CXCL5

Summary

CXCL5 (C-X-C motif chemokine ligand 5, HGNC:10642) is a protein-coding gene on chromosome 4q13.3, encoding C-X-C motif chemokine 5 (P42830). Involved in neutrophil activation.

This gene encodes a protein that is a member of the CXC subfamily of chemokines. Chemokines, which recruit and activate leukocytes, are classified by function (inflammatory or homeostatic) or by structure. This protein is proposed to bind the G-protein coupled receptor chemokine (C-X-C motif) receptor 2 to recruit neutrophils, to promote angiogenesis and to remodel connective tissues. This protein is thought to play a role in cancer cell proliferation, migration, and invasion.

Source: NCBI Gene 6374 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_002994

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10642
Approved symbol	CXCL5
Name	C-X-C motif chemokine ligand 5
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	ENA-78
Ensembl gene	ENSG00000163735
Ensembl biotype	protein_coding
OMIM	600324
Entrez	6374

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000296027

RefSeq mRNA: 1 — MANE Select: NM_002994 NM_002994

CCDS: CCDS34006

Canonical transcript exons

ENST00000296027 — 4 exons

Exon	Start	End
ENSE00001077815	73995642	73997655
ENSE00001522750	73998473	73998677
ENSE00002497929	73998206	73998338
ENSE00002502782	73998012	73998095

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 93.22.

FANTOM5 (CAGE): breadth broad, TPM avg 44.2381 / max 2964.5222, expressed in 807 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52546	43.6331	794
52544	0.2979	136
52545	0.2217	110
52543	0.0854	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	93.22	gold quality
mononuclear cell	CL:0000842	93.11	gold quality
leukocyte	CL:0000738	91.65	gold quality
vermiform appendix	UBERON:0001154	90.01	gold quality
cartilage tissue	UBERON:0002418	86.03	gold quality
epithelial cell of pancreas	CL:0000083	85.00	gold quality
minor salivary gland	UBERON:0001830	83.33	gold quality
caecum	UBERON:0001153	81.13	gold quality
islet of Langerhans	UBERON:0000006	79.97	gold quality
mouth mucosa	UBERON:0003729	77.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.00	gold quality
saliva-secreting gland	UBERON:0001044	75.60	gold quality
pancreatic ductal cell	CL:0002079	74.95	silver quality
gall bladder	UBERON:0002110	73.52	gold quality
palpebral conjunctiva	UBERON:0001812	72.79	gold quality
lymph node	UBERON:0000029	72.09	gold quality
pylorus	UBERON:0001166	71.84	gold quality
upper lobe of lung	UBERON:0008948	71.67	gold quality
upper lobe of left lung	UBERON:0008952	71.47	gold quality
lower lobe of lung	UBERON:0008949	71.18	gold quality
lung	UBERON:0002048	69.16	gold quality
blood	UBERON:0000178	67.63	gold quality
amniotic fluid	UBERON:0000173	66.79	gold quality
nasal cavity mucosa	UBERON:0001826	66.20	gold quality
hypothalamus	UBERON:0001898	66.15	gold quality
granulocyte	CL:0000094	65.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.64	gold quality
eye	UBERON:0000970	64.29	gold quality
nucleus accumbens	UBERON:0001882	62.93	gold quality
cardia of stomach	UBERON:0001162	62.04	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	38.73
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EBF1, EGR1, ETV5, HSF1, NFKB1, NR3C1, RELA, SP1, SP3, TP53, ZNF148

miRNA regulators (miRDB)

102 targeting CXCL5, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 40)

• ENA-78 is produced in bronchial epithelial cells in response to RV16 infection (PMID:12751040)
• ENA-78 is present in increased abundance in the amniotic cavity in response to intrauterine infection and may play a role in infection-driven preterm birth and rupture of membranes secondary to leukocyte recruitment and activation. (PMID:13679321)
• During bacterial meningitis, CXCL5 is elevated in cerebrospinal fluid, where it is involved in the recruitment of neutrophils to the central nervous system. (PMID:14644041)
• ENA-78 may contribute to the pathogenesis of endometriosis, possibly promoting neovascularization. (PMID:14967364)
• Peripheral blood monocytes upregulated both tumor ENA-78 and IL-8 mRNA and protein. Alveolar macrophages only upregulated ENA-78 mRNA and protein. (PMID:15021975)
• induced by Rhinovirus infection of primary human airway fibroblasts (PMID:15714497)
• CXCL5 gene polymorphisms are related to systemic concentrations and leukocyte production of epithelial neutrophil-activating peptide 78 (PMID:16567110)
• The platelet-derived chemokines ENA-78 exhibited particular changes after SCT; results suggest that ENA-78 plays a role in hematopoietic conditions in which G-CSF is not involved (PMID:16635746)
• LDL lipoprotein subunit L5 induces human umbilical vein endothelial cells (HUVEC) to express ENA-78. (PMID:17022986)
• IP-10 may play an important role in regulating lymphocytes into the lung and ENA-78 may be associated with lung parenchymal disease in pulmonary sarcoidosis. (PMID:17052298)
• lack of association of ENA-78 polymorphism with giant cell arteritis (PMID:17428364)
• CXCL5 overexpression is associated with late stage gastric cancer (PMID:17479287)
• This is the first report on the influence of CXCL5 gene variants and their relation to expression of CXCL5 protein in human colorectal cancer. (PMID:17549409)
• Stromal endometrial cells produced ENA-78 and IL-8 under cytokine stimulation. (PMID:17761179)
• unveils a proinflammatory pathway centered on kinin B1 receptor activation of CXCL5 leading to leukocyte trafficking (PMID:17878384)
• CXCL5 may play multiple roles in the etiology of both benign and malignant proliferative diseases in the prostate. (PMID:18320069)
• CXCL5 may be of use for telling diabetic nephropathy from primary renal diseases (PMID:18413205)
• Disrupted expression of CXCL5 in colorectal cancer is associated with rapid tumor formation in rats and poor prognosis in patients. (PMID:18413816)
• Results reveal that platelet-derived growth factor-B-activated fibroblasts play a key role in the recruitment/migration and differentiation of mesenchymal stem cells and implicate a bFGF- and CXCL5-dependent mechanism in mediating these effects. (PMID:18570917)
• CXCL5/ENA-78 has a role in acute coronary syndrome and the statin response (PMID:18769620)
• patients with type 2 diabetes had higher frequency of carrying the G/C or C/C genotype compared with controls; frequency of allele C was increased in patients with diabetes compared to controls; findings suggest role of CXCL5 in pathogenesis of diabetes (PMID:19035625)
• Epithelial neutrophil-activating peptide-78 recruits neutrophils into pleural effusion (PMID:19047312)
• Secretion of CXCL5 by white adipose tissue resident macrophages represents a link between obesity, inflammation, and insulin resistance. (PMID:19356715)
• There was a remarkably high proportion of proangiogenic factors, in particular IP10, ENA-78, and IL-8 accounting for a genetically determined susceptibility to reactive arthritis at the host cell level. (PMID:19506876)
• expression in gingival epithelial cells is induced by thrombin via activation of protease-activated receptor 1 (PMID:19567485)
• No significant differences in allele or genotype frequencies for RANTES or ENA-78 proteins were found in patients with erythema nodosum. (PMID:19646363)
• CXCL5 was significantly correlated with deeper depth of invasion and advanced stage of tumor but not with lymph node status in primary gastric cancer (PMID:19724852)
• 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)
• The 156C allele for ENA-78 may be a risk factor for idiopathic pulmonary fibrosis. (PMID:20137269)
• Elevated circulating CXCL5 concentrations were associated with higher risk of hypercholesterolemia in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors but not insulin resistance. (PMID:20501684)
• The highly divergent effects of modifications of CXCL5 on neutrophil influx underline the potential importance of tissue-specific interactions between chemokines and PAD or proteases. (PMID:20630876)
• CXCL5/ENA78 increased cell migration and epithelial-to-mesenchymal transition of hormone-independent prostate cancer by early growth response-1/snail signaling pathway. (PMID:20945384)
• CD14 and CXCL5 were both expressed in tunica intima and tunica adventitia of adipose tissue blood vessels; CXCL5 exhibited chemoattractant and angiogenic properties. (PMID:21034724)
• Report influence of troglitazone, sodium butyrate, 5-aminosalicylic acid and BAY 11-7082 on the chemokine ENA-78/CXCL5 secretion in the intestinal subepithelial myofibroblasts. (PMID:21229889)
• Plasma CXCL5 levels are lower in patients with chronic liver disease, suggesting that CXCL5 might be involved in the pathogenesis of chronic liver disease. (PMID:21332547)
• Serum CXC ligand 5 is a new marker of subclinical atherosclerosis in type 2 diabetes. (PMID:21609350)
• Data demonstrate that the chemokine CXCL5 is a peripheral mediator of UVB-induced inflammatory pain, likely in humans as well as rats. (PMID:21734176)
• Blockade of CXCL5 can modulate IL-17-induced arthritic inflammation in part by reducing joint blood vessel formation through a non-overlapping IL-17 mechanism. (PMID:21779896)
• Data show that tumour conditioned media obtained from cultured colorectal tumour explant tissue contained high levels of the chemokines CCL2, CXCL1, CXCL5 in addition to VEGF. (PMID:22125641)
• Preoperative serum CXCL5 could serve as a novel predictive marker for prognosis determination of colorectal cancer patients. (PMID:22197219)

