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RDH8

gene
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Also known as PRRDHSDR28C2

Summary

RDH8 (retinol dehydrogenase 8, HGNC:14423) is a protein-coding gene on chromosome 19p13.2, encoding Retinol dehydrogenase 8 (Q9NYR8). Retinol dehydrogenase with a clear preference for NADP.

This gene encodes a member of the short-chain dehydrogenase/reductase family. The encoded protein catalyzes the reduction of all-trans-retinal to all-trans-retinol, the first reaction step of the rhodopsin regeneration pathway. This enzymatic reaction is the rate-limiting step in the visual cycle.

Source: NCBI Gene 50700 — RefSeq curated summary.

At a glance

  • GWAS associations: 1
  • Clinical variants (ClinVar): 28 total — 1 pathogenic
  • Phenotypes (HPO): 10
  • MANE Select transcript: NM_015725

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:14423
Approved symbolRDH8
Nameretinol dehydrogenase 8
Location19p13.2
Locus typegene with protein product
StatusApproved
AliasesPRRDH, SDR28C2
Ensembl geneENSG00000080511
Ensembl biotypeprotein_coding
OMIM608575
Entrez50700

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000587782, ENST00000589570, ENST00000591589, ENST00000651512

RefSeq mRNA: 1 — MANE Select: NM_015725 NM_015725

CCDS: CCDS12223

Canonical transcript exons

ENST00000591589 — 6 exons

ExonStartEnd
ENSE000006758401001705710017215
ENSE000006758411001873110018910
ENSE000006758421002070910020802
ENSE000011887051002125510021438
ENSE000028066811002153410022279
ENSE000038930861001348310013600

Expression profiles

Bgee: expression breadth broad, 64 present calls, max score 76.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0776 / max 36.1013, expressed in 15 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1737110.070515
1737120.00713

Top tissues by expression

202 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
spermCL:000001976.52gold quality
myocardiumUBERON:000234973.22gold quality
vena cavaUBERON:000408768.69gold quality
metanephros cortexUBERON:001053368.11gold quality
lateral nuclear group of thalamusUBERON:000273666.67gold quality
body of tongueUBERON:001187666.53gold quality
periodontal ligamentUBERON:000826666.51gold quality
subthalamic nucleusUBERON:000190666.46gold quality
pharyngeal mucosaUBERON:000035566.31gold quality
pericardiumUBERON:000240766.31gold quality
dorsal plus ventral thalamusUBERON:000189766.13gold quality
right testisUBERON:000453465.97gold quality
saphenous veinUBERON:000731865.74gold quality
cardia of stomachUBERON:000116265.68gold quality
inferior vagus X ganglionUBERON:000536365.66gold quality
tongueUBERON:000172365.62gold quality
secondary oocyteCL:000065565.31gold quality
thymusUBERON:000237065.21gold quality
superior surface of tongueUBERON:000737165.20gold quality
superior vestibular nucleusUBERON:000722765.08gold quality
nippleUBERON:000203065.03gold quality
substantia nigra pars reticulataUBERON:000196664.96gold quality
ventral tegmental areaUBERON:000269164.89gold quality
cerebellar vermisUBERON:000472064.84gold quality
substantia nigra pars compactaUBERON:000196564.82gold quality
ponsUBERON:000098864.79gold quality
lateral globus pallidusUBERON:000247664.79gold quality
tracheaUBERON:000312664.66gold quality
synovial jointUBERON:000221764.58gold quality
layer of synovial tissueUBERON:000761664.56gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-MTAB-7316no29.21
E-ANND-3no1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting RDH8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-6867-5P100.0082.213464
HSA-MIR-453499.9966.581907
HSA-MIR-314899.9775.066478
HSA-MIR-3688-3P99.9772.022834
HSA-MIR-807599.9767.20962
HSA-MIR-797899.8666.90856
HSA-MIR-1287-3P99.6366.93492
HSA-MIR-183-3P99.4169.411598
HSA-MIR-5582-5P99.2771.421879
HSA-MIR-4709-3P98.8868.041594
HSA-MIR-6840-3P98.6865.951923
HSA-MIR-806098.6166.931187
HSA-MIR-138-5P98.4370.491292
HSA-MIR-429497.8665.721110
HSA-MIR-3121-5P97.3066.621146
HSA-MIR-122-5P97.2364.921024
HSA-MIR-1212896.6766.981471
HSA-MIR-449196.5366.20935
HSA-MIR-465796.5366.57895
HSA-MIR-576-3P96.1465.63773
HSA-MIR-6846-3P94.8065.19389

Literature-anchored findings (GeneRIF, showing 5)

  • prRDH is an enzyme that catalyzes reduction of all-trans-retinal in the rod outer segment, most noticeably at higher light intensities and prolonged illumination, but is not an essential enzyme of the retinoid cycle (PMID:15755727)
  • Our family- and population-based data both suggest that the RDH8 gene is unlikely to be associated with high myopia in Chinese (PMID:21043051)
  • Progression of retinal degeneration in Rdh8-deficient Abca4-deficient mice is affected by differential vulnerability of rods and cones to light. (PMID:22220722)
  • Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang. (PMID:34297769)
  • A Splicing Variant in RDH8 Is Associated with Autosomal Recessive Stargardt Macular Dystrophy. (PMID:37628710)

Cross-species orthologs

17 orthologs

OrganismSymbolGene ID
danio_reriordh8aENSDARG00000028048
danio_rerioRDH8ENSDARG00000099217
danio_reriordh8bENSDARG00000105060
mus_musculusRdh8ENSMUSG00000053773
rattus_norvegicusRdh8ENSRNOG00000025767
drosophila_melanogasterCG7601FBGN0027583
drosophila_melanogasterCG31546FBGN0051546
drosophila_melanogasterCG31548FBGN0051548
caenorhabditis_elegansWBGENE00000970
caenorhabditis_elegansWBGENE00000975
caenorhabditis_elegansWBGENE00000981
caenorhabditis_elegansWBGENE00000993
caenorhabditis_elegansWBGENE00008985
caenorhabditis_elegansWBGENE00008986
caenorhabditis_elegansWBGENE00011424
caenorhabditis_elegansWBGENE00022809
caenorhabditis_elegansWBGENE00219274

Paralogs (13): DHRS7 (ENSG00000100612), DHRS2 (ENSG00000100867), DHRS7B (ENSG00000109016), HSD11B1 (ENSG00000117594), HSDL2 (ENSG00000119471), DHRS4 (ENSG00000157326), DHRS1 (ENSG00000157379), CBR1 (ENSG00000159228), CBR3 (ENSG00000159231), HSD11B1L (ENSG00000167733), DHRS7C (ENSG00000184544), DHRS4L2 (ENSG00000187630), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Retinol dehydrogenase 8 — Q9NYR8 (reviewed: Q9NYR8)

Alternative names: Photoreceptor outer segment all-trans retinol dehydrogenase, Short chain dehydrogenase/reductase family 28C member 2

All UniProt accessions (3): Q9NYR8, K7EKT5, K7ELF7

UniProt curated annotations — full annotation on UniProt →

Function. Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinal to all-trans-retinol. May play a role in the regeneration of visual pigment at high light intensity.

Subcellular location. Membrane.

Tissue specificity. Detected in photoreceptor outer segments in the retina (at protein level).

Disease relevance. Stargardt disease 5 (STGD5) [MIM:621259] A form of Stargardt disease, a common hereditary macular degeneration characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD5 is an autosomal recessive form characterized by onset of macular dystrophy in the fifth decade of life. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

RefSeq proteins (1): NP_056540* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR002347SDR_famFamily
IPR01134817beta_DHFamily
IPR020904Sc_DH/Rdtase_CSConserved_site
IPR036291NAD(P)-bd_dom_sfHomologous_superfamily

Pfam: PF00106

Enzyme classification (BRENDA):

  • EC 1.1.1.300 — NADP-retinol dehydrogenase (BRENDA: 11 organisms, 101 substrates, 7 inhibitors, 67 Km, 12 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ALL-TRANS-RETINAL0.0001–0.519
NADPH0.0005–0.2310
NADP+0.0004–0.89
ALL-TRANS-RETINOL0.0006–1.36
NADH2.22–13004
ALL-TRANS-3-HYDROXYRETINAL0.0032–0.00443
ESTRONE0.0096–0.03073
NAD+0.004–6803
9-CIS-RETINAL0.0001–0.192
RETINAL0.007–0.132
11-CIS-RETINAL0.00011
11-CIS-RETINOL0.00161
13-CIS-RETINAL0.621
9-CIS-RETINOL0.00161

Catalyzed reactions (Rhea), 1 shown:

  • all-trans-retinol + NADP(+) = all-trans-retinal + NADPH + H(+) (RHEA:25033)

UniProt features (9 total): transmembrane region 3, binding site 2, sequence variant 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9NYR8-F192.680.76

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 155 (proton acceptor)

