RDH12_HUMAN
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 03-AUG-2022, entry version 173.
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=0.10 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 9-
CC cis-retinal as substrate. kcat is 27 min(-1) for all-trans-retinol as
CC substrate. kcat is 7 min(-1) for 11-cis-retinol as substrate. kcat is
CC 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}.
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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; 51.
DR IntAct; Q96NR8; 20.
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; Q96NR8; -.
DR PeptideAtlas; Q96NR8; -.
DR PRIDE; Q96NR8; -.
DR ProteomicsDB; 77549; -.
DR Antibodypedia; 24894; 103 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 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; SDCKKTW; -.
DR OrthoDB; 1032903at2759; -.
DR PhylomeDB; Q96NR8; -.
DR TreeFam; TF105429; -.
DR BioCyc; MetaCyc:ENSG00000139988-MON; -.
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 1069 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 121 other tissues.
DR ExpressionAtlas; Q96NR8; baseline and differential.
DR Genevisible; Q96NR8; HS.
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 InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
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; early onset; unknown pathological
FT significance; 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; unknown pathological
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; unknown pathological
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; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16269441"
FT /id="VAR_064175"
FT VARIANT 234
FT /note="R -> H (in retinal dystrophy; unknown pathological
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