Cross-species orthologs

0 orthologs

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248), CXCL8 (ENSG00000169429)

Protein

Protein identifiers

C-X-C motif chemokine 5 — P42830 (reviewed: P42830)

Alternative names: ENA-78(1-78), Epithelial-derived neutrophil-activating protein 78, Neutrophil-activating peptide ENA-78, Small-inducible cytokine B5

All UniProt accessions (2): P42830, Q6I9S7

UniProt curated annotations — full annotation on UniProt →

Function. Involved in neutrophil activation. In vitro, ENA-78(8-78) and ENA-78(9-78) show a threefold higher chemotactic activity for neutrophil granulocytes.

Subunit / interactions. Monomer. Homodimer.

Subcellular location. Secreted.

Post-translational modifications. N-terminal processed forms ENA-78(8-78) and ENA-78(9-78) are produced by proteolytic cleavage after secretion from peripheral blood monocytes.

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

RefSeq proteins (1): NP_002985* (*=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 (14 total): strand 4, chain 3, helix 2, disulfide bond 2, signal peptide 1, turn 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8XWS	ELECTRON MICROSCOPY	3.06
8XX7	ELECTRON MICROSCOPY	3.32
2MGS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42830-F1	81.28	0.51

Functional residue map

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

Catalytic / active sites (1): 44–45 (cleavage; by cathepsin g)

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: 270 (showing top): MORF_ITGA2, GGGACCA_MIR133A_MIR133B, MODULE_92, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, MORF_RAD51L3, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, GOBP_CELL_CELL_SIGNALING

GO Biological Process (11): chemotaxis (GO:0006935), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), neutrophil chemotaxis (GO:0030593), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to lipopolysaccharide (GO:0071222), defense response (GO:0006952), immune response (GO:0006955), cell chemotaxis (GO:0060326)

GO Molecular Function (5): chemokine activity (GO:0008009), identical protein binding (GO:0042802), 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
cell communication	2
signaling	2
chemokine receptor binding	2
response to chemical	1
taxis	1
defense response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
granulocyte chemotaxis	1
neutrophil migration	1
antimicrobial humoral response	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
response to stress	1
immune system process	1
response to stimulus	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cytokine activity	1
cell chemotaxis	1
protein binding	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL5	CXCR2	P25025	998
CXCL5	CXCR1	P25024	996
CXCL5	CXCL11	O14625	956
CXCL5	CXCR4	P30991	956
CXCL5	CXCL10	P02778	947
CXCL5	CCR2	P41597	911
CXCL5	ACKR1	Q16570	897
CXCL5	CCL17	Q92583	870
CXCL5	CCL22	O00626	869
CXCL5	CCL5	P13501	849
CXCL5	IL6	P05231	834
CXCL5	CXCL12	P48061	816
CXCL5	CCL3	P10147	814
CXCL5	CXCL13	O43927	808
CXCL5	CCL4	P13236	797

