ID RDH12_HUMAN Reviewed; 316 AA. AC Q96NR8; B2RDA2; Q8TAW6; DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 180. DE RecName: Full=Retinol dehydrogenase 12; DE EC=1.1.1.300 {ECO:0000269|PubMed:12226107, ECO:0000269|PubMed:15865448}; DE AltName: Full=All-trans and 9-cis retinol dehydrogenase; DE AltName: Full=Short chain dehydrogenase/reductase family 7C member 2; GN Name=RDH12; Synonyms=SDR7C2; 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], AND VARIANT GLN-161. RC TISSUE=Cerebellum, and Kidney; 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 GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [3] 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [5] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY. RX PubMed=12226107; DOI=10.1074/jbc.m208882200; RA Haeseleer F., Jang G.-F., Imanishi Y., Driessen C.A.G.G., Matsumura M., RA Nelson P.S., Palczewski K.; RT "Dual-substrate specificity short chain retinol dehydrogenases from the RT vertebrate retina."; RL J. Biol. Chem. 277:45537-45546(2002). RN [6] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, RP SUBCELLULAR LOCATION, SUBSTRATE SPECIFICITY, AND FUNCTION. RX PubMed=15865448; DOI=10.1021/bi050226k; RA Belyaeva O.V., Korkina O.V., Stetsenko A.V., Kim T., Nelson P.S., RA Kedishvili N.Y.; RT "Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): RT catalytic efficiency toward retinoids and C9 aldehydes and effects of RT cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde- RT binding protein (CRALBP) on the oxidation and reduction of retinoids."; RL Biochemistry 44:7035-7047(2005). RN [7] RP FUNCTION, AND CHARACTERIZATION OF VARIANT GLN-161. RX PubMed=19686838; DOI=10.1016/j.freeradbiomed.2009.08.005; RA Marchette L.D., Thompson D.A., Kravtsova M., Ngansop T.N., Mandal M.N., RA Kasus-Jacobi A.; RT "Retinol dehydrogenase 12 detoxifies 4-hydroxynonenal in photoreceptor RT cells."; RL Free Radic. Biol. Med. 48:16-25(2010). RN [8] RP VARIANTS LCA13 ASN-51; ILE-99; ASN-151; ASP-151; PRO-175 AND ALA-230. RX PubMed=15322982; DOI=10.1086/424889; RA Perrault I., Hanein S., Gerber S., Barbet F., Ducroq D., Dollfus H., RA Hamel C., Dufier J.-L., Munnich A., Kaplan J., Rozet J.-M.; RT "Retinal dehydrogenase 12 (RDH12) mutations in Leber congenital RT amaurosis."; RL Am. J. Hum. Genet. 75:639-646(2004). RN [9] RP VARIANTS LCA13 MET-49 AND CYS-226, AND CHARACTERIZATION OF VARIANTS LCA13 RP MET-49 AND CYS-226. RX PubMed=15258582; DOI=10.1038/ng1394; RA Janecke A.R., Thompson D.A., Utermann G., Becker C., Huebner C.A., RA Schmid E., McHenry C.L., Nair A.R., Rueschendorf F., Heckenlively J., RA Wissinger B., Nuernberg P., Gal A.; RT "Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase RT cause childhood-onset severe retinal dystrophy."; RL Nat. Genet. 36:850-854(2004). RN [10] RP VARIANTS RETINAL DYSTROPHY THR-47; MET-55; ILE-99; LYS-125; GLU-145; RP ASP-151; ILE-155; CYS-193; ASP-206; VAL-206; LEU-230; HIS-234; TRP-239; RP PRO-274 AND TYR-285, VARIANTS GLN-65; ASN-101; GLN-161 AND CYS-193, RP CHARACTERIZATION OF VARIANTS RETINAL DYSTROPHY THR-47; MET-55; ILE-99; RP LYS-125; GLU-145; ASP-151; ILE-155; CYS-193; ASP-206; VAL-206; LEU-230; RP HIS-234; TRP-239; PRO-274 AND TYR-285, AND CHARACTERIZATION OF VARIANT RP GLN-161. RX PubMed=16269441; DOI=10.1093/hmg/ddi411; RA Thompson D.A., Janecke A.R., Lange J., Feathers K.L., Hubner C.A., RA McHenry C.L., Stockton D.W., Rammesmayer G., Lupski J.R., Antinolo G., RA Ayuso C., Baiget M., Gouras P., Heckenlively J.R., den Hollander A., RA Jacobson S.G., Lewis R.A., Sieving P.A., Wissinger B., Yzer S., Zrenner E., RA Utermann G., Gal A.; RT "Retinal degeneration associated with RDH12 mutations results from RT decreased 11-cis retinal synthesis due to disruption of the visual cycle."; RL Hum. Mol. Genet. 