CXCL2

Summary

CXCL2 (C-X-C motif chemokine ligand 2, HGNC:4603) is a protein-coding gene on chromosome 4q13.3, encoding C-X-C motif chemokine 2 (P19875). Produced by activated monocytes and neutrophils and expressed at sites of inflammation.

This antimicrobial gene is part of a chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CXC subfamily, is expressed at sites of inflammation and may suppress hematopoietic progenitor cell proliferation.

Source: NCBI Gene 2920 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 22 total
• Druggable target: yes
• MANE Select transcript: NM_002089

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4603
Approved symbol	CXCL2
Name	C-X-C motif chemokine ligand 2
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB2, GROb, MIP-2a, MGSA-b, CINC-2a
Ensembl gene	ENSG00000081041
Ensembl biotype	protein_coding
OMIM	139110
Entrez	2920

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000296031, ENST00000508487, ENST00000510048, ENST00000906203, ENST00000906204

RefSeq mRNA: 1 — MANE Select: NM_002089 NM_002089

CCDS: CCDS34008

Canonical transcript exons

ENST00000508487 — 4 exons

Exon	Start	End
ENSE00001077811	74099021	74099195
ENSE00002069909	74097040	74097771
ENSE00002500685	74098799	74098922
ENSE00003679684	74098601	74098684

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.5660 / max 7556.4460, expressed in 1295 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52558	104.3296	1295
52557	0.2363	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.82	gold quality
right lobe of liver	UBERON:0001114	99.24	gold quality
vena cava	UBERON:0004087	99.23	gold quality
saphenous vein	UBERON:0007318	97.02	gold quality
cartilage tissue	UBERON:0002418	96.88	gold quality
liver	UBERON:0002107	96.84	gold quality
lower lobe of lung	UBERON:0008949	96.20	gold quality
type B pancreatic cell	CL:0000169	96.14	gold quality
upper lobe of lung	UBERON:0008948	95.05	gold quality
upper lobe of left lung	UBERON:0008952	95.04	gold quality
mucosa of stomach	UBERON:0001199	94.29	gold quality
gall bladder	UBERON:0002110	94.18	gold quality
epithelial cell of pancreas	CL:0000083	94.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.05	silver quality
parietal pleura	UBERON:0002400	93.70	gold quality
pleura	UBERON:0000977	93.18	gold quality
omental fat pad	UBERON:0010414	92.85	gold quality
peritoneum	UBERON:0002358	92.81	gold quality
lung	UBERON:0002048	92.44	gold quality
heart right ventricle	UBERON:0002080	92.43	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.32	gold quality
trachea	UBERON:0003126	92.19	gold quality
seminal vesicle	UBERON:0000998	92.12	gold quality
cardia of stomach	UBERON:0001162	92.03	gold quality
cardiac atrium	UBERON:0002081	92.01	gold quality
right atrium auricular region	UBERON:0006631	91.84	gold quality
visceral pleura	UBERON:0002401	91.73	gold quality
pylorus	UBERON:0001166	91.69	gold quality
body of pancreas	UBERON:0001150	91.41	gold quality
mucosa of urinary bladder	UBERON:0001259	91.36	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	9088.45
E-GEOD-135922	yes	6180.61
E-MTAB-6653	yes	3983.38
E-HCAD-1	yes	80.66
E-MTAB-6701	yes	64.82
E-CURD-122	yes	49.50
E-MTAB-8142	yes	47.87
E-MTAB-9467	yes	36.61
E-CURD-46	yes	29.92
E-GEOD-81547	yes	22.22
E-GEOD-130148	yes	11.11
E-HCAD-38	no	3443.27
E-MTAB-8884	no	974.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ATF7, BCL6, CD36, EGR1, ENO1, ETV5, FLI1, FOS, FOXL2, HES1, HSF1, IRF6, JUN, KLF6, MTA1, MYC, MYD88, NFKB1, NFKB, NFKBIA, PITX1, REL, RELA, RELB, SMAD1, SP1, STAT3, TLR4, TLR6, TP53

miRNA regulators (miRDB)

35 targeting CXCL2, 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-4789-3P	99.99	70.75	2484
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-532-5P	98.43	67.53	760

Literature-anchored findings (GeneRIF, showing 40)

