DHRS2

Summary

DHRS2 (dehydrogenase/reductase 2, HGNC:18349) is a protein-coding gene on chromosome 14q11.2, encoding Dehydrogenase/reductase SDR family member 2, mitochondrial (Q13268). NADPH-dependent oxidoreductase which catalyzes the reduction of dicarbonyl compounds.

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

Source: NCBI Gene 10202 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_005794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18349
Approved symbol	DHRS2
Name	dehydrogenase/reductase 2
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HEP27, SDR25C1
Ensembl gene	ENSG00000100867
Ensembl biotype	protein_coding
OMIM	615194
Entrez	10202

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000250383, ENST00000344777, ENST00000432832, ENST00000553600, ENST00000553896, ENST00000556550, ENST00000556701, ENST00000556729, ENST00000557535, ENST00000611765, ENST00000897469, ENST00000897470, ENST00000897471, ENST00000897472

RefSeq mRNA: 3 — MANE Select: NM_005794 NM_001318835, NM_005794, NM_182908

CCDS: CCDS41927, CCDS9604

Canonical transcript exons

ENST00000250383 — 9 exons

Exon	Start	End
ENSE00000654099	23643152	23643219
ENSE00001904739	23636364	23636772
ENSE00003503444	23639179	23639356
ENSE00003512286	23638827	23639004
ENSE00003614030	23644827	23644882
ENSE00003617974	23644111	23644162
ENSE00003623046	23639794	23639895
ENSE00003786475	23644409	23644543
ENSE00003902407	23645142	23645639

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 97.27.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9865 / max 1072.4611, expressed in 363 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138948	5.2468	334
138946	0.4304	97
138947	0.2819	33
138949	0.0149	7
138950	0.0126	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of urinary bladder	UBERON:0001259	97.27	gold quality
urinary bladder	UBERON:0001255	95.69	gold quality
islet of Langerhans	UBERON:0000006	92.81	gold quality
endometrium epithelium	UBERON:0004811	88.06	gold quality
parotid gland	UBERON:0001831	87.91	gold quality
right lobe of liver	UBERON:0001114	84.76	gold quality
spleen	UBERON:0002106	83.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.14	gold quality
left ovary	UBERON:0002119	80.53	gold quality
liver	UBERON:0002107	80.03	gold quality
pancreas	UBERON:0001264	79.81	gold quality
frontal pole	UBERON:0002795	79.66	gold quality
nipple	UBERON:0002030	79.54	gold quality
paraflocculus	UBERON:0005351	79.40	gold quality
middle frontal gyrus	UBERON:0002702	78.89	gold quality
amniotic fluid	UBERON:0000173	78.85	gold quality
placenta	UBERON:0001987	78.76	gold quality
ovary	UBERON:0000992	78.50	gold quality
right ovary	UBERON:0002118	76.61	gold quality
tendon of biceps brachii	UBERON:0008188	76.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.03	gold quality
sperm	CL:0000019	74.42	silver quality
body of pancreas	UBERON:0001150	74.12	gold quality
male germ cell	CL:0000015	73.56	silver quality
cervix squamous epithelium	UBERON:0006922	73.33	gold quality
diaphragm	UBERON:0001103	71.22	gold quality
renal medulla	UBERON:0000362	69.77	gold quality
fundus of stomach	UBERON:0001160	69.74	gold quality
germinal epithelium of ovary	UBERON:0001304	69.40	silver quality
type B pancreatic cell	CL:0000169	68.68	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	20.42
E-MTAB-5061	yes	14.65
E-GEOD-81608	yes	6.76
E-GEOD-83139	no	2.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETV5, MYB, MYBL1

miRNA regulators (miRDB)

18 targeting DHRS2, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-449C-3P	97.75	67.86	462
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-8086	97.21	64.13	331
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-3943	95.87	64.57	523
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725

Literature-anchored findings (GeneRIF, showing 21)

• Complete genomic organization of DHRS2, including two alternative promoter regions: a hepatocyte-specific promoter and a monocyte-derived dendritic cell-specific promoter (PMID:11944995)
• Molecular cloning, sequence and Chr 14 localization of the DHRS2 gene. Nuclear and cytoplasmic localization and normal tissue distribution of the DHRS2-encoded Hep27 protein. (PMID:11997086)
• Hep27 is a NADPH-dependent dicarbonyl reductase enzyme active on xenobiotics. (PMID:16685466)
• The synthesis of the nuclear protein D (Hep27 protein old name) is up-regulated in growth-inhibited HepG2 cells and is inhibited during DNA synthesis. (PMID:1847869)
• In human endometrial carcinoma cells, the Hep27 protein encoded by DHRS2 is specifically upregulated in mitochondria by the ERM/ETV5 transcription factor and Hep27 has a protective role against apoptosis induced by oxidative stress. (PMID:19443906)
• Hep27 is regulated at the transcriptional level by the proto-oncogene c-Myb and is required for c-Myb-induced p53 stabilization. (PMID:20547751)
• c-Myb proto-oncogene has a tumor suppressor role in breast cancer via c-Myb controlled DHRS2 (HEP27) expression. (PMID:20949095)
• A rapid divergent evolution 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)
• Low DHRS2 expression promotes esophageal squamous cell carcinoma. (PMID:29106393)
• Homeobox A13 (HOXA13) played a role of carcinogenesis through directly down-regulating dehydrogenase/reductase 2 (DHRS2) to increase proto-oncogene proteins c-mdm2 (MDM2). (PMID:29436749)
• DHRS2 is dispensable for up-regulation of romidepsin effectors. (PMID:30460772)
• Among these targets, dehydrogenase/reductase member 2 DHRS2 and MYO1B were directly regulated by miR1453p in esophageal squamous cell carcinoma (ESCC) cells by dual luciferase reporter assays. Aberrantly expressed DHRS2 and MYOIB were detected in ESCC clinical specimens, and their overexpression enhanced cancer cell aggressiveness. (PMID:30535463)
• Our report suggests that activating DHRS2 to reprogram lipid homeostasis may be a target for the development of targeted therapies against NPC. (PMID:31291971)
• Decreased DHRS2 expression is associated with HDACi resistance and poor prognosis in ovarian cancer. (PMID:31423895)
• Results show that DHRS2 is highly expressed in oxaliplatin-resistant colorectal cancer (CRC) cell line. Furthermore, DHRS2 regulates ERCC1 to promote oxaliplatin resistance through a p53dependent pathway, and mediates EMT by suppressing Ecadherin expression. (PMID:31436301)
• LEF1 Induces DHRS2 Gene Expression in Human Acute Leukemia Jurkat T-Cells (PMID:32586085)
• DHRS2 inhibits cell growth and metastasis in ovarian cancer by downregulation of CHKalpha to disrupt choline metabolism. (PMID:36192391)
• Regulatory mechanism of DHRS2-modified human umbilical cord mesenchymal stem cells-derived exosomes in prostate cancer cell proliferation and apoptosis. (PMID:37060745)
• Epigenetic regulation of DHRS2 by SUV420H2 inhibits cell apoptosis in renal cell carcinoma. (PMID:37119764)
• Hep27 a cell-cycle regulated protein belongs to the SDR family (short-chain dehydrogenase/reductase family). (PMID:7556196)

Cross-species orthologs

33 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-186j5.2	ENSDARG00000018301
danio_rerio	dhrs4	ENSDARG00000021135
danio_rerio	cbr1l	ENSDARG00000021149
danio_rerio	zgc:101858	ENSDARG00000035129
danio_rerio	zgc:65997	ENSDARG00000043562
danio_rerio	zgc:113054	ENSDARG00000053483
danio_rerio	zgc:158868	ENSDARG00000069379
danio_rerio	zgc:163083	ENSDARG00000099873
danio_rerio	zgc:92161	ENSDARG00000101749
danio_rerio	zgc:123284	ENSDARG00000102720
danio_rerio	zgc:112146	ENSDARG00000104829
mus_musculus	Dhrs2	ENSMUSG00000022209
rattus_norvegicus	Dhrs2	ENSRNOG00000018177
drosophila_melanogaster	CG7601	FBGN0027583
drosophila_melanogaster	Dhrs4	FBGN0035588
drosophila_melanogaster	CG12171	FBGN0037354
drosophila_melanogaster	CG3699	FBGN0040349
drosophila_melanogaster	CG31546	FBGN0051546
drosophila_melanogaster	CG31548	FBGN0051548
drosophila_melanogaster	CG31549	FBGN0051549
drosophila_melanogaster	CG13377	FBGN0261446
caenorhabditis_elegans		WBGENE00000970
caenorhabditis_elegans		WBGENE00000975
caenorhabditis_elegans		WBGENE00000976
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), 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

Dehydrogenase/reductase SDR family member 2, mitochondrial — Q13268 (reviewed: Q13268)

Alternative names: Dicarbonyl reductase HEP27, Protein D, Short chain dehydrogenase/reductase family 25C member 1

All UniProt accessions (4): Q13268, C9JZP6, H0YJG9, H0YJP4

UniProt curated annotations — full annotation on UniProt →

Function. NADPH-dependent oxidoreductase which catalyzes the reduction of dicarbonyl compounds. Displays reductase activity in vitro with 3,4-hexanedione, 2,3-heptanedione and 1-phenyl-1,2-propanedione as substrates. May function as a dicarbonyl reductase in the enzymatic inactivation of reactive carbonyls involved in covalent modification of cellular components. Also displays a minor hydroxysteroid dehydrogenase activity toward bile acids such as ursodeoxycholic acid (UDCA) and isoursodeoxycholic acid (isoUDCA), which makes it unlikely to control hormone levels. Doesn’t show any activity in vitro with retinoids and sugars as substrates. Attenuates MDM2-mediated p53/TP53 degradation, leading to p53/TP53 stabilization and increased transcription activity, resulting in the accumulation of MDM2 and CDKN1A/p21. Reduces proliferation, migration and invasion of cancer cells and well as the production of ROS in cancer.

Subunit / interactions. Directly interacts with MDM2; this interaction occurs in the nucleus and does not target DHRS2 to degradation.

Subcellular location. Mitochondrion matrix. Nucleus.

Tissue specificity. Widely expressed, with highest levels in liver and kidney, followed by heart, spleen, skeletal muscle and placenta. In hemopoietic cells, expressed in dendritic cells, but not in monocytes, macrophages, granulocytes, nor in B and T lymphocytes.

Induction. Up-regulated by IL4 and CSF2 in monocytes/macrophages. Down-regulated by bacterial lipopolysaccharides (LPS) and TNF in monocytice-derived dendritic cells. Up-regulated by MYB.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q13268-1	1	yes
Q13268-2	2

RefSeq proteins (2): NP_005785, NP_878912 (=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

UniProt features (23 total): modified residue 6, sequence conflict 6, binding site 6, transit peptide 1, chain 1, splice variant 1, sequence variant 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13268-F1	89.37	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): 185 (proton acceptor)

Ligand- & substrate-binding residues (6): 46; 48; 172; 185; 189; 220

Post-translational modifications (6): 96, 219, 219, 223, 237, 96

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_93, GOBP_DENDRITIC_CELL_DIFFERENTIATION, FARMER_BREAST_CANCER_CLUSTER_7, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_MYELOID_LEUKOCYTE_ACTIVATION, GOBP_ELECTRON_TRANSPORT_CHAIN

GO Biological Process (7): C21-steroid hormone metabolic process (GO:0008207), negative regulation of cell population proliferation (GO:0008285), response to toxic substance (GO:0009636), electron transport chain (GO:0022900), cellular response to oxidative stress (GO:0034599), myeloid dendritic cell differentiation (GO:0043011), negative regulation of apoptotic process (GO:0043066)

GO Molecular Function (4): carbonyl reductase (NADPH) activity (GO:0004090), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (6): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
steroid metabolic process	1
hormone metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
response to chemical	1
generation of precursor metabolites and energy	1
response to oxidative stress	1
cellular response to chemical stress	1
myeloid dendritic cell activation	1
myeloid leukocyte differentiation	1
dendritic cell differentiation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
alcohol dehydrogenase (NADP+) activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
binding	1
catalytic activity	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3577 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHRS2	DZIP3	Q86Y13	941
DHRS2	TTC3	P78477	870
DHRS2	SHB	Q15464	766
DHRS2	SHD	Q96IW2	766
DHRS2	P3H3	Q8IVL6	703
DHRS2	PALM2AKAP2	Q9Y2D5	478
DHRS2	UPK1A	O00322	462
DHRS2	AKAP10	O43572	455
DHRS2	PDZK1	Q5T2W1	441
DHRS2	TYRP1	P17643	427
DHRS2	RAB22A	Q9UL26	426
DHRS2	DSG1	Q02413	418
DHRS2	CERT1	Q9Y5P4	395
DHRS2	WAS	P42768	390
DHRS2	SEMA4D	Q92854	380

IntAct

69 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
DHRS2	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	DHRS2	psi-mi:“MI:0915”(physical association)	0.560
AP3S1	AP3B1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
HIRA	CSPG5	psi-mi:“MI:0914”(association)	0.530
DHRS2	MAP7D2	psi-mi:“MI:0915”(physical association)	0.400
CCDC141	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
DDX23	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
FBXL18	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
SI	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
DNAH3	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
AMMECR1L	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
PHTF2	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
FBXL19	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
IVL	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
ENPP3	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
PER3	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
SAFB2	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
CLP1	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
STMN2	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
ZNF724	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
CCDC14	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
MYBL2	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
ELOVL4	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
TCERG1	DHRS2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (110): APPBP2 (Two-hybrid), HBB (Affinity Capture-MS), HBA2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), DHRS2 (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, A0A0U5GHD4, A0A1E1FFP5, A0A1Y0BRF8, A0A2I1BSW8, A0A3G9HAL8, A0A455R5K2, A0A6S6QNE4, A0A7T8F1N2, A0A8D5M6H6, A0QYC2, A4IFA7, A7IQF2, A7IQH5, A9CES4, B6H065, B6HV34, C8WGQ3, F4J2Z7, F4J300, G4N1P8, H1VN83, L7I518, N4WE73, O02691, O06413, O08756, O70351, O80713, P06234, P06235, P0A2D1, P0A2D2, P16542, P16544, P19992, P21215, P28486

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 75 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
Defective B4GALT7 causes EDS, progeroid type	5	63.4×	2e-06
Defective B3GAT3 causes JDSSDHD	5	63.4×	2e-06
Defective B3GALT6 causes EDSP2 and SEMDJL1	5	63.4×	2e-06
Glycosaminoglycan-protein linkage region biosynthesis	5	43.8×	7e-06
Glycosaminoglycan metabolism	5	24.4×	5e-05
Non-integrin membrane-ECM interactions	6	20.6×	2e-05
Metabolism of carbohydrates and carbohydrate derivatives	5	13.4×	6e-04
Sensory Perception	5	10.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	13
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1485 predictions. Top by Δscore:

Variant	Effect	Δscore
14:23639170:T:A	acceptor_gain	1.0000
14:23639173:A:AG	acceptor_gain	1.0000
14:23639174:T:G	acceptor_gain	1.0000
14:23639174:TTCAG:T	acceptor_loss	1.0000
14:23639175:TCAGG:T	acceptor_loss	1.0000
14:23639176:CA:C	acceptor_loss	1.0000
14:23639177:A:AG	acceptor_gain	1.0000
14:23639177:AG:A	acceptor_gain	1.0000
14:23639178:G:A	acceptor_loss	1.0000
14:23639178:G:GC	acceptor_gain	1.0000
14:23639178:GG:G	acceptor_gain	1.0000
14:23639178:GGA:G	acceptor_gain	1.0000
14:23639178:GGATC:G	acceptor_gain	1.0000
14:23639288:GGGC:G	donor_gain	1.0000
14:23639353:CAAG:C	donor_loss	1.0000
14:23639356:GGTGA:G	donor_loss	1.0000
14:23639357:G:A	donor_loss	1.0000
14:23639358:T:A	donor_loss	1.0000
14:23640649:TCA:T	donor_gain	1.0000
14:23641774:GCT:G	donor_gain	1.0000
14:23641776:T:G	donor_gain	1.0000
14:23641776:T:TG	donor_gain	1.0000
14:23643143:T:A	acceptor_gain	1.0000
14:23643147:TTCA:T	acceptor_loss	1.0000
14:23643148:TCAG:T	acceptor_loss	1.0000
14:23643149:CA:C	acceptor_loss	1.0000
14:23643150:A:AG	acceptor_gain	1.0000
14:23643150:A:T	acceptor_loss	1.0000
14:23643151:G:GA	acceptor_gain	1.0000
14:23643151:GA:G	acceptor_gain	1.0000

AlphaMissense

1809 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:23639234:A:C	S66R	0.992
14:23639236:C:A	S66R	0.992
14:23639236:C:G	S66R	0.992
14:23644430:A:C	S188R	0.992
14:23644432:C:A	S188R	0.992
14:23644432:C:G	S188R	0.992
14:23644501:C:A	N211K	0.990
14:23644501:C:G	N211K	0.990
14:23644504:C:G	C212W	0.989
14:23644435:G:C	K189N	0.984
14:23644435:G:T	K189N	0.984
14:23639887:T:A	W138R	0.983
14:23639887:T:C	W138R	0.983
14:23639237:A:C	S67R	0.980
14:23639239:C:A	S67R	0.980
14:23639239:C:G	S67R	0.980
14:23645179:T:C	F257L	0.980
14:23645181:C:A	F257L	0.980
14:23645181:C:G	F257L	0.980
14:23644134:C:T	S171F	0.979
14:23638986:T:A	V41D	0.976
14:23638991:G:T	G43W	0.976
14:23644136:T:C	S172P	0.976
14:23638980:C:A	A39D	0.975
14:23644527:C:T	T220I	0.975
14:23639830:T:C	C119R	0.974
14:23645185:T:C	C259R	0.974
14:23643166:C:A	N145K	0.973
14:23643166:C:G	N145K	0.973
14:23639314:C:G	C92W	0.972

dbSNP variants (sampled 300 via entrez): RS1000375600 (14:23637110 A>G), RS1000421704 (14:23645535 G>A,C), RS1000530521 (14:23641635 G>A,C), RS1000664007 (14:23637000 T>C), RS1000722098 (14:23634392 G>A,T), RS1000874239 (14:23628201 C>A), RS1001436485 (14:23640828 G>C), RS1001547018 (14:23631473 C>G,T), RS1001589174 (14:23645831 G>A), RS1001606075 (14:23633111 C>G), RS1001721918 (14:23633310 C>T), RS1001836234 (14:23637161 C>G), RS1002025005 (14:23636061 C>G), RS1002050926 (14:23634923 C>T), RS1002088152 (14:23636641 C>T)

Disease associations

OMIM: gene MIM:615194 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects splicing	9
Valproic Acid	increases expression, affects expression, affects cotreatment	8
Estradiol	affects cotreatment, decreases expression, increases expression, decreases reaction	6
(+)-JQ1 compound	decreases expression, increases expression	5
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	5
Cyclosporine	decreases expression, increases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases expression	4
bisphenol A	increases expression, affects expression	3
Acetaminophen	decreases expression, increases expression	3
trichostatin A	increases expression	2
arsenite	increases expression, affects binding, increases reaction, increases abundance	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Arsenic	affects cotreatment, increases abundance, increases expression	2
Cisplatin	decreases expression, increases reaction	2
Copper	affects binding, decreases expression, increases expression	2
Coumestrol	affects cotreatment, increases expression, affects reaction	2
NADP	affects cotreatment, affects metabolic processing, affects binding, increases activity	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases expression, decreases response to substance	1
OTX015	increases expression	1
FR900359	decreases phosphorylation	1
mivebresib	increases expression	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1

Clinical trials (associated diseases)

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