14:3865-3875(2005). RN [11] RP VARIANT RP53 VAL-126. RX PubMed=19140180; DOI=10.1002/ajmg.a.32634; RA Benayoun L., Spiegel R., Auslender N., Abbasi A.H., Rizel L., Hujeirat Y., RA Salama I., Garzozi H.J., Allon-Shalev S., Ben-Yosef T.; RT "Genetic heterogeneity in two consanguineous families segregating early RT onset retinal degeneration: the pitfalls of homozygosity mapping."; RL Am. J. Med. Genet. A 149:650-656(2009). RN [12] RP VARIANT RP53 ARG-76. RX PubMed=19956407; RA Aldahmesh M.A., Safieh L.A., Alkuraya H., Al-Rajhi A., Shamseldin H., RA Hashem M., Alzahrani F., Khan A.O., Alqahtani F., Rahbeeni Z., Alowain M., RA Khalak H., Al-Hazzaa S., Meyer B.F., Alkuraya F.S.; RT "Molecular characterization of retinitis pigmentosa in Saudi Arabia."; RL Mol. Vis. 15:2464-2469(2009). RN [13] RP VARIANTS VAL-79 AND GLN-161. RX PubMed=21602930; DOI=10.1371/journal.pone.0019458; RA Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., RA Hejtmancik J.F.; RT "Detection of variants in 15 genes in 87 unrelated Chinese patients with RT Leber congenital amaurosis."; RL PLoS ONE 6:E19458-E19458(2011). RN [14] RP VARIANT RP53 ASP-146. RX PubMed=26124963; DOI=10.1155/2015/942740; RA Gong B., Wei B., Huang L., Hao J., Li X., Yang Y., Zhou Y., Hao F., Cui Z., RA Zhang D., Wang L., Zhang H.; RT "Exome Sequencing identified a recessive RDH12 mutation in a family with RT severe early-onset retinitis pigmentosa."; RL J. Ophthalmol. 2015:942740-942740(2015). CC -!- FUNCTION: Retinoids dehydrogenase/reductase with a clear preference for CC NADP. Displays high activity towards 9-cis, 11-cis and all-trans- CC retinal. Shows very weak activity towards 13-cis-retinol CC (PubMed:15865448, PubMed:12226107). Also exhibits activity, albeit with CC lower affinity than for retinaldehydes, towards lipid peroxidation CC products (C9 aldehydes) such as 4-hydroxynonenal and trans-2-nonenal CC (PubMed:19686838, PubMed:15865448). May play an important function in CC photoreceptor cells to detoxify 4-hydroxynonenal and potentially other CC toxic aldehyde products resulting from lipid peroxidation CC (PubMed:19686838). Has no dehydrogenase activity towards steroids CC (PubMed:15865448, PubMed:12226107). {ECO:0000269|PubMed:12226107, CC ECO:0000269|PubMed:15865448, ECO:0000269|PubMed:19686838}. CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-retinol + NADP(+) = all-trans-retinal + H(+) + CC NADPH; Xref=Rhea:RHEA:25033, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17898, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC EC=1.1.1.300; Evidence={ECO:0000269|PubMed:12226107, CC ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=11-cis-retinol + NADP(+) = 11-cis-retinal + H(+) + NADPH; CC Xref=Rhea:RHEA:54912, ChEBI:CHEBI:15378, ChEBI:CHEBI:16066, CC ChEBI:CHEBI:16302, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:12226107, ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=9-cis-retinol + NADP(+) = 9-cis-retinal + H(+) + NADPH; CC Xref=Rhea:RHEA:54916, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78272, ChEBI:CHEBI:78273; CC Evidence={ECO:0000269|PubMed:12226107, ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 4-hydroxynonen-1-ol + NADP(+) = a 4-hydroxynonenal + H(+) + CC NADPH; Xref=Rhea:RHEA:58336, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142593, ChEBI:CHEBI:142606; CC Evidence={ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(E)-non-2-en-1-ol + NADP(+) = (E)-non-2-enal + H(+) + NADPH; CC Xref=Rhea:RHEA:58332, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142592, ChEBI:CHEBI:142604; CC Evidence={ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(Z)-non-6-en-1-ol + NADP(+) = (Z)-non-6-enal + H(+) + NADPH; CC Xref=Rhea:RHEA:58328, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, CC ChEBI:CHEBI:58349, ChEBI:CHEBI:142591, ChEBI:CHEBI:142603; CC Evidence={ECO:0000269|PubMed:15865448}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + nonan-1-ol = H(+) + NADPH + nonanal; CC Xref=Rhea:RHEA:58380, ChEBI:CHEBI:15378, ChEBI:CHEBI:35986, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:84268; CC Evidence={ECO:0000269|PubMed:15865448}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.2 uM for NADPH {ECO:0000269|PubMed:15865448}; CC KM=2200 uM for NADH {ECO:0000269|PubMed:15865448}; CC KM=0.04 uM for all-trans-retinal {ECO:0000269|PubMed:15865448}; CC KM=0.1 uM for 11-cis-retinal {ECO:0000269|PubMed:15865448}; CC KM=0.14 uM for 9-cis-retinal {ECO:0000269|PubMed:15865448}; CC KM=0.16 uM for 11-cis-retinol {ECO:0000269|PubMed:15865448}; CC KM=0.16 uM for 9-cis-retinol {ECO:0000269|PubMed:15865448}; CC KM=0.4 uM for all-trans-retinol {ECO:0000269|PubMed:15865448}; CC KM=3.1 uM for nonanal {ECO:0000269|PubMed:15865448}; CC KM=20 uM for (E)-non-2-enal {ECO:0000269|PubMed:15865448}; CC KM=1 uM for (Z)-non-6-enal {ECO:0000269|PubMed:15865448}; CC Note=kcat is 36 min(-1) for all-trans-retinal as substrate. kcat is CC 45 min(-1) for 11-cis-retinal as substrate. kcat is 14 min(-1) for CC 9-cis-retinal as substrate. kcat is 27 min(-1) for all-trans-retinol CC as substrate. kcat is 7 min(-1) for 11-cis-retinol as substrate. kcat CC is 7 min(-1) for 9-cis-retinol as substrate. kcat is 56 min(-1) for CC nonanal as substrate. kcat is 45 min(-1) for (Z)-non-6-enal as CC substrate. kcat is 28 min(-1) for (E)-non-2-enal. CC {ECO:0000269|PubMed:15865448}; CC -!- PATHWAY: Cofactor metabolism; retinol metabolism. CC {ECO:0000269|PubMed:12226107}. CC -!- INTERACTION: CC Q96NR8; Q6IQ23-2: PLEKHA7; NbExp=3; IntAct=EBI-3916363, EBI-12069346; CC Q96NR8; Q93062: RBPMS; NbExp=3; IntAct=EBI-3916363, EBI-740322; CC Q96NR8; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-3916363, EBI-740343; CC Q96NR8; P0CG48: UBC; NbExp=2; IntAct=EBI-3916363, EBI-3390054; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:15865448}. CC -!- TISSUE SPECIFICITY: Widely expressed, mostly in retina, kidney, brain, CC skeletal muscle, pancreas and stomach. {ECO:0000269|PubMed:15865448}. CC -!