DHRS4L2

Summary

DHRS4L2 (dehydrogenase/reductase 4 like 2, HGNC:19731) is a protein-coding gene on chromosome 14q11.2, encoding Dehydrogenase/reductase SDR family member 4-like 2 (Q6PKH6). Probable oxidoreductase.

This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 317749 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_198083

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19731
Approved symbol	DHRS4L2
Name	dehydrogenase/reductase 4 like 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	SDR25C3
Ensembl gene	ENSG00000187630
Ensembl biotype	protein_coding
OMIM	615196
Entrez	317749

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000335125, ENST00000397071, ENST00000534993, ENST00000537912, ENST00000543805, ENST00000557812, ENST00000558753, ENST00000559387, ENST00000559411, ENST00000560276, ENST00000870058, ENST00000870059, ENST00000870060, ENST00000870061, ENST00000870062

RefSeq mRNA: 5 — MANE Select: NM_198083 NM_001193635, NM_001193636, NM_001193637, NM_001412315, NM_198083

CCDS: CCDS73621, CCDS86376, CCDS9606

Canonical transcript exons

ENST00000335125 — 8 exons

Exon	Start	End
ENSE00001614349	24000863	24000933
ENSE00001625536	24001033	24001084
ENSE00003478501	23990182	23990359
ENSE00003536549	24001384	24001517
ENSE00003634909	24004337	24004392
ENSE00003661549	23995032	23995133
ENSE00003849137	23988929	23989075
ENSE00003849487	24005886	24006403

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.57.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6104 / max 21.6538, expressed in 262 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138962	0.6104	262
138961	0.5366	305
138959	0.3863	202
138960	0.0634	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.57	gold quality
apex of heart	UBERON:0002098	95.02	gold quality
mucosa of transverse colon	UBERON:0004991	94.95	gold quality
adult mammalian kidney	UBERON:0000082	94.82	gold quality
liver	UBERON:0002107	94.56	gold quality
kidney	UBERON:0002113	92.50	gold quality
right testis	UBERON:0004534	92.09	gold quality
heart left ventricle	UBERON:0002084	91.96	gold quality
duodenum	UBERON:0002114	91.95	gold quality
left testis	UBERON:0004533	91.86	gold quality
testis	UBERON:0000473	91.64	gold quality
gastrocnemius	UBERON:0001388	91.63	gold quality
right adrenal gland cortex	UBERON:0035827	91.62	gold quality
cortex of kidney	UBERON:0001225	91.60	gold quality
left adrenal gland cortex	UBERON:0035825	91.52	gold quality
muscle of leg	UBERON:0001383	91.38	gold quality
transverse colon	UBERON:0001157	91.12	gold quality
left adrenal gland	UBERON:0001234	91.07	gold quality
right adrenal gland	UBERON:0001233	90.86	gold quality
granulocyte	CL:0000094	90.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.52	gold quality
lower esophagus	UBERON:0013473	90.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.48	gold quality
small intestine	UBERON:0002108	90.47	gold quality
skin of abdomen	UBERON:0001416	90.42	gold quality
esophagus mucosa	UBERON:0002469	90.35	gold quality
skin of leg	UBERON:0001511	90.33	gold quality
zone of skin	UBERON:0000014	90.30	gold quality
esophagus	UBERON:0001043	90.25	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting DHRS4L2, 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-450B-5P	99.92	71.48	3175
HSA-MIR-2053	99.57	69.15	1635
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-3619-5P	99.00	68.87	2308
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-500A-3P	97.60	67.48	595
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-6869-3P	83.17	65.88	30

Literature-anchored findings (GeneRIF, showing 1)

• DHRS4L2 is a duplicate syntenic form of the human DHRS4 gene. (PMID:23036705)

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), DHRS4 (ENSG00000157326), DHRS1 (ENSG00000157379), CBR1 (ENSG00000159228), CBR3 (ENSG00000159231), HSD11B1L (ENSG00000167733), DHRS7C (ENSG00000184544), DHRS11 (ENSG00000278535)

Protein

Protein identifiers

Dehydrogenase/reductase SDR family member 4-like 2 — Q6PKH6 (reviewed: Q6PKH6)

Alternative names: Short chain dehydrogenase/reductase family 25C member 3

All UniProt accessions (7): A0A087WSZ6, E9PFL3, Q6PKH6, F6TD35, F6VUV4, H0YKN3, H0YLE1

UniProt curated annotations — full annotation on UniProt →

Function. Probable oxidoreductase.

Subcellular location. Secreted.

Miscellaneous. 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 (2)

UniProt ID	Names	Canonical?
Q6PKH6-1	1	yes
Q6PKH6-2	2

RefSeq proteins (5): NP_001180564, NP_001180565, NP_001180566, NP_001399244, NP_932349* (*=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: PF00106

UniProt features (10 total): binding site 3, signal peptide 1, chain 1, active site 1, glycosylation site 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PKH6-F1	85.54	0.74

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): 182 (proton acceptor)

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

Glycosylation sites (1): 183

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): AAAYRNCTG_UNKNOWN, GOBP_RETINAL_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ALDEHYDE_METABOLIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_CH_OH_GROUP_OF_DONORS, GOBP_ISOPRENOID_METABOLIC_PROCESS, GOCC_MICROBODY, GOMF_CARBONYL_REDUCTASE_NADPH_ACTIVITY, GOMF_ALCOHOL_DEHYDROGENASE_NADPPLUS_ACTIVITY, GOMF_ALCOHOL_DEHYDROGENASE_NAD_P_PLUS_ACTIVITY, ARID5B_TARGET_GENES, SNRNP70_TARGET_GENES, ZNF282_TARGET_GENES, MIR2355_5P, MIR7854_3P