• modulation of the GRO beta concentration in the endometrium by inflammatory mediators may contribute to the normal and pathological processes of human reproduction by regulating the trafficking of neutrophils into the endometrium (PMID:12892904)
• CXCL2 has antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• Neutrophil elastase, MIP-2, and TLR-4 have roles in progression of human sepsis and murine peritonitis (PMID:15614130)
• CXCL2 tandem repeat promoter polymorphism is associated with susceptibiltiy to severe sepsis in the Spanish population. (PMID:16421598)
• CXC chemokine CXCL10 and CC chemokine CCL2 serum levels increase with normal aging (PMID:16697212)
• Inhibition of ERK phosphorylation decreased expression of Grob. (PMID:17466952)
• data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis (PMID:17944017)
• Decrease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis in breast cancer cells. (PMID:17999991)
• Peripheral neutrophilia and increased serum chemokines (IL-8 and MIP-2) may indicate hepatic injuries in glycogen storage disease type Ia. (PMID:18191274)
• Resident tissue macrophages are the major source of MIP-2 and KC chemokines; these chemokines are newly synthesized products of signaling through Toll-like receptors. (PMID:18322244)
• In colon epithelial cells, induction of MIP-2 alpha expression by tumor necrosis factor-alpha was accompanied by a concomitant reduction in miR-192 expression and miR-192 was observed to regulate the expression of MIP-2 alpha. (PMID:18835392)
• Report gonadotropin-releasing hormone-regulated CXCL2 expression in human placentation. (PMID:19369450)
• Results indicate that EGR-1 and nuclear factor-kappaB mediate GRO/CXCR2 proliferative signaling in esophageal cancer and may represent potential target molecules for therapeutic intervention. (PMID:19435811)
• A significantly increased expression of GRO-2, GRO-3, and IL-8 in colon carcinoma as compared to normal tissue, is reported. (PMID:20162422)
• G-CSF stimulates the expression of the MIP-2 receptor via STAT3-dependent transcriptional activation of Il8rb (PMID:20185584)
• It can be hypothesized that for some targets, such as CXCL1 and CXCL2, additional signaling may be necessary to fully activate the 3’untranslated region-dependent human antigen R (HuR) function in airway epithelium (PMID:21220697)
• CXCL12 and CXCR4 are related to formation of gastric tumors and lymph node metastasis (PMID:21630055)
• Data suggest that GRObeta may function as an oncogene product and contribute to tumorigenesis and metastasis of esophageal squamous cell carcinoma. (PMID:21677836)
• Anti-human ANXA1 antibodies and, to a lesser extent, anti-human ANXA4 antibodies increased MIP-2 or IL-8 production. (PMID:22056994)
• Suppression of CXCL1 and CXCL2 by siRNA or by progesterone and calcitriol inhibits endometrial and ovarian tumor cell invasiveness. (PMID:22615136)
• Study uncovered a paracrine network, with the chemokines CXCL1 and 2 at its core, that mediates lung metastasis and chemoresistance in breast cancer. (PMID:22770218)
• This is the first report showing the role of CXCL2 in cancer-associated bone destruction. (PMID:22771802)
• Ubiquinol decreases monocytic expression and DNA methylation of the pro-inflammatory CXCL2 gene in humans. (PMID:23021568)
• This study demonistrated that CXCL1, CXCL2, CXCL3, CXCL8, and CXCL11, absent from normal muscle fibers, were induced in DMD myofibers. (PMID:23225384)
• CXCL2, a WAT-produced chemokine being up-regulated in obesity, stimulates neutrophil adhesion to vis WAT endothelial cells. Activated neutrophils in obesity may influence vis WAT-ECs functions and contribute to WAT inflammation. (PMID:23372021)
• Neutrophil priming led to the rapid expression of a common set of transcripts for cytokines, chemokines and cell surface receptors (CXCL1, CXCL2, IL1A, IL1B, IL1RA, ICAM1). (PMID:23554905)
• our results demonstrate the diverse mechanisms by which CXCL2 and CXCL3 mediate normal and asthmatic airway smooth muscle cell migration (PMID:23904157)
• Simultaneous targeting of hCAP-G2 and MIP-2A is a promising strategy for the development of antitumor drugs as a treatment for intractable tumours. (PMID:24098805)
• In this review, a genetic variant in CXCL12 is described that is associated with type 2 diabetes mellitus and its complications. (PMID:25085744)
• Our results demonstrated that resistance to anti-proliferative effects of CXCR2 may also arise from feedback increases in MIP-2 secretion. (PMID:25682075)
• autophagy is required for Hepatitis B virus-induced NF-kappaB activation and release of IL-6, IL-8, and CXCL2 in Hepatocytes (PMID:25708728)
• We have demonstrated that GRObeta, as an oncogene product, contributed to tumorigenesis and metastasis of HCC (PMID:25801245)
• The results link CXCL1 and CXCL2 chemokines with bone marrow adiposity and implicate CXCR2 signaling in promoting effects of marrow fat on progression of skeletal tumors in bone. (PMID:25802102)
• high GRO-beta expression correlates with poor prognosis and contributes to ovarian cancer tumorigenesis and metastasis. (PMID:26063953)
• Polymorphisms in the promoter regions of the CXCL1 and CXCL2 genes contribute to increased risk of alopecia areata in the Korean population (PMID:26345899)
• Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci (PMID:26888013)
• Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 hepatocellular carcinoma cells, and weakened adhesion ability. (PMID:27117207)
• Chronic inflammation contributes to the change of CXCL12 DNA methylation in buccal cells and that DNA methylation profile of CXCL12 promoter plays important role in development and progression of periodontal disease. (PMID:27580404)
• Results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors in bladder cancer. (PMID:27721403)
• Taken together, the data of the present study demonstrated that TcpC can induce MIP2 production, which may contribute to the characteristic histological change associated with pyelonephritis. (PMID:28765918)

