ACKR1

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

Basic information

Region (hg38): 1:159203306-159206500

Previous symbols: [ "FY", "DARC" ]

Links

ENSG00000213088 ∙ NCBI:2532 ∙ OMIM:613665 ∙ HGNC:4035 ∙ Uniprot:Q16570 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Blood group, Duffy system	BG	Hematologic	Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Hematologic	6386656; 8248172; 7663520; 7669660; 7705836; 8547665; 9886340; 9746760; 9731074; 10073905; 10570183; 20932074

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACKR1 gene.

• Inborn genetic diseases (11 variants)
• not specified (1 variants)
• DUFFY BLOOD GROUP SYSTEM, FYA/FYB POLYMORPHISM (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACKR1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			10	1	1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	1	2

Variants in ACKR1

This is a list of pathogenic ClinVar variants found in the ACKR1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-159204886-G-A		ACKR1-related disorder	Likely benign (Apr 25, 2019)
1-159204893-T-C		Resistance to Plasmodium vivax infection • DUFFY BLOOD GROUP SYSTEM, FY(a-b-) PHENOTYPE • White blood cell count quantitative trait locus 1	Pathogenic; association; protective (Dec 11, 2017)
1-159205480-C-T		not specified	Uncertain significance (Oct 12, 2022)
1-159205506-G-A		not specified	Uncertain significance (Dec 20, 2021)
1-159205564-G-A		DUFFY BLOOD GROUP SYSTEM, FYA/FYB POLYMORPHISM • not specified • ACKR1-related disorder	Benign (Oct 16, 2019)
1-159205585-C-T		not specified	Uncertain significance (Jul 06, 2021)
1-159205638-C-T		Duffy Blood group system	Affects (Jul 01, 2021)
1-159205684-T-G		not specified	Uncertain significance (Jun 28, 2023)
1-159205703-C-A		not specified	Uncertain significance (Sep 12, 2023)
1-159205704-C-T		DUFFY BLOOD GROUP SYSTEM, FY(bwk) PHENOTYPE	Pathogenic (Jun 01, 2001)
1-159205718-CCCTGGCTGGCCTGT-C		DUFFY BLOOD GROUP SYSTEM, FY(a-b-) PHENOTYPE	Pathogenic (Apr 01, 2000)
1-159205720-C-G		not specified	Uncertain significance (Mar 31, 2023)
1-159205737-G-A		ACKR1-related disorder	Benign (Oct 21, 2019)
1-159205753-G-A		not specified	Uncertain significance (Sep 20, 2023)
1-159205810-G-A		not specified	Likely benign (Jan 27, 2022)
1-159205921-A-G		not specified	Uncertain significance (Mar 16, 2022)
1-159206042-G-A		ACKR1-related disorder	Likely benign (Sep 17, 2019)
1-159206094-G-A		not specified	Uncertain significance (Nov 08, 2022)
1-159206153-G-A			Benign (Jul 31, 2018)
1-159206168-G-A		not specified	Uncertain significance (Sep 07, 2022)
1-159206274-C-G		not specified	Uncertain significance (Jan 17, 2024)
1-159206397-C-T		not specified	Uncertain significance (May 11, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACKR1	protein_coding	protein_coding	ENST00000368121	1	3194

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000214	0.516	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.489	193	175	1.10	0.00000855	2122
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Malaria - Homo sapiens (human);GPCRs, Other;Peptide GPCRs;Signaling by GPCR;Signal Transduction;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding (Consensus)

Recessive Scores

• pRec: 0.0721

Intolerance Scores

• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.41

Haploinsufficiency Scores

• pHI: 0.0602
• hipred: N
• hipred_score: 0.153
• ghis: 0.448

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Ackr1
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; skeleton phenotype

Gene ontology

• Biological process: defense response;inflammatory response;G protein-coupled receptor signaling pathway;regulation of chemokine production;chemokine-mediated signaling pathway
• Cellular component: early endosome;plasma membrane;integral component of membrane;recycling endosome
• Molecular function: transmembrane signaling receptor activity;G protein-coupled receptor activity;C-C chemokine binding;signaling receptor activity