CLN6_HUMAN
ID CLN6_HUMAN Reviewed; 311 AA.
AC Q9NWW5; A8K560; B4DDH6; Q6IAB1; Q96SR0;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Ceroid-lipofuscinosis neuronal protein 6;
DE Short=Protein CLN6;
GN Name=CLN6;
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] (ISOFORMS 1 AND 2).
RC TISSUE=Adrenal gland;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT CLN6
RP LEU-234.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
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] (ISOFORM 1).
RC TISSUE=Lung, and Urinary bladder;
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 SUBCELLULAR LOCATION.
RX PubMed=15265688; DOI=10.1016/j.yexcr.2004.04.042;
RA Mole S.E., Michaux G., Codlin S., Wheeler R.B., Sharp J.D., Cutler D.F.;
RT "CLN6, which is associated with a lysosomal storage disease, is an
RT endoplasmic reticulum protein.";
RL Exp. Cell Res. 298:399-406(2004).
RN [7]
RP INTERACTION WITH CLN3.
RX PubMed=17237713; DOI=10.1203/pdr.0b013e31802d8a4a;
RA Persaud-Sawin D.A., Mousallem T., Wang C., Zucker A., Kominami E.,
RA Boustany R.M.;
RT "Neuronal ceroid lipofuscinosis: a common pathway?";
RL Pediatr. Res. 61:146-152(2007).
RN [8]
RP INTERACTION WITH CLN5, AND SUBCELLULAR LOCATION.
RX PubMed=19941651; DOI=10.1186/1471-2121-10-83;
RA Lyly A., von Schantz C., Heine C., Schmiedt M.L., Sipilae T., Jalanko A.,
RA Kyttaelae A.;
RT "Novel interactions of CLN5 support molecular networking between neuronal
RT ceroid lipofuscinosis proteins.";
RL BMC Cell Biol. 10:83-83(2009).
RN [9]
RP INTERACTION WITH CRMP2.
RX PubMed=19235893; DOI=10.1002/jnr.22032;
RA Benedict J.W., Getty A.L., Wishart T.M., Gillingwater T.H., Pearce D.A.;
RT "Protein product of CLN6 gene responsible for variant late-onset infantile
RT neuronal ceroid lipofuscinosis interacts with CRMP-2.";
RL J. Neurosci. Res. 87:2157-2166(2009).
RN [10]
RP CHARACTERIZATION OF VARIANT CLN6 THR-241.
RX PubMed=20430023; DOI=10.1016/j.yexcr.2010.04.010;
RA Ng C.L., Oresic K., Tortorella D.;
RT "TRAM1 is involved in disposal of ER membrane degradation substrates.";
RL Exp. Cell Res. 316:2113-2122(2010).
RN [11]
RP VARIANT CLN6 TYR-171 DEL.
RX PubMed=11791207; DOI=10.1086/338190;
RA Gao H., Boustany R.-M.N., Espinola J.A., Cotman S.L., Srinidhi L.,
RA Antonellis K.A., Gillis T., Qin X., Liu S., Donahue L.R., Bronson R.T.,
RA Faust J.R., Stout D., Haines J.L., Lerner T.J., MacDonald M.E.;
RT "Mutations in a novel CLN6-encoded transmembrane protein cause variant
RT neuronal ceroid lipofuscinosis in man and mouse.";
RL Am. J. Hum. Genet. 70:324-335(2002).
RN [12]
RP VARIANTS CLN6 ASP-123 AND ILE-154 DEL.
RX PubMed=11727201; DOI=10.1086/338708;
RA Wheeler R.B., Sharp J.D., Schultz R.A., Joslin J.M., Williams R.E.,
RA Mole S.E.;
RT "The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis
RT (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane
RT protein.";
RL Am. J. Hum. Genet. 70:537-542(2002).
RN [13]
RP VARIANT CLN6 ARG-300.
RX PubMed=12673792; DOI=10.1002/humu.10207;
RA Teixeira C.A., Espinola J., Huo L., Kohlschutter J., Persaud Sawin D.A.,
RA Minassian B., Bessa C.J., Guimaraes A., Stephan D.A., Sa Miranda M.C.,
RA MacDonald M.E., Ribeiro M.G., Boustany R.-M.N.;
RT "Novel mutations in the CLN6 gene causing a variant late infantile neuronal
RT ceroid lipofuscinosis.";
RL Hum. Mutat. 21:502-508(2003).
RN [14]
RP VARIANTS CLN6 HIS-62; SER-221; THR-241; SER-265 DEL AND LEU-299, AND
RP VARIANT GLN-72.
RX PubMed=12815591; DOI=10.1002/humu.10227;
RA Sharp J.D., Wheeler R.B., Parker K.A., Gardiner R.M., Williams R.E.,
RA Mole S.E.;
RT "Spectrum of CLN6 mutations in variant late infantile neuronal ceroid
RT lipofuscinosis.";
RL Hum. Mutat. 22:35-42(2003).
RN [15]
RP VARIANTS CLN6 LEU-159; CYS-221 AND SER-265 DEL.
RX PubMed=19201763; DOI=10.1093/brain/awn366;
RA Kousi M., Siintola E., Dvorakova L., Vlaskova H., Turnbull J., Topcu M.,
RA Yuksel D., Gokben S., Minassian B.A., Elleder M., Mole S.E.,
RA Lehesjoki A.-E.;
RT "Mutations in CLN7/MFSD8 are a common cause of variant late-infantile
RT neuronal ceroid lipofuscinosis.";
RL Brain 132:810-819(2009).
RN [16]
RP VARIANTS CLN4A THR-6; PHE-47; PRO-67; LYS-77; GLN-103; HIS-149 AND THR-238,
RP AND VARIANTS THR-34 AND THR-308.
RX PubMed=21549341; DOI=10.1016/j.ajhg.2011.04.004;
RA Arsov T., Smith K.R., Damiano J., Franceschetti S., Canafoglia L.,
RA Bromhead C.J., Andermann E., Vears D.F., Cossette P., Rajagopalan S.,
RA McDougall A., Sofia V., Farrell M., Aguglia U., Zini A., Meletti S.,
RA Morbin M., Mullen S., Andermann F., Mole S.E., Bahlo M., Berkovic S.F.;
RT "Kufs disease, the major adult form of neuronal ceroid lipofuscinosis,
RT caused by mutations in CLN6.";
RL Am. J. Hum. Genet. 88:566-573(2011).
RN [17]
RP VARIANTS CLN6 SER-17; LYS-90; PHE-104; CYS-149; PRO-169; SER-186; LEU-234;
RP HIS-252; SER-259 AND THR-297, AND VARIANT THR-12.
RX PubMed=21990111; DOI=10.1002/humu.21624;
RA Kousi M., Lehesjoki A.E., Mole S.E.;
RT "Update of the mutation spectrum and clinical correlations of over 360
RT mutations in eight genes that underlie the neuronal ceroid
RT lipofuscinoses.";
RL Hum. Mutat. 33:42-63(2012).
RN [18]
RP VARIANT GLN-72.
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).
CC -!- SUBUNIT: Interacts with CRMP2 (PubMed:19235893). Interacts with CLN5
CC (PubMed:19941651). Interacts with CLN3 (PubMed:17237713).
CC {ECO:0000269|PubMed:17237713, ECO:0000269|PubMed:19235893,
CC ECO:0000269|PubMed:19941651}.
CC -!- INTERACTION:
CC Q9NWW5; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-6165897, EBI-11343438;
CC Q9NWW5; P11912: CD79A; NbExp=3; IntAct=EBI-6165897, EBI-7797864;
CC Q9NWW5; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-6165897, EBI-1045797;
CC Q9NWW5; O95471: CLDN7; NbExp=3; IntAct=EBI-6165897, EBI-740744;
CC Q9NWW5; Q8IUN9: CLEC10A; NbExp=3; IntAct=EBI-6165897, EBI-2873246;
CC Q9NWW5; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-6165897, EBI-18013275;
CC Q9NWW5; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-6165897, EBI-6942903;
CC Q9NWW5; Q9BQA9: CYBC1; NbExp=3; IntAct=EBI-6165897, EBI-2680384;
CC Q9NWW5; O00559: EBAG9; NbExp=3; IntAct=EBI-6165897, EBI-8787095;
CC Q9NWW5; P29323-3: EPHB2; NbExp=3; IntAct=EBI-6165897, EBI-25838727;
CC Q9NWW5; P34910-2: EVI2B; NbExp=3; IntAct=EBI-6165897, EBI-17640610;
CC Q9NWW5; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-6165897, EBI-18304435;
CC Q9NWW5; Q8TBE3: FNDC9; NbExp=3; IntAct=EBI-6165897, EBI-12142257;
CC Q9NWW5; P48165: GJA8; NbExp=3; IntAct=EBI-6165897, EBI-17458373;
CC Q9NWW5; Q5T7V8: GORAB; NbExp=3; IntAct=EBI-6165897, EBI-3917143;
CC Q9NWW5; P43628: KIR2DL3; NbExp=3; IntAct=EBI-6165897, EBI-8632435;
CC Q9NWW5; Q9H400: LIME1; NbExp=3; IntAct=EBI-6165897, EBI-2830566;
CC Q9NWW5; Q8N386: LRRC25; NbExp=3; IntAct=EBI-6165897, EBI-11304917;
CC Q9NWW5; Q7Z5B4-5: RIC3; NbExp=3; IntAct=EBI-6165897, EBI-12375429;
CC Q9NWW5; A1A5C7-2: SLC22A23; NbExp=3; IntAct=EBI-6165897, EBI-12081840;
CC Q9NWW5; O14863: SLC30A4; NbExp=3; IntAct=EBI-6165897, EBI-13918058;
CC Q9NWW5; Q16623: STX1A; NbExp=3; IntAct=EBI-6165897, EBI-712466;
CC Q9NWW5; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-6165897, EBI-10329860;
CC Q9NWW5; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-6165897, EBI-7238458;
CC Q9NWW5; Q96Q45-2: TMEM237; NbExp=3; IntAct=EBI-6165897, EBI-10982110;
CC Q9NWW5; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-6165897, EBI-12345267;
CC Q9NWW5; O00308: WWP2; NbExp=3; IntAct=EBI-6165897, EBI-743923;
CC Q9NWW5; A0A142I5B9; Xeno; NbExp=4; IntAct=EBI-6165897, EBI-20625235;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:15265688}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15265688}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:19941651}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NWW5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NWW5-2; Sequence=VSP_056197;
CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 6 (CLN6) [MIM:601780]: An
CC autosomal recessive form of neuronal ceroid lipofuscinosis. Neuronal
CC ceroid lipofuscinoses are progressive neurodegenerative, lysosomal
CC storage diseases characterized by intracellular accumulation of
CC autofluorescent liposomal material, and clinically by seizures,
CC dementia, visual loss, and/or cerebral atrophy. The lipopigment
CC patterns observed most often in neuronal ceroid lipofuscinosis type 6
CC comprise mixed combinations of granular, curvilinear, and fingerprint
CC profiles. {ECO:0000269|PubMed:11727201, ECO:0000269|PubMed:11791207,
CC ECO:0000269|PubMed:12673792, ECO:0000269|PubMed:12815591,
CC ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:20430023,
CC ECO:0000269|PubMed:21990111, ECO:0000269|Ref.2}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Ceroid lipofuscinosis, neuronal, 4A (Kufs type), autosomal
CC recessive (CLN4A) [MIM:204300]: An adult-onset neuronal ceroid
CC lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive
CC neurodegenerative, lysosomal storage diseases characterized by
CC intracellular accumulation of autofluorescent liposomal material, and
CC clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
CC CLN4A has no visual involvement and is characterized by progressive
CC myoclonic epilepsy. {ECO:0000269|PubMed:21549341}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=NCL CLN6; Note=Neural Ceroid Lipofuscinoses mutation
CC db;
CC URL="https://www.ucl.ac.uk/ncl/cln6.shtml";
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DR EMBL; AK000568; BAA91260.1; -; mRNA.
DR EMBL; AK027604; BAB55226.1; -; mRNA.
DR EMBL; AK291175; BAF83864.1; -; mRNA.
DR EMBL; AK293197; BAG56737.1; -; mRNA.
DR EMBL; CR457244; CAG33525.1; -; mRNA.
DR EMBL; AC107871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77811.1; -; Genomic_DNA.
DR EMBL; BC010849; AAH10849.1; -; mRNA.
DR EMBL; BC013130; AAH13130.1; -; mRNA.
DR CCDS; CCDS10227.1; -. [Q9NWW5-1]
DR RefSeq; NP_060352.1; NM_017882.2. [Q9NWW5-1]
DR AlphaFoldDB; Q9NWW5; -.
DR BioGRID; 120318; 109.
DR IntAct; Q9NWW5; 64.
DR STRING; 9606.ENSP00000249806; -.
DR TCDB; 9.B.386.1.1; the ceroid-lipofuscinosis neuronal protein-6 (cln6) family.
DR iPTMnet; Q9NWW5; -.
DR PhosphoSitePlus; Q9NWW5; -.
DR BioMuta; CLN6; -.
DR DMDM; 32129457; -.
DR EPD; Q9NWW5; -.
DR jPOST; Q9NWW5; -.
DR MassIVE; Q9NWW5; -.
DR MaxQB; Q9NWW5; -.
DR PaxDb; Q9NWW5; -.
DR PeptideAtlas; Q9NWW5; -.
DR PRIDE; Q9NWW5; -.
DR ProteomicsDB; 3862; -.
DR ProteomicsDB; 82991; -. [Q9NWW5-1]
DR Antibodypedia; 26301; 182 antibodies from 29 providers.