Cross-species orthologs

0 orthologs

Paralogs (12): PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), 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 2 — P19875 (reviewed: P19875)

Alternative names: Growth-regulated protein beta, Macrophage inflammatory protein 2-alpha

All UniProt accessions (1): P19875

UniProt curated annotations — full annotation on UniProt →

Function. Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-73) shows a highly enhanced hematopoietic activity.

Subcellular location. Secreted.

Post-translational modifications. The N-terminal processed form GRO-beta(5-73) is produced by proteolytic cleavage after secretion from bone marrow stromal cells.

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

RefSeq proteins (1): NP_002080* (*=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 6, chain 2, helix 2, disulfide bond 2, signal peptide 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5OB5	X-RAY DIFFRACTION	1.65
8XXH	ELECTRON MICROSCOPY	2.8
8XVU	ELECTRON MICROSCOPY	3.09
1QNK	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19875-F1	82.15	0.46

Antibody-complex structures (SAbDab): 2 — 5OB5, 8XXH

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

3 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 signaling

MSigDB gene sets: 475 (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_CD11B_DC_DN, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, HALMOS_CEBPA_TARGETS_UP, KYNG_DNA_DAMAGE_DN, GAURNIER_PSMD4_TARGETS, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, AMIT_SERUM_RESPONSE_40_MCF10A

GO Biological Process (7): response to molecule of bacterial origin (GO:0002237), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), defense response (GO:0006952), signal transduction (GO:0007165), cell chemotaxis (GO:0060326)

GO Molecular Function (3): chemokine activity (GO:0008009), 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-3 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Interleukins	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL2	CXCR2	P25025	998
CXCL2	CXCR1	P25024	989
CXCL2	CXCR4	P30991	981
CXCL2	CXCL10	P02778	923
CXCL2	IL1B	P01584	898
CXCL2	CXCR3	P49682	896
CXCL2	CXCL11	O14625	893
CXCL2	CCR5	P51681	879
CXCL2	IL1A	P01583	870
CXCL2	CXCL12	P48061	869
CXCL2	CXCL8	P10145	866
CXCL2	CCL3	P10147	862
CXCL2	CCR2	P41597	861
CXCL2	IL6	P05231	855
CXCL2	TNF	P01375	845

IntAct

27 interactions, top by confidence:

A	B	Type	Score
DPP4	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.620
DPP4	CXCL2	psi-mi:“MI:0194”(cleavage reaction)	0.620
CXCL2	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL2	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL2	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL2	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	XCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL21	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL9	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	EPS8	psi-mi:“MI:0915”(physical association)	0.370
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CXCL2	CXCL1	psi-mi:“MI:0914”(association)	0.350
COA3	COX5B	psi-mi:“MI:0914”(association)	0.350
CXCL3	IFI30	psi-mi:“MI:0914”(association)	0.350
PIK3R5	CXCL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): CXCL2 (Reconstituted Complex), CXCL2 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL8 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL12 (Reconstituted Complex), CXCL14 (Reconstituted Complex), PF4 (Reconstituted Complex), CXCL5 (Reconstituted Complex), CXCL6 (Reconstituted Complex), XCL2 (Reconstituted Complex), CXCL2 (Reconstituted Complex), CXCL2 (Reconstituted Complex), CXCL2 (Affinity Capture-RNA)

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

2 interactions.

A	Effect	B	Mechanism
CXCL2	“up-regulates activity”	CXCR2	binding
CXCL2	up-regulates	Neutrophil_activation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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	14	124.8×	2e-26
G alpha (i) signalling events	11	20.4×	2e-11
Class A/1 (Rhodopsin-like receptors)	5	17.7×	1e-04
Peptide ligand-binding receptors	5	17.7×	1e-04
GPCR ligand binding	5	15.3×	2e-04
Signaling by GPCR	5	9.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	10	135.0×	1e-17
neutrophil chemotaxis	7	83.3×	7e-11
antimicrobial humoral immune response mediated by antimicrobial peptide	11	74.3×	8e-17
chemotaxis	11	62.3×	4e-16
cell chemotaxis	6	46.3×	9e-08
response to virus	5	30.0×	1e-05
cell-cell signaling	9	26.1×	1e-09
inflammatory response	14	22.0×	7e-15

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

223 predictions. Top by Δscore:

Variant	Effect	Δscore
4:74097767:TGCCA:T	acceptor_gain	1.0000
4:74097768:GCCA:G	acceptor_gain	1.0000
4:74097769:CCA:C	acceptor_gain	1.0000
4:74097769:CCAC:C	acceptor_gain	1.0000
4:74097770:CA:C	acceptor_gain	1.0000
4:74097770:CAC:C	acceptor_gain	1.0000
4:74097771:ACTG:A	acceptor_loss	1.0000
4:74097772:C:CC	acceptor_gain	1.0000
4:74097772:CTGTA:C	acceptor_loss	1.0000
4:74098597:TTAC:T	donor_loss	1.0000
4:74098598:TACTT:T	donor_loss	1.0000
4:74098599:A:AC	donor_gain	1.0000
4:74098600:C:CG	donor_gain	1.0000
4:74098600:CT:C	donor_gain	1.0000
4:74098600:CTT:C	donor_gain	1.0000
4:74098600:CTTT:C	donor_gain	1.0000
4:74098600:CTTTT:C	donor_gain	1.0000
4:74098680:TGGCT:T	acceptor_gain	1.0000
4:74098681:GGCT:G	acceptor_gain	1.0000
4:74098682:GCT:G	acceptor_gain	1.0000
4:74098683:CT:C	acceptor_gain	1.0000
4:74098683:CTC:C	acceptor_gain	1.0000
4:74098684:TCT:T	acceptor_gain	1.0000
4:74098684:TCTGC:T	acceptor_loss	1.0000
4:74098685:C:CC	acceptor_gain	1.0000
4:74098685:C:G	acceptor_gain	1.0000
4:74098685:C:T	acceptor_loss	1.0000
4:74098686:T:A	acceptor_loss	1.0000
4:74098688:C:CT	acceptor_gain	1.0000
4:74098792:GACTT:G	donor_loss	1.0000

AlphaMissense

676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:74098682:G:T	A76D	0.991
4:74098652:A:T	L86H	0.975
4:74098655:C:G	C85S	0.972
4:74098656:A:T	C85S	0.972
4:74098802:A:T	V74D	0.969
4:74098889:C:G	C45S	0.969
4:74098890:A:T	C45S	0.969
4:74098817:C:G	C69S	0.966
4:74098818:A:T	C69S	0.966
4:74098853:A:T	I57N	0.966
4:74098656:A:G	C85R	0.964
4:74098817:C:T	C69Y	0.962
4:74098853:A:C	I57S	0.962
4:74098816:G:C	C69W	0.958
4:74098853:A:G	I57T	0.958
4:74098890:A:G	C45R	0.958
4:74098818:A:G	C69R	0.956
4:74098895:C:G	C43S	0.954
4:74098896:A:G	C43R	0.954
4:74098896:A:T	C43S	0.954
4:74098844:A:T	V60E	0.952
4:74098652:A:G	L86P	0.948
4:74098817:C:A	C69F	0.947
4:74098654:A:C	C85W	0.946
4:74098655:C:T	C85Y	0.944
4:74098683:C:G	A76P	0.944
4:74098676:A:G	L78P	0.938
4:74098888:G:C	C45W	0.932
4:74098656:A:C	C85G	0.928
4:74098804:T:A	E73D	0.927

