CCR5

Chr 3

C-C motif chemokine receptor 5

Also known as: CC-CKR-5, CCCKR5, CCR-5, CD195, CKR-5, CKR5, CMKBR5, IDDM22

NCBI Gene: 1234ENSG00000160791UniProt: P51681OMIM: 601373

This gene encodes a G protein-coupled chemokine receptor expressed on T cells and macrophages that responds to inflammatory chemokines including MIP-1-alpha, MIP-1-beta, and RANTES by increasing intracellular calcium and promoting T-lymphocyte migration to infection sites. Mutations cause increased susceptibility to HIV infection, West Nile virus, and insulin-dependent diabetes mellitus type 22, while some variants confer resistance to hepatitis C virus. The gene is extremely tolerant to loss-of-function variants (pLI near zero, LOEUF 1.93), suggesting that complete loss of function may be well-tolerated or even protective in certain contexts.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 1.934 OMIM phenotypes
Clinical Summary— CCR5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 30 VUS of 55 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — CCR5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.93LOEUF
pLI 0.000
Z-score -1.33
OE 1.51 (0.93–1.93)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.45Z-score
OE missense 1.30 (1.17–1.45)
242 obs / 186.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.51 (0.93–1.93)
0≤0.351.4
Missense OE1.30 (1.17–1.45)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 12 / 7.9Missense obs/exp: 242 / 186.1Syn Z: -1.20
DN
0.79top 25%
GOF
0.72top 25%
LOF
0.2777th %ile

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

DNprediction above median
GOFprediction 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

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS30
Likely Benign4
Benign5
Conflicting1
7
Pathogenic
1
Likely Pathogenic
30
VUS
4
Likely Benign
5
Benign
1
Conflicting

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
29
1
0
30
Likely Benign
0
1
0
3
4
Benign
2
2
1
0
5
Conflicting
—1
Total23210348

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

View in ClinVar →

Protein Context — Lollipop Plot

CCR5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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
Adeno-associated virus gene therapy-mediated CCR5 blockade suppresses virus replication long term in SHIV-infected macaques.
Wu HL et al.·Sci Transl Med
2026
CCR5+ NK cells drive hypoxemia in endotoxin-induced acute lung injury.
Bharti R et al.·Am J Respir Cell Mol Biol
2026
Novel NK cell-like phenotype expressing CCR5 and its ligands elicits tumor-specific acquired immunity to carcinomatous peritonitis via host NK-derived IFN-γ.
Zheng S et al.·J Immunother Cancer
2026
CCR5 as a key mediator: Insights into the molecular mechanisms by which air pollutants induce Alzheimer's disease via network toxicology and molecular docking.
Zhang Y et al.·Brain Res Bull
2026Functional
Flow cytometry-based detection of functional CCR5 variants: A scalable screening approach for HIV-resistant cord blood stem cells.
Simard C et al.·Transfusion
2026Functional
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