ADGRE2

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

Basic information

Region (hg38): 19:14732391-14778560

Previous symbols: [ "EMR2" ]

Links

ENSG00000127507 ∙ NCBI:30817 ∙ OMIM:606100 ∙ HGNC:3337 ∙ Uniprot:Q9UHX3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant vibratory urticaria (Limited), mode of inheritance: Unknown
• autosomal dominant vibratory urticaria (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vibratory urticaria	AD	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	Dermatologic	7294069; 26841242

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADGRE2 gene.

• Vibratory urticaria (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADGRE2 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			3	67	13	83
missense	1		172	14	31	218
nonsense			13	2	5	20
start loss			1			1
frameshift			6	1	5	12
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)			7		1	8
splice region			8	21	4	33
non coding			3	43	11	57
Total	1	0	208	127	67

Variants in ADGRE2

This is a list of pathogenic ClinVar variants found in the ADGRE2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-14736249-AAT-A			Likely benign (Oct 03, 2022)
19-14736249-A-AAT		ADGRE2-related disorder	Likely benign (Nov 19, 2023)
19-14743401-G-A			Likely benign (Oct 28, 2022)
19-14743409-C-T			Likely benign (Jan 02, 2024)
19-14743419-C-T			Uncertain significance (Jan 13, 2024)
19-14743420-C-A			Uncertain significance (Apr 07, 2023)
19-14743421-G-A			Benign (Jan 31, 2024)
19-14743425-TG-T			Uncertain significance (Oct 13, 2023)
19-14743427-G-C		not specified	Uncertain significance (May 29, 2024)
19-14743438-G-A			Likely benign (Jan 12, 2023)
19-14743446-T-A			Uncertain significance (Mar 26, 2022)
19-14743449-C-T			Uncertain significance (Jul 14, 2022)
19-14743452-T-C			Uncertain significance (Feb 22, 2023)
19-14743466-T-C		not specified	Uncertain significance (Dec 01, 2022)
19-14743476-A-T			Uncertain significance (Jul 25, 2023)
19-14743494-T-C		not specified	Uncertain significance (Dec 27, 2023)
19-14743497-T-TCC			Uncertain significance (Apr 15, 2023)
19-14743507-C-T		not specified	Benign (May 04, 2022)
19-14743519-T-C			Likely benign (Feb 19, 2022)
19-14743526-C-T			Benign (Jan 31, 2024)
19-14743527-G-A			Uncertain significance (Jul 10, 2022)
19-14743537-A-G			Likely benign (Jan 06, 2023)
19-14743546-G-A			Benign (Jan 29, 2024)
19-14743607-C-A			Likely benign (Dec 09, 2022)
19-14743614-A-T			Uncertain significance (Dec 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADGRE2	protein_coding	protein_coding	ENST00000315576	20	46149

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.76e-28	0.000200	124800	1	947	125748	0.00378

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.654	430	470	0.915	0.0000273	5328
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00287	0.00287
Ashkenazi Jewish	0.000595	0.000595
East Asian	0.00908	0.00912
Finnish	0.000185	0.000185
European (Non-Finnish)	0.00224	0.00224
Middle Eastern	0.00908	0.00912
South Asian	0.0138	0.0139
Other	0.00261	0.00245

dbNSFP

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.
• Pathway: GPCRs, Other;GPCRs, Class B Secretin-like;Signaling by GPCR;Signal Transduction;Class B/2 (Secretin family receptors);GPCR ligand binding (Consensus)

Intolerance Scores

• rvis_EVS: 2.36
• rvis_percentile_EVS: 98.44

Haploinsufficiency Scores

• pHI: 0.0961
• hipred: N
• hipred_score: 0.187
• ghis: 0.422

Essentials

• essential_gene_gene_trap: N

Gene ontology

• 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;cell migration;regulation of mast cell degranulation;granulocyte chemotaxis
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;leading edge membrane;ruffle membrane
• Molecular function: G protein-coupled receptor activity;calcium ion binding;chondroitin sulfate binding