CXCL3

Summary

CXCL3 (C-X-C motif chemokine ligand 3, HGNC:4604) is a protein-coding gene on chromosome 4q13.3, encoding C-X-C motif chemokine 3 (P19876). Ligand for CXCR2.

This antimicrobial gene encodes a member of the CXC subfamily of chemokines. The encoded protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2. This protein plays a role in inflammation and as a chemoattractant for neutrophils.

Source: NCBI Gene 2921 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total — 1 likely-pathogenic
• MANE Select transcript: NM_002090

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4604
Approved symbol	CXCL3
Name	C-X-C motif chemokine ligand 3
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB3, GROg, MIP-2b, CINC-2b
Ensembl gene	ENSG00000163734
Ensembl biotype	protein_coding
OMIM	139111
Entrez	2921

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000296026, ENST00000502974, ENST00000510390, ENST00000511669

RefSeq mRNA: 1 — MANE Select: NM_002090 NM_002090

CCDS: CCDS34007

Canonical transcript exons

ENST00000296026 — 4 exons

Exon	Start	End
ENSE00001210973	74036589	74037277
ENSE00002492744	74038512	74038689
ENSE00003621163	74038290	74038413
ENSE00003694657	74038093	74038176

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 94.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.2036 / max 3236.9159, expressed in 1149 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52549	44.9901	1005
52553	1.0014	403
52550	0.2121	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	94.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.75	gold quality
pylorus	UBERON:0001166	86.55	gold quality
epithelial cell of pancreas	CL:0000083	85.02	gold quality
vermiform appendix	UBERON:0001154	83.85	gold quality
upper lobe of left lung	UBERON:0008952	83.77	gold quality
rectum	UBERON:0001052	83.33	gold quality
upper lobe of lung	UBERON:0008948	82.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.81	gold quality
islet of Langerhans	UBERON:0000006	80.55	gold quality
vena cava	UBERON:0004087	79.76	gold quality
lung	UBERON:0002048	79.38	gold quality
gall bladder	UBERON:0002110	78.62	gold quality
lower lobe of lung	UBERON:0008949	78.42	silver quality
right lung	UBERON:0002167	78.08	gold quality
palpebral conjunctiva	UBERON:0001812	76.79	gold quality
body of stomach	UBERON:0001161	76.30	gold quality
granulocyte	CL:0000094	76.29	gold quality
caecum	UBERON:0001153	76.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.82	silver quality
monocyte	CL:0000576	75.72	gold quality
mucosa of stomach	UBERON:0001199	75.62	gold quality
endothelial cell	CL:0000115	75.61	silver quality
mononuclear cell	CL:0000842	75.20	gold quality
pleura	UBERON:0000977	74.98	gold quality
visceral pleura	UBERON:0002401	74.89	gold quality
parietal pleura	UBERON:0002400	74.78	gold quality
leukocyte	CL:0000738	74.59	gold quality
omental fat pad	UBERON:0010414	74.37	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-36	yes	8012.88
E-HCAD-29	yes	6063.44
E-MTAB-7052	yes	4873.28
E-MTAB-6308	yes	4056.81
E-CURD-122	yes	65.66
E-MTAB-8142	yes	45.81
E-CURD-46	yes	21.42
E-CURD-114	yes	20.73
E-MTAB-9801	yes	5.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, FOXL2, HSF1, NFKB1, PPARG, RELA, XBP1

miRNA regulators (miRDB)

42 targeting CXCL3, 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-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258

Literature-anchored findings (GeneRIF, showing 35)