GO Biological Process (1): retinal metabolic process (GO:0042574)

GO Molecular Function (2): carbonyl reductase (NADPH) activity (GO:0004090), oxidoreductase activity (GO:0016491)

GO Cellular Component (3): extracellular region (GO:0005576), mitochondrion (GO:0005739), peroxisome (GO:0005777)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid metabolic process	1
aldehyde metabolic process	1
olefinic compound metabolic process	1
alcohol dehydrogenase (NADP+) activity	1
catalytic activity	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
microbody	1

Protein interactions and networks

STRING

2975 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHRS4L2	FAM72B	Q86X60	485
DHRS4L2	GTF2H2C	Q6P1K8	473
DHRS4L2	GTF2H2	Q13888	453
DHRS4L2	ANKRD20A4P	Q4UJ75	453
DHRS4L2	OXLD1	Q5BKU9	453
DHRS4L2	ANKRD20A2P	Q5SQ80	453
DHRS4L2	FOXD4L6	Q3SYB3	449
DHRS4L2	FAM72A	Q5TYM5	434
DHRS4L2	DHRS4	Q9BTZ2	421
DHRS4L2	ZNG1F	Q4V339	400
DHRS4L2	ZNG1C	Q5JTY5	399
DHRS4L2	TIMM21	Q9BVV7	386
DHRS4L2	ZCWPW2	Q504Y3	370
DHRS4L2	TMEM123	Q8N131	365
DHRS4L2	TBC1D1	Q86TI0	359

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DHRS4L2	PCNA	psi-mi:“MI:0915”(physical association)	0.370
DHRS4L2	MYCBP2	psi-mi:“MI:0915”(physical association)	0.370
PFDN5	GTPBP10	psi-mi:“MI:0914”(association)	0.350
DHRS4L2	ACOT7	psi-mi:“MI:0914”(association)	0.350
DHRS4L2	DHRS4L1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A097ZPC9, A0A0H3KNE7, A0A4V1DXC3, A0A7T8F1N2, A0A8I6GJ95, A5W4G5, C8CP46, E9Q3D4, E9QUT3, H1VN83, I6Y778, K2RLM6, O52384, O53547, O69264, P05406, P08088, P08694, P0C622, P0CG22, P0CU71, P13859, P19871, P22441, P23102, P27100, P33008, P37440, P39884, P47227, P50206, P55434, P55541, P72220, P95727, P9WEW9, P9WGQ2, P9WGQ3, Q45219, Q46381

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1110 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23989074:GG:G	donor_gain	1.0000
14:23989075:GG:G	donor_gain	1.0000
14:23989075:GGTG:G	donor_loss	1.0000
14:23989076:GTGA:G	donor_loss	1.0000
14:23990177:CACAG:C	acceptor_loss	1.0000
14:23990179:CAGG:C	acceptor_loss	1.0000
14:23990180:A:AG	acceptor_gain	1.0000
14:23990180:AG:A	acceptor_gain	1.0000
14:23990180:AGGAT:A	acceptor_loss	1.0000
14:23990181:G:GA	acceptor_gain	1.0000
14:23990181:GG:G	acceptor_gain	1.0000
14:23990181:GGATC:G	acceptor_gain	1.0000
14:24000941:GA:G	donor_gain	1.0000
14:24000943:G:GG	donor_gain	1.0000
14:24001513:GGATG:G	donor_gain	1.0000
14:24001514:G:GT	donor_gain	1.0000
14:24001523:G:GT	donor_gain	1.0000
14:24001582:G:T	donor_gain	1.0000
14:24004335:A:AG	acceptor_gain	1.0000
14:24004336:G:GG	acceptor_gain	1.0000
14:23989071:GACGG:G	donor_gain	0.9900
14:23989076:G:GG	donor_gain	0.9900
14:23990173:T:TA	acceptor_gain	0.9900
14:23990178:ACAG:A	acceptor_gain	0.9900
14:23990181:GGA:G	acceptor_gain	0.9900
14:23990181:GGAT:G	acceptor_gain	0.9900
14:23990267:G:GT	donor_gain	0.9900
14:23990291:GGGC:G	donor_gain	0.9900
14:23990403:G:GT	donor_gain	0.9900
14:24000939:GAGA:G	donor_gain	0.9900

AlphaMissense

1493 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000018297 (14:23999391 T>A), RS1000350673 (14:23982010 C>T), RS1000406302 (14:23982106 C>T), RS1000450623 (14:23987701 A>G), RS1000693919 (14:23983110 G>C), RS1000740734 (14:23987029 C>T), RS1000805345 (14:23987992 A>G), RS1000845219 (14:23991010 C>A,G,T), RS1000865608 (14:23975691 C>A,T), RS1000900565 (14:23990835 TCA>T), RS1001216795 (14:23995380 C>G,T), RS1001273720 (14:24006443 C>G,T), RS1001583449 (14:23982355 C>T), RS1001684529 (14:23976202 T>C), RS1001867881 (14:23983504 C>G,T)

Disease associations

OMIM: gene MIM:615196 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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