ACKR3

atypical chemokine receptor 3, the group of Atypical chemokine receptors

Basic information

Region (hg38): 2:236567786-236582354

Previous symbols: [ "CMKOR1", "CXCR7" ]

Links

ENSG00000144476 ∙ NCBI:57007 ∙ OMIM:610376 ∙ HGNC:23692 ∙ Uniprot:P25106 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oculomotor-abducens synkinesis (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oculomotor-abducens synkinesis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	30372748

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACKR3 gene.

• Inborn genetic diseases (14 variants)
• not provided (4 variants)
• Premature ovarian failure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACKR3 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					2	2
missense			14	2	1	17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	14	2	3

Variants in ACKR3

This is a list of pathogenic ClinVar variants found in the ACKR3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-236580557-C-T		not specified	Uncertain significance (Nov 08, 2022)
2-236580601-A-G		not specified	Uncertain significance (Aug 02, 2022)
2-236580602-C-T		not specified	Uncertain significance (Oct 04, 2022)
2-236580631-G-A		not specified	Uncertain significance (Dec 14, 2021)
2-236580655-G-C			Likely benign (Feb 26, 2018)
2-236580695-A-G		not specified	Uncertain significance (Dec 16, 2022)
2-236580778-G-A		not specified	Uncertain significance (Nov 07, 2022)
2-236580812-C-T		not specified	Uncertain significance (Aug 22, 2023)
2-236580842-T-A		not specified	Uncertain significance (Jan 12, 2024)
2-236580874-T-G		not specified	Uncertain significance (Nov 06, 2023)
2-236580949-C-T		not specified	Uncertain significance (Dec 21, 2022)
2-236581040-A-G		not specified	Uncertain significance (Feb 14, 2023)
2-236581068-C-T			Benign (Dec 31, 2019)
2-236581095-C-T			Benign (Mar 19, 2018)
2-236581097-G-T		not specified	Uncertain significance (Sep 22, 2023)
2-236581144-A-G		not specified	Likely benign (Oct 26, 2022)
2-236581151-C-G		not specified	Uncertain significance (Dec 27, 2023)
2-236581153-G-A			Benign (Dec 31, 2019)
2-236581164-C-G		not specified	Uncertain significance (Jan 26, 2023)
2-236581187-C-T		not specified	Uncertain significance (May 23, 2023)
2-236581237-G-A		Oculomotor-abducens synkinesis	Pathogenic (Mar 04, 2021)
2-236581327-C-T		not specified	Uncertain significance (Sep 01, 2021)
2-236581351-G-A		not specified	Uncertain significance (Jul 20, 2021)
2-236581385-A-C		not specified	Uncertain significance (Aug 22, 2023)
2-236581420-A-C		not specified	Uncertain significance (May 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACKR3	protein_coding	protein_coding	ENST00000272928	1	14572

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.391	0.600	125746	0	2	125748	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.946	180	219	0.820	0.0000146	2390
Missense in Polyphen		36	67.634	0.53228		855
Synonymous	-0.312	107	103	1.04	0.00000803	733
Loss of Function	2.20	2	9.23	0.217	4.06e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
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. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein- mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates. {ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:16940167, ECO:0000269|PubMed:17804806, ECO:0000269|PubMed:18653785, ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:19380869, ECO:0000269|PubMed:19641136, ECO:0000269|PubMed:20018651, ECO:0000269|PubMed:20161793, ECO:0000269|PubMed:20388803, ECO:0000269|PubMed:20887389, ECO:0000269|PubMed:22300987}.
• Pathway: Cytokine-cytokine receptor interaction - Homo sapiens (human);Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;Myometrial Relaxation and Contraction Pathways;VEGFA-VEGFR2 Signaling Pathway;GPCRs, Class A Rhodopsin-like;Signaling by GPCR;Signal Transduction;Chemokine receptors bind chemokines;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.183

Intolerance Scores

• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.31

Haploinsufficiency Scores

• pHI: 0.0945
• hipred: Y
• hipred_score: 0.593
• ghis: 0.490

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: 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: Ackr3
• Phenotype: immune system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: ackr3a
• Affected structure: posterior lateral line neuromast primordium migration
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: angiogenesis;vasculogenesis;chemotaxis;immune response;cell adhesion;G protein-coupled receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;viral process;calcium-mediated signaling;receptor internalization;cell chemotaxis;chemokine-mediated signaling pathway;positive regulation of ERK1 and ERK2 cascade;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;positive regulation of mesenchymal stem cell migration
• Cellular component: nucleus;endosome;early endosome;plasma membrane;clathrin-coated pit;external side of plasma membrane;cell surface;integral component of membrane;intracellular membrane-bounded organelle;perinuclear region of cytoplasm;recycling endosome
• Molecular function: scavenger receptor activity;protein binding;coreceptor activity;C-C chemokine receptor activity;C-X-C chemokine receptor activity;chemokine binding;C-C chemokine binding;C-X-C chemokine binding