CXCL1

Summary

CXCL1 (C-X-C motif chemokine ligand 1, HGNC:4602) is a protein-coding gene on chromosome 4q13.3, encoding Growth-regulated alpha protein (P09341). Has chemotactic activity for neutrophils.

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. Aberrant expression of this protein is associated with the growth and progression of certain tumors. A naturally occurring processed form of this protein has increased chemotactic activity. Alternate splicing results in coding and non-coding variants of this gene. A pseudogene of this gene is found on chromosome 4.

Source: NCBI Gene 2919 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_001511

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4602
Approved symbol	CXCL1
Name	C-X-C motif chemokine ligand 1
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB1, GROa, MGSA-a, NAP-3
Ensembl gene	ENSG00000163739
Ensembl biotype	protein_coding
OMIM	155730
Entrez	2919

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000395761, ENST00000509101, ENST00000951020

RefSeq mRNA: 1 — MANE Select: NM_001511 NM_001511

CCDS: CCDS47074

Canonical transcript exons

ENST00000395761 — 4 exons

Exon	Start	End
ENSE00001077828	73869906	73869989
ENSE00001785277	73870521	73871308
ENSE00002031450	73869393	73869570
ENSE00003603970	73869669	73869792

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 224.9672 / max 9978.6473, expressed in 1284 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48228	224.9672	1284

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	98.38	gold quality
periodontal ligament	UBERON:0008266	98.14	gold quality
spleen	UBERON:0002106	97.40	gold quality
cartilage tissue	UBERON:0002418	97.18	gold quality
palpebral conjunctiva	UBERON:0001812	96.84	gold quality
epithelium of bronchus	UBERON:0002031	96.61	gold quality
bronchus	UBERON:0002185	96.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.51	gold quality
bronchial epithelial cell	CL:0002328	96.22	gold quality
nasal cavity epithelium	UBERON:0005384	94.74	gold quality
nasal cavity mucosa	UBERON:0001826	94.14	gold quality
epithelium of nasopharynx	UBERON:0001951	93.25	gold quality
vermiform appendix	UBERON:0001154	92.76	gold quality
islet of Langerhans	UBERON:0000006	92.51	gold quality
trachea	UBERON:0003126	91.36	gold quality
epithelial cell of pancreas	CL:0000083	91.27	gold quality
caecum	UBERON:0001153	88.38	gold quality
pancreatic ductal cell	CL:0002079	86.52	silver quality
rectum	UBERON:0001052	86.52	gold quality
pancreas	UBERON:0001264	85.28	gold quality
gall bladder	UBERON:0002110	84.82	gold quality
mucosa of urinary bladder	UBERON:0001259	84.49	gold quality
parietal pleura	UBERON:0002400	84.46	gold quality
upper lobe of left lung	UBERON:0008952	83.29	gold quality
granulocyte	CL:0000094	83.12	gold quality
bone marrow cell	CL:0002092	83.08	gold quality
bone marrow	UBERON:0002371	82.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.92	gold quality
blood	UBERON:0000178	82.92	gold quality
tonsil	UBERON:0002372	82.69	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	14405.03
E-GEOD-81547	yes	8950.06
E-HCAD-11	yes	4648.78
E-GEOD-130148	yes	2633.01
E-MTAB-10885	yes	2566.38
E-MTAB-6075	yes	2284.30
E-MTAB-8559	yes	982.53
E-CURD-46	yes	22.09
E-GEOD-86618	no	10001.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
GLI2	Activation
GLI3	Activation

Upstream regulators (CollecTRI, top): AP1, ATF3, BRCA1, CD36, CEBPD, CUX1, EGR1, ESR1, GATA3, HMGA1, HSF1, IRF3, IRF6, JUN, MTA1, MYD88, NFKB1, NFKB, PARP1, PGR, RELA, SMAD2, SMAD3, SP1, SP3, TFAP2A, TFAP2C, TFAP2E, TLR4, TLR6, TP53, VDR

miRNA regulators (miRDB)

43 targeting CXCL1, 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-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3182	99.40	68.15	2454

Literature-anchored findings (GeneRIF, showing 40)

