CXCL6

Summary

CXCL6 (C-X-C motif chemokine ligand 6, HGNC:10643) is a protein-coding gene on chromosome 4q13.3, encoding C-X-C motif chemokine 6 (P80162). Chemotactic for neutrophil granulocytes.

The protein encoded by this gene is a member CXC chemokine family. The encoded protein is a chemotactic for neutrophil granulocytes and has antibacterial action against gram-negative and gram-positive bacteria. This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q.

Source: NCBI Gene 6372 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_002993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10643
Approved symbol	CXCL6
Name	C-X-C motif chemokine ligand 6
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	GCP-2, CKA-3
Ensembl gene	ENSG00000124875
Ensembl biotype	protein_coding
OMIM	138965
Entrez	6372

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000226317, ENST00000503446, ENST00000515050

RefSeq mRNA: 1 — MANE Select: NM_002993 NM_002993

CCDS: CCDS3560

Canonical transcript exons

ENST00000226317 — 4 exons

Exon	Start	End
ENSE00000851055	73837623	73838760
ENSE00002066065	73836678	73836859
ENSE00002439231	73836964	73837096
ENSE00002452663	73837203	73837286

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.38.

FANTOM5 (CAGE): breadth broad, TPM avg 83.8928 / max 6536.4554, expressed in 601 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48216	83.3232	592
48217	0.4833	143
48218	0.0863	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.38	gold quality
palpebral conjunctiva	UBERON:0001812	96.37	gold quality
spleen	UBERON:0002106	95.29	gold quality
epithelium of bronchus	UBERON:0002031	94.51	gold quality
bronchus	UBERON:0002185	93.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.65	gold quality
cartilage tissue	UBERON:0002418	91.40	gold quality
islet of Langerhans	UBERON:0000006	89.22	gold quality
type B pancreatic cell	CL:0000169	88.42	gold quality
parietal pleura	UBERON:0002400	87.92	gold quality
jejunal mucosa	UBERON:0000399	87.17	gold quality
epithelial cell of pancreas	CL:0000083	85.79	gold quality
sperm	CL:0000019	85.40	gold quality
nasal cavity epithelium	UBERON:0005384	85.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.10	gold quality
gall bladder	UBERON:0002110	83.73	gold quality
nasal cavity mucosa	UBERON:0001826	83.30	gold quality
periodontal ligament	UBERON:0008266	83.12	gold quality
germinal epithelium of ovary	UBERON:0001304	82.61	gold quality
male germ cell	CL:0000015	82.41	gold quality
vermiform appendix	UBERON:0001154	78.25	gold quality
duodenum	UBERON:0002114	77.28	gold quality
pleura	UBERON:0000977	76.31	gold quality
pancreas	UBERON:0001264	76.28	gold quality
mucosa of paranasal sinus	UBERON:0005030	76.01	gold quality
seminal vesicle	UBERON:0000998	75.29	gold quality
jejunum	UBERON:0002115	73.79	gold quality
pancreatic ductal cell	CL:0002079	73.71	silver quality
epithelium of nasopharynx	UBERON:0001951	72.31	gold quality
caecum	UBERON:0001153	71.90	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7249	yes	1666.30
E-MTAB-8559	yes	943.36
E-GEOD-86618	yes	470.44
E-MTAB-10553	yes	21.27
E-GEOD-83139	yes	11.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FLI1, HIF1A, PITX2, VDR

miRNA regulators (miRDB)

88 targeting CXCL6, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-548D-3P	99.87	70.67	4362

Literature-anchored findings (GeneRIF, showing 34)

• results suggest that granulocyte chemotactic protein-2 is an additional ELR(+)-CXC chemokine expressed in endometrial stromal cells (PMID:12524079)
• induction in mesenchymal cells by interleukin-1beta and down-regulation by interferon-gamma (PMID:12533683)
• Neutrophil recruitment to inflammatory sites is mediated by two related receptors: CXCR1 and CXCR2. Both receptors share two ligands, interleukin-8 (CXCL8) and GCP-2 (CXCL6). (PMID:12628493)
• expression in inflamed intestinal tissue in Crohn’s disease (PMID:15214047)
• production of GCP-2 by endothelial cells within the tumor can contribute to tumor development through neovascularization due to endothelial cell chemotaxis and to tumor cell invasion and metastasis (PMID:15652347)
• LDL lipoprotein subunit L5 induces human umbilical vein endothelial cells (HUVEC) to express CXCL6. (PMID:17022986)
• These findings indicate that the equilibrium between angiostatic and angiogenic factors during inflammation and tumor progression is rather complex and differs depending on the chemokine, cell type, and stimulus. (PMID:17827342)
• These observations suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity. (PMID:18782286)
• The level of expression of granulocyte chemotactic protein 2 correlates with the severity of periodontitis and appears to act as a yet unrecognized functional adjunct to interleukin-8 in pathological gingival tissues. (PMID:18842116)
• Report gonadotropin-releasing hormone-regulated CXCL6 expression in human placentation. (PMID:19369450)
• The aim of this study was to investigate the role of the transcription factors, AP-1 and NF-kappaB, in IL-6 and CXCL8 regulation in Jurkat T-cells. (PMID:20507572)
• Studies show that functional blocking of GCP-2 inhibits tumor growth and metastases. (PMID:21236563)
• Overexpression of GCP-2 in mesenchymal stem cells has the potential to enhance their angiogenic and survival properties. (PMID:22886775)
• Data suggest that expression of CXCL6 in trophoblasts is up-regulated during pregnancy development/placentation; CXCL6 expression inhibits trophoblast cell migration and invasion by down-regulating activity of MMP2 (matrix metalloproteinase 2). (PMID:23814098)
• Expression of the CXCL8, CXCL6 and CXCL1 genes are under the primary control of 1,25-dihydroxyvitamin D3 and its receptor. (PMID:24250750)
• HIF-1alpha promotes HCC progression and metastasis by upregulating CXCL6 transcription in HCC cells. (PMID:25323032)
• The neutrophil-recruiting chemokine GCP-2/CXCL6 is expressed in cystic fibrosis airways and retains its functional properties after binding to extracellular DNA. (PMID:25993443)
• This is the first study to note that elevated systemic CCL5 and CXCL6 were associated with moderate/severe lumbar disc degeneration. These chemokines may be systemic biomarkers for the diagnosis and monitoring of disc degeneration. (PMID:26728495)
• CXCL6 level is high in the serum of chronic hepatitis B patients.CXCL6 promotes human hepatocyte proliferation through the CXCR1-NFkappaB pathway and inhibits collagen I secretion by hepatic stellate cells. (PMID:27032929)
• The role of PITX2 in glaucoma may be mediated partly by regulating the expression of CXCL6 and BBS5 and thus affecting immune functions and intraocular pressure. (PMID:27520585)
• There was underexpression of the majority of genes after sunitinib treatment. The lower expression levels of IGFBP1, CCL20, CXCL6 and FGB were confirmed by qRT-PCR in all cases. The downregulation of gene expression leads us to search for methylation as a mechanism of action of the tyrosine kinase inhibitors (PMID:27834463)
• CXCL6 expression is upregulated by Fli1 deficiency in fibroblasts and endothelial cells, potentially contributing to the development of fibrosis and vasculopathy in the skin, lung, and heart of systemic sclerosis. (PMID:28507181)
• Study has provided the first report of fibroblast-derived CXCL12 enhancement of CXCL6 secretion in colon cancer cells, and of both CXCL12 and CXCL6 co-operatively regulating metastasis through the PI3K/Akt/mTOR signaling pathway. (PMID:28811711)
• The results suggest a notable angiogenic potential of cardiac progenitor cells and identify CXCL6 as an important paracrine factor for cardiac progenitor cells that signals mainly through CXCR2. (PMID:28970523)
• CXCL6 could reduce the expression of miR-515-5p in NSCLC cells; MiR-515-5p acted as a tumor suppressor by targeting CXCL6 in non-small cell lung cancer cell cells. (PMID:29136957)
• our results reveal that CXCL6 plays an important role in liver fibrosis through stimulating the release of TGF-beta by Kupffer cells and thereby activating hepatic stellate cell. (PMID:30106235)
• High CXCL6 expression in the wound exudate is associated with rapid wound healing of diabetic foot ulcers. (PMID:30605352)
• Diagnostic value of GCP-2/CXCL-6 and hs-CRP in the diagnosis of acute appendicitis.", trans “Akut apandisit tanisinda GCP-2/CXCL-6 ve hs-CRP’nin tanisal degeri. (PMID:32185759)
• Potential Repressive Impact of microRNA-20a on Renal Tubular Damage in Diabetic Kidney Disease by Targeting C-X-C Motif Chemokine Ligand 6. (PMID:32868134)
• Hypoxia-CXCL6 axis affects arteriolar niche remodeling in acute myeloid leukemia. (PMID:33167688)
• CXCL6 regulates cell permeability, proliferation, and apoptosis after ischemia-reperfusion injury by modulating Sirt3 expression via AKT/FOXO3a activation. (PMID:33241954)
• CXCL6 fuels the growth and metastases of esophageal squamous cell carcinoma cells both in vitro and in vivo through upregulation of PD-L1 via activation of STAT3 pathway. (PMID:33368292)
• circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6. (PMID:36892025)
• CXCL6: A potential therapeutic target for inflammation and cancer. (PMID:37612429)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cxcl5	ENSMUSG00000029371
rattus_norvegicus	Cxcl6	ENSRNOG00000002843