• CXCL3 displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• demonstrates, for the first time, that BIRC3 (anti-apoptotic protein), COL3A1 (matrix protein synthesis), and CXCL3 (chemokine) were up-regulated in the thrombin-stimulated human umbilical vein endothelial cells (PMID:16356540)
• GRO-gamma is a promising candidate for Th2-associated glomerular permeability factor in minimal change disease. (PMID:17389786)
• Inhibition of ERK phosphorylation decreased expression of GRO3. (PMID:17466952)
• Report gonadotropin-releasing hormone-regulated CXCL3 expression in human placentation. (PMID:19369450)
• propose that chemokines belonging to the CXC family could play an important role in the etiology of tendon xanthoma (TX), with CXCL3 being a possible biological marker of onset and development of TX (PMID:19448742)
• overexpression of CXCL13 in the intestine during inflammatory conditions favors mobilization of B cells and of LTi and NK cells with immunomodulatory and reparative functions. (PMID:19741597)
• A significantly increased expression of GRO-2, GRO-3, and IL-8 in colon carcinoma as compared to normal tissue, is reported. (PMID:20162422)
• Data show that mesenchymal stem cells (MSCs) directly regulate T cell proliferation by induction of CXCL3 chemokine and its receptor, CXCR2 on the surface in T cells. (PMID:23023221)
• This study demonistrated that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL11, absent from normal muscle fibers, were induced in DMD myofibers. (PMID:23225384)
• secreted growth-regulated oncogene chemokines, specifically GRO-gamma, in human Mesenchymal stromal cell-conditioned media have an effect on the differentiation and the function of human monocyte-derived dendritic cells. (PMID:23589610)
• our results demonstrate the diverse mechanisms by which CXCL2 and CXCL3 mediate normal and asthmatic airway smooth muscle cell migration (PMID:23904157)
• results support a functional role of CXCL3 in breast cancer metastasis and as a viable target for cancer therapy (PMID:24605943)
• Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis. (PMID:26837773)
• Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression. (PMID:27255419)
• This report demonstrates that Cxcl3 induces the migration of normal and neoplastic cerebellar precursor cells (GCPs) from the surface to the internal part of the cerebellum, a region where the GCPs differentiate, thus exiting the neoplastic program. In this way Cxcl3 counteracts the growth of medulloblastoma, tumor of the cerebellum originating from the GCPs. (PMID:28018222)
• The studies revealed that, although overall structural and oligomerization features of CXCL3 and CXCL2 are similar, prominent differences were observed in their surface characteristics, thus implicating a functional divergence. (PMID:28928065)
• CXCL3 exerts its carcinogenic potential by directly and/or indirectly regulating the downstream signaling pathways and the expression of transcription factors in PCa. (PMID:29524043)
• Migration, invasion, proliferation and tube-formation capability of HTR-8/SVneo trophoblast cells transfected with siRNA-CXCL3 were suppressed by down-regulation of CXCL3, while those behaviors of HTR-8/SVneo cells transfected with pEZ-CXCL3 were enhanced by upregulation of CXCL3. Nevertheless, the apoptosis of HTR-8/SVneo cells was not affected by either siRNA or overexpression plasmid. (PMID:29884302)
• hydrophobic pocket is in the vicinity of GAG binding region of CXCL3, a molecular determinant in leukocyte trafficking (PMID:30528777)
• Study demonstrated that CXCL3 is not only considerably upregulated in colon cancer (CC) tumor tissue but also has potential diagnostic value in patients with CC. Survival analysis suggested that CXCL3 may serve as a potential prognostic biomarker in CC. (PMID:31545503)
• CXCL3 overexpression promotes the tumorigenic potential of uterine cervical cancer cells via the MAPK/ERK pathway. (PMID:31667838)
• Gene expression and methylation profiles identified CXCL3 and CXCL8 as key genes for diagnosis and prognosis of colon adenocarcinoma. (PMID:31709538)
• Relationship between polymorphisms of CXCL3 gene and preeclampsia. (PMID:31931644)
• CX3 CL1 promotes tumour cell by inducing tyrosine phosphorylation of cortactin in lung cancer. (PMID:33191645)
• Inflammatory cell-derived CXCL3 promotes pancreatic cancer metastasis through a novel myofibroblast-hijacked cancer escape mechanism. (PMID:33568427)
• Expression levels of chemokine (C-X-C motif) ligands CXCL1 and CXCL3 as prognostic biomarkers in rectal adenocarcinoma: evidence from Gene Expression Omnibus (GEO) analyses. (PMID:34269159)
• CXCL3 overexpression affects the malignant behavior of oral squamous cell carcinoma cells via the MAPK signaling pathway. (PMID:34392586)
• Clinical significance and biological functions of chemokine CXCL3 in head and neck squamous cell carcinoma. (PMID:34870709)
• Tumor suppressive lncRNA MEG3 binds to EZH2 and enhances CXCL3 methylation in gallbladder cancer. (PMID:35188401)
• Plasma CXCL3 Levels Are Associated with Tumor Progression and an Unfavorable Colorectal Cancer Prognosis. (PMID:35664357)
• Knockdown of CXCL3-inhibited apoptosis and inflammation in lipopolysaccharide-treated BEAS-2B and HPAEC through inactivating MAPKs pathway. (PMID:35789398)
• Chronic restraint stress promotes the tumorigenic potential of oral squamous cell carcinoma cells by reprogramming fatty acid metabolism via CXCL3 mediated Wnt/beta-catenin pathway. (PMID:36343679)
• Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner. (PMID:38031087)
• Comprehensive analysis of the clinical and biological significances for chemokine CXCL3 in cholangiocarcinoma. (PMID:38489741)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cxcl3	ENSMUSG00000029379
mus_musculus	Cxcl1	ENSMUSG00000029380
mus_musculus	Cxcl2	ENSMUSG00000058427
rattus_norvegicus	Cxcl2	ENSRNOG00000002792
rattus_norvegicus	Cxcl1	ENSRNOG00000002802
rattus_norvegicus	Cxcl3	ENSRNOG00000028043

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

C-X-C motif chemokine 3 — P19876 (reviewed: P19876)

Alternative names: GRO-gamma(1-73), Growth-regulated protein gamma, Macrophage inflammatory protein 2-beta

All UniProt accessions (1): P19876

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for CXCR2. Has chemotactic activity for neutrophils. May play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion. In vitro, the processed form GRO-gamma(5-73) shows a fivefold higher chemotactic activity for neutrophilic granulocytes.

Subcellular location. Secreted.

Post-translational modifications. N-terminal processed form GRO-gamma(5-73) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (1): NP_002081* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001089	Chemokine_CXC	Family
IPR001811	Chemokine_IL8-like_dom	Domain
IPR018048	Chemokine_CXC_CS	Conserved_site
IPR033899	CXC_Chemokine_domain	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (13 total): strand 4, chain 2, helix 2, disulfide bond 2, signal peptide 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8XX3	ELECTRON MICROSCOPY	3.38
8XWF	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19876-F1	82.50	0.50

Antibody-complex structures (SAbDab): 1 — 8XX3

Functional residue map

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

Disulfide bonds (2): 43–69, 45–85

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 420 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, HALMOS_CEBPA_TARGETS_UP, SOUCEK_MYC_TARGETS, GAURNIER_PSMD4_TARGETS, HNF1_Q6, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN

GO Biological Process (6): inflammatory response (GO:0006954), immune response (GO:0006955), neutrophil chemotaxis (GO:0030593), chemotaxis (GO:0006935), defense response (GO:0006952), signal transduction (GO:0007165)

GO Molecular Function (2): chemokine activity (GO:0008009), cytokine activity (GO:0005125)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	1
immune system process	1
response to stimulus	1
granulocyte chemotaxis	1
neutrophil migration	1
response to chemical	1
taxis	1
response to stress	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
receptor ligand activity	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL3	CXCR2	P25025	997
CXCL3	CXCR1	P25024	963
CXCL3	CXCL10	P02778	938
CXCL3	CXCL11	O14625	927
CXCL3	IL1A	P01583	820
CXCL3	CXCR4	P30991	802
CXCL3	CCL20	P78556	802
CXCL3	IL1B	P01584	787
CXCL3	CCL2	P13500	777
CXCL3	CXCL14	O95715	768
CXCL3	CXCL5	P42830	744
CXCL3	CCR7	P32248	728
CXCL3	CXCR3	P49682	714
CXCL3	CCL18	P55774	714
CXCL3	CXCL12	P48061	708

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CXCL3	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL3	XCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL3	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL3	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL1	psi-mi:“MI:0914”(association)	0.350
CXCL3	CXCL1	psi-mi:“MI:0914”(association)	0.350
CXCL3	IFI30	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): CCL11 (Reconstituted Complex), CXCL5 (Reconstituted Complex), CXCL6 (Reconstituted Complex), XCL2 (Reconstituted Complex), TRAF2 (Affinity Capture-MS), CXCL3 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), CXCL1 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), IFI30 (Affinity Capture-MS), CXCL2 (Affinity Capture-MS), CXCL3 (Proximity Label-MS)

ESM2 similar proteins: A9QWQ1, O14625, O46675, O46676, O46677, O46678, O89098, O97919, P08317, P09340, P09341, P10147, P10855, P10889, P12850, P13236, P13501, P14095, P14097, P16619, P19875, P19876, P30782, P30882, P42831, P46632, P47854, P50229, P50230, P50231, P97272, Q17QA1, Q5EBF6, Q5I1Z0, Q5RA36, Q68A92, Q68AZ0, Q711P4, Q8HYQ1, Q8HYQ2

Diamond homologs: A0A0R4INB9, A9QWP9, A9QWQ1, B0R191, O14625, O46678, P02775, P02778, P08317, P09341, P12850, P17515, P19875, P19876, P22952, P42830, P48973, P50228, P80162, P80221, P82535, P97885, Q07325, Q2KIQ8, Q5KSV9, Q865F5, Q8MIZ1, Q9JHH5, O46675, O46676, O46677, O55235, O62812, P02776, P06765, P09340, P10145, P10720, P10889, P14095

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CXCL3	“up-regulates activity”	CXCR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
148549	GRCh38/hg38 4q13.2-13.3(chr4:67799665-74240920)x1	Likely pathogenic

SpliceAI

278 predictions. Top by Δscore:

Variant	Effect	Δscore
4:74038091:A:AC	donor_gain	1.0000
4:74038092:C:CC	donor_gain	1.0000
4:74038172:TGGCT:T	acceptor_gain	1.0000
4:74038173:GGCT:G	acceptor_gain	1.0000
4:74038174:GCT:G	acceptor_gain	1.0000
4:74038175:CT:C	acceptor_gain	1.0000
4:74038175:CTC:C	acceptor_gain	1.0000
4:74038175:CTCT:C	acceptor_loss	1.0000
4:74038176:TCT:T	acceptor_gain	1.0000
4:74038176:TCTGC:T	acceptor_loss	1.0000
4:74038177:C:CC	acceptor_gain	1.0000
4:74038177:C:G	acceptor_gain	1.0000
4:74038180:C:CT	acceptor_gain	1.0000
4:74038288:A:AC	donor_gain	1.0000
4:74038289:C:CC	donor_gain	1.0000
4:74038289:CATGA:C	donor_gain	1.0000
4:74038409:CGCTC:C	acceptor_gain	1.0000
4:74038411:CTC:C	acceptor_gain	1.0000
4:74038412:TC:T	acceptor_gain	1.0000
4:74038413:CC:C	acceptor_gain	1.0000
4:74038414:C:CC	acceptor_gain	1.0000
4:74038414:CTA:C	acceptor_loss	1.0000
4:74038507:CCCA:C	donor_loss	1.0000
4:74038509:CA:C	donor_loss	1.0000
4:74038510:A:C	donor_loss	1.0000
4:74038511:CCTG:C	donor_gain	1.0000
4:74038086:AACTC:A	donor_loss	0.9900
4:74038087:ACTCA:A	donor_loss	0.9900
4:74038088:CT:C	donor_loss	0.9900
4:74038089:TCAC:T	donor_loss	0.9900

AlphaMissense

680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:74038174:G:T	A76D	0.991
4:74038144:A:T	L86H	0.976
4:74038293:A:T	V74D	0.971
4:74038344:A:T	I57N	0.969
4:74038308:C:G	C69S	0.967
4:74038309:A:T	C69S	0.967
4:74038344:A:C	I57S	0.966
4:74038344:A:G	I57T	0.966
4:74038147:C:G	C85S	0.965
4:74038148:A:T	C85S	0.965
4:74038380:C:G	C45S	0.962
4:74038381:A:T	C45S	0.962
4:74038386:C:G	C43S	0.956
4:74038387:A:T	C43S	0.956
4:74038148:A:G	C85R	0.955
4:74038307:G:C	C69W	0.951
4:74038308:C:T	C69Y	0.951
4:74038335:A:T	V60E	0.951
4:74038309:A:G	C69R	0.949
4:74038387:A:G	C43R	0.949
4:74038381:A:G	C45R	0.948
4:74038144:A:G	L86P	0.945
4:74038296:T:C	E73G	0.940
4:74038175:C:G	A76P	0.939
4:74038146:A:C	C85W	0.934
4:74038295:T:A	E73D	0.932
4:74038295:T:G	E73D	0.932
4:74038308:C:A	C69F	0.929
4:74038147:C:T	C85Y	0.928
4:74038168:A:G	L78P	0.927

dbSNP variants (sampled 300 via entrez): RS1000284139 (4:74039924 G>T), RS1000802322 (4:74040265 A>G), RS1001479805 (4:74037534 T>C), RS1003633939 (4:74037038 T>A), RS1004470332 (4:74039448 T>C), RS1004759988 (4:74039047 C>A), RS1005837867 (4:74038735 G>A,C,T), RS1005934645 (4:74036252 A>G), RS1006141022 (4:74039997 C>T), RS1006165215 (4:74040269 C>T), RS1007598071 (4:74039426 A>G), RS1007705171 (4:74036293 T>A,C), RS1007819577 (4:74036596 T>C), RS1008018361 (4:74036951 C>T), RS1008704761 (4:74037679 A>G)

Disease associations

OMIM: gene MIM:139111 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST002826_4	Urate levels (BMI interaction)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression	6
Particulate Matter	increases abundance, increases expression, decreases expression	5
Lipopolysaccharides	increases expression, affects expression, affects response to substance, affects cotreatment, decreases reaction	4
Silicon Dioxide	increases expression	4
Benzo(a)pyrene	increases expression, increases methylation, decreases expression	3
Cannabidiol	decreases reaction, increases expression	3
Methotrexate	decreases expression, increases expression	3
Valproic Acid	affects expression, decreases methylation, increases expression	3
Asbestos, Crocidolite	increases expression	3
1-nitropyrene	increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Air Pollutants	increases expression, increases abundance	2
Cadmium	increases expression	2
Dexamethasone	decreases expression, affects cotreatment	2
Estradiol	affects expression, decreases expression	2
Piroxicam	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
huai qi huang	decreases reaction, increases expression	1
Glupearl 19S	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
Asian ginseng	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
primycin	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1

Clinical trials (associated diseases)

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