ADGRE2

protein-coding

adhesion G protein-coupled receptor E2, the group of Adhesion G protein-coupled receptors, subfamily E|CD molecules

Gene summary

This gene encodes a member of the class B seven-span transmembrane (TM7) subfamily of G-protein coupled receptors. These proteins are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor-like domains coupled to a TM7 domain via a mucin-like spacer domain. The encoded protein is expressed mainly in myeloid cells where it promotes cell-cell adhesion through interaction with chondroitin sulfate chains. This gene is situated in a cluster of related genes on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

Previous symbols:

EMR2

MANE transcript

NM_013447.4

Inheritance

ClinVar variants

P:2U:338B:202

Top phenotype

Vibratory urticaria

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr19:14,732,392-14,778,560

External References & Databases

Ensembl (ENSG00000127507)

Transcript & Mutation Effects

hg38 • Region Span ~46.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal dominant vibratory urticariaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007447

Submitter: Labcorp Genetics (formerly Invitae)

autosomal dominant vibratory urticariaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007447

Submitter: G2P

autosomal dominant vibratory urticariaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007447

Submitter: Orphanet

Clinical Genomic Database (CGD)

Vibratory urticariaAD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 7294069; 26841242

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADGRE2 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 518

not specifiedTotal: 215

ADGRE2-related disorderTotal: 26

Vibratory urticariaTotal: 10

Autosomal dominant vibratory urticariaTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013447.4. 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			9 clinvar	114 clinvar	5 clinvar	128
missense		1 clinvar	291 clinvar	40 clinvar	25 clinvar	357
nonsense		1 clinvar	16 clinvar	4 clinvar	4 clinvar	25
start loss			2 clinvar			2
frameshift			8 clinvar	3 clinvar	6 clinvar	17
splice donor/acceptor (+/-2bp)			12 clinvar		1 clinvar	13
Total	0	2	338	161	41	542

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013447.4	RefSeq	NP_038475.2	20	MANE Select
ENST00000315576.8	Ensembl	ENSP00000319883.3	20	MANE Select
NM_001271052.1	RefSeq	NP_001257981.1	19	Standard
NM_152916.2	RefSeq	NP_690880.1	19	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

GPCRs, Other
GPCRs, Class B Secretin-like
Signaling by GPCR
Signal Transduction
Class B/2 (Secretin family receptors)

Biological Process

inflammatory response
cell adhesion
cell surface receptor signaling pathway
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway

Molecular Function

G protein-coupled receptor activity
calcium ion binding
chondroitin sulfate binding

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane
leading edge membrane
ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315576
Coding exons: 20
Length: 46149
Individuals with no LoFs: 124800
Homozygous LoFs: 1
Heterozygous LoFs: 947
Defined: 125748
p: 0.00378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.654	430	470	0.915	0.0000273	5328
Missense (PolyPhen)		109	136.43	0.79893		1742
Synonymous	0.405	191	198	0.963	0.0000127	1616
Loss of Function	0.176	43	44.3	0.972	0.00000199	495

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0010	0.0010	notable
Latino/Admixed American	0.0018	0.0018	notable
Ashkenazi Jewish	0.00060	0.00060	rare
East Asian	0.0091	0.0091	notable
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.0022	0.0022	notable
South Asian	0.014	0.014	notable
Other	0.0026	0.0024	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cell surface receptor that binds to the chondroitin sulfate moiety of glycosaminoglycan chains and promotes cell attachment. Promotes granulocyte chemotaxis, degranulation and adhesion. In macrophages, promotes the release of inflammatory cytokines, including IL8 and TNF. Signals probably through G- proteins. Is a regulator of mast cell degranulation (PubMed:26841242). {ECO:0000269|PubMed:12829604, ECO:0000269|PubMed:17928360, ECO:0000269|PubMed:22310662, ECO:0000269|PubMed:22575658, ECO:0000269|PubMed:26841242}.;
Disease: DISEASE: Vibratory urticaria (VBU) [MIM:125630]: An autosomal dominant disorder characterized by localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. {ECO:0000269|PubMed:26841242}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

RVIS EVS: 2.36
RVIS percentile EVS: 98.44

Essentials

Essential (gene trap): N