dbSNP variants (sampled 300 via entrez): RS1000028688 (4:74100846 A>C), RS1000543594 (4:74100277 AT>A), RS1000652738 (4:74096860 A>G), RS1001712689 (4:74098394 G>A,C), RS1002270561 (4:74100099 C>A), RS1002355316 (4:74096920 G>A), RS1002456067 (4:74099649 C>T), RS1003361647 (4:74098680 T>C,G), RS1003468343 (4:74098892 T>A,C,G), RS1004499222 (4:74097585 A>T), RS1005460744 (4:74100602 A>G), RS1005699438 (4:74097773 T>A,C), RS1006873286 (4:74098137 T>C), RS1006959055 (4:74100668 G>A), RS1008849291 (4:74100454 T>C)

Disease associations

OMIM: gene MIM:139110 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001133_2	White blood cell count	2.000000e-17
GCST001134_11	White blood cell types	3.000000e-07
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST004608_86	Granulocyte percentage of myeloid white cells	2.000000e-39
GCST004609_125	Monocyte percentage of white cells	1.000000e-24
GCST004610_70	White blood cell count	2.000000e-71
GCST004613_131	Sum neutrophil eosinophil counts	3.000000e-85
GCST004614_150	Granulocyte count	1.000000e-84
GCST004617_95	Eosinophil percentage of granulocytes	4.000000e-12
GCST004620_145	Sum basophil neutrophil counts	2.000000e-86
GCST004623_1	Neutrophil percentage of granulocytes	8.000000e-17
GCST004626_38	Myeloid white cell count	8.000000e-81
GCST004629_62	Neutrophil count	2.000000e-86
GCST004632_105	Lymphocyte percentage of white cells	4.000000e-36
GCST004633_47	Neutrophil percentage of white cells	3.000000e-48
GCST005973_26	White blood cell count	9.000000e-25
GCST005974_13	Neutrophil count	2.000000e-28
GCST009391_1069	Metabolite levels	6.000000e-06
GCST90002380_147	Basophil percentage of white cells	3.000000e-19
GCST90002389_48	Lymphocyte percentage of white cells	6.000000e-92
GCST90002398_454	Neutrophil count	5.000000e-225
GCST90002399_375	Neutrophil percentage of white cells	4.000000e-126
GCST90002407_435	White blood cell count	3.000000e-175

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
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:0010364	lysophosphatidylcholine 20:5 measurement
EFO:0007992	basophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3286076 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, affects reaction, decreases reaction	9
Tobacco Smoke Pollution	affects expression, increases expression	7
sodium arsenite	decreases reaction, increases expression, decreases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	6
Cadmium	decreases expression, increases expression	4
Lipopolysaccharides	decreases reaction, increases expression, affects response to substance, affects cotreatment	4
Tetrachlorodibenzodioxin	affects expression, increases expression	4
Resveratrol	affects cotreatment, decreases expression, increases expression	3
Acetaminophen	decreases expression	3
Air Pollutants	increases abundance, increases expression	3
Vehicle Emissions	increases abundance, increases expression, affects cotreatment, decreases expression	3
Cannabidiol	decreases reaction, increases expression	3
Estradiol	affects expression, affects cotreatment, decreases expression	3
Plant Extracts	decreases reaction, increases abundance, increases expression, affects cotreatment, decreases expression	3
Silicon Dioxide	increases expression	3
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Asbestos, Crocidolite	increases expression	3
nickel chloride	increases expression, increases reaction	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Temozolomide	affects response to substance, decreases secretion	2
Arsenic Trioxide	increases expression, decreases reaction	2
Troglitazone	increases expression	2
Acetylcysteine	decreases reaction, increases expression	2
Allergens	decreases expression, affects cotreatment	2
Arsenic	decreases expression, increases expression	2
Bleomycin	increases expression	2
Cisplatin	increases reaction, increases response to substance, affects cotreatment, decreases expression, increases activity	2
Copper	affects binding, affects expression, increases expression	2
Dexamethasone	decreases expression, affects cotreatment, increases expression	2
Drugs, Chinese Herbal	increases expression, decreases expression, increases reaction	2

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3293900	Binding	Binding affinity to human recombinant CXCL2 by surface plasmon resonance assay	Synthesis and biological evaluation of a unique heparin mimetic hexasaccharide for structure-activity relationship studies. — J Med Chem

Clinical trials (associated diseases)

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