Ligand- & substrate-binding residues (2): 9–18; 142

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

IDPathway
R-HSA-2453902The canonical retinoid cycle in rods (twilight vision)

MSigDB gene sets: 54 (showing top): GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_HORMONE_BIOSYNTHETIC_PROCESS, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_SENSORY_PERCEPTION, GOBP_ESTROGEN_BIOSYNTHETIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOBP_PRIMARY_ALCOHOL_METABOLIC_PROCESS, GOBP_ESTROGEN_METABOLIC_PROCESS, GOBP_STEROID_METABOLIC_PROCESS

GO Biological Process (5): steroid biosynthetic process (GO:0006694), estrogen biosynthetic process (GO:0006703), visual perception (GO:0007601), retinol metabolic process (GO:0042572), lipid metabolic process (GO:0006629)

GO Molecular Function (4): estradiol 17-beta-dehydrogenase [NAD(P)+] activity (GO:0004303), all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), all-trans-retinol dehydrogenase (NADP+) activity (GO:0052650), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Visual phototransduction1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure3
steroid metabolic process1
lipid biosynthetic process1
estrogen metabolic process1
hormone biosynthetic process1
steroid hormone biosynthetic process1
sensory perception of light stimulus1
retinoid metabolic process1
primary alcohol metabolic process1
hormone metabolic process1
olefinic compound metabolic process1
primary metabolic process1
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor1
alcohol dehydrogenase (NAD+) activity1
alcohol dehydrogenase (NADP+) activity1
retinol metabolic process1
catalytic activity1
cytoplasm1
membrane1
cell periphery1
intracellular anatomical structure1

Protein interactions and networks

STRING

2975 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RDH8RLBP1P12271891
RDH8RHOP08100803
RDH8ABCA4P78363786
RDH8RDH12Q96NR8727
RDH8RDH11Q8TC12667
RDH8RPE65Q16518640
RDH8LRATO95237603
RDH8PRPH2P23942585
RDH8SORDQ00796569
RDH8RCVRNP35243457
RDH8RBP3P10745447
RDH8RGRP47804442
RDH8STRA6Q9BX79416
RDH8BCO1Q9HAY6400
RDH8RBP1P09455399
RDH8RBP4P02753399

IntAct

3 interactions, top by confidence:

ABTypeScore
PDGFALAMB1psi-mi:“MI:0914”(association)0.350
RDH8CCT3psi-mi:“MI:0914”(association)0.350

BioGRID (9): RDH8 (Synthetic Lethality), RDH8 (Affinity Capture-MS), CAMK2B (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), PPP2CA (Affinity Capture-MS), NBEA (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), PRAME (Affinity Capture-MS)

ESM2 similar proteins: A0A0H3KNE7, A0A3Q8GL18, A0A3Q8GLE8, A0A3Q8GYY4, A0A7N9VSG0, A0A7T8F1N2, A0A8F5XX49, A0A8I6GJ95, A0AAT9JA24, A5W4G5, A8C7R7, B8A5W4, D4A2B7, E9Q3D4, E9QUT3, G4N290, O35048, P0C622, P14061, P23102, P37440, P51656, P51661, P9WES5, P9WGQ2, P9WGQ3, Q08632, Q13268, Q17QU7, Q17QW3, Q4WR19, Q5C9I9, Q5R9W5, Q5SS80, Q7FAE1, Q7ZY31, Q8SPU8, Q8VBZ0, Q8XBJ4, Q91WL8

Diamond homologs: A0A017SE81, A0A0E3D8L9, A0A0U1LQE2, A0A140JWS5, A0A1U8QWA2, A0A5B8YU68, A0QYC2, A7IQF2, C0KTJ6, G0RH19, G4N286, G9N4A9, O16881, O55240, P05406, P0CU71, P0DKC7, P14061, P25970, P35731, P37694, P37959, P40471, P42317, P43713, P45200, P45375, P50160, P50203, P51658, P54554, P55006, P55336, P80873, Q04520, Q09851, Q0IH28, Q0VFE7, Q1QU27, Q1R183

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance15
Likely benign2
Benign3

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
3911902NM_015725.4(RDH8):c.262+1G>APathogenic

SpliceAI

1132 predictions. Top by Δscore:

VariantEffectΔscore
19:10013309:GATT:Gdonor_gain1.0000
19:10017052:CGCAG:Cacceptor_loss1.0000
19:10017053:GCA:Gacceptor_loss1.0000
19:10017054:CAG:Cacceptor_loss1.0000
19:10017055:A:AGacceptor_gain1.0000
19:10017055:A:Gacceptor_loss1.0000
19:10017055:AGTC:Aacceptor_gain1.0000
19:10017056:G:GAacceptor_gain1.0000
19:10017056:GTC:Gacceptor_gain1.0000
19:10017056:GTCG:Gacceptor_gain1.0000
19:10017056:GTCGT:Gacceptor_gain1.0000
19:10017197:G:GTdonor_gain1.0000
19:10018729:A:AGacceptor_gain1.0000
19:10018730:G:GGacceptor_gain1.0000
19:10018730:GT:Gacceptor_gain1.0000
19:10018909:GG:Gdonor_gain1.0000
19:10018910:GG:Gdonor_gain1.0000
19:10020704:CACA:Cacceptor_loss1.0000
19:10020707:A:ACacceptor_loss1.0000
19:10020707:A:AGacceptor_gain1.0000
19:10020708:G:GGacceptor_gain1.0000
19:10020708:GGT:Gacceptor_gain1.0000
19:10020803:G:GGdonor_gain1.0000
19:10021533:GGCC:Gacceptor_gain1.0000
19:10013599:GG:Gdonor_gain0.9900
19:10013600:GG:Gdonor_gain0.9900
19:10017047:T:TAacceptor_gain0.9900
19:10017051:CCGCA:Cacceptor_loss0.9900
19:10017052:C:Aacceptor_gain0.9900
19:10017056:GT:Gacceptor_gain0.9900

AlphaMissense

1993 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:10018889:A:CS141R0.992
19:10018891:C:AS141R0.992
19:10018891:C:GS141R0.992
19:10018892:A:CS142R0.991
19:10018894:T:AS142R0.991
19:10018894:T:GS142R0.991
19:10020744:T:CF160L0.991
19:10020746:C:AF160L0.991
19:10020746:C:GF160L0.991
19:10020739:C:TS158F0.987
19:10020768:A:CS168R0.985
19:10020770:C:AS168R0.985
19:10020770:C:GS168R0.985
19:10017063:C:AA37D0.984
19:10020739:C:AS158Y0.984
19:10020736:C:AA157D0.982
19:10018858:G:CK130N0.981
19:10018858:G:TK130N0.981
19:10020748:C:AA161D0.976
19:10018845:T:CL126P0.975
19:10018890:G:TS141I0.972
19:10013536:C:GC13W0.971
19:10020792:T:CF176L0.968
19:10020794:C:AF176L0.968
19:10020794:C:GF176L0.968
19:10018893:G:TS142I0.966
19:10018810:C:AN114K0.965
19:10018810:C:GN114K0.965
19:10018854:T:CM129T0.965
19:10018878:T:AI137N0.965

dbSNP variants (sampled 300 via entrez): RS1000453173 (19:10013245 G>A,T), RS1001033567 (19:10012185 C>T), RS1001091759 (19:10016808 G>A,C), RS1001867320 (19:10012131 G>A), RS1002092963 (19:10018409 C>T), RS1002131807 (19:10014330 G>C), RS1002332372 (19:10016406 C>T), RS1002432945 (19:10014518 A>T), RS1002659975 (19:10021571 T>G), RS1003038855 (19:10014472 G>A), RS1003096895 (19:10019205 C>A,G,T), RS1003327109 (19:10011905 C>A,T), RS1003636477 (19:10019109 C>T), RS1003854234 (19:10020300 A>C), RS1004048109 (19:10022536 G>A)

Disease associations

OMIM: gene MIM:608575 | disease phenotypes: MIM:621259

GenCC curated gene-disease

Mondo (1): Stargardt disease 5 (MONDO:0980722)

Orphanet (0):

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000512Abnormal electroretinogram
HP:0000822Hypertension
HP:0003596Middle age onset
HP:0007722Retinal pigment epithelial atrophy
HP:0007906Ocular hypertension
HP:0012045Retinal flecks
HP:0031528Subretinal deposits
HP:0032037Mildly reduced visual acuity
HP:6000367Central thinning of the outer nuclear layer of the retina

GWAS associations

1 associations (top):

StudyTraitp-value
GCST002541_117Menarche (age at onset)2.000000e-13

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004703age at menarche

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Fdecreases expression1
abrineincreases expression1
bisphenol Sdecreases expression1
Amiodaroneincreases expression1
Atrazineincreases expression1
Benzo(a)pyreneaffects methylation1
NADPaffects binding, increases activity1
Silicon Dioxideincreases expression1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

  • Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): Stargardt disease 5

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

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