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

C-X-C motif chemokine 6 — P80162 (reviewed: P80162)

Alternative names: Chemokine alpha 3, Granulocyte chemotactic protein 2, Small-inducible cytokine B6

All UniProt accessions (2): P80162, D6RF92

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic for neutrophil granulocytes. Signals through binding and activation of its receptors (CXCR1 and CXCR2). In addition to its chemotactic and angiogenic properties, it has strong antibacterial activity against Gram-positive and Gram-negative bacteria (90-fold-higher when compared to CXCL5 and CXCL7).

Subcellular location. Secreted.

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

RefSeq proteins (1): NP_002984* (*=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): chain 4, strand 4, helix 2, disulfide bond 2, signal peptide 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8XXX	ELECTRON MICROSCOPY	3.17
8XWM	ELECTRON MICROSCOPY	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80162-F1	81.78	0.53

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

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): 49–75, 51–91

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: 318 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_92, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (18): leukocyte homeostasis (GO:0001776), chemotaxis (GO:0006935), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), neutrophil chemotaxis (GO:0030593), regulation of chemokine production (GO:0032642), neutrophil activation (GO:0042119), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), regulation of neutrophil mediated killing of gram-negative bacterium (GO:0070951), cellular response to lipopolysaccharide (GO:0071222), antibacterial innate immune response (GO:0140367), defense response (GO:0006952), immune response (GO:0006955), response to lipopolysaccharide (GO:0032496), defense response to bacterium (GO:0042742), cell chemotaxis (GO:0060326)

GO Molecular Function (5): chemokine activity (GO:0008009), heparin binding (GO:0008201), CXCR chemokine receptor binding (GO:0045236), cytokine activity (GO:0005125), protein binding (GO:0005515)

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
immune system process	2
defense response	2
cell communication	2
signaling	2
chemokine receptor binding	2
homeostasis of number of cells	1
response to chemical	1
taxis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
granulocyte chemotaxis	1
neutrophil migration	1
regulation of cytokine production	1
chemokine production	1
granulocyte activation	1
antimicrobial humoral response	1
G protein-coupled receptor signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
neutrophil-mediated killing of gram-negative bacterium	1
regulation of neutrophil mediated killing of bacterium	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
defense response to bacterium	1
innate immune response	1
response to stress	1
response to stimulus	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
response to bacterium	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cytokine activity	1
cell chemotaxis	1
glycosaminoglycan binding	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL6	CXCR1	P25024	996
CXCL6	CXCR2	P25025	996
CXCL6	CXCL11	O14625	949
CXCL6	CXCL16	Q9H2A7	855
CXCL6	CCL13	Q99616	759
CXCL6	IL1B	P01584	753
CXCL6	CCL5	P13501	724
CXCL6	CXCL13	O43927	719
CXCL6	CXCL12	P48061	717
CXCL6	CXCL17	Q6UXB2	673
CXCL6	CCL19	Q99731	673
CXCL6	IL1A	P01583	660
CXCL6	CXCL8	P10145	652
CXCL6	IL10	P22301	652
CXCL6	CCL4	P13236	651

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CXCL6	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL6	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL6	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL5	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL6	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL6	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL7	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL1	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL3	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL10	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL6	PPBP	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL6	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
SSX2IP	CXCL6	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): CXCL6 (Biochemical Activity), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CXCL6 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCL8 (Reconstituted Complex), PPBP (Reconstituted Complex), UTP11L (Affinity Capture-MS), RRP36 (Affinity Capture-MS), MYH14 (Affinity Capture-MS)

ESM2 similar proteins: A9QWP9, B1AWI6, D7PDD4, O00175, O00585, O15467, O35903, O55038, O70460, P02775, P02777, P10148, P14844, P18340, P27784, P28292, P30034, P35572, P43030, P47992, P47993, P50228, P51670, P51672, P55773, P80162, P84444, P86792, P86793, P97885, Q07325, Q08782, Q1L6U9, Q4PR21, Q62401, Q68A93, Q68FP3, Q68Y86, Q6MG59, Q8HYP4

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 13 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
Chemokine receptors bind chemokines	10	170.2×	4e-21
G alpha (i) signalling events	8	28.4×	5e-10

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	6	149.6×	6e-11
chemotaxis	8	83.6×	1e-12
antimicrobial humoral immune response mediated by antimicrobial peptide	6	74.8×	3e-09
intracellular calcium ion homeostasis	5	55.9×	5e-07
inflammatory response	10	29.0×	3e-12
positive regulation of cell migration	5	23.7×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

267 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73837261:A:T	donor_gain	1.0000
4:73837285:AGGT:A	donor_loss	1.0000
4:73837286:GGTA:G	donor_loss	1.0000
4:73837287:GT:G	donor_loss	1.0000
4:73837288:T:G	donor_loss	1.0000
4:73837621:A:AG	acceptor_gain	1.0000
4:73837621:AGT:A	acceptor_gain	1.0000
4:73837622:G:GA	acceptor_gain	1.0000
4:73837622:GT:G	acceptor_gain	1.0000
4:73837622:GTG:G	acceptor_gain	1.0000
4:73837092:GTGGT:G	donor_gain	0.9900
4:73837095:GT:G	donor_gain	0.9900
4:73837097:G:GG	donor_gain	0.9900
4:73837196:A:AG	acceptor_gain	0.9900
4:73837202:G:C	acceptor_gain	0.9900
4:73837202:G:GA	acceptor_loss	0.9900
4:73837202:GA:G	acceptor_gain	0.9900
4:73837202:GAGC:G	acceptor_gain	0.9900
4:73837619:ACAG:A	acceptor_loss	0.9900
4:73837621:A:AT	acceptor_loss	0.9900
4:73837621:AGTG:A	acceptor_gain	0.9900
4:73837622:G:GC	acceptor_loss	0.9900
4:73837622:GTGG:G	acceptor_gain	0.9900
4:73837622:GTGGA:G	acceptor_gain	0.9900
4:73836857:GCG:G	donor_gain	0.9800
4:73837089:G:GT	donor_gain	0.9800
4:73837093:TGGT:T	donor_gain	0.9800
4:73837094:GGTG:G	donor_gain	0.9800
4:73837197:C:G	acceptor_gain	0.9800
4:73837199:TCAG:T	acceptor_gain	0.9800

AlphaMissense

712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73837231:T:A	C91S	0.978
4:73837232:G:C	C91S	0.978
4:73837205:C:A	A82D	0.972
4:73837231:T:C	C91R	0.971
4:73837077:T:A	C75S	0.970
4:73837078:G:C	C75S	0.970
4:73836999:T:A	C49S	0.961
4:73837000:G:C	C49S	0.961
4:73837077:T:C	C75R	0.957
4:73837233:T:G	C91W	0.948
4:73837232:G:A	C91Y	0.944
4:73837042:T:A	I63N	0.941
4:73836999:T:C	C49R	0.939
4:73837005:T:C	C51R	0.937
4:73837005:T:A	C51S	0.935
4:73837006:G:C	C51S	0.935
4:73837079:C:G	C75W	0.931
4:73837006:G:A	C51Y	0.926
4:73837231:T:G	C91G	0.921
4:73837007:T:G	C51W	0.920
4:73837000:G:A	C49Y	0.916
4:73837078:G:A	C75Y	0.916
4:73837093:T:A	V80E	0.911
4:73837091:A:C	E79D	0.910
4:73837091:A:T	E79D	0.910
4:73837001:C:G	C49W	0.906
4:73837090:A:G	E79G	0.905
4:73837204:G:C	A82P	0.905
4:73837232:G:T	C91F	0.891
4:73837000:G:T	C49F	0.887

dbSNP variants (sampled 300 via entrez): RS1000312194 (4:73838086 C>A,G,T), RS1000491662 (4:73838494 A>G), RS1001466738 (4:73837358 T>C), RS1001982796 (4:73838557 A>G), RS1003761336 (4:73836397 C>G), RS1003884731 (4:73836172 G>C), RS1004399887 (4:73837419 C>A,G,T), RS1004773270 (4:73837802 T>C), RS1005368788 (4:73839124 G>A), RS1005820098 (4:73838764 A>T), RS1006377595 (4:73835079 A>G), RS1007117418 (4:73836173 C>T), RS1008616887 (4:73838405 T>C), RS1008711538 (4:73836438 G>T), RS1010254074 (4:73836654 G>C,T)

Disease associations

OMIM: gene MIM:138965 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST004608_85	Granulocyte percentage of myeloid white cells	5.000000e-23
GCST004609_124	Monocyte percentage of white cells	5.000000e-13
GCST004610_69	White blood cell count	3.000000e-34
GCST004613_130	Sum neutrophil eosinophil counts	2.000000e-45
GCST004614_149	Granulocyte count	8.000000e-45
GCST004617_94	Eosinophil percentage of granulocytes	9.000000e-11
GCST004620_144	Sum basophil neutrophil counts	2.000000e-46
GCST004623_35	Neutrophil percentage of granulocytes	4.000000e-14
GCST004626_37	Myeloid white cell count	2.000000e-42
GCST004629_61	Neutrophil count	2.000000e-46
GCST004632_104	Lymphocyte percentage of white cells	4.000000e-24
GCST004633_46	Neutrophil percentage of white cells	5.000000e-32
GCST004634_23	Basophil percentage of granulocytes	7.000000e-12
GCST006622_15	Neonatal cytokine/chemokine levels (fetal genetic effect)	6.000000e-09
GCST009731_42	Blood protein levels in cardiovascular risk	3.000000e-130
GCST90002380_146	Basophil percentage of white cells	1.000000e-09
GCST90002389_46	Lymphocyte percentage of white cells	5.000000e-09
GCST90002389_47	Lymphocyte percentage of white cells	2.000000e-57
GCST90002394_56	Monocyte percentage of white cells	3.000000e-28
GCST90002398_450	Neutrophil count	1.000000e-12
GCST90002398_451	Neutrophil count	1.000000e-104
GCST90002398_452	Neutrophil count	6.000000e-10
GCST90002399_373	Neutrophil percentage of white cells	9.000000e-11
GCST90002399_374	Neutrophil percentage of white cells	1.000000e-75
GCST90002407_433	White blood cell count	5.000000e-69

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0004747	protein measurement
EFO:0007959	fetal genotype effect measurement
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, affects cotreatment, increases expression	8
sodium arsenite	increases abundance, increases expression, increases reaction	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	3
Plant Extracts	decreases reaction, increases abundance, increases expression, affects cotreatment, decreases expression	3
Resveratrol	affects cotreatment, decreases expression	2
Arsenic	increases expression, increases reaction, increases abundance	2
Doxorubicin	decreases expression	2
Hydrogen Peroxide	decreases secretion, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression	2
Cyclosporine	decreases expression	2
Asbestos, Crocidolite	increases expression	2
Cadmium Chloride	decreases reaction, increases expression, increases secretion	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
apocarotenal	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
zinc chloride	decreases expression	1
nickel chloride	increases expression	1
manganese chloride	increases expression	1
nickel sulfate	increases expression, increases reaction	1
1-nitropyrene	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
macrophage stimulatory lipopeptide 2	increases expression, increases reaction	1
lipopolysaccharide, E. coli O26-B6	increases expression	1

Clinical trials (associated diseases)

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