CCR9

Chr 3

C-C motif chemokine receptor 9

Also known as: CC-CKR-9, CDw199, GPR-9-6, GPR28

NCBI Gene: 10803ENSG00000173585UniProt: P51686OMIM: 604738

CCR9 encodes a G protein-coupled chemokine receptor that binds CCL25/TECK and regulates T lymphocyte homing to the small intestine by increasing intracellular calcium levels. Biallelic mutations cause combined immunodeficiency with intestinal atresias, a severe early-onset disorder affecting both immune function and gastrointestinal development. This condition follows autosomal recessive inheritance.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.13
Clinical Summary— CCR9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 54 VUS of 71 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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
1.13LOEUF
pLI 0.004
Z-score 1.31
OE 0.54 (0.28–1.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.96Z-score
OE missense 0.81 (0.71–0.92)
165 obs / 203.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.28–1.13)
0≤0.351.4
Missense OE0.81 (0.71–0.92)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 5 / 9.3Missense obs/exp: 165 / 203.4Syn Z: 0.68
DN
0.83top 10%
GOF
0.78top 25%
LOF
0.1994th %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

71 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS54
Likely Benign2
Benign2
Conflicting1
7
Pathogenic
1
Likely Pathogenic
54
VUS
2
Likely Benign
2
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
51
3
0
54
Likely Benign
0
1
1
0
2
Benign
0
1
0
1
2
Conflicting
—1
Total05312167

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

View in ClinVar →

Protein Context — Lollipop Plot

CCR9 · 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
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