ID CLRN1_HUMAN Reviewed; 232 AA. AC P58418; D3DNJ3; E1ACU9; Q8N6A9; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 2. DT 27-MAR-2024, entry version 169. DE RecName: Full=Clarin-1; DE AltName: Full=Usher syndrome type-3 protein; GN Name=CLRN1; Synonyms=USH3A; 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 2), AND VARIANTS USH3A LYS-120 AND RP 153-ILE-LEU-154 DELINS MET. RX PubMed=11524702; DOI=10.1086/323610; RA Joensuu T., Haemaelaeinen R., Yuan B., Johnson C., Tegelberg S., RA Gasparini P., Zelante L., Pirvola U., Pakarinen L., Lehesjoki A.-E., RA de la Chapelle A., Sankila E.-M.; RT "Mutations in a novel gene with transmembrane domains underlie Usher RT syndrome type 3."; RL Am. J. Hum. Genet. 69:673-684(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS USH3A LYS-48 AND RP PRO-150. RX PubMed=12145752; DOI=10.1086/342098; RA Fields R.R., Zhou G., Huang D., Davis J.R., Moeller C., Jacobson S.G., RA Kimberling W.J., Sumegi J.; RT "Usher syndrome type III: revised genomic structure of the USH3 gene and RT identification of novel mutations."; RL Am. J. Hum. Genet. 71:607-617(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT USH3A LYS-48, AND FUNCTION. RC TISSUE=Retina; RX PubMed=12080385; DOI=10.1038/sj.ejhg.5200831; RA Adato A., Vreugde S., Joensuu T., Avidan N., Hamalainen R., Belenkiy O., RA Olender T., Bonne-Tamir B., Ben-Asher E., Espinos C., Millan J.M., RA Lehesjoki A.-E., Flannery J.G., Avraham K.B., Pietrokovski S., RA Sankila E.-M., Beckmann J.S., Lancet D.; RT "USH3A transcripts encode clarin-1, a four-transmembrane-domain protein RT with a possible role in sensory synapses."; RL Eur. J. Hum. Genet. 10:339-350(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND ALTERNATIVE SPLICING. RC TISSUE=Retina; RX PubMed=20717163; DOI=10.1038/ejhg.2010.140; RA Vastinsalo H., Jalkanen R., Dinculescu A., Isosomppi J., Geller S., RA Flannery J.G., Hauswirth W.W., Sankila E.M.; RT "Alternative splice variants of the USH3A gene Clarin 1 (CLRN1)."; RL Eur. J. Hum. Genet. 19:30-35(2011). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP VARIANT USH3A GLY-40. RX PubMed=15521980; DOI=10.1111/j.1399-0004.2004.00352.x; RA Aller E., Jaijo T., Oltra S., Alio J., Galan F., Najera C., Beneyto M., RA Millan J.M.; RT "Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher RT syndrome: low prevalence and phenotypic variability."; RL Clin. Genet. 66:525-529(2004). RN [9] RP VARIANT USH3A PRO-105. RX PubMed=18273898; DOI=10.1002/humu.9524; RA Dreyer B., Brox V., Tranebjaerg L., Rosenberg T., Sadeghi A.M., Moeller C., RA Nilssen O.; RT "Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome RT type II."; RL Hum. Mutat. 29:451-451(2008). RN [10] RP VARIANTS RP61 LEU-31 AND TRP-154, CHARACTERIZATION OF VARIANTS RP61 LEU-31 RP AND TRP-154, AND SUBCELLULAR LOCATION. RX PubMed=21310491; DOI=10.1016/j.ophtha.2010.10.047; RA Khan M.I., Kersten F.F., Azam M., Collin R.W., Hussain A., Shah S.T., RA Keunen J.E., Kremer H., Cremers F.P., Qamar R., den Hollander A.I.; RT "CLRN1 mutations cause nonsyndromic retinitis pigmentosa."; RL Ophthalmology 118:1444-1448(2011). RN [11] RP VARIANT USH3A ASN-168. RX PubMed=23304067; RA Garcia-Garcia G., Aparisi M.J., Rodrigo R., Sequedo M.D., Espinos C., RA Rosell J., Olea J.L., Mendivil M.P., Ramos-Arroyo M.A., Ayuso C., Jaijo T., RA Aller E., Millan J.M.; RT "Two novel disease-causing mutations in the CLRN1 gene in patients with RT Usher syndrome type 3."; RL Mol. Vis. 18:3070-3078(2012). CC -!- FUNCTION: May have a role in the excitatory ribbon synapse junctions CC between hair cells and cochlear ganglion cells and presumably also in CC analogous synapses within the retina. {ECO:0000269|PubMed:12080385}. CC -!- INTERACTION: CC P58418; Q9BVK2: ALG8; NbExp=3; IntAct=EBI-17274839, EBI-3921603; CC P58418; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-17274839, EBI-12244618; CC P58418; O14523: C2CD2L; NbExp=3; IntAct=EBI-17274839, EBI-12822627; CC P58418; Q8WVQ1: CANT1; NbExp=3; IntAct=EBI-17274839, EBI-16770554; CC P58418; Q8NHW4: CCL4L2; NbExp=3; IntAct=EBI-17274839, EBI-10271156; CC P58418; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-17274839, EBI-12256978; CC P58418; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-17274839, EBI-12019274; CC P58418; Q8N682: DRAM1; NbExp=3; IntAct=EBI-17274839, EBI-10305400; CC P58418; Q8N5W8: FAM24B; NbExp=3; IntAct=EBI-17274839, EBI-13383724; CC P58418; Q9Y231: FUT9; NbExp=3; IntAct=EBI-17274839, EBI-3922408; CC P58418; P11215: ITGAM; NbExp=3; IntAct=EBI-17274839, EBI-2568251; CC P58418; Q6N075: MFSD5; NbExp=3; IntAct=EBI-17274839, EBI-3920969; CC P58418; O14880: MGST3; NbExp=3; IntAct=EBI-17274839, EBI-724754; CC P58418; Q8IXM6: NRM; NbExp=3; IntAct=EBI-17274839, EBI-10262547; CC P58418; O75396: SEC22B; NbExp=3; IntAct=EBI-17274839, EBI-1058865; CC P58418; Q8N130: SLC34A3; NbExp=3; IntAct=EBI-17274839, EBI-17769653; CC P58418; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-17274839, EBI-2844246; CC P58418; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-17274839, EBI-348587; CC P58418; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-17274839, EBI-347385; CC P58418; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-17274839, EBI-11528917; CC P58418; P56557: TMEM50B; NbExp=3; IntAct=EBI-17274839, EBI-12366453; CC P58418; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-17274839, EBI-2548832; CC P58418; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-17274839, EBI-11724433; CC P58418; Q9NRS4: TMPRSS4; NbExp=3; IntAct=EBI-17274839, EBI-10313040; CC P58418; Q53HI1: UNC50; NbExp=3; IntAct=EBI-17274839, EBI-7601760; CC P58418; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-17274839, EBI-12837904; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21310491}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=P58418-3; Sequence=Displayed; CC Name=2; Synonyms=A; CC IsoId=P58418-1; Sequence=VSP_022868, VSP_022869; CC Name=3; Synonyms=0-2-2b-3; CC IsoId=P58418-4; Sequence=VSP_043303; CC -!- TISSUE SPECIFICITY: Widely expressed. Found in the retina. CC -!- DISEASE: Usher syndrome 3A (USH3A) [MIM:276902]: USH is a genetically CC heterogeneous condition characterized by the association of retinitis CC pigmentosa with sensorineural deafness. Age at onset and differences in CC auditory and vestibular function distinguish Usher syndrome type 1 CC (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). CC USH3 is characterized by postlingual, progressive hearing loss, CC variable vestibular dysfunction, and onset of retinitis pigmentosa CC symptoms, including nyctalopia, constriction of the visual fields, and CC loss of central visual acuity, usually by the second decade of life. CC {ECO:0000269|PubMed:11524702, ECO:0000269|PubMed:12080385, CC ECO:0000269|PubMed:12145752, ECO:0000269|PubMed:15521980, CC ECO:0000269|PubMed:18273898, ECO:0000269|PubMed:23304067}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Retinitis pigmentosa 61 (RP61) [MIM:614180]: 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:21310491}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the clarin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mutations of the USH3A gene; Note=Retina CC International's Scientific Newsletter; CC URL="https://www.retina-international.org/files/sci-news/ush3mut.htm"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF388366; AAL09581.1; -; mRNA. DR EMBL; AF482697; AAN07148.1; -; mRNA. DR EMBL; AF495717; AAM88774.1; -; mRNA. DR EMBL; HM626132; ADM63096.1; -; mRNA. DR EMBL; AC020636; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78814.1; -; Genomic_DNA. DR EMBL; CH471052; EAW78815.1; -; Genomic_DNA. DR EMBL; BC074970; AAH74970.1; -; mRNA. DR EMBL; BC074971; AAH74971.1; -; mRNA. DR CCDS; CCDS3153.1; -. [P58418-3] DR CCDS; CCDS35492.1; -. [P58418-1] DR CCDS; CCDS56285.1; -. [P58418-4] DR RefSeq; NP_001182723.1; NM_001195794.1. [P58418-4] DR RefSeq; NP_443721.1; NM_052995.2. [P58418-1] DR RefSeq; NP_777367.1; NM_174878.2. [P58418-3] DR AlphaFoldDB; P58418; -. DR BioGRID; 113244; 30. DR IntAct; P58418; 26. DR STRING; 9606.ENSP00000329158; -. DR TCDB; 9.A.46.1.1; the clarin (clrn) family. DR GlyCosmos; P58418; 1 site, No reported glycans. DR GlyGen; P58418; 1 site. DR iPTMnet; P58418; -. DR PhosphoSitePlus; P58418; -. DR BioMuta; CLRN1; -. DR DMDM; 125987806; -. DR PaxDb; 9606-ENSP00000329158; -. DR ProteomicsDB; 57075; -. [P58418-1] DR Antibodypedia; 52945; 34 antibodies from 12 providers. DR DNASU; 7401; -. DR Ensembl; ENST00000295911.6; ENSP00000295911.2; ENSG00000163646.12. [P58418-1] DR Ensembl; ENST00000327047.6; ENSP00000322280.1; ENSG00000163646.12. [P58418-3] DR Ensembl; ENST00000328863.8; ENSP00000329158.4; ENSG00000163646.12. [P58418-4] DR GeneID; 7401; -. DR KEGG; hsa:7401; -. DR MANE-Select; ENST00000327047.6; ENSP00000322280.1; NM_174878.3; NP_777367.1. DR UCSC; uc003eyj.3; human. [P58418-3] DR AGR; HGNC:12605; -. DR CTD; 7401; -. DR DisGeNET; 7401; -. DR GeneCards; CLRN1; -. DR GeneReviews; CLRN1; -. DR HGNC; HGNC:12605; CLRN1. DR HPA; ENSG00000163646; Group enriched (adrenal gland, retina). DR MalaCards; CLRN1; -. DR MIM; 276902; phenotype. DR MIM; 606397; gene. DR MIM; 614180; phenotype. DR neXtProt; NX_P58418; -. DR OpenTargets; ENSG00000163646; -. DR Orphanet; 791; Retinitis pigmentosa. DR Orphanet; 231183; Usher syndrome type 3. DR PharmGKB; PA37231; -. DR VEuPathDB; HostDB:ENSG00000163646; -. DR eggNOG; ENOG502QQVB; Eukaryota. DR GeneTree; ENSGT00850000132319; -. DR HOGENOM; CLU_095723_0_0_1; -. DR InParanoid; P58418; -. DR OMA; MPNRQKQ; -. DR OrthoDB; 4150254at2759; -. DR PhylomeDB; P58418; -. DR TreeFam; TF331875; -. DR PathwayCommons; P58418; -. DR SignaLink; P58418; -. DR BioGRID-ORCS; 7401; 11 hits in 1142 CRISPR screens. DR ChiTaRS; CLRN1; human. DR GeneWiki; CLRN1; -. DR GenomeRNAi; 7401; -. DR Pharos; P58418; Tbio. DR PRO; PR:P58418; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P58418; Protein. DR Bgee; ENSG00000163646; Expressed in adrenal tissue and 45 other cell types or tissues. DR ExpressionAtlas; P58418; baseline and differential. DR GO; GO:0045178; C:basal part of cell; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; IDA:MGI. DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl. DR GO; GO:0005902; C:microvillus; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0032420; C:stereocilium; IEA:Ensembl. DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IEA:Ensembl. DR GO; GO:0007015; P:actin filament organization; IDA:MGI. DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl. DR GO; GO:0048870; P:cell motility; IDA:MGI. DR GO; GO:0050957; P:equilibrioception; IMP:HGNC-UCL. DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:HGNC-UCL. DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IDA:MGI. DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW. DR GO; GO:0050953; P:sensory perception of light stimulus; IMP:HGNC-UCL. DR GO; GO:0007605; P:sensory perception of sound; IMP:HGNC-UCL. DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW. DR InterPro; IPR026748; Clarin. DR PANTHER; PTHR31548; CLARIN; 1. DR PANTHER; PTHR31548:SF4; CLARIN-1; 1. DR Genevisible; P58418; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Deafness; Disease variant; KW Glycoprotein; Hearing; Membrane; Reference proteome; Retinitis pigmentosa; KW Sensory transduction; Transmembrane; Transmembrane helix; Usher syndrome; KW Vision. FT CHAIN 1..232 FT /note="Clarin-1" FT /id="PRO_0000065729" FT TRANSMEM 8..28 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 101..121 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 135..155 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 186..206 FT /note="Helical" FT /evidence="ECO:0000255" FT CARBOHYD 48 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..85 FT /note="MPSQQKKIIFCMAGVFSFACALGVVTALGTPLWIKATVLCKTGALLVNASGQ FT ELDKFMGEMQYGLFHGEGVRQCGLGARPFRFSF -> MQALQQQPV (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:11524702" FT /id="VSP_022868" FT VAR_SEQ 144 FT /note="S -> SVALWLPATRHQAQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:20717163" FT /id="VSP_043303" FT VAR_SEQ 191..232 FT /note="VIFFCFFVHFLNGLLIRLAGFQFPFAKSKDAETTNVAADLMY -> LTKGHS FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11524702" FT /id="VSP_022869" FT VARIANT 7 FT /note="K -> I (in dbSNP:rs3796241)" FT /id="VAR_053825" FT VARIANT 31 FT /note="P -> L (in RP61; the mutant protein is retained in FT the endoplasmic reticulum; dbSNP:rs374390376)" FT /evidence="ECO:0000269|PubMed:21310491" FT /id="VAR_066673" FT VARIANT 40 FT /note="C -> G (in USH3A; dbSNP:rs121908143)" FT /evidence="ECO:0000269|PubMed:15521980" FT /id="VAR_054555" FT VARIANT 48 FT /note="N -> K (in USH3A; dbSNP:rs111033258)" FT /evidence="ECO:0000269|PubMed:12080385, FT ECO:0000269|PubMed:12145752" FT /id="VAR_030345" FT VARIANT 105 FT /note="S -> P (in USH3A)" FT /evidence="ECO:0000269|PubMed:18273898" FT /id="VAR_054556" FT VARIANT 120 FT /note="M -> K (in USH3A; dbSNP:rs121908141)" FT /evidence="ECO:0000269|PubMed:11524702" FT /id="VAR_012241" FT VARIANT 150 FT /note="L -> P (in USH3A; dbSNP:rs121908142)" FT /evidence="ECO:0000269|PubMed:12145752" FT /id="VAR_030346" FT VARIANT 153..154 FT /note="IL -> M (in USH3A)" FT /evidence="ECO:0000269|PubMed:11524702" FT /id="VAR_012242" FT VARIANT 154 FT /note="L -> W (in RP61; the mutant protein is retained in FT the endoplasmic reticulum; dbSNP:rs775098953)" FT /evidence="ECO:0000269|PubMed:21310491" FT /id="VAR_066674" FT VARIANT 168 FT /note="I -> N (in USH3A)" FT /evidence="ECO:0000269|PubMed:23304067" FT /id="VAR_071434" SQ SEQUENCE 232 AA; 25719 MW; 2713C621FEBE4281 CRC64; MPSQQKKIIF CMAGVFSFAC ALGVVTALGT PLWIKATVLC KTGALLVNAS GQELDKFMGE MQYGLFHGEG VRQCGLGARP FRFSFFPDLL KAIPVSIHVN VILFSAILIV LTMVGTAFFM YNAFGKPFET LHGPLGLYLL SFISGSCGCL VMILFASEVK IHHLSEKIAN YKEGTYVYKT QSEKYTTSFW VIFFCFFVHF LNGLLIRLAG FQFPFAKSKD AETTNVAADL MY //