ACKR1

Chr 1

atypical chemokine receptor 1 (Duffy blood group)

Also known as: CCBP1, CD234, DARC, DARC/ACKR1, Dfy, FY, GPD, GpFy

NCBI Gene: 2532 ENSG00000213088 UniProt: Q16570

The protein encoded by this gene is a glycosylated membrane protein and a non-specific receptor for several chemokines. The encoded protein is the receptor for the human malarial parasites Plasmodium vivax and Plasmodium knowlesi. Polymorphisms in this gene are the basis of the Duffy blood group system. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.60

Clinical Summary— ACKR1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 40 VUS of 55 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 →

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?

1.60LOEUF

pLI 0.000

Z-score 0.41

OE 0.83 (0.46–1.60)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.49Z-score

OE missense 1.10 (0.98–1.24)

193 obs / 174.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.46–1.60)

0≤0.351.4

Missense OE?1.10 (0.98–1.24)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 6 / 7.2Missense obs/exp: 193 / 174.8Syn Z: -0.34

This gene — mechanism propensity

0.76top 25%

GOF

0.75top 25%

LOF

0.2582th %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

Pathogenic1

VUS40

Likely Benign5

Benign3

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	40	0	0	40
Likely Benign	0	3	1	1	5
Benign	0	2	0	1	3
Total	1	45	1	2	49

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ACKR1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →