EDA2R

protein-coding

ectodysplasin A2 receptor, the group of Tumor necrosis factor receptor superfamily

Gene summary

The protein encoded by this gene is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily, and contains cysteine-rich repeats and a single transmembrane domain. This protein binds to the EDA-A2 isoform of ectodysplasin, which plays an important role in maintenance of hair and teeth. Alternatively spliced transcript variants encodes distinct protein isoforms. [provided by RefSeq, Apr 2016]

MANE transcript

NM_021783.5

Inheritance

ClinVar variants

P:1U:42B:14

Top phenotype

X-linked hypohidrotic ectodermal dysplasia

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chrX:66,595,637-66,639,298

External References & Databases

Ensembl (ENSG00000131080)

Transcript & Mutation Effects

hg38 • Region Span ~43.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

X-linked hypohidrotic ectodermal dysplasiaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010585

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EDA2R variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 9

Hypohidrotic X-linked ectodermal dysplasiaTotal: 1

HypodontiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021783.5. 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			2 clinvar	4 clinvar	2 clinvar	8
missense			32 clinvar	7 clinvar	1 clinvar	40
nonsense			3 clinvar			3
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	42	11	3	57

Highest pathogenic variant AF is 0.000005471597

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 90 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021783.5	RefSeq	NP_068555.2	5	MANE Select
ENST00000374719.8	Ensembl	ENSP00000363851.3	5	MANE Select
NM_001199687.3	RefSeq	NP_001186616.2	5	Standard
NM_001242310.1	RefSeq	NP_001229239.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cytokine-cytokine receptor interaction - Homo sapiens (human)
Ectoderm Differentiation
TNFR2 non-canonical NF-kB pathway
Cytokine Signaling in Immune system
Immune System

Biological Process

multicellular organism development
epidermis development
ectodermal cell differentiation
tumor necrosis factor-mediated signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB signaling

Molecular Function

tumor necrosis factor-activated receptor activity
protein binding
signaling receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000450752
Coding exons: 6
Length: 43630
Individuals with no LoFs: 125542
Homozygous LoFs: 14
Heterozygous LoFs: 16
Defined: 125572
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.205	114	108	1.06	0.00000813	2061
Missense (PolyPhen)		33	28.791	1.1462		625
Synonymous	-1.91	57	41.4	1.38	0.00000317	602
Loss of Function	0.877	6	8.81	0.681	6.29e-7	163

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00046	0.00037	rare
Latino/Admixed American	0.000078	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00015	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.000097	rare
South Asian	0.00049	0.00026	rare
Other	0.00023	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for EDA isoform A2, but not for EDA isoform A1. Mediates the activation of the NF-kappa-B and JNK pathways. Activation seems to be mediated by binding to TRAF3 and TRAF6. {ECO:0000269|PubMed:12270937}.;

Recessive Scores

pRec: 0.0974

Intolerance Scores

LoFtool: 0.386
RVIS EVS: 0.48
RVIS percentile EVS: 79.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0615

Gene Damage Prediction

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