DHRS12

Summary

DHRS12 (dehydrogenase/reductase 12, HGNC:25832) is a protein-coding gene on chromosome 13q14.3, encoding Dehydrogenase/reductase SDR family member 12 (A0PJE2). Putative oxidoreductase.

This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. Alternative splicing results in multiple transcript variants and protein isoforms.

Source: NCBI Gene 79758 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001377533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25832
Approved symbol	DHRS12
Name	dehydrogenase/reductase 12
Location	13q14.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13639, SDR40C1
Ensembl gene	ENSG00000102796
Ensembl biotype	protein_coding
OMIM	616163
Entrez	79758

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000218981, ENST00000280056, ENST00000444610, ENST00000461948, ENST00000469957, ENST00000472372, ENST00000489680, ENST00000490949, ENST00000497151, ENST00000650833, ENST00000682342, ENST00000893247, ENST00000893248, ENST00000893249, ENST00000893250, ENST00000893251, ENST00000893252, ENST00000893253, ENST00000893254, ENST00000893255, ENST00000959877, ENST00000959878

RefSeq mRNA: 9 — MANE Select: NM_001377533 NM_001031719, NM_001270424, NM_001377533, NM_001377929, NM_001377930, NM_001377931, NM_001377932, NM_001377933, NM_024705

CCDS: CCDS31976, CCDS58292, CCDS91809, CCDS9430

Canonical transcript exons

ENST00000444610 — 9 exons

Exon	Start	End
ENSE00003691504	51799534	51799667
ENSE00003842285	51767993	51768296
ENSE00003917072	51804054	51804163
ENSE00003969029	51773930	51774034
ENSE00003969030	51771821	51771911
ENSE00003969032	51769156	51769293
ENSE00003969033	51791165	51791257
ENSE00003969034	51777060	51777121
ENSE00003969035	51790011	51790092

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 97.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.7387 / max 53.5941, expressed in 1446 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137387	1.7225	933
137388	1.3701	918
137386	0.5115	195
137385	0.1223	37
137384	0.0123	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.00	gold quality
mucosa of stomach	UBERON:0001199	93.81	gold quality
left ovary	UBERON:0002119	91.88	gold quality
right lobe of liver	UBERON:0001114	91.24	gold quality
right ovary	UBERON:0002118	91.00	gold quality
metanephros cortex	UBERON:0010533	90.83	gold quality
tibial nerve	UBERON:0001323	90.79	gold quality
left lobe of thyroid gland	UBERON:0001120	90.72	gold quality
left uterine tube	UBERON:0001303	90.55	gold quality
adenohypophysis	UBERON:0002196	90.36	gold quality
tibial artery	UBERON:0007610	90.05	gold quality
popliteal artery	UBERON:0002250	90.04	gold quality
right lobe of thyroid gland	UBERON:0001119	90.03	gold quality
granulocyte	CL:0000094	90.02	gold quality
body of uterus	UBERON:0009853	90.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.99	gold quality
pancreas	UBERON:0001264	89.96	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.88	gold quality
lower esophagus	UBERON:0013473	89.85	gold quality
skin of leg	UBERON:0001511	89.61	gold quality
omental fat pad	UBERON:0010414	89.48	gold quality
skin of abdomen	UBERON:0001416	89.42	gold quality
peritoneum	UBERON:0002358	89.40	gold quality
right uterine tube	UBERON:0001302	89.38	gold quality
minor salivary gland	UBERON:0001830	89.38	gold quality
body of stomach	UBERON:0001161	89.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.05	gold quality
thyroid gland	UBERON:0002046	88.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.90	gold quality
apex of heart	UBERON:0002098	88.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting DHRS12, 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-4692	100.00	67.32	2066
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-6876-3P	98.97	65.69	765
HSA-MIR-626	98.89	66.21	762
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-1199-5P	98.44	66.51	829

Literature-anchored findings (GeneRIF, showing 2)

• DHRS12 inhibits the proliferation and metastasis of osteosarcoma via Wnt3a/beta-catenin pathway. (PMID:32250163)
• Genetic architecture of asthma in African American patients. (PMID:36089080)

Cross-species orthologs

0 orthologs

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), 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

Dehydrogenase/reductase SDR family member 12 — A0PJE2 (reviewed: A0PJE2)

Alternative names: Short-chain dehydrogenase/reductase family 40C member 1

All UniProt accessions (4): A0PJE2, A0A087WUE0, A0A494C138, A0A8C8L8Z5

UniProt curated annotations — full annotation on UniProt →

Function. Putative oxidoreductase.

