CCR5

protein-coding

C-C motif chemokine receptor 5, the group of CD molecules|C-C motif chemokine receptors

Gene summary

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2015]

Previous symbols:

CMKBR5

MANE transcript

NM_001394783.1

Inheritance

—

ClinVar variants

U:34B:8

Top phenotype

CCR5-related disorder

gnomAD constraint

pLI —, LoF o/e 1.51

Max pathogenic AF

—

Genomic locus

chr3:46,370,946-46,376,206

External References & Databases

Ensembl (ENSG00000160791)

Transcript & Mutation Effects

hg38 • Region Span ~5.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCR5 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 26

CCR5-related disorderTotal: 7

not providedTotal: 4

Susceptibility to HIV infectionTotal: 3

West Nile virus, susceptibility toTotal: 1

CCR5 POLYMORPHISM, AFRICAN-AMERICANTotal: 1

CCR5 POLYMORPHISM, ORIENTAL 1Total: 1

CCR5 POLYMORPHISM, ORIENTAL 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394783.1. 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				4 clinvar		4
missense			33 clinvar	1 clinvar	2 clinvar	36
nonsense			1 clinvar			1
start loss						0
frameshift					1 clinvar	1
splice donor/acceptor (+/-2bp)						0
Total	0	0	34	5	3	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394783.1	RefSeq	NP_001381712.1	1	MANE Select
ENST00000292303.5	Ensembl	ENSP00000292303.4	1	MANE Select
NM_000579.4	RefSeq	NP_000570.1	1	Standard
NM_001100168.2	RefSeq	NP_001093638.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
Endocytosis - Homo sapiens (human)
Chemokine signaling pathway - Homo sapiens (human)
Toxoplasmosis - Homo sapiens (human)
Viral carcinogenesis - Homo sapiens (human)

Biological Process

MAPK cascade
dendritic cell chemotaxis
calcium ion transport
chemotaxis
inflammatory response

Molecular Function

virus receptor activity
actin binding
phosphatidylinositol phospholipase C activity
chemokine receptor activity
protein binding

Cellular Component

cytoplasm
endosome
plasma membrane
integral component of plasma membrane
external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000343801
Coding exons: 1
Length: 6065
Individuals with no LoFs: 107830
Homozygous LoFs: 970
Heterozygous LoFs: 16943
Defined: 125743
p: 0.0740

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.46	242	186	1.30	0.00000990	2313
Missense (PolyPhen)		74	53.581	1.3811		728
Synonymous	-1.20	92	78.4	1.17	0.00000456	711
Loss of Function	-1.33	12	7.94	1.51	4.10e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.021	0.021	notable
Latino/Admixed American	0.030	0.030	notable
Ashkenazi Jewish	0.13	0.13	notable
East Asian	0.00016	0.00016	rare
Finnish	0.13	0.13	notable
European (Non-Finnish)	0.11	0.11	notable
South Asian	0.016	0.016	notable
Other	0.075	0.073	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. {ECO:0000269|PubMed:10383387, ECO:0000269|PubMed:11323418, ECO:0000269|PubMed:8639485, ECO:0000269|PubMed:8663314, ECO:0000269|PubMed:8699119}.;
Disease: DISEASE: Diabetes mellitus, insulin-dependent, 22 (IDDM22) [MIM:612522]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:19073967}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.807
RVIS EVS: 0.49
RVIS percentile EVS: 79.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.869

Gene Damage Prediction

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