CXCR1

protein-coding

C-X-C motif chemokine receptor 1, the group of CD molecules|Interleukin receptors|C-X-C motif chemokine receptors

Gene summary

The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. This gene, IL8RB, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. [provided by RefSeq, Jul 2008]

Previous symbols:

CMKAR1
IL8RA

MANE transcript

NM_000634.3

Inheritance

—

ClinVar variants

U:67B:12

Top phenotype

CXCR1-related disorder

gnomAD constraint

pLI —, LoF o/e 1.24

Max pathogenic AF

—

Genomic locus

chr2:218,162,841-218,166,962

External References & Databases

Ensembl (ENSG00000163464)

Transcript & Mutation Effects

hg38 • Region Span ~4.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CXCR1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 8

CXCR1-related disorderTotal: 5

Susceptibility to HIV infectionTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000634.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar	1 clinvar	6
missense			66 clinvar	4 clinvar	2 clinvar	72
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	67	9	3	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000634.3	RefSeq	NP_000625.1	1	MANE Select
ENST00000295683.3	Ensembl	ENSP00000295683.2	1	MANE Select
ENST00001137677.1	Ensembl	ENSP00000805029.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cxcr1	Danio rerio	Structure: blood island Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

cxcr1

Danio rerio

Structure: blood island

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Chemokine signaling pathway - Homo sapiens (human)
Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
Phospholipase D signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)

Biological Process

dendritic cell chemotaxis
chemotaxis
immune response
cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway

Molecular Function

interleukin-8 receptor activity
G protein-coupled receptor activity
chemokine receptor activity
C-C chemokine receptor activity
chemokine binding

Cellular Component

plasma membrane
external side of plasma membrane
integral component of membrane
secretory granule membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295683
Coding exons: 1
Length: 4151
Individuals with no LoFs: 125615
Homozygous LoFs: 1
Heterozygous LoFs: 120
Defined: 125736
p: 0.000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.411	214	198	1.08	0.0000122	2270
Missense (PolyPhen)		57	53.197	1.0715		681
Synonymous	-1.42	101	84.4	1.20	0.00000467	759
Loss of Function	-0.594	9	7.27	1.24	4.05e-7	84

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.0021	0.0021	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activate a phosphatidylinositol-calcium second messenger system. This receptor binds to IL-8 with a high affinity and to MGSA (GRO) with a low affinity.;

Recessive Scores

pRec: 0.307

Intolerance Scores

LoFtool: 0.750
RVIS EVS: 0.46
RVIS percentile EVS: 78.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium