ACKR2

atypical chemokine receptor 2, the group of Atypical chemokine receptors

Basic information

Region (hg38): 3:42804752-42887974

Previous symbols: [ "CMKBR9", "CCBP2" ]

Links

ENSG00000144648 ∙ NCBI:1238 ∙ OMIM:602648 ∙ HGNC:1565 ∙ Uniprot:O00590 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACKR2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACKR2 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						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in ACKR2

This is a list of pathogenic ClinVar variants found in the ACKR2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-42864668-A-G		not specified	Uncertain significance (Nov 12, 2021)
3-42864678-T-G		not specified	Uncertain significance (Sep 30, 2021)
3-42865008-G-C		not specified	Uncertain significance (Aug 10, 2021)
3-42865017-C-G		not specified	Uncertain significance (Jun 18, 2021)
3-42865076-G-A		not specified	Uncertain significance (Aug 10, 2021)
3-42865244-G-A		not specified	Uncertain significance (Jul 09, 2021)
3-42865449-G-T		not specified	Uncertain significance (Dec 21, 2023)
3-42865451-C-T		not specified	Uncertain significance (Dec 21, 2023)
3-42874490-T-C		not specified	Uncertain significance (Jul 05, 2023)
3-42874509-G-T			Likely benign (Jun 01, 2022)
3-42874524-C-T		not specified	Uncertain significance (Dec 21, 2023)
3-42874543-T-A		not specified	Uncertain significance (Apr 26, 2023)
3-42874572-C-T			Likely benign (Jun 01, 2022)
3-42874613-C-T			Benign (Mar 28, 2018)
3-42874628-G-A		not specified	Uncertain significance (Dec 16, 2023)
3-42874637-G-A		not specified	Uncertain significance (May 10, 2024)
3-42874643-T-C		not specified	Likely benign (Jun 06, 2023)
3-42874654-A-G		not specified	Uncertain significance (Jun 22, 2021)
3-42874688-G-A		not specified	Uncertain significance (Jun 11, 2021)
3-42874746-G-A			Benign (Apr 04, 2018)
3-42874748-G-A			Benign (Jul 31, 2018)
3-42874753-G-T		not specified	Uncertain significance (Aug 10, 2021)
3-42874772-G-A		not specified	Uncertain significance (Jan 29, 2024)
3-42875019-C-A			Benign (Dec 31, 2019)
3-42875038-T-A		not specified	Uncertain significance (May 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACKR2	protein_coding	protein_coding	ENST00000422265	1	83223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00139	0.679	125710	1	37	125748	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.263	205	216	0.950	0.0000130	2525
Missense in Polyphen		67	61.346	1.0922		858
Synonymous	-0.0139	92	91.8	1.00	0.00000570	795
Loss of Function	0.712	5	7.04	0.710	3.08e-7	82

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000723	0.000723
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.000229	0.000229
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. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein- independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1- LIMK1 signaling pathway. Activation of this pathway results in up- regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs. {ECO:0000269|PubMed:23479571, ECO:0000269|PubMed:23633677}.
• Pathway: GPCRs, Class A Rhodopsin-like (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.69

Haploinsufficiency Scores

• pHI: 0.0673
• hipred: N
• hipred_score: 0.123
• ghis: 0.519

Essentials

• essential_gene_CRISPR: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ackr2
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: receptor-mediated endocytosis;chemotaxis;inflammatory response;immune response;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;multicellular organism development;calcium-mediated signaling;cell chemotaxis;chemokine-mediated signaling pathway
• Cellular component: nucleoplasm;early endosome;cytosol;actin filament;plasma membrane;integral component of plasma membrane;external side of plasma membrane;nuclear membrane;intracellular membrane-bounded organelle;recycling endosome
• Molecular function: chemokine receptor activity;scavenger receptor activity;C-C chemokine receptor activity;chemokine binding;C-C chemokine binding