- DISEASE: Leber congenital amaurosis 13 (LCA13) [MIM:612712]: A severe CC dystrophy of the retina, typically becoming evident in the first years CC of life. Visual function is usually poor and often accompanied by CC nystagmus, sluggish or near-absent pupillary responses, photophobia, CC high hyperopia and keratoconus. {ECO:0000269|PubMed:15258582, CC ECO:0000269|PubMed:15322982}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Retinitis pigmentosa 53 (RP53) [MIM:612712]: 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. RP53 inheritance is autosomal CC dominant or autosomal recessive. {ECO:0000269|PubMed:19140180, CC ECO:0000269|PubMed:19956407, ECO:0000269|PubMed:26124963}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: Shows clear specificity for the pro-S hydrogen on C4 of CC NADPH and the pro-R hydrogen on C15 of retinols. CC {ECO:0000269|PubMed:12226107}. CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) CC family. {ECO:0000305}. 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; AK054835; BAB70811.1; -; mRNA. DR EMBL; AK315462; BAG37849.1; -; mRNA. DR EMBL; AL049779; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471061; EAW80951.1; -; Genomic_DNA. DR EMBL; BC025724; AAH25724.1; -; mRNA. DR CCDS; CCDS9787.1; -. DR RefSeq; NP_689656.2; NM_152443.2. DR AlphaFoldDB; Q96NR8; -. DR SMR; Q96NR8; -. DR BioGRID; 126895; 53. DR IntAct; Q96NR8; 21. DR MINT; Q96NR8; -. DR STRING; 9606.ENSP00000449079; -. DR DrugBank; DB00162; Vitamin A. DR DrugCentral; Q96NR8; -. DR SwissLipids; SLP:000001789; -. DR iPTMnet; Q96NR8; -. DR PhosphoSitePlus; Q96NR8; -. DR BioMuta; RDH12; -. DR DMDM; 116242750; -. DR jPOST; Q96NR8; -. DR MassIVE; Q96NR8; -. DR MaxQB; Q96NR8; -. DR PaxDb; 9606-ENSP00000449079; -. DR PeptideAtlas; Q96NR8; -. DR ProteomicsDB; 77549; -. DR Antibodypedia; 24894; 106 antibodies from 19 providers. DR DNASU; 145226; -. DR Ensembl; ENST00000267502.3; ENSP00000267502.3; ENSG00000139988.10. DR Ensembl; ENST00000551171.6; ENSP00000449079.1; ENSG00000139988.10. DR GeneID; 145226; -. DR KEGG; hsa:145226; -. DR MANE-Select; ENST00000551171.6; ENSP00000449079.1; NM_152443.3; NP_689656.2. DR UCSC; uc001xjz.5; human. DR AGR; HGNC:19977; -. DR CTD; 145226; -. DR DisGeNET; 145226; -. DR GeneCards; RDH12; -. DR GeneReviews; RDH12; -. DR HGNC; HGNC:19977; RDH12. DR HPA; ENSG00000139988; Group enriched (retina, skin). DR MalaCards; RDH12; -. DR MIM; 608830; gene. DR MIM; 612712; phenotype. DR neXtProt; NX_Q96NR8; -. DR OpenTargets; ENSG00000139988; -. DR Orphanet; 65; Leber congenital amaurosis. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA134864793; -. DR VEuPathDB; HostDB:ENSG00000139988; -. DR eggNOG; KOG1208; Eukaryota. DR GeneTree; ENSGT00940000161505; -. DR HOGENOM; CLU_010194_44_5_1; -. DR InParanoid; Q96NR8; -. DR OMA; LQGEKHY; -. DR OrthoDB; 2466675at2759; -. DR PhylomeDB; Q96NR8; -. DR TreeFam; TF105429; -. DR BioCyc; MetaCyc:ENSG00000139988-MONOMER; -. DR BRENDA; 1.1.1.105; 2681. DR BRENDA; 1.1.1.300; 2681. DR PathwayCommons; Q96NR8; -. DR Reactome; R-HSA-2453864; Retinoid cycle disease events. DR Reactome; R-HSA-2453902; The canonical retinoid cycle in rods (twilight vision). DR SignaLink; Q96NR8; -. DR UniPathway; UPA00912; -. DR BioGRID-ORCS; 145226; 10 hits in 1147 CRISPR screens. DR GeneWiki; RDH12; -. DR GenomeRNAi; 145226; -. DR Pharos; Q96NR8; Tbio. DR PRO; PR:Q96NR8; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q96NR8; Protein. DR Bgee; ENSG00000139988; Expressed in upper arm skin and 122 other cell types or tissues. DR ExpressionAtlas; Q96NR8; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB. DR GO; GO:0060342; C:photoreceptor