IntAct

35 interactions, top by confidence:

A	B	Type	Score
CXCL5	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
ALPP	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
CXCL5	ACTN3	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
GRN	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
VWC2L	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
FBLN1	CXCL5	psi-mi:“MI:0915”(physical association)	0.560
CXCL5	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL5	XCL2	psi-mi:“MI:0407”(direct interaction)	0.440
CCL20	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL1	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL3	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL5	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.370
	TOR1B	psi-mi:“MI:0914”(association)	0.350
CXCL5	OLFM2	psi-mi:“MI:0914”(association)	0.350
CXCL5	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
ALPP	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
FBLN1	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
ACTN3	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
EFEMP2	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
GRN	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
	CXCL5	psi-mi:“MI:0915”(physical association)	0.000
VWC2L	CXCL5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): NOTCH2NL (Two-hybrid), CXCL5 (Biochemical Activity), CXCL5 (Two-hybrid), CXCL5 (Two-hybrid), CXCL5 (Two-hybrid), CXCL5 (Two-hybrid), MGAT5B (Two-hybrid), EFEMP2 (Two-hybrid), VWC2L (Two-hybrid), ACTN3 (Two-hybrid), CXCL5 (Affinity Capture-MS), CXCL5 (Proximity Label-MS), CXCL5 (Reconstituted Complex), CXCL5 (Reconstituted Complex), CXCL5 (Reconstituted Complex)

ESM2 similar proteins: F5HET8, O00626, O88430, O89093, P08317, P10889, P12850, P13500, P14095, P19874, P28291, P30348, P36925, P42830, P42831, P46653, P49873, P51671, P52203, P55774, P61274, P61275, P78556, P80075, P80098, P80221, P82943, Q03366, Q09141, Q16627, Q5RA36, Q62401, Q68AY9, Q68Y88, Q6W5C0, Q8HYP8, Q8HYP9, Q8I021, Q8MIT7, Q8SQB1

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

4 interactions.

A	Effect	B	Mechanism
CXCL5	“up-regulates activity”	CXCR2	binding
DDR1	“up-regulates quantity by expression”	CXCL5	“transcriptional regulation”
CXCL5	up-regulates	Neutrophil_activation
CXCL5	up-regulates	Metastasis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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	6	86.4×	7e-10

GO biological processes:

GO term	Partners	Fold	FDR
chemotaxis	5	42.5×	1e-05
inflammatory response	6	14.1×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

391 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73997656:C:CC	acceptor_gain	1.0000
4:73998204:A:AC	donor_gain	1.0000
4:73998205:C:CC	donor_gain	1.0000
4:73998205:CA:C	donor_gain	1.0000
4:73998205:CACCA:C	donor_gain	1.0000
4:73997653:CCA:C	acceptor_gain	0.9900
4:73997654:CA:C	acceptor_gain	0.9900
4:73997654:CAC:C	acceptor_gain	0.9900
4:73998037:T:A	donor_gain	0.9900
4:73998204:ACAC:A	donor_gain	0.9900
4:73998205:CACC:C	donor_gain	0.9900
4:73998212:T:TA	donor_gain	0.9900
4:73998256:A:AC	donor_gain	0.9900
4:73998257:C:CC	donor_gain	0.9900
4:73998472:CCG:C	donor_gain	0.9900
4:73997652:TCCA:T	acceptor_gain	0.9800
4:73997653:CCAC:C	acceptor_gain	0.9800
4:73998094:CT:C	acceptor_gain	0.9800
4:73998096:C:CC	acceptor_gain	0.9800
4:73998199:AACTT:A	donor_loss	0.9800
4:73998200:ACTT:A	donor_loss	0.9800
4:73998201:CTTAC:C	donor_loss	0.9800
4:73998202:TTAC:T	donor_loss	0.9800
4:73998203:T:TG	donor_loss	0.9800
4:73998205:C:CT	donor_loss	0.9800
4:73998261:T:C	donor_gain	0.9800
4:73998335:CCAG:C	acceptor_gain	0.9800
4:73998336:CAG:C	acceptor_gain	0.9800
4:73998336:CAGC:C	acceptor_gain	0.9800
4:73998015:T:TA	donor_gain	0.9700

