CXCR3
protein-codingC-X-C motif chemokine receptor 3, the group of CD molecules|C-X-C motif chemokine receptors
Gene summary
This gene encodes a G protein-coupled receptor with selectivity for three chemokines, termed CXCL9/Mig (monokine induced by interferon-g), CXCL10/IP10 (interferon-g-inducible 10 kDa protein) and CXCL11/I-TAC (interferon-inducible T cell a-chemoattractant). Binding of chemokines to this protein induces cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the isoforms (CXCR3-B) shows high affinity binding to chemokine, CXCL4/PF4 (PMID:12782716). [provided by RefSeq, Jun 2011]
- GPR9
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.6 kbGenCC 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 CXCR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001504.2. 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 | 3 | 3 | ||||
| missense | 30 | 4 | 34 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 30 | 7 | 0 | 37 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001495.1 | 2 | MANE Select | |
| Ensembl | ENSP00000362797.3 | 2 | MANE Select | |
| RefSeq | NP_001136269.1 | 1 | Standard | |
| Ensembl | ENSP00000362795.4 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cxcr3.2 | Danio rerio | Structure: trunk Quality: decreased cellular motility abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chemokine signaling pathway - Homo sapiens (human)
- Cytokine-cytokine receptor interaction - Homo sapiens (human)
- GPCRs, Other
- Peptide GPCRs
- Chemokine signaling pathway
Biological Process
- angiogenesis
- regulation of leukocyte migration
- apoptotic process
- chemotaxis
- inflammatory response
Molecular Function
- chemokine receptor activity
- C-C chemokine receptor activity
- C-X-C chemokine receptor activity
- chemokine binding
- C-C chemokine binding
Cellular Component
- cytoplasm
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000373691
- Coding exons
- 1
- Length
- 2602
- Individuals with no LoFs
- 125583
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 2
- Defined
- 125587
- p
- 0.0000159
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.74 | 111 | 176 | 0.630 | 0.0000162 | 2599 |
| Missense (PolyPhen) | 20 | 54.007 | 0.37032 | 823 | ||
| Synonymous | 0.948 | 76 | 87.3 | 0.871 | 0.00000827 | 962 |
| Loss of Function | 1.63 | 2 | 6.50 | 0.308 | 4.86e-7 | 106 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000081 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000072 | 0.000046 | rare |
| European (Non-Finnish) | 0.000028 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 1: Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway (PubMed:12782716). Binds to CCL21. Probably promotes cell chemotaxis response. {ECO:0000269|PubMed:12782716}.; FUNCTION: Isoform 3: Mediates the activity of CXCL11.;
Recessive Scores
- pRec
- 0.384
Intolerance Scores
- LoFtool
- 0.509
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 46.49
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |