ACKR1

protein-coding

atypical chemokine receptor 1 (Duffy blood group), the group of Atypical chemokine receptors|CD molecules|Blood group antigens

Gene summary

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]

Previous symbols:

FY
DARC

MANE transcript

NM_002036.4

Inheritance

ClinVar variants

P:1U:46B:7

Top phenotype

Blood group, Duffy system

gnomAD constraint

pLI —, LoF o/e 0.83

Max pathogenic AF

—

Genomic locus

chr1:159,204,875-159,206,500

External References & Databases

Ensembl (ENSG00000213088)

Transcript & Mutation Effects

hg38 • Region Span ~1.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, Duffy systemBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 6386656; 8248172; 7663520; 7669660; 7705836; 8547665; 9886340; 9746760; 9731074; 10073905; 10570183; 20932074

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACKR1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 45

ACKR1-related disorderTotal: 4

not providedTotal: 1

DUFFY BLOOD GROUP SYSTEM, FY(a-b-) PHENOTYPETotal: 1

Duffy Blood group systemTotal: 1

DUFFY BLOOD GROUP SYSTEM, FY(bwk) PHENOTYPETotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002036.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	3 clinvar	1 clinvar	5
missense			45 clinvar	3 clinvar		48
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)						0
Total	1	0	46	6	1	54

Highest pathogenic variant AF is 6.8414425e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002036.4	RefSeq	NP_002027.2	2	MANE Select
ENST00000368122.4	Ensembl	ENSP00000357104.1	2	MANE Select
NM_001122951.3	RefSeq	NP_001116423.1	1	Standard
ENST00000368121.6	Ensembl	ENSP00000357103.2	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Malaria - Homo sapiens (human)
GPCRs, Other
Peptide GPCRs
Signaling by GPCR
Signal Transduction

Biological Process

defense response
inflammatory response
G protein-coupled receptor signaling pathway
regulation of chemokine production
chemokine-mediated signaling pathway

Molecular Function

transmembrane signaling receptor activity
G protein-coupled receptor activity
C-C chemokine binding
signaling receptor activity

Cellular Component

early endosome
plasma membrane
integral component of membrane
recycling endosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368121
Coding exons: 1
Length: 3194
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.489	193	175	1.10	0.00000855	2122
Missense (PolyPhen)		62	59.501	1.042		779
Synonymous	-0.338	87	83.1	1.05	0.00000412	799
Loss of Function	0.411	6	7.19	0.835	3.11e-7	80

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.;

Recessive Scores

pRec: 0.0721

Intolerance Scores

RVIS EVS: 0.28
RVIS percentile EVS: 71.41

Essentials

Essential (gene trap): N