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RDH16

gene
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Also known as RODH-4SDR9C8

Summary

RDH16 (retinol dehydrogenase 16, HGNC:29674) is a protein-coding gene on chromosome 12q13.3, encoding Retinol dehydrogenase 16 (O75452). Oxidoreductase with a preference for NAD.

Enables all-trans-retinol dehydrogenase (NAD+) activity; androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity; and androsterone dehydrogenase [NAD(P)+] activity. Involved in steroid metabolic process. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 8608 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 74 total
  • MANE Select transcript: NM_003708

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29674
Approved symbolRDH16
Nameretinol dehydrogenase 16
Location12q13.3
Locus typegene with protein product
StatusApproved
AliasesRODH-4, SDR9C8
Ensembl geneENSG00000139547
Ensembl biotypeprotein_coding
OMIM620043
Entrez8608

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000360752, ENST00000398138, ENST00000869320, ENST00000869321, ENST00000869322, ENST00000869323, ENST00000869324, ENST00000869325

RefSeq mRNA: 2 — MANE Select: NM_003708 NM_001320108, NM_003708

CCDS: CCDS41797

Canonical transcript exons

ENST00000398138 — 4 exons

ExonStartEnd
ENSE000011422295695490656955164
ENSE000024333345695715056957608
ENSE000024724165695143156952246
ENSE000036008195695282756952990

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 99.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3287 / max 120.0874, expressed in 36 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
1316080.19687
1316070.064130
1316060.02196
1316090.02086
1316050.01825
1316100.00704

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right lobe of liverUBERON:000111499.04gold quality
liverUBERON:000210796.51gold quality
spermCL:000001977.49gold quality
esophagus squamous epitheliumUBERON:000692076.83silver quality
male germ cellCL:000001576.75gold quality
gingival epitheliumUBERON:000194974.71gold quality
epithelium of esophagusUBERON:000197674.39silver quality
squamous epitheliumUBERON:000691473.19gold quality
gingivaUBERON:000182871.31gold quality
granulocyteCL:000009468.97gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450268.49gold quality
skin of legUBERON:000151168.15gold quality
skin of abdomenUBERON:000141667.79gold quality
spleenUBERON:000210666.86gold quality
zone of skinUBERON:000001466.79gold quality
mammalian vulvaUBERON:000099766.24gold quality
olfactory bulbUBERON:000226465.68gold quality
type B pancreatic cellCL:000016965.56gold quality
triceps brachiiUBERON:000150965.29gold quality
vastus lateralisUBERON:000137965.15gold quality
biceps brachiiUBERON:000150764.66gold quality
gluteal muscleUBERON:000200064.63gold quality
quadriceps femorisUBERON:000137764.25gold quality
mucosa of paranasal sinusUBERON:000503064.19gold quality
lower esophagus mucosaUBERON:003583463.93gold quality
prostate glandUBERON:000236763.63gold quality
myocardiumUBERON:000234963.29gold quality
heart right ventricleUBERON:000208063.22gold quality
esophagus mucosaUBERON:000246963.10gold quality
oocyteCL:000002362.80gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3no0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting RDH16, 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-12118100.0065.881270
HSA-MIR-150-5P99.9966.691976
HSA-MIR-548AR-3P99.8571.263889
HSA-MIR-548AZ-3P99.8270.563549
HSA-MIR-548BC99.8270.613524
HSA-MIR-548E-3P99.8270.593514
HSA-MIR-548F-3P99.8270.593540
HSA-MIR-548A-3P99.7670.583524
HSA-MIR-29A-5P99.0868.591813
HSA-MIR-6814-5P99.0366.681273
HSA-MIR-6840-3P98.6865.951923
HSA-MIR-5581-3P98.5570.311161
HSA-MIR-6852-3P98.5467.601468
HSA-MIR-66597.6065.641781

Literature-anchored findings (GeneRIF, showing 3)

  • In endometrial cancers, hRoDH-4 immunoreactivity was markedly reduced. (PMID:11967490)
  • Characterization of the retinol dehydrogenase activity of RoDH-4 identifies it as the enzyme capable of accessing the bound form of retinol for retinoic acid production. (PMID:12534290)
  • RDH16 is a stemness suppressor that partially rescues stem cell-like glioma cells from the NSPc1-induced increase in neurosphere formation. (PMID:28394339)

Cross-species orthologs

9 orthologs

OrganismSymbolGene ID
mus_musculusRdh7ENSMUSG00000040134
mus_musculusRdh19ENSMUSG00000054052
mus_musculusRdh9ENSMUSG00000056148
mus_musculusRdh16ENSMUSG00000069456
mus_musculusRdh16f2ENSMUSG00000074639
mus_musculusRdh1ENSMUSG00000089789
rattus_norvegicusRdh7ENSRNOG00000004391
rattus_norvegicusLOC120093075ENSRNOG00000029651
rattus_norvegicusENSRNOG00000081739

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), WWOX (ENSG00000186153), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

Retinol dehydrogenase 16 — O75452 (reviewed: O75452)

Alternative names: Human epidermal retinol dehydrogenase, Microsomal NAD(+)-dependent retinol dehydrogenase 4, Short chain dehydrogenase/reductase family 9C member 8, Sterol/retinol dehydrogenase

All UniProt accessions (1): O75452

UniProt curated annotations — full annotation on UniProt →

Function. Oxidoreductase with a preference for NAD. Oxidizes all-trans-retinol, 9-cis-retinol, 11-cis-retinol and 13-cis-retinol to the corresponding aldehydes. Has higher activity towards CRBP-bound retinol than with free retinol. Also oxidizes 3-alpha-hydroxysteroids. Oxidizes androstanediol and androsterone to dihydrotestosterone and androstanedione. Can also catalyze the reverse reaction.

Subunit / interactions. Homodimer.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in adult liver (at protein level). Detected in endometrium, liver and foreskin. Detected in the spineous layers of adult skin, and at lower levels in basal and granular skin layers. Detected in fetal liver and lung.

Post-translational modifications. Not N-glycosylated.

Activity regulation. Inhibited by citral, perillyl alcohol, geraniol, farnesol and geranyl geraniol.

Domain organisation. The C-terminal region plays a crucial role in controlling the activity of RDH16 and its required for endoplasmic reticulum (ER) retention.

Induction. Transiently up-regulated by retinoic acid.

Pathway. Cofactor metabolism; retinol metabolism.

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

RefSeq proteins (2): NP_001307037, NP_003699* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR002347SDR_famFamily
IPR020904Sc_DH/Rdtase_CSConserved_site
IPR036291NAD(P)-bd_dom_sfHomologous_superfamily

Pfam: PF00106

Enzyme classification (BRENDA):

  • EC 1.1.1.105 — all-trans-retinol dehydrogenase (NAD+) (BRENDA: 12 organisms, 80 substrates, 15 inhibitors, 31 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
ALL-TRANS-RETINOL—6
NADH0.011–0.2246
ALL-TRANS-RETINAL0.0018–0.575
NAD+0.0002–0.463
11-CIS-RETINOL0.0001–0.0862
9-CIS-RETINOL0.00221
ALL-TRANS RETINAL0.00051
ALL-TRANS-RETINALDEHYDE0.00051
ANDROSTERONE0.00021
NADP+0.0271
NADPH0.00151
RETINOL0.121
RETINOL BOUND TO CELLULAR RETINOL BINDING PROTEI0.00271

Catalyzed reactions (Rhea), 7 shown:

  • androsterone + NAD(+) = 5alpha-androstan-3,17-dione + NADH + H(+) (RHEA:20381)
  • all-trans-retinol + NAD(+) = all-trans-retinal + NADH + H(+) (RHEA:21284)
  • 5alpha-androstane-3alpha,17beta-diol + NAD(+) = 17beta-hydroxy-5alpha-androstan-3-one + NADH + H(+) (RHEA:42004)
  • 9-cis-retinol + NAD(+) = 9-cis-retinal + NADH + H(+) (RHEA:42052)
  • 13-cis-retinol + NAD(+) = 13-cis-retinal + NADH + H(+) (RHEA:42056)
  • 11-cis-retinol + NAD(+) = 11-cis-retinal + NADH + H(+) (RHEA:42060)
  • all-trans-retinol–[retinol-binding protein] + NAD(+) = all-trans-retinal–[retinol-binding protein] + NADH + H(+) (RHEA:48488)

UniProt features (11 total): sequence conflict 4, binding site 2, mutagenesis site 2, chain 1, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-O75452-F196.300.95

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): 176 (proton acceptor)

Ligand- & substrate-binding residues (2): 33–57; 164

Mutagenesis-validated functional residues (2):

PositionPhenotype
176decreases androsterone dehydrogenase activity; when associated with r-180.
180decreases androsterone dehydrogenase activity; when associated with f-176.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-2453902The canonical retinoid cycle in rods (twilight vision)
R-HSA-5365859RA biosynthesis pathway

MSigDB gene sets: 106 (showing top): GNF2_GSTM1, GNF2_HPN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, 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, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, SMID_BREAST_CANCER_LUMINAL_B_UP, GNF2_LCAT, CAIRO_HEPATOBLASTOMA_DN, GOBP_LIPID_METABOLIC_PROCESS, GNF2_HPX, SANSOM_APC_TARGETS_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS

GO Biological Process (3): lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), retinol metabolic process (GO:0042572)

GO Molecular Function (8): all-trans-retinol dehydrogenase (NAD+) activity (GO:0004745), electron transfer activity (GO:0009055), identical protein binding (GO:0042802), androsterone dehydrogenase [NAD(P)+] activity (GO:0047023), androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity (GO:0047044), 11-cis-retinol dehydrogenase (NAD+) activity (GO:0106429), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
Visual phototransduction1
Signaling by Retinoic Acid1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
alcohol dehydrogenase (NAD+) activity2
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor2
primary metabolic process1
lipid metabolic process1
retinoid metabolic process1
primary alcohol metabolic process1
hormone metabolic process1
olefinic compound metabolic process1
molecular_function1
protein binding1
catalytic activity1
oxidoreductase activity, acting on CH-OH group of donors1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
intracellular anatomical structure1
membrane-bounded organelle1
intracellular organelle1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
cellular anatomical structure1

Protein interactions and networks

STRING

668 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
RDH16LRATO95237491
RDH16PCK1P35558476
RDH16CYP26A1O43174455
RDH16RBP1P09455449
RDH16HMGCS1Q01581418
RDH16RXRAP19793412
RDH16SERINC4A6NH21391
RDH16AKR1C2P52895387
RDH16THRSPQ92748384
RDH16ALDH1A2O94788378
RDH16FDPSP14324378
RDH16AKR1C3P42330369
RDH16SRD5A1P18405366
RDH16ALDH8A1Q9H2A2365
RDH16HMGCRP04035364
RDH16IFITM1P13164364

IntAct

1 interactions, top by confidence:

ABTypeScore
KRASIGKV2D-24psi-mi:“MI:0914”(association)0.350

BioGRID (1): RDH16 (Affinity Capture-MS)

ESM2 similar proteins: A6QP05, B0BNF8, B2GV72, O00764, O14756, O35331, O54753, O54909, O75452, O75828, O88451, P16152, P17516, P42330, P46597, P47727, P47844, P48758, P50170, P52895, P55006, P80508, Q04828, Q1XAA8, Q28960, Q3SZD7, Q3SZM9, Q3T001, Q3U0B3, Q3ZBV9, Q5R7C9, Q5RCU5, Q5REQ0, Q6SKR2, Q6UWP2, Q6W8P9, Q71R50, Q8C436, Q8HZJ0, Q8K183

Diamond homologs: A0A017SE81, A0A0E3D8L9, A0A0U1LQE2, A0A140JWS5, A0A2G0QDN4, A0A3R5XUE6, A0A5B8YU68, A0A8F5XX49, A7LB60, D2WKD9, F1QLP1, G4N286, G9N4A9, N4WE73, O05730, O14756, O16881, O54753, O55240, O67610, O74628, O75452, P0A2D1, P0A2D2, P0AFP4, P0AFP5, P0CU71, P0DKC5, P0DKC6, P15047, P16152, P25970, P29147, P37059, P37959, P39577, P40471, P50170, P54554, P66778

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance58
Likely benign4
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1069 predictions. Top by Δscore:

VariantEffectΔscore
12:56952242:CTTAT:Cacceptor_gain1.0000
12:56952244:TATCT:Tacceptor_loss1.0000
12:56952246:TC:Tacceptor_loss1.0000
12:56952247:C:CCacceptor_gain1.0000
12:56952819:TTAC:Tdonor_loss1.0000
12:56952820:TAC:Tdonor_loss1.0000
12:56952821:A:ACdonor_gain1.0000
12:56952822:C:CCdonor_gain1.0000
12:56952822:CT:Cdonor_gain1.0000
12:56952822:CTCA:Cdonor_gain1.0000
12:56952823:TCACA:Tdonor_loss1.0000
12:56952824:CA:Cdonor_loss1.0000
12:56952825:A:ACdonor_gain1.0000
12:56952826:C:CAdonor_gain1.0000
12:56952826:CA:Cdonor_gain1.0000
12:56952826:CAG:Cdonor_gain1.0000
12:56952826:CAGT:Cdonor_gain1.0000
12:56952856:T:TAdonor_gain1.0000
12:56952860:TG:Tdonor_gain1.0000
12:56952986:CCCTC:Cacceptor_gain1.0000
12:56952987:CCTC:Cacceptor_gain1.0000
12:56952987:CCTCC:Cacceptor_gain1.0000
12:56952988:CTC:Cacceptor_gain1.0000
12:56952988:CTCC:Cacceptor_gain1.0000
12:56952989:TC:Tacceptor_gain1.0000
12:56952989:TCCT:Tacceptor_gain1.0000
12:56952990:CC:Cacceptor_gain1.0000
12:56952991:C:CCacceptor_gain1.0000
12:56952991:C:CGacceptor_loss1.0000
12:56952992:T:Aacceptor_loss1.0000

AlphaMissense

2043 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:56954942:G:AS179F0.992
12:56954986:A:CS164R0.992
12:56954986:A:TS164R0.992
12:56954988:T:GS164R0.992
12:56954952:A:GY176H0.991
12:56952936:G:CF209L0.989
12:56952936:G:TF209L0.989
12:56952938:A:GF209L0.989
12:56957340:G:CF41L0.989
12:56957340:G:TF41L0.989
12:56957342:A:GF41L0.989
12:56954942:G:TS179Y0.988
12:56955145:A:CN111K0.988
12:56955145:A:TN111K0.988
12:56954987:C:AS164I0.983
12:56954995:G:CN161K0.983
12:56954995:G:TN161K0.983
12:56954999:A:TV160D0.982
12:56955067:G:CN137K0.982
12:56955067:G:TN137K0.982
12:56952144:C:GR280P0.981
12:56954933:C:TG182D0.979
12:56952145:G:TR280S0.978
12:56954919:A:GS187P0.978
12:56954920:G:CF186L0.977
12:56954920:G:TF186L0.977
12:56954922:A:GF186L0.977
12:56957352:A:CC37W0.976
12:56954938:C:AK180N0.975
12:56954938:C:GK180N0.975

dbSNP variants (sampled 300 via entrez): RS1001141359 (12:56955593 G>C), RS1002185876 (12:56954742 C>T), RS1002710708 (12:56956307 C>T), RS1002785309 (12:56954782 T>A,C,G), RS1003083037 (12:56957935 C>G), RS1003157431 (12:56953733 C>T), RS1003336674 (12:56959136 C>A), RS1003420885 (12:56958118 G>A), RS1003821255 (12:56958999 C>G), RS1004037755 (12:56953709 C>A), RS1004655118 (12:56956037 C>T), RS1005304330 (12:56958730 C>A,T), RS1005438770 (12:56958985 A>C,T), RS1006051051 (12:56956846 A>C,T), RS1006505429 (12:56955506 A>G)

Disease associations

OMIM: gene MIM:620043 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

StudyTraitp-value
GCST007563_7Allergic disease (asthma, hay fever or eczema)1.000000e-09
GCST007564_27Asthma or allergic disease (pleiotropy)8.000000e-13
GCST008916_110Asthma1.000000e-27
GCST008916_18Asthma8.000000e-18
GCST008916_2Asthma2.000000e-08
GCST010002_217Refractive error6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Benzo(a)pyrenedecreases methylation, increases methylation, decreases expression4
Aflatoxin B1affects expression, decreases expression, decreases methylation4
Acetaminophendecreases expression, increases expression, affects cotreatment3
Tetrachlorodibenzodioxinaffects expression, decreases expression3
sodium arsenitedecreases expression2
Estradiolaffects cotreatment, increases expression, decreases expression2
Valproic Aciddecreases expression2
Cyclosporinedecreases expression, affects cotreatment2
lasiocarpinedecreases expression1
methyleugenoldecreases expression1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium saltaffects cotreatment, decreases expression1
bisphenol Aincreases expression1
nefazodoneaffects cotreatment, decreases expression1
di-n-butylphosphoric acidaffects expression1
perfluoro-n-nonanoic aciddecreases expression1
erucylphospho-N,N,N-trimethylpropylammoniumdecreases expression1
heptylparabendecreases activity1
Resveratrolaffects cotreatment, decreases expression1
Air Pollutantsdecreases expression, increases abundance1
Chenodeoxycholic Acidaffects cotreatment, decreases expression1
Copperaffects cotreatment, decreases expression1
Dichlorodiphenyl Dichloroethyleneincreases expression1
Deoxycholic Acidaffects cotreatment, decreases expression1
Glycochenodeoxycholic Acidaffects cotreatment, decreases expression1
Glycocholic Acidaffects cotreatment, decreases expression1
Glycodeoxycholic Acidaffects cotreatment, decreases expression1
N-Nitrosopyrrolidinedecreases expression1
NADaffects binding, increases activity1
Phthalic Acidsincreases methylation1
Tartrazinedecreases expression, affects cotreatment1

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

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
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BioBTree
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Sources 75

This page pulls from 75 datasets indexed by BioBTree:

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