GeneBe

EDA

protein-coding

ectodysplasin A, the group of MicroRNA protein coding host genes|Tumor necrosis factor superfamily

Gene summary

The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:
  • ED1
  • EDA2
  • ODT1

MANE transcript

NM_001399.5

Inheritance

AD, XL, XLR

ClinVar variants

P:289U:127B:147

Top phenotype

Ectodermal dysplasia 1, hypohidrotic, X-linked; Tooth agenesis, selective, X-linked, 1

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:69,616,067-70,039,472

External References & Databases

Ensembl (ENSG00000158813)NCBI Gene (1896)OMIM (300451)HGNC:3157GenCCUniProt (Q92838)AlphaFoldClinVar (EDA)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~423.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

tooth agenesisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005486

Submitter: Orphanet

X-linked hypohidrotic ectodermal dysplasiaDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010585

Submitter: G2P

tooth agenesis, selective, X-linked, 1DEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010741

Submitter: G2P

X-linked hypohidrotic ectodermal dysplasiaDEFINITIVE

Inheritance Pattern: XLR

Disease ID:MONDO:0010585

Submitter: Natera

X-linked hypohidrotic ectodermal dysplasiaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010585

Submitter: PanelApp Australia

X-linked hypohidrotic ectodermal dysplasiaSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010585

Submitter: Labcorp Genetics (formerly Invitae)

tooth agenesis, selective, X-linked, 1STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010741

Submitter: Labcorp Genetics (formerly Invitae)

X-linked hypohidrotic ectodermal dysplasiaSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010585

Submitter: Orphanet

Clinical Genomic Database (CGD)

Ectodermal dysplasia 1, hypohidrotic, X-linked; Tooth agenesis, selective, X-linked, 1XL

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Dental; 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

Comments: Frequent respiratory infections have been reported, possibly related to paucity/absence of mucus glands

Refs: 13913306; 5771499; 517571; 7446529; 2301459; 8434608; 8775234; 8696334; 9683615; 11388598; 17066260; 16583127; 17256800; 18657636; 18510547; 18231121; 18627052; 19533796; 22008666; 22350046Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EDA variants in ClinVar

13 Conditions Cataloged
Hypohidrotic X-linked ectodermal dysplasiaTotal: 539
not providedTotal: 106
EDA-related disorderTotal: 73
not specifiedTotal: 42
Tooth agenesis, selective, X-linked, 1Total: 26
Inborn genetic diseasesTotal: 9
Anhidrotic ectodermal dysplasiaTotal: 5
Ectodermal dysplasiaTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001399.5. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
10
clinvar
111
clinvar
9
clinvar
 132
missense
48
clinvar
100
clinvar
109
clinvar
17
clinvar
10
clinvar
 284
nonsense
24
clinvar
6
clinvar
4
clinvar
 34
start loss
4
clinvar
 4
frameshift
56
clinvar
24
clinvar
1
clinvar
 81
splice donor/acceptor (+/-2bp)
16
clinvar
9
clinvar
3
clinvar
 28
Total14914012712819563

Highest pathogenic variant AF is 0.00004313248

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001399.5RefSeqNP_001390.18MANE Select
ENST00000374552.9EnsemblENSP00000363680.48MANE Select
NM_001005609.2RefSeqNP_001005609.18Standard
NM_001005610.4RefSeqNP_001005610.22Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
edaDanio rerio

Structure: lepidotrichium

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Cytokine-cytokine receptor interaction - Homo sapiens (human)
  • Hair Follicle Development- Induction (Part 1 of 3)
  • Ectoderm Differentiation
  • EDA Signalling in Hair Follicle Development
  • TNFR2 non-canonical NF-kB pathway

Biological Process

  • immune response
  • cell-matrix adhesion
  • gene expression
  • positive regulation of gene expression
  • cell differentiation

Molecular Function

  • signaling receptor binding
  • tumor necrosis factor receptor binding
  • protein binding

Cellular Component

  • extracellular region
  • collagen trimer
  • endoplasmic reticulum membrane
  • lipid droplet
  • cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000374552
Coding exons
8
Length
423409
Individuals with no LoFs
102534
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
102535
p
0.00000488
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.78961590.6020.00001202492
Missense (PolyPhen)1236.9280.32496553
Synonymous0.7255764.40.8850.00000484833
Loss of Function3.11011.20.007.64e-7201

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000390.000032rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Functions as a ligand activating the DEATH-domain containing receptors EDAR and EDA2R (PubMed:8696334, PubMed:11039935, PubMed:27144394). May also play a role in cell adhesion (By similarity). {ECO:0000250|UniProtKB:O54693, ECO:0000269|PubMed:11039935, ECO:0000269|PubMed:27144394, ECO:0000269|PubMed:8696334}.; FUNCTION: Isoform 3: Binds only to the receptor EDA2R. {ECO:0000269|PubMed:11039935, ECO:0000269|PubMed:27144394}.;
Disease
DISEASE: Ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM:305100]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. It is the most common form of over 150 clinically distinct ectodermal dysplasias. {ECO:0000269|PubMed:10469321, ECO:0000269|PubMed:10951256, ECO:0000269|PubMed:11279189, ECO:0000269|PubMed:11295832, ECO:0000269|PubMed:11309369, ECO:0000269|PubMed:11343303, ECO:0000269|PubMed:11378824, ECO:0000269|PubMed:11416205, ECO:0000269|PubMed:12225002, ECO:0000269|PubMed:12932274, ECO:0000269|PubMed:17256800, ECO:0000269|PubMed:18231121, ECO:0000269|PubMed:19127222, ECO:0000269|PubMed:19438931, ECO:0000269|PubMed:20486090, ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:22008666, ECO:0000269|PubMed:22350046, ECO:0000269|PubMed:24724966, ECO:0000269|PubMed:27144394, ECO:0000269|PubMed:27657131, ECO:0000269|PubMed:8696334, ECO:0000269|PubMed:9507389, ECO:0000269|PubMed:9630076, ECO:0000269|PubMed:9683615, ECO:0000269|PubMed:9736768}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tooth agenesis, selective, X-linked, 1 (STHAGX1) [MIM:313500]: A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). {ECO:0000269|PubMed:16583127, ECO:0000269|PubMed:18657636, ECO:0000269|PubMed:19278982, ECO:0000269|PubMed:23603338, ECO:0000269|PubMed:23625373, ECO:0000269|PubMed:24487376, ECO:0000269|PubMed:27144394}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.0995

Intolerance Scores

RVIS EVS
0.26
RVIS percentile EVS
70.06

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.801

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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