 19.
DR ComplexPortal; CPX-5021; IFT-A complex.
DR CORUM; Q7Z4L5; -.
DR IntAct; Q7Z4L5; 14.
DR MINT; Q7Z4L5; -.
DR STRING; 9606.ENSP00000243344; -.
DR iPTMnet; Q7Z4L5; -.
DR PhosphoSitePlus; Q7Z4L5; -.
DR BioMuta; TTC21B; -.
DR DMDM; 313104038; -.
DR EPD; Q7Z4L5; -.
DR jPOST; Q7Z4L5; -.
DR MassIVE; Q7Z4L5; -.
DR MaxQB; Q7Z4L5; -.
DR PaxDb; Q7Z4L5; -.
DR PeptideAtlas; Q7Z4L5; -.
DR PRIDE; Q7Z4L5; -.
DR ProteomicsDB; 69206; -. [Q7Z4L5-1]
DR ProteomicsDB; 69207; -. [Q7Z4L5-2]
DR Antibodypedia; 47994; 48 antibodies from 9 providers.
DR DNASU; 79809; -.
DR Ensembl; ENST00000243344.8; ENSP00000243344.7; ENSG00000123607.16. [Q7Z4L5-1]
DR Ensembl; ENST00000680888.1; ENSP00000506276.1; ENSG00000123607.16. [Q7Z4L5-1]
DR Ensembl; ENST00000681952.1; ENSP00000506400.1; ENSG00000123607.16. [Q7Z4L5-1]
DR GeneID; 79809; -.
DR KEGG; hsa:79809; -.
DR MANE-Select; ENST00000243344.8; ENSP00000243344.7; NM_024753.5; NP_079029.3.
DR UCSC; uc002udk.4; human. [Q7Z4L5-1]
DR CTD; 79809; -.
DR DisGeNET; 79809; -.
DR GeneCards; TTC21B; -.
DR GeneReviews; TTC21B; -.
DR HGNC; HGNC:25660; TTC21B.
DR HPA; ENSG00000123607; Low tissue specificity.
DR MalaCards; TTC21B; -.
DR MIM; 612014; gene.
DR MIM; 613819; phenotype.
DR MIM; 613820; phenotype.
DR neXtProt; NX_Q7Z4L5; -.
DR OpenTargets; ENSG00000123607; -.
DR Orphanet; 93591; Infantile nephronophthisis.
DR Orphanet; 474; Jeune syndrome.
DR PharmGKB; PA134882767; -.
DR VEuPathDB; HostDB:ENSG00000123607; -.
DR eggNOG; ENOG502QQAB; Eukaryota.
DR GeneTree; ENSGT00390000005979; -.
DR HOGENOM; CLU_006149_0_0_1; -.
DR InParanoid; Q7Z4L5; -.
DR OMA; PEWGQQA; -.
DR PhylomeDB; Q7Z4L5; -.
DR TreeFam; TF314664; -.
DR PathwayCommons; Q7Z4L5; -.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-5620924; Intraflagellar transport.
DR SignaLink; Q7Z4L5; -.
DR BioGRID-ORCS; 79809; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; TTC21B; human.
DR GenomeRNAi; 79809; -.
DR Pharos; Q7Z4L5; Tbio.
DR PRO; PR:Q7Z4L5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q7Z4L5; protein.
DR Bgee; ENSG00000123607; Expressed in right uterine tube and 101 other tissues.
DR ExpressionAtlas; Q7Z4L5; baseline and differential.
DR GO; GO:0097542; C:ciliary tip; TAS:Reactome.
DR GO; GO:0005929; C:cilium; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0030991; C:intraciliary transport particle A; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IEA:Ensembl.
DR GO; GO:0060271; P:cilium assembly; IC:ComplexPortal.
DR GO; GO:0021798; P:forebrain dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0035721; P:intraciliary retrograde transport; IBA:GO_Central.
DR GO; GO:1903999; P:negative regulation of eating behavior; IEA:Ensembl.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0061512; P:protein localization to cilium; IMP:MGI.
DR GO; GO:0097499; P:protein localization to non-motile cilium; IEA:Ensembl.
DR GO; GO:1905799; P:regulation of intraciliary retrograde transport; IMP:UniProtKB.
DR GO; GO:0008589; P:regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0021591; P:ventricular system development; IEA:Ensembl.
DR Gene3D; 1.25.40.10; -; 5.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR InterPro; IPR040364; TTC21A/TTC21B.
DR PANTHER; PTHR14699; PTHR14699; 1.
DR Pfam; PF13181; TPR_8; 3.
DR SMART; SM00028; TPR; 18.
DR SUPFAM; SSF48452; SSF48452; 4.
DR PROSITE; PS50005; TPR; 10.
