CCR2

protein-coding

C-C motif chemokine receptor 2, the group of C-C motif chemokine receptors|CD molecules

Gene summary

The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3. [provided by RefSeq, Aug 2017]

Previous symbols:

CMKBR2

MANE transcript

NM_001123396.4

Inheritance

ClinVar variants

P:5U:35B:7

Top phenotype

Polycystic lung disease

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr3:46,353,864-46,360,940

External References & Databases

Ensembl (ENSG00000121807)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Polycystic lung diseaseAR

Manifestation: Allergy/Immunology/Infectious; Pulmonary

Intervention: Allergy/Immunology/Infectious; Pulmonary

Rationale: Individuals are at increased risk of recurrent respiratory infections, and have been reported to have adverse reactions to BCG, and awareness may allow early medical management related to pulmonary health as well as vaccine regimens

Refs: 38157855

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCR2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 28

Cystic disease of lungTotal: 8

not providedTotal: 3

CCR2-related disorderTotal: 2

Susceptibility to HIV infectionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001123396.4. 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	4 clinvar	1 clinvar	6
missense	3 clinvar		33 clinvar	2 clinvar		38
nonsense		1 clinvar				1
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	4	1	35	6	1	47

Highest pathogenic variant AF is 0.0000068148333

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001123396.4	RefSeq	NP_001116868.1	1	MANE Select
ENST00000445132.3	Ensembl	ENSP00000399285.2	1	MANE Select
NM_001123041.3	RefSeq	NP_001116513.2	2	Standard
ENST00000400888.2	Ensembl	ENSP00000383681.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chemokine signaling pathway - Homo sapiens (human)
Cytokine-cytokine receptor interaction - Homo sapiens (human)
Peptide GPCRs
Spinal Cord Injury
Lung fibrosis

Biological Process

blood vessel remodeling
dendritic cell chemotaxis
monocyte chemotaxis
positive regulation of T-helper 1 type immune response
negative regulation of type 2 immune response

Molecular Function

chemokine receptor activity
protein binding
C-C chemokine receptor activity
chemokine binding
C-C chemokine binding

Cellular Component

cytoplasm
cytosol
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: ENST00000292301
Coding exons: 2
Length: 7195
Individuals with no LoFs: 125727
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125738
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0339	195	196	0.993	0.0000111	2443
Missense (PolyPhen)		44	51.845	0.84868		719
Synonymous	-0.384	86	81.6	1.05	0.00000527	779
Loss of Function	1.63	4	9.37	0.427	5.75e-7	104

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the CCL2, CCL7 and CCL13 chemokines (PubMed:23408426). Receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Transduces a signal by increasing intracellular calcium ion levels (By similarity). Upon CCL2 ligation, mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable). {ECO:0000250|UniProtKB:P51683, ECO:0000269|PubMed:23408426, ECO:0000269|PubMed:23938203, ECO:0000305|PubMed:15995708}.;

Intolerance Scores

LoFtool: 0.390
RVIS EVS: -0.09
RVIS percentile EVS: 46.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.121

Gene Damage Prediction

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