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

Isoforms (4)

UniProt ID	Names	Canonical?
A0PJE2-1	1	yes
A0PJE2-2	2
A0PJE2-3	3
A0PJE2-4	4

RefSeq proteins (9): NP_001026889, NP_001257353, NP_001364462, NP_001364858, NP_001364859, NP_001364860, NP_001364861, NP_001364862, NP_078981 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002347	SDR_fam	Family
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR052992	SDR_member_12	Family

Pfam: PF00106

UniProt features (12 total): binding site 6, splice variant 4, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0PJE2-F1	95.35	0.90

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): 201 (proton acceptor)

Ligand- & substrate-binding residues (6): 50; 52; 175; 201; 205; 234

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): SCHLOSSER_SERUM_RESPONSE_DN, chr13q14, PARENT_MTOR_SIGNALING_UP, MODULE_69, FIGUEROA_AML_METHYLATION_CLUSTER_1_UP, FIGUEROA_AML_METHYLATION_CLUSTER_2_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_4_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_UP, FIGUEROA_AML_METHYLATION_CLUSTER_7_UP, MODULE_37, HES2_TARGET_GENES, SKIL_TARGET_GENES, ZFP91_TARGET_GENES, ZNF423_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): oxidoreductase activity (GO:0016491)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	1

Protein interactions and networks

STRING

2989 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHRS12	TMEM225	Q6GV28	646
DHRS12	ACSF3	Q4G176	573
DHRS12	TMCO5A	Q8N6Q1	543
DHRS12	NUDT17	P0C025	543
DHRS12	ITPK1	Q13572	513
DHRS12	TRIM69	Q86WT6	497
DHRS12	PARVG	Q9HBI0	476
DHRS12	TLCD1	Q96CP7	470
DHRS12	TRAFD1	O14545	462
DHRS12	ALS2CL	Q60I27	415
DHRS12	MAP2K6	P52564	410
DHRS12	MXI1	P50539	406
DHRS12	DFFA	O00273	405
DHRS12	NAALAD2	Q9Y3Q0	405
DHRS12	SNX16	P57768	396

IntAct

5 interactions, top by confidence:

A	B	Type	Score
CENPK	DHRS12	psi-mi:“MI:0914”(association)	0.530
DHRS12	IGLL5	psi-mi:“MI:0914”(association)	0.350
DHRS12	VSIG8	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): PRR4 (Affinity Capture-MS), LTF (Affinity Capture-MS), DHRS12 (Affinity Capture-MS), SCGB2A1 (Affinity Capture-MS), LACRT (Affinity Capture-MS), IGLL5 (Affinity Capture-MS), NEU2 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), S100A3 (Affinity Capture-MS), PLCD1 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), FAM26D (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS)

ESM2 similar proteins: A0PJE2, A4FUZ6, A6QP05, D2WKD9, F1QWW8, O49213, O66148, O75884, O88736, O88851, P13653, P15904, P23591, P30043, P52556, P56658, P56937, Q06136, Q0IH28, Q0VCN1, Q0VFE7, Q13630, Q2KIJ5, Q3T0R4, Q41578, Q42850, Q566S6, Q59987, Q5R6U1, Q5RBE5, Q5RJY4, Q5ZID0, Q62904, Q66KC4, Q67WR2, Q6GV12, Q6IAN0, Q6P5L8, Q6PAY8, Q7XKF3

Diamond homologs: A0A017SEY2, A0A023I4F1, A0A078IS66, A0A078ISJ6, A0A0U1LQE2, A0A0U5CNP2, A0A1B7YCL6, A0A1V0QS34, A0A1V6PAN1, A0A223HDI5, A0A2H3CNT9, A0A2H3D905, A0A443HJZ3, A0A482ND39, A0A823A767, A0PJE2, A2RVM0, A6QP05, B2X050, B6H062, B8A5W4, C8VI80, D7UTD0, G1XTZ5, I1RL15, O32291, O74959, P0DXW2, P16152, P19871, P21218, P35320, P40747, P47727, P50163, P51657, P59837, Q01289, Q03326, Q08651

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1862 predictions. Top by Δscore:

Variant	Effect	Δscore
13:51773926:TGAC:T	donor_loss	1.0000
13:51773927:GAC:G	donor_loss	1.0000
13:51773929:CCT:C	donor_loss	1.0000
13:51774030:GTTAT:G	acceptor_gain	1.0000
13:51774031:TTAT:T	acceptor_gain	1.0000
13:51774032:TAT:T	acceptor_gain	1.0000
13:51774033:AT:A	acceptor_gain	1.0000
13:51774035:C:CC	acceptor_gain	1.0000
13:51774035:CTGCA:C	acceptor_loss	1.0000
13:51797820:GCTCA:G	donor_loss	1.0000
13:51797821:CTCAC:C	donor_loss	1.0000
13:51797822:TCA:T	donor_loss	1.0000
13:51797825:C:CT	donor_loss	1.0000
13:51797908:CC:C	acceptor_loss	1.0000
13:51797910:T:C	acceptor_loss	1.0000
13:51799528:GCTTA:G	donor_loss	1.0000
13:51799529:CTTAC:C	donor_loss	1.0000
13:51799530:TTA:T	donor_loss	1.0000
13:51799531:TA:T	donor_loss	1.0000
13:51799532:ACCTC:A	donor_loss	1.0000
13:51799533:CCTCG:C	donor_gain	1.0000
13:51799663:CACTC:C	acceptor_gain	1.0000
13:51799665:CTC:C	acceptor_gain	1.0000
13:51799666:TCCT:T	acceptor_loss	1.0000
13:51799667:CCT:C	acceptor_loss	1.0000
13:51799668:CT:C	acceptor_loss	1.0000
13:51799669:T:A	acceptor_loss	1.0000
13:51804052:A:AC	donor_gain	1.0000
13:51804053:C:CC	donor_gain	1.0000
13:51769115:AGC:A	donor_gain	0.9900

AlphaMissense

2160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:51773930:C:A	K205N	0.993
13:51773930:C:G	K205N	0.993
13:51771855:A:C	F224L	0.990
13:51771855:A:T	F224L	0.990
13:51771857:A:G	F224L	0.990
13:51771836:A:G	W231R	0.988
13:51771836:A:T	W231R	0.988
13:51771909:C:A	R206S	0.988
13:51771909:C:G	R206S	0.988
13:51773960:A:C	F195L	0.987
13:51773960:A:T	F195L	0.987
13:51773962:A:G	F195L	0.987
13:51771844:T:C	H228R	0.986
13:51769160:A:C	F280L	0.985
13:51769160:A:T	F280L	0.985
13:51769162:A:G	F280L	0.985
13:51769268:G:C	F244L	0.983
13:51769268:G:T	F244L	0.983
13:51769270:A:G	F244L	0.983
13:51771834:C:A	W231C	0.982
13:51771834:C:G	W231C	0.982
13:51771843:A:C	H228Q	0.982
13:51771843:A:T	H228Q	0.982
13:51771910:C:G	R206T	0.982
13:51773931:T:G	K205T	0.980
13:51769163:G:C	F279L	0.978
13:51769163:G:T	F279L	0.978
13:51769165:A:G	F279L	0.978
13:51799595:A:C	F43L	0.977
13:51799595:A:T	F43L	0.977

dbSNP variants (sampled 300 via entrez): RS1000018825 (13:51778405 G>A), RS1000048560 (13:51779369 CAACA>C), RS1000090524 (13:51778025 C>T), RS1000105221 (13:51779174 C>T), RS1000177014 (13:51754988 T>C), RS1000225748 (13:51803766 G>A,C), RS1000267595 (13:51760042 C>A,G,T), RS1000273157 (13:51802703 G>A), RS1000283341 (13:51803162 G>A), RS1000283537 (13:51789482 A>G), RS1000290446 (13:51761835 G>A), RS1000297739 (13:51803411 TAATC>T), RS1000432902 (13:51796476 A>G), RS1000567655 (13:51802197 ACACACACACACACACACACAC>A), RS1000573985 (13:51795921 G>A)

Disease associations

OMIM: gene MIM:616163 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006979_1029	Heel bone mineral density	1.000000e-09
GCST008926_2	Lysophosphatidylethanolamine levels	1.000000e-08
GCST009391_854	Metabolite levels	8.000000e-06
GCST90002407_609	White blood cell count	2.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0010225	lysophosphatidylethanolamine measurement
EFO:0010398	sphingomyelin 24:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	3
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
bisphenol A	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
naringenin	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	affects expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Methapyrilene	increases methylation	1
NADP	affects binding, increases activity	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Dihydrotestosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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