ACKR3

Chr 2AR

atypical chemokine receptor 3

Also known as: CMKOR1, CXC-R7, CXCR-7, CXCR7, GPR159, RDC-1, RDC1

NCBI Gene: 57007 ENSG00000144476 UniProt: P25106 OMIM: 610376

ACKR3 encodes an atypical chemokine receptor that regulates chemokine levels through high-affinity binding and internalization, and controls axon guidance in the oculomotor system by regulating CXCL12 levels. Mutations cause oculomotor-abducens synkinesis with autosomal recessive inheritance. This gene has moderate constraint against loss-of-function variants (LOEUF 0.68).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the G-protein coupled receptor family. Although this protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP), it is now considered to be an orphan receptor, in that its endogenous ligand has not been identified. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Oculomotor-abducens synkinesisMIM #619215

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.391

Z-score 2.20

OE 0.22 (0.09–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.95Z-score

OE missense 0.82 (0.73–0.93)

180 obs / 219.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.09–0.68)

0≤0.351.4

Missense OE?0.82 (0.73–0.93)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 2 / 9.2Missense obs/exp: 180 / 219.4Syn Z: -0.31

Background carrier burden — how many people carry a rare variant somewhere in ACKR3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

415 rare PASS variants

Rare truncating (LoF)

1 in 17,000

16 rare PASS variants

Rare synonymous (reference)

1 in 150

224 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACKR3. 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 170	1 in 15,000
South Asian	~43k	1 in 85	none seen
Remaining (unassigned)	~30k	1 in 110	none seen
European (Finnish)	~27k	1 in 270	none seen
Admixed American	~22k	1 in 130	none seen
African / African American	~21k	1 in 140	≈ 1 in 9,300
East Asian	~20k	1 in 200	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 97	none seen

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 ↓