DR DNASU; 54982; -.
DR Ensembl; ENST00000249806.11; ENSP00000249806.5; ENSG00000128973.13. [Q9NWW5-1]
DR Ensembl; ENST00000538696.5; ENSP00000445770.1; ENSG00000128973.13. [Q9NWW5-2]
DR GeneID; 54982; -.
DR KEGG; hsa:54982; -.
DR MANE-Select; ENST00000249806.11; ENSP00000249806.5; NM_017882.3; NP_060352.1.
DR UCSC; uc002arf.3; human. [Q9NWW5-1]
DR CTD; 54982; -.
DR DisGeNET; 54982; -.
DR GeneCards; CLN6; -.
DR HGNC; HGNC:2077; CLN6.
DR HPA; ENSG00000128973; Low tissue specificity.
DR MalaCards; CLN6; -.
DR MIM; 204300; phenotype.
DR MIM; 601780; phenotype.
DR MIM; 606725; gene.
DR neXtProt; NX_Q9NWW5; -.
DR OpenTargets; ENSG00000128973; -.
DR Orphanet; 228340; CLN4A disease.
DR Orphanet; 228363; CLN6 disease.
DR PharmGKB; PA26604; -.
DR VEuPathDB; HostDB:ENSG00000128973; -.
DR eggNOG; ENOG502QSUV; Eukaryota.
DR GeneTree; ENSGT00400000022240; -.
DR HOGENOM; CLU_077437_0_0_1; -.
DR InParanoid; Q9NWW5; -.
DR OMA; VFPLQWF; -.
DR PhylomeDB; Q9NWW5; -.
DR TreeFam; TF333294; -.
DR PathwayCommons; Q9NWW5; -.
DR SignaLink; Q9NWW5; -.
DR BioGRID-ORCS; 54982; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; CLN6; human.
DR GeneWiki; CLN6; -.
DR GenomeRNAi; 54982; -.
DR Pharos; Q9NWW5; Tbio.
DR PRO; PR:Q9NWW5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NWW5; protein.
DR Bgee; ENSG00000128973; Expressed in monocyte and 99 other tissues.
DR ExpressionAtlas; Q9NWW5; baseline and differential.
DR Genevisible; Q9NWW5; HS.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0035727; F:lysophosphatidic acid binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0120146; F:sulfatide binding; IDA:UniProtKB.
DR GO; GO:0044265; P:cellular macromolecule catabolic process; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:UniProtKB.
DR GO; GO:0001573; P:ganglioside metabolic process; IMP:UniProtKB.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IMP:UniProtKB.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IEA:Ensembl.
DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR GO; GO:0007040; P:lysosome organization; IBA:GO_Central.
DR GO; GO:0045862; P:positive regulation of proteolysis; IMP:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; NAS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR InterPro; IPR029255; CLN6.
DR PANTHER; PTHR16244; PTHR16244; 1.
DR Pfam; PF15156; CLN6; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; Endoplasmic reticulum; Membrane;
KW Neurodegeneration; Neuronal ceroid lipofuscinosis; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..311
FT /note="Ceroid-lipofuscinosis neuronal protein 6"
FT /id="PRO_0000089862"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 81..101
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 111..131
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..28
FT /note="MEATRRRQHLGATGGPGAQLGASFLQAR -> MAAVAGKERRARGRPRPETL
FT GAIPRREGGEAGLSRAFKPLAQAPLSCETSLRKLKFKGKK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056197"
FT VARIANT 6
FT /note="R -> T (in CLN4A; dbSNP:rs154774636)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065834"
FT VARIANT 12
FT /note="A -> T (in dbSNP:rs112239768)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066904"
FT VARIANT 17
FT /note="G -> S (in CLN6; unknown pathological significance;
FT dbSNP:rs763944821)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066905"
FT VARIANT 34
FT /note="A -> T (in dbSNP:rs146198681)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065835"
FT VARIANT 47
FT /note="L -> F (in CLN4A; dbSNP:rs154774635)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065836"
FT VARIANT 62
FT /note="R -> H (in CLN6; dbSNP:rs751486476)"
FT /evidence="ECO:0000269|PubMed:12815591"
FT /id="VAR_021549"
FT VARIANT 67
