CXCR2

protein-coding

C-X-C motif chemokine receptor 2, the group of C-X-C motif chemokine receptors|CD molecules|Interleukin 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. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, 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. Alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2009]

Previous symbols:

IL8RB

MANE transcript

NM_001557.4

Inheritance

ClinVar variants

P:7U:122B:111

Top phenotype

WHIM syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr2:218,125,289-218,137,251

External References & Databases

Ensembl (ENSG00000180871)

Transcript & Mutation Effects

hg38 • Region Span ~12.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive severe congenital neutropenia due to CXCR2 deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0018487

Submitter: Orphanet

autosomal recessive severe congenital neutropenia due to CXCR2 deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0018487

Submitter: Ambry Genetics

WHIM syndrome 2STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030374

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CXCR2 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 203

not specifiedTotal: 70

CXCR2-related disorderTotal: 9

WHIM syndrome 2Total: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001557.4. 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			1 clinvar	94 clinvar	3 clinvar	98
missense	1 clinvar	1 clinvar	120 clinvar	12 clinvar	2 clinvar	136
nonsense	1 clinvar	1 clinvar				2
start loss						0
frameshift	3 clinvar		1 clinvar			4
splice donor/acceptor (+/-2bp)						0
Total	5	2	122	106	5	240

Highest pathogenic variant AF is 0.000009912977

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001557.4	RefSeq	NP_001548.1	1	MANE Select
ENST00000318507.7	Ensembl	ENSP00000319635.2	1	MANE Select
NM_001168298.2	RefSeq	NP_001161770.1	1	Standard
ENST00000415392.5	Ensembl	ENSP00000392348.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cxcr2	Danio rerio	Structure: vasculature Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

cxcr2

Danio rerio

Structure: vasculature

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
acute inflammatory response to antigenic stimulus
chemotaxis
inflammatory response
immune response

Molecular Function

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

Cellular Component

plasma membrane
integral component of plasma membrane
external side of plasma membrane
cell surface
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318507
Coding exons: 1
Length: 11965
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.182	192	199	0.964	0.0000124	2328
Missense (PolyPhen)		69	85.077	0.81103		1024
Synonymous	-1.55	106	87.6	1.21	0.00000508	781
Loss of Function	1.33	4	8.08	0.495	4.39e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.;

Recessive Scores

pRec: 0.325

Intolerance Scores

LoFtool: 0.475
RVIS EVS: 0.6
RVIS percentile EVS: 82.74

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