XCR1

Chr 3

X-C motif chemokine receptor 1

Also known as: CCXCR1, GPR5

NCBI Gene: 2829ENSG00000173578UniProt: P46094OMIM: 600552

The protein encoded by this gene is a chemokine receptor that binds XCL1/lymphotactin and transduces signals by increasing intracellular calcium levels. This gene is not well-established as a cause of Mendelian disease in clinical practice, and the gene shows tolerance to loss-of-function variants with a low constraint score (pLI 0.016, LOEUF 1.084). While some studies have suggested associations with COVID-19 susceptibility and cancer, these do not represent established pediatric neurogenetic conditions.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.08
Clinical Summary— XCR1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 51 VUS of 63 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.016
Z-score 1.42
OE 0.47 (0.23–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.12Z-score
OE missense 0.78 (0.68–0.89)
158 obs / 202.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.23–1.08)
0≤0.351.4
Missense OE0.78 (0.68–0.89)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 4 / 8.4Missense obs/exp: 158 / 202.9Syn Z: 0.32
DN
0.78top 25%
GOF
0.79top 25%
LOF
0.1894th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS51
Likely Benign4
7
Pathogenic
1
Likely Pathogenic
51
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
48
3
0
51
Likely Benign
0
3
1
0
4
Benign
0
0
0
0
0
Total05112063

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

XCR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients