ISG20

Summary

ISG20 (interferon stimulated exonuclease gene 20, HGNC:6130) is a protein-coding gene on chromosome 15q26.1, encoding Interferon-stimulated gene 20 kDa protein (Q96AZ6). Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA.

Enables 3’-5’ exonuclease activity and RNA binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and nucleobase-containing compound catabolic process. Located in cytoplasm and nuclear lumen.

Source: NCBI Gene 3669 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_002201

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6130
Approved symbol	ISG20
Name	interferon stimulated exonuclease gene 20
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	HEM45, CD25
Ensembl gene	ENSG00000172183
Ensembl biotype	protein_coding
OMIM	604533
Entrez	3669

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000306072, ENST00000379224, ENST00000546338, ENST00000557824, ENST00000558236, ENST00000558942, ENST00000558992, ENST00000559876, ENST00000560573, ENST00000560741, ENST00000560746, ENST00000890260, ENST00000890261, ENST00000890262, ENST00000890263, ENST00000890264, ENST00000890265, ENST00000890266, ENST00000890267, ENST00000949856, ENST00000949857, ENST00000949858, ENST00000949859

RefSeq mRNA: 5 — MANE Select: NM_002201 NM_001303233, NM_001303234, NM_001303236, NM_001303237, NM_002201

CCDS: CCDS10345, CCDS92053

Canonical transcript exons

ENST00000306072 — 4 exons

Exon	Start	End
ENSE00001480192	88655415	88656483
ENSE00001938266	88639016	88639076
ENSE00003619392	88652110	88652310
ENSE00003627798	88639343	88639594

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.0015 / max 1313.3385, expressed in 1354 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148297	22.2563	1010
148298	12.1151	878
148295	2.6870	522
148291	2.6598	128
148294	1.7237	593
148290	0.6416	89
148293	0.2903	130
148299	0.2596	131
148292	0.2392	107
148300	0.0903	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	97.66	gold quality
blood	UBERON:0000178	97.50	gold quality
granulocyte	CL:0000094	97.48	gold quality
lymph node	UBERON:0000029	96.90	gold quality
cartilage tissue	UBERON:0002418	96.63	gold quality
vermiform appendix	UBERON:0001154	96.57	gold quality
duodenum	UBERON:0002114	95.23	gold quality
jejunal mucosa	UBERON:0000399	95.03	gold quality
epithelium of nasopharynx	UBERON:0001951	95.00	gold quality
lower esophagus mucosa	UBERON:0035834	94.60	gold quality
right lung	UBERON:0002167	94.58	gold quality
bone marrow cell	CL:0002092	94.52	gold quality
gall bladder	UBERON:0002110	93.95	gold quality
upper lobe of left lung	UBERON:0008952	93.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.49	gold quality
palpebral conjunctiva	UBERON:0001812	93.44	gold quality
bone marrow	UBERON:0002371	93.20	gold quality
caecum	UBERON:0001153	93.02	gold quality
ileal mucosa	UBERON:0000331	92.61	gold quality
body of stomach	UBERON:0001161	92.59	gold quality
small intestine	UBERON:0002108	92.57	gold quality
upper lobe of lung	UBERON:0008948	92.53	gold quality
periodontal ligament	UBERON:0008266	92.37	gold quality
thymus	UBERON:0002370	92.24	gold quality
adenohypophysis	UBERON:0002196	91.50	gold quality
mucosa of transverse colon	UBERON:0004991	91.47	gold quality
left lobe of thyroid gland	UBERON:0001120	91.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.02	gold quality
tibial nerve	UBERON:0001323	90.54	gold quality
tonsil	UBERON:0002372	90.23	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-GEOD-139324	yes	1506.86
E-MTAB-9467	yes	1189.52
E-HCAD-9	yes	546.95
E-GEOD-135922	yes	414.65
E-MTAB-7052	yes	397.97
E-HCAD-15	yes	387.70
E-HCAD-1	yes	56.82
E-CURD-114	yes	45.87
E-MTAB-8410	yes	43.19
E-HCAD-6	yes	42.79
E-HCAD-4	yes	39.97
E-CURD-122	yes	36.62
E-HCAD-11	yes	22.87
E-CURD-46	yes	20.52
E-MTAB-6701	yes	16.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC, NFKB1, RELA, SP1, STAT1, USF1

miRNA regulators (miRDB)

32 targeting ISG20, 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-4531	99.99	69.70	3181
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-612	97.26	65.95	1597

Literature-anchored findings (GeneRIF, showing 23)

• ISG20has distinctive residues, Met14 and Arg53, to accommodate hydrogen bonds with the 2’-OH group of the UMP ribose, and these residues may be responsible for the preference of ISG20 for RNA substrates (PMID:15527770)
• ISG20 has a role in reducing the synthesis of HBV proteins (PMID:18278447)
• ISG20 inhibited infections by hepatitis C virus, bovine viral diarrhea virus and hepatitis A virus. Moreover, ISG20 demonstrated cell-type specific antiviral activity against yellow fever virus, a classical flavivirus. (PMID:21036379)
• The results suggest that hantavirus infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts. (PMID:23830076)
• these data provide a detailed explanation for the specific antiviral action of ISG20 and suggest that ISG20 may act as a promising antiviral drug candidate against IAV. (PMID:27342813)
• Interferon-stimulated gene of 20 kDa protein (ISG20) acts as an innate anti-HBV effector that selectively degrades hepatitis B virus (HBV) RNA and blocks replication of infectious HBV particles. (PMID:27626689)
• We discovered two genome-wide significant SNPs. The first was novel and near ISG20. The second was in TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. Motivated by our TRIOBP results, we also looked at exons in known hearing loss genes, and identified two additional SNPs, rs2877561 in ILDR1 and rs9493672 in EYA4 (at a significance threshold adjusted for number of SNPs in those regions). (PMID:27764096)
• Variation at rs12913965 may affect the risk for shoulder dislocation by affecting the activity of either TICRR or ISG20. (PMID:28521375)
• we have identified a novel mechanism involving ISG20 induction by T3 via the IL-8/p-JAK2/p-STAT3 signaling pathway to promote tumor angiogenesis in HCC. (PMID:29195126)
• In conclusion, the authors identified that the influenza A virus-upregulated Long noncoding RNA lnc-ISG20 is a novel interferon-stimulated gene that elicits its inhibitory effect on influenza A virus replication by enhancing ISG20 expression. They demonstrated that lnc-ISG20 functions as a competitive endogenous RNA to bind miR-326 to reduce its inhibition of ISG20 translation. (PMID:29899085)
• ISG20 and nuclear exosome promote destabilization of nascent transcripts for spliceosomal U snRNAs and U1 variants. (PMID:33147372)
• Host Interferon-Stimulated Gene 20 Inhibits Pseudorabies Virus Proliferation. (PMID:33830434)
• High expression of ISG20 predicts a poor prognosis in acute myeloid leukemia. (PMID:33896836)
• Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20. (PMID:33969602)
• Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection. (PMID:34405956)
• The regulation of ISG20 expression on SARS-CoV-2 infection in cancer patients and healthy individuals. (PMID:36177004)
• Internal RNA 2’O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect. (PMID:36354007)
• Characterization of the induction kinetics and antiviral functions of IRF1, ISG15 and ISG20 in cells infected with gammacoronavirus avian infectious bronchitis virus. (PMID:37058744)
• Expression of interferon-stimulated gene 20 (ISG20), an antiviral effector protein, in glomerular endothelial cells: possible involvement of ISG20 in lupus nephritis. (PMID:37340981)
• ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer. (PMID:37342328)
• Causal relationships between CD25 on immune cells and hip osteoarthritis. (PMID:37731506)
• The PTPRZ1-MET/STAT3/ISG20 axis in glioma stem-like cells modulates tumor-associated macrophage polarization. (PMID:38685521)
• FOSL2-mediated transcription of ISG20 induces M2 polarization of macrophages and enhances tumorigenic ability of glioblastoma cells. (PMID:39073688)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	isg20l2	ENSDARG00000102266
mus_musculus	Isg20	ENSMUSG00000039236
rattus_norvegicus	Isg20	ENSRNOG00000054561

Paralogs (5): REXO5 (ENSG00000005189), REXO1 (ENSG00000079313), ISG20L2 (ENSG00000143319), REXO4 (ENSG00000148300), AEN (ENSG00000181026)

Protein

Protein identifiers

Interferon-stimulated gene 20 kDa protein — Q96AZ6 (reviewed: Q96AZ6)

Alternative names: Estrogen-regulated transcript 45 protein, Promyelocytic leukemia nuclear body-associated protein ISG20

All UniProt accessions (3): Q96AZ6, H0YMM4, H3BLY5

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA. Exhibits antiviral activity against RNA viruses including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV). Inhibition of several viruses such as chikungunya virus (CHIKV) does not involve the degradation of viral RNAs, but rather the inhibition of translation of viral proteins. Exerts a translational control over a large panel of non-self RNA substrates while sparing endogenous transcripts. This activity correlates with the protein’s ability to localize in cytoplasmic processing bodies. May also act as master regulator of over hundred interferon stimulated genes leading to viral genome translation inhibition. May play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis.

Subunit / interactions. Associates with PML and SP100 in the PML NB complex. Associates with survival motor neuron protein (SMN)-containing macromolecular nuclear complexes and U1 and U2 snRNAs and U3 snoRNA.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cajal body. P-body.

Tissue specificity. Highly expressed in peripheral blood leukocytes, spleen, thymus, colon and lung. Up regulated by E2 in estrogen receptor-positive breast cancer lines.

Cofactor. Binds 2 manganese ions per subunit.

Induction. Induced by interferons alpha and beta. Weaker induction was seen with interferon gamma. Increased expression was seen at the transcriptional level.

Similarity. Belongs to the exonuclease superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96AZ6-1	1	yes
Q96AZ6-2	2

RefSeq proteins (5): NP_001290162, NP_001290163, NP_001290165, NP_001290166, NP_002192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR013520	Ribonucl_H	Domain
IPR036397	RNaseH_sf	Homologous_superfamily
IPR047021	REXO1/3/4-like	Family

Pfam: PF00929

UniProt features (23 total): helix 8, strand 6, binding site 5, splice variant 2, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1WLJ	X-RAY DIFFRACTION	1.9
7UGB	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AZ6-F1	95.61	0.94

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 11; 13; 90; 93; 154

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 563 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BROWNE_HCMV_INFECTION_8HR_UP, GOMF_NUCLEASE_ACTIVITY, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_45, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP

GO Biological Process (10): DNA catabolic process (GO:0006308), rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401), response to virus (GO:0009615), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), defense response to virus (GO:0051607), immune system process (GO:0002376), DNA metabolic process (GO:0006259)

GO Molecular Function (12): 3’-5’-RNA exonuclease activity (GO:0000175), exonuclease activity (GO:0004527), single-stranded DNA 3’-5’ DNA exonuclease activity (GO:0008310), exoribonuclease II activity (GO:0008859), U1 snRNA binding (GO:0030619), U2 snRNA binding (GO:0030620), U3 snoRNA binding (GO:0034511), metal ion binding (GO:0046872), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), nuclease activity (GO:0004518), hydrolase activity (GO:0016787)

GO Cellular Component (7): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Cajal body (GO:0015030), PML body (GO:0016605)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Interferon Signaling	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleic acid catabolic process	2
snRNA binding	2
nuclear lumen	2
cellular anatomical structure	2
DNA nuclease activity	1
DNA metabolic process	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
response to other organism	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
biological_process	1
nucleic acid metabolic process	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
3’-5’-DNA exonuclease activity	1
single-stranded DNA exodeoxyribonuclease activity	1
3’-5’-RNA exonuclease activity	1
snoRNA binding	1
cation binding	1
binding	1
nucleic acid binding	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISG20	ISG15	P05161	818
ISG20	IFIT2	P09913	766
ISG20	GBP1	P32455	739
ISG20	CALCOCO2	Q13137	724
ISG20	IFIT1	P09914	720
ISG20	MX1	P20591	713
ISG20	IFNB1	P01574	694
ISG20	OAS2	P29728	693
ISG20	IFIH1	Q9BYX4	688
ISG20	RSAD2	Q8WXG1	685
ISG20	SP100	P23497	677
ISG20	OAS1	P00973	666
ISG20	CXCL10	P02778	654
ISG20	MX2	P20592	642
ISG20	IRF7	Q92985	642