FT /note="L -> P (in CLN4A; dbSNP:rs154774633)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065837"
FT VARIANT 72
FT /note="E -> Q (in dbSNP:rs104894483)"
FT /evidence="ECO:0000269|PubMed:12815591,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_021550"
FT VARIANT 77
FT /note="N -> K (in CLN4A; dbSNP:rs154774641)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065838"
FT VARIANT 90
FT /note="N -> K (in CLN6)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066906"
FT VARIANT 103
FT /note="R -> Q (in CLN4A; dbSNP:rs154774634)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065839"
FT VARIANT 104
FT /note="S -> F (in CLN6)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066907"
FT VARIANT 123
FT /note="G -> D (in CLN6; dbSNP:rs104894484)"
FT /evidence="ECO:0000269|PubMed:11727201"
FT /id="VAR_015683"
FT VARIANT 149
FT /note="R -> C (in CLN6; dbSNP:rs747229909)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066908"
FT VARIANT 149
FT /note="R -> H (in CLN4A; dbSNP:rs154774638)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065840"
FT VARIANT 154
FT /note="Missing (in CLN6)"
FT /evidence="ECO:0000269|PubMed:11727201"
FT /id="VAR_015684"
FT VARIANT 159
FT /note="P -> L (in CLN6; dbSNP:rs919850756)"
FT /evidence="ECO:0000269|PubMed:19201763"
FT /id="VAR_058436"
FT VARIANT 169
FT /note="L -> P (in CLN6; dbSNP:rs1344658850)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066909"
FT VARIANT 171
FT /note="Missing (in CLN6; dbSNP:rs121908079)"
FT /evidence="ECO:0000269|PubMed:11791207"
FT /id="VAR_015685"
FT VARIANT 186
FT /note="F -> S (in CLN6)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066910"
FT VARIANT 221
FT /note="Y -> C (in CLN6; dbSNP:rs764571295)"
FT /evidence="ECO:0000269|PubMed:19201763"
FT /id="VAR_058437"
FT VARIANT 221
FT /note="Y -> S (in CLN6; dbSNP:rs764571295)"
FT /evidence="ECO:0000269|PubMed:12815591"
FT /id="VAR_021551"
FT VARIANT 234
FT /note="F -> L (in CLN6; dbSNP:rs959199004)"
FT /evidence="ECO:0000269|PubMed:21990111, ECO:0000269|Ref.2"
FT /id="VAR_066911"
FT VARIANT 238
FT /note="F -> T (in CLN4A; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065841"
FT VARIANT 241
FT /note="M -> T (in CLN6; decreased protein level, resulting
FT from ER membrane-to-cytosol dislocation of the protein
FT followed by proteasome degradation.; dbSNP:rs1555438255)"
FT /evidence="ECO:0000269|PubMed:12815591,
FT ECO:0000269|PubMed:20430023"
FT /id="VAR_021552"
FT VARIANT 252
FT /note="R -> H (in CLN6; dbSNP:rs374681194)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066912"
FT VARIANT 259
FT /note="G -> S (in CLN6; dbSNP:rs150363441)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066913"
FT VARIANT 265
FT /note="Missing (in CLN6)"
FT /evidence="ECO:0000269|PubMed:12815591,
FT ECO:0000269|PubMed:19201763"
FT /id="VAR_021553"
FT VARIANT 297
FT /note="P -> T (in CLN6; dbSNP:rs1194940137)"
FT /evidence="ECO:0000269|PubMed:21990111"
FT /id="VAR_066914"
FT VARIANT 299
FT /note="P -> L (in CLN6; dbSNP:rs758921701)"
FT /evidence="ECO:0000269|PubMed:12815591"
FT /id="VAR_021554"
FT VARIANT 300
FT /note="W -> R (in CLN6; dbSNP:rs750937323)"
FT /evidence="ECO:0000269|PubMed:12673792"
FT /id="VAR_015686"
FT VARIANT 308
FT /note="S -> T (in dbSNP:rs143578698)"
FT /evidence="ECO:0000269|PubMed:21549341"
FT /id="VAR_065842"
FT CONFLICT 281
FT /note="W -> R (in Ref. 1; BAB55226)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 311 AA; 35919 MW; C718E6F2DC20CE0F CRC64;
MEATRRRQHL GATGGPGAQL GASFLQARHG SVSADEAART APFHLDLWFY FTLQNWVLDF
GRPIAMLVFP LEWFPLNKPS VGDYFHMAYN VITPFLLLKL IERSPRTLPR SITYVSIIIF
IMGASIHLVG DSVNHRLLFS GYQHHLSVRE NPIIKNLKPE TLIDSFELLY YYDEYLGHCM
WYIPFFLILF MYFSGCFTAS KAESLIPGPA LLLVAPSGLY YWYLVTEGQI FILFIFTFFA
MLALVLHQKR KRLFLDSNGL FLFSSFALTL LLVALWVAWL WNDPVLRKKY PGVIYVPEPW
AFYTLHVSSR H
