CCR4

Chr 3

C-C motif chemokine receptor 4

Also known as: CC-CKR-4, CD194, CKR4, CMKBR4, ChemR13, HGCN:14099, K5-5

NCBI Gene: 1233 ENSG00000183813 UniProt: Q9UK39

The encoded protein is a phosphatase that converts NADP+ to NAD+ and regulates post-transcriptional control of metabolic genes under circadian control, playing key roles in nutrient metabolism, adipogenesis, and early embryonic development. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability, seizures, and metabolic dysfunction. The gene shows low constraint to loss-of-function variants, consistent with recessive inheritance patterns.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the G-protein-coupled receptor family . It is a receptor for the CC chemokine - MIP-1, RANTES, TARC and MCP-1. Chemokines are a group of small polypeptide, structurally related molecules that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

283

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.97

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.069

Z-score 1.63

OE 0.38 (0.17–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.75Z-score

OE missense 0.85 (0.75–0.97)

164 obs / 193.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.17–0.97)

0≤0.351.4

Missense OE?0.85 (0.75–0.97)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 3 / 8.0Missense obs/exp: 164 / 193.2Syn Z: -1.74

Background carrier burden — how many people carry a rare variant somewhere in CCR4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

416 rare PASS variants

Rare truncating (LoF)

1 in 5,600

49 rare PASS variants

Rare synonymous (reference)

1 in 210

226 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCR4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 290	1 in 7,800
South Asian	~43k	1 in 200	1 in 2,100
Remaining (unassigned)	~30k	1 in 200	1 in 6,000
European (Finnish)	~27k	1 in 1,200	≈ 1 in 6,700
Admixed American	~22k	1 in 180	≈ 1 in 7,600
African / African American	~21k	1 in 270	≈ 1 in 4,900
East Asian	~20k	1 in 220	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 720	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 360	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