DHRS4

Summary

DHRS4 (dehydrogenase/reductase 4, HGNC:16985) is a protein-coding gene on chromosome 14q11.2, encoding Dehydrogenase/reductase SDR family member 4 (Q9BTZ2). NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones.

Enables identical protein binding activity; oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Involved in several processes, including ketone metabolic process; positive regulation of reactive oxygen species metabolic process; and steroid metabolic process. Located in nucleus and peroxisomal membrane.

Source: NCBI Gene 10901 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_021004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16985
Approved symbol	DHRS4
Name	dehydrogenase/reductase 4
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SCAD-SRL, SDR-SRL, humNRDR, FLJ11008, SDR25C2
Ensembl gene	ENSG00000157326
Ensembl biotype	protein_coding
OMIM	611596
Entrez	10901

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000313250, ENST00000397074, ENST00000397075, ENST00000543741, ENST00000558263, ENST00000558581, ENST00000559632, ENST00000559975, ENST00000875626, ENST00000875627, ENST00000875628, ENST00000875629, ENST00000875630, ENST00000875631

RefSeq mRNA: 7 — MANE Select: NM_021004 NM_001282987, NM_001282988, NM_001282989, NM_001282990, NM_001282991, NM_001411004, NM_021004

CCDS: CCDS61408, CCDS61409, CCDS61410, CCDS61411, CCDS61412, CCDS91852, CCDS9605

Canonical transcript exons

ENST00000313250 — 8 exons

Exon	Start	End
ENSE00001527204	23953770	23953916
ENSE00001627632	23959902	23960003
ENSE00001676573	23955035	23955212
ENSE00001679388	23966283	23966417
ENSE00001713910	23965762	23965832
ENSE00002563434	23968757	23969279
ENSE00003508721	23965932	23965983
ENSE00003643850	23967211	23967266

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.5209 / max 144.7872, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138958	28.5209	1809
138962	0.6104	262

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.06	gold quality
adult mammalian kidney	UBERON:0000082	95.73	gold quality
duodenum	UBERON:0002114	95.48	gold quality
liver	UBERON:0002107	95.10	gold quality
mucosa of transverse colon	UBERON:0004991	95.00	gold quality
monocyte	CL:0000576	94.82	gold quality
lower esophagus mucosa	UBERON:0035834	94.81	gold quality
leukocyte	CL:0000738	94.45	gold quality
apex of heart	UBERON:0002098	93.33	gold quality
left adrenal gland cortex	UBERON:0035825	93.06	gold quality
heart left ventricle	UBERON:0002084	92.98	gold quality
gastrocnemius	UBERON:0001388	92.95	gold quality
kidney	UBERON:0002113	92.82	gold quality
left adrenal gland	UBERON:0001234	92.77	gold quality
right adrenal gland cortex	UBERON:0035827	92.75	gold quality
muscle of leg	UBERON:0001383	92.69	gold quality
skeletal muscle organ	UBERON:0014892	92.61	gold quality
transverse colon	UBERON:0001157	92.52	gold quality
right adrenal gland	UBERON:0001233	92.34	gold quality
lower esophagus	UBERON:0013473	92.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.28	gold quality
cortex of kidney	UBERON:0001225	92.12	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.99	gold quality
esophagus	UBERON:0001043	91.81	gold quality
small intestine	UBERON:0002108	91.72	gold quality
esophagus mucosa	UBERON:0002469	91.72	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.68	gold quality
colon	UBERON:0001155	91.60	gold quality
skin of leg	UBERON:0001511	91.53	gold quality
skin of abdomen	UBERON:0001416	91.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting DHRS4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-3922-3P	99.25	64.96	1136
HSA-MIR-3176	99.25	64.35	954
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-6869-3P	83.17	65.88	30

Literature-anchored findings (GeneRIF, showing 11)

• Alternatively spliced variant of NADP(H)-dependent retinol dehydrogenase/reductase with deletion of exon 3 is associated with cervical squamous carcinoma (PMID:17230527)
• Results suggest a novel mechanism of cold inactivation and role of the inducible human DHRS4 in 3beta-hydroxysteroid synthesis and xenobiotic carbonyl metabolism (PMID:18571493)
• Novel alternative splicing variants, transcribed from an alternative transcrioption start sites within the DHRS4 gene cluster were identified in this study. (PMID:18754758)
• Analysis of exon composition in the transcripts of DHRS4 gene cluster revealed that exon 1 was absent in all the transcripts initiated from exon a1 of DHRS4L2 and exon a2 of DHRS4L1. (PMID:20525226)
• This study demonstrates that AS1DHRS4, as a long noncoding RNA, simultaneously controls the chromatin state of each gene within the DHRS4 gene cluster in a discriminative manner. (PMID:22891334)
• A rapid evolution rate brought the human DHRS2 gene, duplicated form of the DHRS4 one, to code a SDR enzyme having subcellular localization, synthesis regulation and specialized cellular functions very different from those of the human DHRS4 enzyme. (PMID:23036705)
• DHRS2 and DHRS4 genes are syntenic outparalogues originating from a duplication of the DHRS4 gene that took place before the formation of the mammalian clade (PMID:23036705)
• NRDRB1, an alternatively spliced isoform of NRDR in vivo functions better than NRDR as a dicarbonyl reductase for xenobiotics containing reactive carbonyls. (PMID:23128527)
• AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster. (PMID:26864944)
• An analysis of the relationship between the promoter characteristics and RNA expression of the DHRS4 gene cluster indicated that the development of CpG islands, in addition to the promoter sequence, during mammalian evolution could modulate the dose compensatory regulation of the copy number-varied DHRS4 gene cluster (PMID:27323117)
• LncRNA DHRS4-AS1 ameliorates hepatocellular carcinoma by suppressing proliferation and promoting apoptosis via miR-522-3p/SOCS5 axis. (PMID:34666613)

Cross-species orthologs

25 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbr1l	ENSDARG00000021149
danio_rerio	zgc:101858	ENSDARG00000035129
danio_rerio	zgc:163083	ENSDARG00000099873
danio_rerio	zgc:92161	ENSDARG00000101749
danio_rerio	zgc:123284	ENSDARG00000102720
danio_rerio	zgc:112146	ENSDARG00000104829
mus_musculus	Dhrs4	ENSMUSG00000022210
rattus_norvegicus	Dhrs4	ENSRNOG00000018239
drosophila_melanogaster	CG7601	FBGN0027583
drosophila_melanogaster	CG12171	FBGN0037354
drosophila_melanogaster	CG3699	FBGN0040349
drosophila_melanogaster	CG31546	FBGN0051546
drosophila_melanogaster	CG31548	FBGN0051548
drosophila_melanogaster	CG31549	FBGN0051549
caenorhabditis_elegans		WBGENE00000970
caenorhabditis_elegans		WBGENE00000975
caenorhabditis_elegans		WBGENE00000981
caenorhabditis_elegans		WBGENE00000993
caenorhabditis_elegans		WBGENE00008985
caenorhabditis_elegans		WBGENE00008986
caenorhabditis_elegans		WBGENE00011424
caenorhabditis_elegans	Y47G6A.21	WBGENE00021646
caenorhabditis_elegans	Y47G6A.22	WBGENE00021647
caenorhabditis_elegans		WBGENE00022809
caenorhabditis_elegans		WBGENE00219274

Paralogs (13): RDH8 (ENSG00000080511), DHRS7 (ENSG00000100612), DHRS2 (ENSG00000100867), DHRS7B (ENSG00000109016), HSD11B1 (ENSG00000117594), HSDL2 (ENSG00000119471), DHRS1 (ENSG00000157379), CBR1 (ENSG00000159228), CBR3 (ENSG00000159231), HSD11B1L (ENSG00000167733), DHRS7C (ENSG00000184544), DHRS4L2 (ENSG00000187630), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Dehydrogenase/reductase SDR family member 4 — Q9BTZ2 (reviewed: Q9BTZ2)

Alternative names: NADPH-dependent carbonyl reductase, NADPH-dependent retinol dehydrogenase/reductase, Peroxisomal short-chain alcohol dehydrogenase, SCAD-SRL, Short chain dehydrogenase/reductase family 25C member 2, Short-chain dehydrogenase/reductase family member 4

All UniProt accessions (3): Q9BTZ2, F5GWZ1, H0YNP7

UniProt curated annotations — full annotation on UniProt →

Function. NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones. Reduces 3-ketosteroids and benzil into 3beta-hydroxysteroids and R-benzoin, respectively, in contrast to the stereoselectivity of non-primate DHRS4s which produce 3alpha-hydroxysteroids and S-benzoin. Displays low activity toward all-trans-retinal and no activity toward 9-cis-retinal as compared to non-primate mammals. In the reverse reaction, catalyze the NAD-dependent oxidation of 3beta-hydroxysteroids and alcohol, but with much lower efficiency. Involved in the metabolism of 3beta-hydroxysteroids, isatin and xenobiotic carbonyl compounds. No detected catalytic activity in vitro, possibly due to the lack of catalytic site. NADPH-dependent oxidoreductase which catalyzes the reduction of a variety of compounds bearing carbonyl groups including ketosteroids, alpha-dicarbonyl compounds, aldehydes, aromatic ketones and quinones. Involved in the metabolism of 3beta-hydroxysteroids, isatin and xenobiotic carbonyl compounds. Has a higher catalytic activity for xenobiotic alpha-dicarbonyl compounds, sucha as benzil, than isoform 1 and is involved in benzil detoxification.

Subunit / interactions. Homotetramer.

Subcellular location. Peroxisome Nucleus.

Tissue specificity. Predominantly expressed in normal cervix (at protein level). Expressed in some neoplastic cervical tissues, but not in normal cervix (at protein level). Expressed in a few neoplastic cervical tissues. Expressed in a few neoplastic cervical tissues. High expression in liver.

Activity regulation. Inhibited by flavonoids (quercetin and genistein), cetylpyridium chloride, phenylhexane and valproic acid. Low inhibition is observed with fatty acids (myristic acid and lauric acid). No significant inhibition is observed with barbital, dicumarol, indomethacin, metyrapone, ethacrynic acid, disulfiram, hexestrol and benzodiazepines (diazepam and nitrazepam).

Domain organisation. The C-terminus peroxisomal targeting signal tripeptide is important for peroxisomal import. Once in the peroxisome, it is involved in intersubunit interactions. Three specific residues, Ser-176, Phe-179 and Thr-195 are conserved between primates whereas the respective residues are phenylalanine, leucine, and asparagine in the other mammal enzymes. The two residues at positions 176 and 179 are molecular determinants responsible for the stereoselective reduction of 3-ketosteroids and benzil. The presence of an asparagine at position 195 is important for the maintenance of the quaternary structure and stability at cold temperature. The absence of an asparagine at position 195 destabilizes the quaternary structure, thereby affecting catalytic efficiency toward some substrates and decreasing stability at cold temperature.

Induction. Induced by PPARA ligands clofibrate and Wy14,643.

Miscellaneous. Primate DHRS4s display different stereoselectivity and catalytic efficiency in the oxidoreduction of some substrates as compared to other mammal DHRS4s due to a difference in conserved amino acid residues. Three homologous proteins DHRS4, DHRS4L1, and DHRS4L2 are derived from gene duplication of DHRS4, and the gene cluster is arranged in tandem in chromosome 14.

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

Isoforms (8)

UniProt ID	Names	Canonical?
Q9BTZ2-1	1, SDR-SRL3	yes
Q9BTZ2-2	2, SDR-SRL1
Q9BTZ2-3	3, SDR-SRL2
Q9BTZ2-4	4, NRDRB1
Q9BTZ2-5	5, NRDRB2
Q9BTZ2-6	6, NRDRA1
Q9BTZ2-7	7, NRDRA2
Q9BTZ2-8	8, NRDRB1

RefSeq proteins (7): NP_001269916, NP_001269917, NP_001269918, NP_001269919, NP_001269920, NP_001397933, NP_066284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR020904	Sc_DH/Rdtase_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily

Pfam: PF13561

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.

Substrate	Km (mM)	Measurements
ALL-TRANS-RETINAL	0.0001–0.5	19
NADPH	0.0005–0.23	10
NADP+	0.0004–0.8	9
ALL-TRANS-RETINOL	0.0006–1.3	6
NADH	2.22–1300	4
ALL-TRANS-3-HYDROXYRETINAL	0.0032–0.0044	3
ESTRONE	0.0096–0.0307	3
NAD+	0.004–680	3
9-CIS-RETINAL	0.0001–0.19	2
RETINAL	0.007–0.13	2
11-CIS-RETINAL	0.0001	1
11-CIS-RETINOL	0.0016	1
13-CIS-RETINAL	0.62	1
9-CIS-RETINOL	0.0016	1

Catalyzed reactions (Rhea), 7 shown:

• a secondary alcohol + NADP(+) = a ketone + NADPH + H(+) (RHEA:19257)
• 3beta-hydroxy-5beta-pregnane-20-one + NADP(+) = 5beta-pregnan-3,20-dione + NADPH + H(+) (RHEA:22944)
• lithocholate + NADP(+) = 3-oxo-5beta-cholan-24-oate + NADPH + H(+) (RHEA:47496)
• 3-oxo-5beta-cholan-24-oate + NADPH + H(+) = isolithocholate + NADP(+) (RHEA:47520)
• isatin + NADPH + H(+) = 3-hydroxyindolin-2-one + NADP(+) (RHEA:68608)
• 5beta-dihydrotestosterone + NADPH + H(+) = 5beta-androstane-3beta,17beta-diol + NADP(+) (RHEA:69012)
• 5beta-androstane-3,17-dione + NADPH + H(+) = 3beta-hydroxy-5beta-androstane-17-one + NADP(+) (RHEA:69036)

UniProt features (57 total): helix 13, modified residue 9, splice variant 8, strand 7, sequence conflict 5, mutagenesis site 3, binding site 3, sequence variant 2, turn 2, site 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3O4R	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTZ2-F1	91.40	0.81

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 (3): 182 (proton acceptor); 176 (responsible for the stereoselective reduction of 3-ketosteroids into 3beta-hydroxysteroids and benzil into r-benzoin); 179 (responsible for the stereoselective reduction of 3-ketosteroids into 3beta-hydroxysteroids and benzil into r-benzoin)

Ligand- & substrate-binding residues (3): 36–60; 169; 186

Post-translational modifications (9): 105, 216, 216, 220, 227, 234, 140, 92, 92

Mutagenesis-validated functional residues (3):

Position	Phenotype
176	decreased reduction activity for benzil, isatin and retinal and increased activity for 5beta-pregnane-3,20-dione and 5be
179	decreased reduction activity for isatin and increased activity for 5beta-pregnane-3,20-dione, 5beta-dihydrotestosterone,
195	loss of cold catalytic inactivation. loss of cold catalytic inactivation; when associated with f-176 and l-179. switch i

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5365859	RA biosynthesis pathway
R-HSA-9033241	Peroxisomal protein import

MSigDB gene sets: 103 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_RETINOL_METABOLIC_PROCESS, AAAYRNCTG_UNKNOWN, GOBP_KETONE_METABOLIC_PROCESS, GOMF_STEROID_DEHYDROGENASE_ACTIVITY_ACTING_ON_THE_CH_OH_GROUP_OF_DONORS_NAD_OR_NADP_AS_ACCEPTOR, GOBP_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, OCT1_06, GOBP_RETINAL_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, GOCC_MICROBODY_MEMBRANE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_NAD_P_H, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS

GO Biological Process (6): alcohol metabolic process (GO:0006066), steroid metabolic process (GO:0008202), ketone metabolic process (GO:0042180), retinal metabolic process (GO:0042574), positive regulation of reactive oxygen species metabolic process (GO:2000379), retinol metabolic process (GO:0042572)

GO Molecular Function (8): 3-beta-hydroxysteroid 3-dehydrogenase (NADP+) activity (GO:0000253), carbonyl reductase (NADPH) activity (GO:0004090), oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor (GO:0016655), alcohol dehydrogenase [NAD(P)+] activity (GO:0018455), 3-beta-hydroxy-5-beta-steroid dehydrogenase (NADP+) activity (GO:0033703), identical protein binding (GO:0042802), all-trans-retinol dehydrogenase (NADP+) activity (GO:0052650), oxidoreductase activity (GO:0016491)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), peroxisome (GO:0005777), peroxisomal membrane (GO:0005778), peroxisomal matrix (GO:0005782), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Retinoic Acid	1
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid metabolic process	2
olefinic compound metabolic process	2
steroid dehydrogenase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
alcohol dehydrogenase (NADP+) activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
peroxisome	2
small molecule metabolic process	1
lipid metabolic process	1
metabolic process	1
aldehyde metabolic process	1
positive regulation of metabolic process	1
reactive oxygen species metabolic process	1
regulation of reactive oxygen species metabolic process	1
primary alcohol metabolic process	1
hormone metabolic process	1
oxidoreductase activity, acting on NAD(P)H	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
protein binding	1
retinol metabolic process	1
catalytic activity	1
microbody	1
microbody membrane	1
microbody lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

3410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHRS4	ACADS	P16219	819
DHRS4	AVP	P01185	692
DHRS4	EHHADH	Q08426	618
DHRS4	ALDH1A1	P00352	535
DHRS4	CBR4	Q8N4T8	497
DHRS4	ZNF780A	O75290	482
DHRS4	RDH11	Q8TC12	468
DHRS4	ACER3	Q9NUN7	464
DHRS4	GRTP1	Q5TC63	449
DHRS4	CYP1A1	P04798	447
DHRS4	AKR1C4	P17516	441
DHRS4	TIMM21	Q9BVV7	438
DHRS4	AOX1	Q06278	437
DHRS4	SIRT3	Q9NTG7	437
DHRS4	MYOZ3	Q8TDC0	436

IntAct

93 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
PCCB	PCCA	psi-mi:“MI:0914”(association)	0.770
HEXA	HEXB	psi-mi:“MI:0914”(association)	0.730
RCC1L	NME6	psi-mi:“MI:0914”(association)	0.720
MRPL37	HSPD1	psi-mi:“MI:0914”(association)	0.710
KLHL6	NUDCD3	psi-mi:“MI:0914”(association)	0.670
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
BIRC7	HTRA2	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
SUN2	POTEF	psi-mi:“MI:0914”(association)	0.530
PRELP	AMD1	psi-mi:“MI:0914”(association)	0.530
ALDH1B1	DHRS4	psi-mi:“MI:0914”(association)	0.530
DHRS4	NDUFS2	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
ATP5F1D	NDUFB5	psi-mi:“MI:0914”(association)	0.530
PRDX3	OPA1	psi-mi:“MI:0914”(association)	0.530
FAHD1	CLUH	psi-mi:“MI:0914”(association)	0.530
ACADVL	APC	psi-mi:“MI:0914”(association)	0.530
SUN2	PIP4K2A	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
SUN2	PIP	psi-mi:“MI:0914”(association)	0.530
DGKA	DHRS4	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (128): DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DHRS4 (Co-fractionation), DHRS4 (Affinity Capture-MS), CLPB (Affinity Capture-MS), NDUFAF5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4GU97, A0A1A9TAK5, A0A1C9II22, A0A1Y0BRF8, A0A384JQF5, A0A3G9HAL8, A0A3Q8GYY4, A0A411PQN6, A0A5B8YU81, A0A6S6QNE4, A0A8F5XX49, A3LZU7, B0ZT44, B6HV34, D3J0Z1, E9ET40, F4IKM1, F4J300, F9XMW6, O00058, O49332, O80714, O93868, P0DKI3, P50162, P50163, P50164, P50165, P9WES5, Q13268, Q14RS1, Q21929, Q42182, Q4WZ66, Q5RCF8, Q8RX32, Q8SPU8, Q99LB2, Q9BTZ2, Q9C826

Diamond homologs: A0A023I4C8, A0A097ZPC9, A0A0F7U1Z1, A0A0H3KNE7, A0A0U5GHD4, A0A1E1FFP5, A0A1U8QWA2, A0A1Y0BRF8, A0A2I1BSW8, A0A384JQF5, A0A3G9HAL8, A0A455R5K2, A0A6S6QNE4, A0A8D5M6H6, A0QYC2, A6SSW9, A7IQH5, A9CES4, B6H065, B6HV34, G5DGA8, I6YCF0, K2RLM6, N4WE73, O02691, O32291, O74628, P0DMP5, P0DOV5, P15428, P19992, P46331, P55541, P55575, P66782, P9WEP2, P9WEQ5, P9WGQ4, P9WGQ5, P9WGQ8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Phase I - Functionalization of compounds	5	12.9×	3e-03
Peroxisomal protein import	6	12.2×	1e-03
Mitochondrial protein degradation	9	12.1×	2e-05
Respiratory electron transport	6	6.7×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
fatty acid beta-oxidation	5	17.0×	3e-03
aerobic respiration	5	11.3×	9e-03
mitochondrion organization	6	8.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1220 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23955032:CAGGA:C	acceptor_loss	1.0000
14:23955033:A:AG	acceptor_gain	1.0000
14:23955033:AG:A	acceptor_gain	1.0000
14:23955033:AGGA:A	acceptor_loss	1.0000
14:23955034:G:A	acceptor_loss	1.0000
14:23955034:G:GT	acceptor_gain	1.0000
14:23955034:GG:G	acceptor_gain	1.0000
14:23955034:GGATC:G	acceptor_gain	1.0000
14:23965838:GAGA:G	donor_gain	1.0000
14:23965840:GA:G	donor_gain	1.0000
14:23965842:G:GG	donor_gain	1.0000
14:23965984:G:GG	donor_gain	1.0000
14:23966413:GGATG:G	donor_gain	1.0000
14:23966414:G:GT	donor_gain	1.0000
14:23966423:G:GT	donor_gain	1.0000
14:23966424:A:T	donor_gain	1.0000
14:23966428:G:T	donor_gain	1.0000
14:23966482:G:T	donor_gain	1.0000
14:23967209:A:AG	acceptor_gain	1.0000
14:23967210:G:GG	acceptor_gain	1.0000
14:23955026:T:A	acceptor_gain	0.9900
14:23955031:ACAG:A	acceptor_gain	0.9900
14:23955034:GGA:G	acceptor_gain	0.9900
14:23955034:GGAT:G	acceptor_gain	0.9900
14:23955208:CCACG:C	donor_loss	0.9900
14:23955209:CACG:C	donor_loss	0.9900
14:23955212:GGTG:G	donor_loss	0.9900
14:23955213:G:C	donor_loss	0.9900
14:23955213:G:GG	donor_gain	0.9900
14:23955214:T:G	donor_loss	0.9900

AlphaMissense

1800 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23966308:A:T	K186I	0.999
14:23955090:A:C	S62R	0.998
14:23955092:C:A	S62R	0.998
14:23955092:C:G	S62R	0.998
14:23959995:T:A	W134R	0.997
14:23959995:T:C	W134R	0.997
14:23966309:A:C	K186N	0.997
14:23966309:A:T	K186N	0.997
14:23966375:C:A	N208K	0.997
14:23966375:C:G	N208K	0.997
14:23955040:G:A	G45D	0.996
14:23966304:A:C	S185R	0.996
14:23966306:T:A	S185R	0.996
14:23966306:T:G	S185R	0.996
14:23966378:C:G	C209W	0.996
14:23965957:T:C	S169P	0.994
14:23953907:C:A	S40Y	0.993
14:23965776:T:A	N141K	0.993
14:23965776:T:G	N141K	0.993
14:23965958:C:A	S169Y	0.993
14:23966295:T:C	Y182H	0.993
14:23953907:C:T	S40F	0.992
14:23955093:A:C	S63R	0.992
14:23955094:G:T	S63I	0.992
14:23955095:C:A	S63R	0.992
14:23955095:C:G	S63R	0.992
14:23966401:C:T	T217I	0.992
14:23953910:C:T	T41I	0.991
14:23953916:G:A	G43E	0.991
14:23955058:G:C	R51P	0.991

dbSNP variants (sampled 300 via entrez): RS1000147013 (14:23954276 G>A,C), RS1000533366 (14:23951858 G>A,T), RS1000987488 (14:23952050 C>G), RS1001262882 (14:23955638 A>T), RS1001315120 (14:23955891 A>G), RS1001518884 (14:23967185 T>A,C), RS1002236431 (14:23968331 T>C), RS1002288883 (14:23968556 T>C), RS1002567214 (14:23969701 G>A,C), RS1002781681 (14:23961033 C>A), RS1002857425 (14:23960005 T>C), RS1002928326 (14:23956738 G>A), RS1002982086 (14:23956868 G>C,T), RS1003035752 (14:23952144 T>C), RS1003211130 (14:23957465 A>C,G)

Disease associations

OMIM: gene MIM:611596 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006865_15	Bipolar disorder	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
jinfukang	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
NADP	affects binding, increases activity	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SK78	HAP1 DHRS4 (-) 1	Cancer cell line	Male
CVCL_SK79	HAP1 DHRS4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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