• GRO-alpha levels in blood, quantities released from platelets ex vivo, and quantities released from SFFLRN stimulated platelets ex vivo were compared for preeclamptic and normal pregnancies. (PMID:11816717)
• may play a role in the pathogenesis of endometriosis, possibly by chemoattraction and activation of neutrophils present in higher numbers in the peritoneal fluid of women with endometriosis (PMID:12012624)
• mediates angiogenesis in Kaposi’s sarcoma (PMID:12388718)
• Eosinophils produce large amounts of the CXC chemokine GRO-alpha, which may be important during resolution of inflammation and may explain the interaction between eosinophils and certain tumors. (PMID:12734381)
• The role of GROa in cultured nasal epithelial cells was studied for its ability to synthesize and deliver neutrophil chemotactic factors following TNF-alpha induction. (PMID:12744776)
• This protein displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• Recombinant GROalpha induces articular chondrocyte hypertrophy and calcification through p38 MAP kinase and transglutaminase 2. (PMID:14530367)
• expression of GRO-1 in 9 oral squamous cell carcinoma (OSCC) cell lines and 94 OSCC specimens; findings suggest a possible relationship between the expression level of GRO-1 and tumor progression (PMID:15218300)
• This suggests that GRO-alpha plays a role in the infiltration of neutrophils into the lesional skin and in bulla formation in linear IgA bullous dermatosis. (PMID:15492419)
• KC (CXCL1) mRNA is regulated by functionally independent AU-rich sequence motifs (PMID:15994316)
• We propose that the concurrence of CXCR2 on oligodendrocytes and induced CXCL1 on hypertrophic astrocytes in MS provides a novel mechanism for recruitment of oligodendrocytes to areas of damage, an essential prerequisite for lesion repair. (PMID:16086366)
• endothelin-1 (ET-1) induces CXCL1 and CXCL8 secretion in three human melanoma cell lines (PMID:16098041)
• CXCL1 released from prostaglandin E2-treated carcinoma cells induces microvascular endothelial cell migration and tube formation in vitro. (PMID:16567391)
• IL-1beta- and TNF-alpha-stimulated expression of GRO-alpha from airway smooth muscle is regulated by independent pathways involving NF-kappaB activation and ERK and JNK pathways (PMID:16617094)
• GRO-1 can promote tumor growth and metastasis of laryngeal squamous cell carcinoma. (PMID:16941962)
• LDL lipoprotein subunit L5 induces human umbilical vein endothelial cells (HUVEC) to express GRO-alpha. (PMID:17022986)
• Gro-1 may be a therapeutic target as well as a diagnostic marker in ovarian cancer (PMID:17060621)
• Coexpression of fibulin-1 with GROalpha abrogates key aspects of the transformed phenotype, including colonic tumor formation in a murine xenograft model. (PMID:17062666)
• GROalpha led to p38 MAPK activation in chondrocytes cultured in micromass but not as a high-density monolayer. This caused the downstream triggering of chondrocyte hypertrophy and apoptosis/anoikis following concurrence of matrix degrading activity. (PMID:17096385)
• CX3CR1 and CX3CL1 mediate heterotypic anchorage of foam cells to coronary artery smooth muscle cells in the context of atherosclerosis (PMID:17456471)
• Inhibition of ERK decreased expression of Groa. (PMID:17466952)
• PAR-2 plays a role in serine protease-mediated regulation of IL-8 and GRO-alpha in nasal epithelial cells and may be involved in the pathophysiology of rhinosinusitis. (PMID:17581194)
• During treatment of ulceretive colitis with corticosteroids CXCL1/CXCL9 were decreased. (PMID:17703315)
• rease of CXCL1 and -2 mediated by Curcumin is involved in the inhibition of metastasis in breast cancer cells. (PMID:17999991)
• GRO-alpha may be a novel diagnostic marker for age-related pathology, including cancer. (PMID:18056965)
• The production of GRO-alpha, IL-6 and IL-8 was shown to account for the ability of the HeLa cell culture medium to stimulate the migration of monocytes/macrophages, suggesting a key role for p38 MAPK and ERK1/ERK2. (PMID:18065201)
• In addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of C. neoformans. (PMID:18211687)
• GROalpha could be involved in atherogenesis and plaque destabilization, potentially contributing to inflammation, matrix degradation, and lipid accumulation within the atherosclerotic lesion. (PMID:18276907)
• CXCL1 secreted by endothelial cells induces tumor cell invasion (PMID:18283335)
• results suggest that CXCL1 modulates the invasive abilities of bladder cancer cells and this chemokine may be a potential candidate of urinary biomarker for invasive bladder cancer and a possible therapeutic target for preventing tumor invasion (PMID:18451219)
• observed that CCL4, CXCL1 and CXCL8 secretion, following PROK1 induction (PMID:19103522)
• Vascular endothelial growth factor induces protein kinase D-dependent production of proinflammatory cytokine GRO-alpha in endothelial cells. (PMID:19176759)
• a novel mechanism by which mutant p53 acquires its gain of function via transactivating the GRO1 gene in cancer cells. (PMID:19258312)
• Data show that oral fibroblasts respond to LPS stimulation by increasing GROalpha production via the transcription factor NF-kappaB, suggesting that this mechanism may be involved in development of periodontal inflammation. (PMID:19430878)
• 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)
• Data show that expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue compared with normal endometrium. (PMID:19549892)
• The expression levels of four of the up-regulated genes, CXCL1, SPARC, SPP1 and SULF, were significantly higher in the cancerous tissue compared with the normal tissue (fold change 3.4-8.9). (PMID:19780053)
• Data show that the knockdown of Ron in PC-3 or DU145 cells results in a significant decrease in angiogenic chemokine production and is associated with a decreased activation of NF-kappaB. (PMID:19838218)
• Lysophosphatidic acid mediates trophoblast cells to produce GRO-alpha, IL-8, and MCP-1 via LPA1 receptors and nuclear factor-kappaB-dependent signal pathways. (PMID:19906815)
• CXCL1 transgene mRNA stabilization is dependent on AUUUA-containing sequence motifs that are recognized by the RNA binding protein tristetraprolin. (PMID:20042592)