inner segment membrane; TAS:Reactome. DR GO; GO:0102354; F:11-cis-retinol dehydrogenase activity; IEA:RHEA. DR GO; GO:0004745; F:NAD-retinol dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0052650; F:NADP-retinol dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0110095; P:cellular detoxification of aldehyde; IDA:UniProtKB. DR GO; GO:0045494; P:photoreceptor cell maintenance; TAS:UniProtKB. DR GO; GO:0001523; P:retinoid metabolic process; TAS:Reactome. DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB. DR GO; GO:0007601; P:visual perception; IMP:UniProtKB. DR CDD; cd09807; retinol-DH_like_SDR_c; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR002347; SDR_fam. DR PANTHER; PTHR43157; PHOSPHATIDYLINOSITOL-GLYCAN BIOSYNTHESIS CLASS F PROTEIN-RELATED; 1. DR PANTHER; PTHR43157:SF32; RETINOL DEHYDROGENASE 12; 1. DR Pfam; PF00106; adh_short; 1. DR PRINTS; PR00081; GDHRDH. DR PRINTS; PR00080; SDRFAMILY. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR Genevisible; Q96NR8; HS. PE 1: Evidence at protein level; KW Disease variant; Endoplasmic reticulum; Leber congenital amaurosis; KW Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome; KW Retinitis pigmentosa; Sensory transduction; Vision. FT CHAIN 1..316 FT /note="Retinol dehydrogenase 12" FT /id="PRO_0000054766" FT ACT_SITE 200 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 46..52 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250" FT BINDING 175 FT /ligand="substrate" FT /evidence="ECO:0000250" FT VARIANT 47 FT /note="A -> T (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs761231974)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064163" FT VARIANT 49 FT /note="T -> M (in LCA13; abolishes protection against the FT toxicity of 4-hydroxynonenal in the retina; results in FT aberrant activity in interconverting isomers of retinol and FT retinal; the activity profiles depend on presence or FT absence of variant Q-161; genetic background may act as a FT modifier of variant effect; dbSNP:rs28940314)" FT /evidence="ECO:0000269|PubMed:15258582, FT ECO:0000269|PubMed:19686838" FT /id="VAR_020858" FT VARIANT 51 FT /note="I -> N (in LCA13; dbSNP:rs104894473)" FT /evidence="ECO:0000269|PubMed:15322982" FT /id="VAR_020859" FT VARIANT 55 FT /note="T -> M (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs766631462)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064164" FT VARIANT 65 FT /note="R -> Q (in dbSNP:rs745471670)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064165" FT VARIANT 76 FT /note="G -> R (in RP53; dbSNP:rs368489658)" FT /evidence="ECO:0000269|PubMed:19956407" FT /id="VAR_064166" FT VARIANT 79 FT /note="A -> V (found in a patient with LCA13; FT dbSNP:rs763414313)" FT /evidence="ECO:0000269|PubMed:21602930" FT /id="VAR_067193" FT VARIANT 99 FT /note="L -> I (in LCA13; exhibits a profound loss of FT catalytic activity; dbSNP:rs28940315)" FT /evidence="ECO:0000269|PubMed:15322982, FT ECO:0000269|PubMed:16269441" FT /id="VAR_020860" FT VARIANT 101 FT /note="D -> N (in dbSNP:rs148334092)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064167" FT VARIANT 125 FT /note="N -> K (in retinal dystrophy; exhibits a profound FT loss of catalytic activity)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064168" FT VARIANT 126 FT /note="A -> V (in RP53; dbSNP:rs202126574)" FT /evidence="ECO:0000269|PubMed:19140180" FT /id="VAR_064169" FT VARIANT 145 FT /note="G -> E (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs907600014)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064170" FT VARIANT 146 FT /note="V -> D (in RP53; uncertain significance; FT dbSNP:rs116649873)" FT /evidence="ECO:0000269|PubMed:26124963" FT /id="VAR_081222" FT VARIANT 151 FT /note="H -> D (in LCA13; exhibits a profound loss of FT catalytic activity; dbSNP:rs104894475)" FT /evidence="ECO:0000269|PubMed:15322982, FT ECO:0000269|PubMed:16269441" FT /id="VAR_020861" FT VARIANT 151 FT /note="H -> N (in LCA13; dbSNP:rs104894475)" FT /evidence="ECO:0000269|PubMed:15322982" FT /id="VAR_020862" FT VARIANT 155 FT /note="T -> I (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs121434337)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064171" FT VARIANT 161 FT /note="R -> Q (does not affect the protection against the FT toxicity of 4-hydroxynonenal in the retina; FT dbSNP:rs17852293)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:16269441, ECO:0000269|PubMed:19686838, FT ECO:0000269|PubMed:21602930" FT /id="VAR_028281" FT VARIANT 175 FT /note="S -> P (in LCA13; dbSNP:rs104894472)" FT /evidence="ECO:0000269|PubMed:15322982" FT /id="VAR_020863" FT VARIANT 193 FT /note="R -> C (in retinal dystrophy; uncertain FT significance; dbSNP:rs148629905)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064172" FT VARIANT 206 FT /note="A -> D (in retinal dystrophy; exhibits a profound FT loss of catalytic activity)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064173" FT VARIANT 206 FT /note="A -> V (in retinal dystrophy; uncertain FT significance; dbSNP:rs1254096311)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064174" FT VARIANT 226 FT /note="Y -> C (in LCA13; diminished activity in FT interconverting isomers of retinol and retinal; FT dbSNP:rs28940313)" FT /evidence="ECO:0000269|PubMed:15258582" FT /id="VAR_020864" FT VARIANT 230 FT /note="P -> A (in LCA13; dbSNP:rs104894476)" FT /evidence="ECO:0000269|PubMed:15322982" FT /id="VAR_020865" FT VARIANT 230 FT /note="P -> L (in retinal dystrophy; uncertain FT significance)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064175" FT VARIANT 234 FT /note="R -> H (in retinal dystrophy; uncertain FT significance; exhibits a loss of catalytic activity; FT dbSNP:rs750636662)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064176" FT VARIANT 239 FT /note="R -> W (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs751589863)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064177" FT VARIANT 274 FT /note="L -> P (in retinal dystrophy; exhibits a profound FT loss of catalytic activity)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064178" FT VARIANT 285 FT /note="C -> Y (in retinal dystrophy; exhibits a profound FT loss of catalytic activity; dbSNP:rs973306929)" FT /evidence="ECO:0000269|PubMed:16269441" FT /id="VAR_064179" SQ SEQUENCE 316 AA; 35094 MW; EA0915E1E484879B CRC64; MLVTLGLLTS FFSFLYMVAP SIRKFFAGGV CRTNVQLPGK VVVITGANTG IGKETARELA SRGARVYIAC RDVLKGESAA SEIRVDTKNS QVLVRKLDLS DTKSIRAFAE GFLAEEKQLH ILINNAGVMM CPYSKTADGF ETHLGVNHLG HFLLTYLLLE RLKVSAPARV VNVSSVAHHI GKIPFHDLQS EKRYSRGFAY CHSKLANVLF TRELAKRLQG TGVTTYAVHP GVVRSELVRH SSLLCLLWRL FSPFVKTARE GAQTSLHCAL AEGLEPLSGK YFSDCKRTWV SPRARNNKTA ERLWNVSCEL LGIRWE //