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ISG20	SRC	psi-mi:“MI:0914”(association)	0.350
PLXNB1	HBB	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): EEPD1 (Affinity Capture-MS), PTPRG (Affinity Capture-MS), SRC (Affinity Capture-MS), EFR3A (Affinity Capture-MS), ERICH5 (Affinity Capture-MS), GNAZ (Affinity Capture-MS), CSNK1G3 (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), NCAM1 (Affinity Capture-MS), GNAQ (Affinity Capture-MS), ISG20 (Proximity Label-MS), ISG20 (Affinity Capture-RNA), ISG20 (Affinity Capture-MS), EEPD1 (Affinity Capture-MS), SRC (Affinity Capture-MS)

ESM2 similar proteins: A4II96, B2RXZ1, B8BBT7, O64773, O65583, O80902, O94375, P07953, P0C5A1, P16118, P25114, P49872, P70266, Q00IB6, Q08BM8, Q16875, Q16877, Q17345, Q17819, Q28901, Q3KQ85, Q3ZC01, Q4R8B6, Q556Y2, Q5JLQ9, Q5R9C1, Q5ZJV9, Q60809, Q66UW5, Q6BIK6, Q6DTY7, Q6IDB6, Q80VY9, Q852Q1, Q8R0F9, Q91348, Q91WL8, Q96AZ6, Q9D8X5, Q9FKS0

Diamond homologs: A1A5R7, A3KPE8, B2GUW6, G0SAK8, O94375, O94443, P0CQ44, P0CQ45, P48778, P53331, Q08237, Q10124, Q12090, Q2T9U5, Q2YDK1, Q3U1G5, Q4IEV5, Q4PER6, Q4R9F7, Q5A3Q0, Q5AL29, Q5B367, Q5F450, Q5REE2, Q66UW5, Q6AXU3, Q6BIK6, Q6CE69, Q6CFE7, Q6CJB5, Q6CMT3, Q6DEW6, Q6FIU7, Q6FQA0, Q6PAQ4, Q750A5, Q757I9, Q7S9B7, Q7TT28, Q8IX06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	3
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1041 predictions. Top by Δscore:

Variant	Effect	Δscore
15:88636288:TAAAG:T	donor_loss	0.9900
15:88636289:AAAGG:A	donor_loss	0.9900
15:88636290:AAGG:A	donor_loss	0.9900
15:88636293:GTA:G	donor_loss	0.9900
15:88636294:T:G	donor_loss	0.9900
15:88652308:CAGG:C	donor_loss	0.9800
15:88652309:AGGTG:A	donor_loss	0.9800
15:88652310:GGT:G	donor_loss	0.9800
15:88652312:T:A	donor_loss	0.9800
15:88636287:T:G	donor_gain	0.9700
15:88636422:GGTTC:G	donor_gain	0.9700
15:88655413:A:AG	acceptor_gain	0.9700
15:88655414:G:GG	acceptor_gain	0.9700
15:88655414:GAACA:G	acceptor_gain	0.9700
15:88652103:T:TA	acceptor_gain	0.9600
15:88655412:CAGAA:C	acceptor_loss	0.9600
15:88655413:AGAAC:A	acceptor_loss	0.9600
15:88655414:G:A	acceptor_loss	0.9600
15:88639342:GC:G	acceptor_gain	0.9500
15:88639452:GCCTC:G	acceptor_gain	0.9500
15:88639341:A:AG	acceptor_gain	0.9400
15:88639342:G:GG	acceptor_gain	0.9400
15:88639342:GCAT:G	acceptor_gain	0.9400
15:88655414:GAAC:G	acceptor_gain	0.9400
15:88655414:GA:G	acceptor_gain	0.9300
15:88639468:C:CA	acceptor_gain	0.9200
15:88639534:C:A	donor_gain	0.9200
15:88636259:G:GT	donor_gain	0.9100
15:88639590:TAGAG:T	donor_loss	0.9100
15:88639591:AGAGG:A	donor_loss	0.9100

AlphaMissense

1170 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:88639399:C:A	D11E	0.995
15:88639399:C:G	D11E	0.995
15:88655447:T:A	D154E	0.993
15:88655447:T:G	D154E	0.993
15:88652162:A:T	D94V	0.992
15:88652163:C:A	D94E	0.992
15:88652163:C:G	D94E	0.992
15:88652162:A:C	D94A	0.991
15:88639451:A:C	S29R	0.990
15:88639453:C:A	S29R	0.990
15:88639453:C:G	S29R	0.990
15:88655446:A:C	D154A	0.990
15:88655445:G:C	D154H	0.989
15:88652162:A:G	D94G	0.987
15:88655454:G:C	A157P	0.987
15:88639398:A:T	D11V	0.986
15:88639405:G:C	E13D	0.985
15:88639405:G:T	E13D	0.985
15:88639448:T:C	C28R	0.985
15:88655446:A:T	D154V	0.985
15:88639398:A:C	D11A	0.984
15:88639404:A:T	E13V	0.984
15:88639450:C:G	C28W	0.984
15:88655432:C:A	H149Q	0.983
15:88655432:C:G	H149Q	0.983
15:88639397:G:C	D11H	0.982
15:88639535:A:C	S57R	0.982
15:88639537:C:A	S57R	0.982
15:88639537:C:G	S57R	0.982
15:88652310:G:C	Q143H	0.982

dbSNP variants (sampled 300 via entrez): RS1000119046 (15:88656015 C>A,G), RS1000245559 (15:88645281 C>T), RS1000298002 (15:88645031 AGAG>A), RS1000420011 (15:88639263 G>C), RS1000465614 (15:88635377 C>T), RS1000555561 (15:88655652 C>T), RS1000747560 (15:88634348 A>C,G), RS1000816335 (15:88635617 T>C), RS1000825631 (15:88635467 G>A), RS1001137910 (15:88644224 G>A,T), RS1001202622 (15:88634183 G>T), RS1001209725 (15:88638426 C>A), RS1001352756 (15:88634809 C>T), RS1001406654 (15:88634592 T>C), RS1001463258 (15:88644589 G>A,C)

Disease associations

OMIM: gene MIM:604533 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001144_8	Dupuytren’s disease	8.000000e-07
GCST001762_93	Obesity-related traits	5.000000e-06
GCST003542_130	Night sleep phenotypes	9.000000e-06
GCST003763_1	Age-related hearing impairment	3.000000e-13
GCST003763_3	Age-related hearing impairment	4.000000e-11
GCST004858_21	Dupuytren’s disease	7.000000e-17
GCST008898_1	Adult hearing aid use	6.000000e-07
GCST008899_2	Adult hearing difficulty	5.000000e-07
GCST009432_5	Age-related hearing impairment (low/mid frequency)	3.000000e-06
GCST010317_4	Serum omega-6 polyunsaturated fatty acid concentration in metabolic syndrome	9.000000e-06
GCST010319_2	Serum total polyunsaturated fatty acid concentration in metabolic syndrome	7.000000e-06
GCST012227_258	Hip circumference adjusted for BMI	6.000000e-11
GCST012442_28	Age-related hearing impairment	6.000000e-13
GCST90002390_427	Mean corpuscular hemoglobin	3.000000e-09
GCST90020028_1444	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0006335	systolic blood pressure
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0010733	polyunsaturated fatty acid measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression, increases reaction, affects expression	5
Cyclosporine	affects expression, decreases methylation, increases expression	5
bisphenol A	decreases expression, affects expression, increases expression, affects cotreatment, decreases methylation	4
Benzo(a)pyrene	increases expression, increases methylation, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Silicon Dioxide	decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	2
Acetaminophen	increases expression, decreases expression	2
Nickel	increases expression	2
Ozone	affects cotreatment, increases expression, decreases expression	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	affects expression, increases expression	2
Aflatoxin B1	increases expression, affects expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
TL8-506	increases expression, affects cotreatment	1
bufotalin	decreases expression	1
triphenyl phosphate	affects expression	1
senecionine	increases expression	1
senkirkine	increases expression	1
heliotrine	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
1,6-hexamethylene diisocyanate	increases methylation	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
tanshinone	increases expression	1
nickel chloride	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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