Cross-species orthologs

0 orthologs

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

Growth-regulated alpha protein — P09341 (reviewed: P09341)

Alternative names: C-X-C motif chemokine 1, GRO-alpha(1-73), Melanoma growth stimulatory activity, Neutrophil-activating protein 3

All UniProt accessions (1): P09341

UniProt curated annotations — full annotation on UniProt →

Function. Has chemotactic activity for neutrophils. May play a role in inflammation and exerts its effects on endothelial cells in an autocrine fashion. In vitro, the processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) show a 30-fold higher chemotactic activity.

Subcellular location. Secreted.

Post-translational modifications. N-terminal processed forms GRO-alpha(4-73), GRO-alpha(5-73) and GRO-alpha(6-73) are produced by proteolytic cleavage after secretion from peripheral blood monocytes.

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

RefSeq proteins (1): NP_001502* (*=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 (18 total): strand 8, chain 4, helix 2, disulfide bond 2, signal peptide 1, turn 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9EJC	ELECTRON MICROSCOPY	2.98
8K4O	ELECTRON MICROSCOPY	3.01
8XWV	ELECTRON MICROSCOPY	3.07
8XWA	ELECTRON MICROSCOPY	3.48
1MGS	SOLUTION NMR
1MSG	SOLUTION NMR
1MSH	SOLUTION NMR
1ROD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09341-F1	81.47	0.36

Antibody-complex structures (SAbDab): 2 — 8XWV, 9EJC

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

4 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 413 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MODULE_64, GNF2_PTX3

GO Biological Process (11): chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), nervous system development (GO:0007399), negative regulation of cell population proliferation (GO:0008285), actin cytoskeleton organization (GO:0030036), intracellular signal transduction (GO:0035556), defense response (GO:0006952), cell chemotaxis (GO:0060326)

GO Molecular Function (6): signaling receptor binding (GO:0005102), chemokine activity (GO:0008009), enzyme activator activity (GO:0008047), growth factor activity (GO:0008083), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), specific granule lumen (GO:0035580), tertiary granule lumen (GO:1904724)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
receptor ligand activity	2
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
system development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cytoskeleton organization	1
actin filament-based process	1
intracellular anatomical structure	1
response to stress	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
protein binding	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
binding	1
cellular anatomical structure	1
secretory granule lumen	1
specific granule	1
intracellular organelle lumen	1
tertiary granule	1

Protein interactions and networks

STRING

3334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL1	CXCR2	P25025	999
CXCL1	CXCR1	P25024	996
CXCL1	CXCR4	P30991	995
CXCL1	CCR2	P41597	988
CXCL1	ACKR1	Q16570	988
CXCL1	CXCL10	P02778	984
CXCL1	CX3CR1	P49238	950
CXCL1	CCL2	P13500	949
CXCL1	CCR1	P32246	942
CXCL1	IL6	P05231	936
CXCL1	CSF3	P09919	935
CXCL1	CCL11	P50877	930
CXCL1	CCL20	P78556	929
CXCL1	CCR5	P51681	928
CXCL1	IL1B	P01584	926

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CXCL1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
CXCL1	TRAF2	psi-mi:“MI:0914”(association)	0.530
CXCL1	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL1	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL1	CXCL6	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL1	SDR9C7	psi-mi:“MI:0915”(physical association)	0.400
CXCL1	ESR1	psi-mi:“MI:0915”(physical association)	0.370
CXCL1	HRAS	psi-mi:“MI:0915”(physical association)	0.370
PTEN	CXCL1	psi-mi:“MI:0915”(physical association)	0.370
CXCL1	XRCC3	psi-mi:“MI:0915”(physical association)	0.370
CXCL2	CXCL1	psi-mi:“MI:0914”(association)	0.350
CXCL3	CXCL1	psi-mi:“MI:0914”(association)	0.350
CXCL1	XIAP	psi-mi:“MI:0914”(association)	0.350
CXCL1	PDE2A	psi-mi:“MI:0914”(association)	0.350
CXCL1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
purL	CXCL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): CXCL1 (Affinity Capture-RNA), CXCL1 (Two-hybrid), CXCL1 (Two-hybrid), CXCL1 (Two-hybrid), CXCL1 (Two-hybrid), ACKR1 (Reconstituted Complex), CXCL1 (Affinity Capture-MS), CXCL1 (Two-hybrid), CXCL1 (Co-crystal Structure), SDR9C7 (Proximity Label-MS), CCL11 (Reconstituted Complex), CXCL5 (Reconstituted Complex), CXCL6 (Reconstituted Complex), SEH1L (Affinity Capture-MS), BIRC2 (Affinity Capture-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

14 interactions.

A	Effect	B	Mechanism
FZD3	up-regulates	CXCL1	binding
CXCL1	up-regulates	GLI1
CXCL1	“up-regulates quantity by expression”	GLI2	“transcriptional regulation”
CXCL1	“up-regulates quantity by expression”	GLI3	“transcriptional regulation”
Cyclopamine	down-regulates	CXCL1	“chemical inhibition”
SMO	up-regulates	CXCL1	binding
CXCL1	up-regulates	PLCE1	binding
CXCL1	down-regulates	PRKACA	binding
MTA1	“up-regulates quantity by expression”	CXCL1	“transcriptional regulation”
CXCL1	“up-regulates activity”	CXCR2	binding
CXCL1	up-regulates	Neutrophil_activation
hsa-miR-141-5p	“down-regulates quantity by repression”	CXCL1	“post transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	CXCL1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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	5	72.0×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
chemotaxis	5	48.5×	1e-05
inflammatory response	5	13.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

271 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73869567:GCAG:G	donor_gain	1.0000
4:73869568:CAGG:C	donor_loss	1.0000
4:73869570:GGT:G	donor_loss	1.0000
4:73869571:G:GG	donor_gain	1.0000
4:73869571:GT:G	donor_loss	1.0000
4:73869667:A:AG	acceptor_gain	1.0000
4:73869667:AG:A	acceptor_gain	1.0000
4:73869667:AGG:A	acceptor_loss	1.0000
4:73869668:G:GT	acceptor_gain	1.0000
4:73869668:GG:G	acceptor_gain	1.0000
4:73869668:GGA:G	acceptor_gain	1.0000
4:73869668:GGAGC:G	acceptor_gain	1.0000
4:73869788:GTCAT:G	donor_gain	1.0000
4:73869789:TCAT:T	donor_gain	1.0000
4:73869790:CAT:C	donor_gain	1.0000
4:73869791:AT:A	donor_gain	1.0000
4:73869791:ATGTA:A	donor_loss	1.0000
4:73869793:G:GG	donor_gain	1.0000
4:73869794:TAAG:T	donor_loss	1.0000
4:73869901:TGCA:T	acceptor_loss	1.0000
4:73869903:CAGA:C	acceptor_loss	1.0000
4:73869904:A:AG	acceptor_gain	1.0000
4:73869905:G:GG	acceptor_gain	1.0000
4:73869905:G:GT	acceptor_loss	1.0000
4:73869905:GA:G	acceptor_gain	1.0000
4:73869905:GAGC:G	acceptor_gain	1.0000
4:73869905:GAGCC:G	acceptor_gain	1.0000
4:73869988:AGGTG:A	donor_loss	1.0000
4:73869990:G:GC	donor_loss	1.0000
4:73869990:G:GG	donor_gain	1.0000

AlphaMissense

675 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73869908:C:A	A76D	0.992
4:73869934:T:A	C85S	0.977
4:73869935:G:C	C85S	0.977
4:73869701:T:A	C45S	0.976
4:73869702:G:C	C45S	0.976
4:73869938:T:A	L86H	0.976
4:73869738:T:G	I57S	0.971
4:73869773:T:A	C69S	0.971
4:73869774:G:C	C69S	0.971
4:73869789:T:A	V74D	0.971
4:73869738:T:A	I57N	0.970
4:73869738:T:C	I57T	0.970
4:73869701:T:C	C45R	0.966
4:73869934:T:C	C85R	0.965
4:73869695:T:A	C43S	0.964
4:73869696:G:C	C43S	0.964
4:73869774:G:A	C69Y	0.964
4:73869695:T:C	C43R	0.960
4:73869773:T:C	C69R	0.955
4:73869907:G:C	A76P	0.955
4:73869775:C:G	C69W	0.954
4:73869936:C:G	C85W	0.953
4:73869935:G:A	C85Y	0.951
4:73869959:T:A	V93D	0.951
4:73869747:T:A	V60E	0.950
4:73869938:T:C	L86P	0.947
4:73869774:G:T	C69F	0.945
4:73869914:T:C	L78P	0.944
4:73869787:A:C	E73D	0.943
4:73869787:A:T	E73D	0.943

dbSNP variants (sampled 300 via entrez): RS1001317244 (4:73871314 C>A), RS1001588641 (4:73869158 G>A,C,T), RS1001871719 (4:73870381 T>C), RS1002558056 (4:73871398 G>A), RS1002606331 (4:73867893 A>G), RS1002759266 (4:73871672 A>T), RS1006228640 (4:73871541 C>T), RS1006691466 (4:73871069 T>C,G), RS1007544910 (4:73870728 T>C), RS1008512916 (4:73868868 C>T), RS1009736699 (4:73868151 G>A), RS1010054167 (4:73871373 C>T), RS1010499401 (4:73871620 G>T), RS1011522737 (4:73868570 G>A), RS1011575255 (4:73868277 G>A)

Disease associations

OMIM: gene MIM:155730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST002696_15	Anxiety disorder	4.000000e-06
GCST004457_19	Growth-regulated protein alpha levels	8.000000e-42
GCST006585_2456	Blood protein levels	9.000000e-08
GCST009731_55	Blood protein levels in cardiovascular risk	1.000000e-30

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008146	growth-regulated alpha protein measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases reaction, increases expression, decreases expression	12
Tobacco Smoke Pollution	affects cotreatment, decreases reaction, affects expression, decreases expression, decreases secretion (+3 more)	11
Particulate Matter	increases abundance, increases expression, increases reaction, decreases reaction, increases secretion (+2 more)	11
Lipopolysaccharides	affects response to substance, decreases reaction, increases expression, affects cotreatment, increases secretion (+1 more)	9
Air Pollutants	increases abundance, increases expression, decreases expression	5
Silicon Dioxide	increases expression	5
Vehicle Emissions	increases expression, affects cotreatment, decreases expression, affects expression, increases reaction (+1 more)	4
Hydrogen Peroxide	decreases reaction, increases expression, affects secretion	4
Asbestos, Crocidolite	increases expression	4
titanium dioxide	affects expression, affects binding, increases secretion	3
1-nitropyrene	increases expression	3
perfluorooctane sulfonic acid	decreases expression, increases expression	3
Arsenic	affects expression, increases expression	3
Bleomycin	increases expression, decreases reaction	3
Methotrexate	increases expression, affects cotreatment, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Nanotubes, Carbon	decreases expression, increases expression	3
bisphenol A	decreases expression, increases expression	2
deoxynivalenol	affects reaction, affects binding, increases activity, increases expression, increases reaction (+2 more)	2
sulforaphane	affects cotreatment, decreases reaction, increases expression, decreases expression	2
2-tert-butylhydroquinone	increases expression	2
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	2
perfluorooctanoic acid	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
nickel sulfate	affects cotreatment, increases reaction, increases secretion, increases expression	2
chromium hexavalent ion	decreases expression, increases abundance, increases expression	2
SB 203580	decreases reaction, increases expression	2
SB 225002	decreases reaction, increases expression, increases secretion	2
bisphenol S	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression, affects cotreatment	2

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1PN	Abcam HeLa CXCL1 KO	Cancer cell line	Female
CVCL_D7N7	Ubigene A-549 CXCL1 KO	Cancer cell line	Male
CVCL_D8JP	Ubigene HCT 116 CXCL1 KO	Cancer cell line	Male
CVCL_E0BC	Ubigene HeLa CXCL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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