CX3CR1
protein-codingC-X3-C motif chemokine receptor 1, the group of C-X-3-C motif chemokine receptors
Gene summary
Fractalkine is a transmembrane protein and chemokine involved in the adhesion and migration of leukocytes. The protein encoded by this gene is a receptor for fractalkine. The encoded protein also is a coreceptor for HIV-1, and some variations in this gene lead to increased susceptibility to HIV-1 infection and rapid progression to AIDS. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
- GPR13
- CMKBRL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.2 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 CX3CR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001337.4. 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 | 5 | 2 | 7 | |||
| missense | 38 | 4 | 1 | 43 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 9 | 3 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001328.1 | 1 | MANE Select | |
| Ensembl | ENSP00000382166.3 | 1 | MANE Select | |
| RefSeq | NP_001164642.1 | 1 | Standard | |
| RefSeq | NP_001164643.1 | 1 | Standard |
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)
- Peptide GPCRs
- Chemokine signaling pathway
- GPCRs, Class A Rhodopsin-like
Biological Process
- positive regulation of neuroblast proliferation
- response to ischemia
- chemotaxis
- immune response
- cellular defense response
Molecular Function
- G protein-coupled receptor activity
- chemokine receptor activity
- protein binding
- G protein-coupled peptide receptor activity
- C-C chemokine receptor activity
Cellular Component
- nucleus
- nucleoplasm
- plasma membrane
- integral component of plasma membrane
- external side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358309
- Coding exons
- 2
- Length
- 18242
- Individuals with no LoFs
- 124787
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124794
- p
- 0.0000280
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.08 | 162 | 206 | 0.788 | 0.0000115 | 2563 |
| Missense (PolyPhen) | 47 | 68.084 | 0.69032 | 917 | ||
| Synonymous | -0.944 | 101 | 89.6 | 1.13 | 0.00000579 | 764 |
| Loss of Function | 1.56 | 3 | 7.67 | 0.391 | 3.30e-7 | 108 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000056 | 0.000056 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Receptor for the CX3C chemokine fractalkine (CX3CL1); binds to CX3CL1 and mediates both its adhesive and migratory functions (PubMed:9390561, PubMed:23125415). Acts as coreceptor with CD4 for HIV-1 virus envelope protein (in vitro) (PubMed:9726990). Isoform 2 and isoform 3 seem to be more potent HIV-1 coreceptors than isoform 1 (PubMed:14607932). {ECO:0000269|PubMed:14607932, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:9390561, ECO:0000269|PubMed:9726990}.;
- Disease
- DISEASE: Macular degeneration, age-related, 12 (ARMD12) [MIM:613784]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:15208270}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.366
Intolerance Scores
- LoFtool
- 0.397
- RVIS EVS
- 0.93
- RVIS percentile EVS
- 89.79
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00346
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |