CCR2

Chr 3AR

C-C motif chemokine receptor 2

Also known as: CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2, CKR2A, CKR2B

CCR2 encodes a G-protein coupled receptor that binds chemokines including CCL2 to mediate monocyte and macrophage chemotaxis and migration, playing key roles in immune cell recruitment and inflammatory responses. Autosomal recessive mutations cause polycystic lung disease and affect susceptibility to HIV infection. The gene shows low constraint to loss-of-function variants (pLI 0.02, LOEUF 0.976), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.982 OMIM phenotypes
Clinical SummaryCCR2
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 39 VUS of 68 total submissions
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.023
Z-score 1.63
OE 0.43 (0.210.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.03Z-score
OE missense 0.99 (0.881.12)
195 obs / 196.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.43 (0.210.98)
00.351.4
Missense OE0.99 (0.881.12)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 4 / 9.4Missense obs/exp: 195 / 196.3Syn Z: -0.38
DN
0.86top 5%
GOF
0.82top 10%
LOF
0.1895th %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

68 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS39
Likely Benign6
Benign4
12
Pathogenic
1
Likely Pathogenic
39
VUS
6
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
4
7
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
38
1
0
39
Likely Benign
0
2
0
4
6
Benign
0
1
0
3
4
Total1459762

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

View in ClinVar →

Protein Context — Lollipop Plot

CCR2 · 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 ↗