AlphaMissense

724 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73998093:G:T	A82D	0.988
4:73998066:C:G	C91S	0.983
4:73998067:A:T	C91S	0.983
4:73998224:C:G	C75S	0.980
4:73998225:A:T	C75S	0.980
4:73998067:A:G	C91R	0.975
4:73998225:A:G	C75R	0.973
4:73998296:C:G	C51S	0.972
4:73998297:A:T	C51S	0.972
4:73998065:A:C	C91W	0.969
4:73998297:A:G	C51R	0.969
4:73998302:C:G	C49S	0.965
4:73998303:A:T	C49S	0.965
4:73998063:A:T	L92H	0.963
4:73998303:A:G	C49R	0.963
4:73998223:G:C	C75W	0.962
4:73998066:C:T	C91Y	0.961
4:73998260:A:C	I63S	0.961
4:73998260:A:G	I63T	0.953
4:73998296:C:T	C51Y	0.951
4:73998260:A:T	I63N	0.950
4:73998209:A:T	V80E	0.949
4:73998067:A:C	C91G	0.947
4:73998224:C:T	C75Y	0.946
4:73998211:T:A	E79D	0.945
4:73998211:T:G	E79D	0.945
4:73998295:A:C	C51W	0.945
4:73998302:C:T	C49Y	0.945
4:73998251:A:G	L66P	0.939
4:73998094:C:G	A82P	0.934

dbSNP variants (sampled 300 via entrez): RS1001818154 (4:73995484 G>A,C), RS1001986761 (4:73998665 T>A,G), RS1002036535 (4:73998461 A>C,G,T), RS1002602681 (4:74000133 A>G,T), RS1003458284 (4:73999879 G>A), RS1003583846 (4:74000123 A>G), RS1004497201 (4:73997202 C>T), RS1005961925 (4:73996583 GT>G,GTT), RS1006387742 (4:74000529 C>T), RS1006502848 (4:74000213 A>G,T), RS1007090829 (4:73995921 T>C), RS1007469321 (4:73996258 C>G), RS1007833872 (4:73997464 T>C), RS1008082372 (4:74000629 T>G), RS1008735567 (4:73995890 G>A,C)

Disease associations

OMIM: gene MIM:600324 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001639_7	Metabolite levels	3.000000e-10
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST002826_4	Urate levels (BMI interaction)	3.000000e-06
GCST009566_1	CXCL5 levels	4.000000e-26

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0009422	CXCL5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs352046	Efficacy	3	HMG-CoA reductase inhibitors	Acute coronary syndrome

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs352046	CXCL5	3	4.50	1	HMG-CoA reductase inhibitors

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	5
Particulate Matter	increases abundance, increases expression, decreases expression	5
Silicon Dioxide	increases expression	4
bisphenol A	decreases expression, increases expression, increases methylation, affects cotreatment	3
trichostatin A	decreases acetylation, increases expression	3
Air Pollutants	increases expression, increases abundance, decreases expression	3
Asbestos, Crocidolite	increases expression	3
methylmercuric chloride	increases expression	2
sodium arsenite	increases expression	2
cobaltous chloride	decreases expression, increases expression	2
entinostat	affects cotreatment, increases expression	2
belinostat	increases expression, affects cotreatment	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium	increases expression	2
Cannabidiol	decreases reaction, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Hydrogen Peroxide	increases expression, increases secretion	2
Lipopolysaccharides	affects expression, affects response to substance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Plant Extracts	decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
saroglitazar	affects cotreatment, decreases reaction, increases secretion	1
Glupearl 19S	increases expression	1
bisphenol F	decreases expression, affects cotreatment	1
GW 506033X	increases expression	1
lanifibranor	affects cotreatment, decreases reaction, increases secretion	1
sotorasib	affects cotreatment, increases expression	1
Asian ginseng	decreases reaction, increases expression	1

Clinical trials (associated diseases)

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