DR PROSITE; PS50293; TPR_REGION; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Ciliopathy; Cilium; Cytoplasm;
KW Cytoskeleton; Disease variant; Intellectual disability; Joubert syndrome;
KW Meckel syndrome; Nephronophthisis; Obesity; Reference proteome; Repeat;
KW TPR repeat.
FT CHAIN 1..1316
FT /note="Tetratricopeptide repeat protein 21B"
FT /id="PRO_0000291917"
FT REPEAT 108..141
FT /note="TPR 1"
FT REPEAT 145..178
FT /note="TPR 2"
FT REPEAT 180..211
FT /note="TPR 3"
FT REPEAT 285..323
FT /note="TPR 4"
FT REPEAT 324..357
FT /note="TPR 5"
FT REPEAT 492..525
FT /note="TPR 6"
FT REPEAT 563..596
FT /note="TPR 7"
FT REPEAT 617..650
FT /note="TPR 8"
FT REPEAT 722..755
FT /note="TPR 9"
FT REPEAT 757..789
FT /note="TPR 10"
FT REPEAT 791..822
FT /note="TPR 11"
FT REPEAT 831..864
FT /note="TPR 12"
FT REPEAT 884..917
FT /note="TPR 13"
FT REPEAT 919..951
FT /note="TPR 14"
FT REPEAT 952..985
FT /note="TPR 15"
FT REPEAT 1023..1056
FT /note="TPR 16"
FT REPEAT 1197..1230
FT /note="TPR 17"
FT REPEAT 1232..1264
FT /note="TPR 18"
FT REPEAT 1266..1299
FT /note="TPR 19"
FT VAR_SEQ 463..482
FT /note="PASPGQPLCPLLRRCISVLE -> VSNYGTYFQGCVYLMFYERT (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12880961"
FT /id="VSP_026306"
FT VAR_SEQ 483..1316
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12880961"
FT /id="VSP_026307"
FT VARIANT 60
FT /note="F -> Y (found in a patient with Meckel-Gruber like
FT syndrome also carrying variant C-671 in BBS7; unknown
FT pathological significance; hypomorphic variant in vitro;
FT dbSNP:rs371571631)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065514"
FT VARIANT 66
FT /note="K -> R"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065515"
FT VARIANT 150
FT /note="W -> R (in NPHP12; with extra-renal features;
FT functionally null mutation in vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065516"
FT VARIANT 157
FT /note="K -> E (found in a patient with Bardet-Biedl
FT syndrome; probably acts as disease modifier; the patient
FT also carries a frameshift mutation and variant M-501 in
FT BBS12; hypomorphic variant in vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065517"
FT VARIANT 201
FT /note="V -> M (in dbSNP:rs1432273)"
FT /evidence="ECO:0000269|PubMed:12880961,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_032888"
FT VARIANT 209
FT /note="P -> L (in NPHP12; also found in a patient with
FT Bardet-Biedl syndrome carrying two variants in BBS4;
FT hypomorphic variant in vitro; dbSNP:rs140511594)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065518"
FT VARIANT 222
FT /note="Q -> L (found in a patient with Meckel-Gruber like
FT syndrome also carrying variant V-280 on the same allele and
FT variant G-1183 in RPGRIP1L; unknown pathological
FT significance; hypomorphic variant in vitro;
FT dbSNP:rs80026831)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065519"
FT VARIANT 231
FT /note="T -> S (in SRTD4 and NPHP12; also found in a patient
FT with Bardet-Biedl syndrome carrying variants L-159 and T-
FT 346 in BBS12; also found in a patient with Meckel-Gruber
FT syndrome carrying a homozygous variant in TMEM216;
FT hypomorphic variant in vitro; dbSNP:rs149925563)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065520"
FT VARIANT 242
FT /note="D -> N (in dbSNP:rs74447004)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065521"
FT VARIANT 255
FT /note="Y -> C (found in a patient with Bardet-Biedl
FT syndrome; probably acts as disease modifier; the patient
FT also carries a frameshift mutation and variant P-34 in
FT BBS10; hypomorphic variant in vitro; dbSNP:rs377061787)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065522"
FT VARIANT 276
FT /note="T -> A (in dbSNP:rs7592429)"
FT /evidence="ECO:0000269|PubMed:12880961,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_032889"
FT VARIANT 280
FT /note="M -> V (found in a patient with Meckel-Gruber like
FT syndrome also carrying L-222 on the same allele and variant
FT G-1183 in RPGRIP1L; unknown pathological significance;
FT hypomorphic variant in vitro; dbSNP:rs112868646)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065523"
FT VARIANT 327
FT /note="A -> S (found in a patient with Meckel-Gruber
FT syndrome also carrying a mutation in CC2D2A; unknown
FT pathological significance; hypomorphic variant in vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065524"
FT VARIANT 347
FT /note="Y -> C (found in a patient with Meckel-Gruber
FT syndrome also carrying N-1041 on the same allele; unknown
FT pathological significance; hypomorphic variant in vitro;
FT dbSNP:rs779121249)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065525"
FT VARIANT 411
FT /note="R -> G (found in a patient with Bardet-Biedl
FT syndrome; probably acts as disease modifier; the patient
FT also carries a homozygous frameshift mutation in BBS7;
FT hypomorphic variant in vitro; dbSNP:rs185089786)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065526"
FT VARIANT 412
FT /note="Q -> R (in dbSNP:rs199873923)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065527"
FT VARIANT 424
FT /note="D -> E (in dbSNP:rs533077805)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065528"
FT VARIANT 463
FT /note="P -> S (in dbSNP:rs16851307)"
FT /id="VAR_032890"
FT VARIANT 473
FT /note="L -> F (in dbSNP:rs2163649)"
FT /id="VAR_032891"
FT VARIANT 566
FT /note="H -> R (in NPHP12; unknown pathological
FT significance; functionally null mutation in vitro;
FT dbSNP:rs146320075)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065529"
FT VARIANT 591
FT /note="S -> N (in JBTS11; hypomorphic variant in vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065530"
FT VARIANT 616
FT /note="R -> C (in dbSNP:rs139441507)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065531"
FT VARIANT 624
FT /note="I -> V (in dbSNP:rs77106136)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065532"
FT VARIANT 645
FT /note="H -> R (in dbSNP:rs200291881)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065533"
FT VARIANT 724
FT /note="S -> T (in dbSNP:rs759317777)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065534"
FT VARIANT 753
FT /note="P -> L (found in a patient with Meckel-Gruber like
FT syndrome carrying variant D-559 in BBS1 and a variant in
FT CC2D2A; unknown pathological significance; functionally
FT null mutation in vitro; dbSNP:rs539769126)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065535"
FT VARIANT 755
FT /note="D -> Y (in SRTD4; functionally null mutation in
FT vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065536"
FT VARIANT 795
FT /note="L -> P (in SRTD4; functionally null mutation in
FT vitro; dbSNP:rs387907060)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065537"
FT VARIANT 844
FT /note="M -> V (found in a patient with Meckel-Gruber
FT syndrome; unknown pathological significance; functionally
FT null mutation in vitro; dbSNP:rs766811699)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065538"
FT VARIANT 846
FT /note="K -> R (in dbSNP:rs7595010)"
FT /id="VAR_032892"
FT VARIANT 867
FT /note="R -> C (in JBTS11; functionally null mutation in
FT vitro; dbSNP:rs746700857)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065539"
FT VARIANT 867
FT /note="R -> H (found in a patient with Meckel-Gruber
FT syndrome also carrying a homozygous variant in CC2D2A; also
FT found in a patient with short-rib thoracic dysplasia
FT without polydactyly compoud heterozygous for causative
FT mutations in IFT81; probably acts as disease modifier;
FT functionally null mutation in vitro; dbSNP:rs76726265)"
FT /evidence="ECO:0000269|PubMed:21258341,
FT ECO:0000269|PubMed:27666822"
FT /id="VAR_065540"
FT VARIANT 869
FT /note="Q -> R (found in a patient with Meckel-Gruber like
FT syndrome; unknown pathological significance; hypomorphic
FT variant in vitro; dbSNP:rs137926033)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065541"
FT VARIANT 939
FT /note="R -> Q (hypomorphic variant in vitro;
FT dbSNP:rs751382210)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065542"
FT VARIANT 939
FT /note="R -> W (functionally null mutation in vitro;
FT dbSNP:rs151227843)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065543"
FT VARIANT 1002
FT /note="L -> V (found in a patient with Meckel-Gruber like
FT syndrome; also found in patients with Bardet-Bied syndrome;
FT also found in a patient with nephronophthisis with extra-
FT renal features; unknown pathological significance;
FT hypomorphic variant in vitro; dbSNP:rs146496725)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065544"
FT VARIANT 1011
FT /note="M -> T (in JBTS11; dbSNP:rs777427926)"
FT /evidence="ECO:0000269|PubMed:22425360"
FT /id="VAR_068172"
FT VARIANT 1011
FT /note="M -> V (in dbSNP:rs761842893)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065545"
FT VARIANT 1035
FT /note="Y -> C (in dbSNP:rs757541819)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065546"
FT VARIANT 1041
FT /note="D -> N (found in a patient with Meckel-Gruber
FT syndrome also carrying C-347 on the same allele; unknown
FT pathological significance; functionally null mutation in
FT vitro)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065547"
FT VARIANT 1103
FT /note="T -> R (found in a patient with Bardet-Biedl
FT syndrome; probably acts as disease modifier; the patient
FT also carries two mutations in BBS6; hypomorphic variant in
FT vitro; dbSNP:rs1482808126)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065548"
FT VARIANT 1167
FT /note="Y -> C (in NPHP12; hypomorphic variant in vitro;
FT dbSNP:rs1040877016)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065549"
FT VARIANT 1186
FT /note="M -> V (in JBTS11; hypomorphic variant in vitro;
FT dbSNP:rs376308209)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065550"
FT VARIANT 1208
FT /note="I -> S (found in a patient with Bardet-Biedl
FT syndrome; probably acts as disease modifier; the patients
FT also carries two mutations in BBS1; functionally null
FT mutation in vitro; dbSNP:rs189519760)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065551"
FT VARIANT 1284
FT /note="D -> H (in dbSNP:rs139537546)"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065552"
FT VARIANT 1311
FT /note="R -> G"
FT /evidence="ECO:0000269|PubMed:21258341"
FT /id="VAR_065553"
FT CONFLICT 227
FT /note="D -> N (in Ref. 1; BAE45724)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="D -> G (in Ref. 4; BAB71404)"
FT /evidence="ECO:0000305"
FT CONFLICT 1187
FT /note="N -> D (in Ref. 4; BAB13836)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1316 AA; 150937 MW; 2C8505224012736B CRC64;
MDSQELKTLI NYYCQERYFH HVLLVASEGI KRYGSDPVFR FYHAYGTLME GKTQEALREF
EAIKNKQDVS LCSLLALIYA HKMSPNPDRE AILESDARVK EQRKGAGEKA LYHAGLFLWH
IGRHDKAREY IDRMIKISDG SKQGHVLKAW LDITRGKEPY TKKALKYFEE GLQDGNDTFA
LLGKAQCLEM RQNYSGALET VNQIIVNFPS FLPAFVKKMK LQLALQDWDQ TVETAQRLLL
QDSQNVEALR MQALYYVCRE GDIEKASTKL ENLGNTLDAM EPQNAQLFYN ITLAFSRTCG
RSQLILQKIQ TLLERAFSLN PQQSEFATEL GYQMILQGRV KEALKWYKTA MTLDETSVSA
LVGFIQCQLI EGQLQDADQQ LEFLNEIQQS IGKSAELIYL HAVLAMKKNK RQEEVINLLN
DVLDTHFSQL EGLPLGIQYF EKLNPDFLLE IVMEYLSFCP MQPASPGQPL CPLLRRCISV
LETVVRTVPG LLQTVFLIAK VKYLSGDIEA AFNNLQHCLE HNPSYADAHL LLAQVYLSQE
KVKLCSQSLE LCLSYDFKVR DYPLYHLIKA QSQKKMGEIA DAIKTLHMAM SLPGMKRIGA
STKSKDRKTE VDTSHRLSIF LELIDVHRLN GEQHEATKVL QDAIHEFSGT SEEVRVTIAN
ADLALAQGDI ERALSILQNV TAEQPYFIEA REKMADIYLK HRKDKMLYIT CFREIAERMA
NPRSFLLLGD AYMNILEPEE AIVAYEQALN QNPKDGTLAS KMGKALIKTH NYSMAITYYE
AALKTGQKNY LCYDLAELLL KLKWYDKAEK VLQHALAHEP VNELSALMED GRCQVLLAKV
YSKMEKLGDA ITALQQAREL QARVLKRVQM EQPDAVPAQK HLAAEICAEI AKHSVAQRDY
EKAIKFYREA LVHCETDNKI MLELARLYLA QDDPDSCLRQ CALLLQSDQD NEAATMMMAD
LMFRKQDYEQ AVFHLQQLLE RKPDNYMTLS RLIDLLRRCG KLEDVPRFFS MAEKRNSRAK
LEPGFQYCKG LYLWYTGEPN DALRHFNKAR KDRDWGQNAL YNMIEICLNP DNETVGGEVF
ENLDGDLGNS TEKQESVQLA VRTAEKLLKE LKPQTVQGHV QLRIMENYCL MATKQKSNVE
QALNTFTEIA ASEKEHIPAL LGMATAYMIL KQTPRARNQL KRIAKMNWNA IDAEEFEKSW
LLLADIYIQS AKYDMAEDLL KRCLRHNRSC CKAYEYMGYI MEKEQAYTDA ALNYEMAWKY
SNRTNPAVGY KLAFNYLKAK RYVDSIDICH QVLEAHPTYP KIRKDILDKA RASLRP
