EDA

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

Basic information

Region (hg38): X:69616066-70039472

Previous symbols: [ "ED1", "EDA2", "ODT1" ]

Links

ENSG00000158813 ∙ NCBI:1896 ∙ OMIM:300451 ∙ HGNC:3157 ∙ Uniprot:Q92838 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked hypohidrotic ectodermal dysplasia (Definitive), mode of inheritance: XLR
• tooth agenesis, selective, X-linked, 1 (Definitive), mode of inheritance: XLR
• X-linked hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: XL
• tooth agenesis (Supportive), mode of inheritance: AD
• X-linked hypohidrotic ectodermal dysplasia (Definitive), mode of inheritance: XL
• tooth agenesis, selective, X-linked, 1 (Definitive), mode of inheritance: XL
• X-linked hypohidrotic ectodermal dysplasia (Strong), mode of inheritance: XL
• tooth agenesis, selective, X-linked, 1 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectodermal dysplasia 1, hypohidrotic, X-linked; Tooth agenesis, selective, X-linked, 1	XL	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	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic	13913306; 5771499; 517571; 7446529; 2301459; 8434608; 8775234; 8696334; 9683615; 11388598; 17066260; 16583127; 17256800; 18657636; 18510547; 18231121; 18627052; 19533796; 22008666; 22350046
Frequent respiratory infections have been reported, possibly related to paucity/absence of mucus glands

ClinVar

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

• Hypohidrotic X-linked ectodermal dysplasia (378 variants)
• not provided (97 variants)
• not specified (24 variants)
• Tooth agenesis, selective, X-linked, 1 (7 variants)
• Tooth agenesis, selective, X-linked, 1;Hypohidrotic X-linked ectodermal dysplasia (6 variants)
• Inborn genetic diseases (6 variants)
• EDA-related condition (6 variants)
• Anhidrotic ectodermal dysplasia (4 variants)
• Hypohidrotic X-linked ectodermal dysplasia;Tooth agenesis, selective, X-linked, 1 (3 variants)
• - (2 variants)
• Partial congenital absence of teeth (2 variants)
• Abnormality of the dentition (1 variants)
• See cases (1 variants)
• Tooth agenesis, selective, 2 (1 variants)
• Ectodermal dysplasia (1 variants)
• EDA-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EDA 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	1			83	10	94
missense	35	59	47	9	8	158
nonsense	21					21
start loss	4					4
frameshift	41	7				48
inframe indel	8	3	6	2		19
splice donor/acceptor (+/-2bp)	12	5				17
splice region	5	2	4	12		23
non coding			3	18	32	53
Total	122	74	56	112	50

Highest pathogenic variant AF is 0.0000178

Variants in EDA

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

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

Position	Type	Phenotype	Significance	ClinVar
X-69616229-G-T			Uncertain significance (Dec 06, 2021)
X-69616270-GGCTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCA-G		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Jul 01, 2019)
X-69616309-A-G		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Oct 14, 2020)
X-69616310-T-C		Hypohidrotic X-linked ectodermal dysplasia • Tooth agenesis, selective, X-linked, 1;Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (May 13, 2021)
X-69616310-T-G		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Aug 14, 2023)
X-69616312-G-AT		Hypohidrotic X-linked ectodermal dysplasia	Likely pathogenic (Apr 12, 2022)
X-69616316-AC-A		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (May 22, 2022)
X-69616319-C-G		Hypohidrotic X-linked ectodermal dysplasia	Uncertain significance (Jul 27, 2022)
X-69616330-C-A		EDA-related disorder	Uncertain significance (May 10, 2023)
X-69616336-G-A			Uncertain significance (Oct 15, 2019)
X-69616336-G-C		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Nov 08, 2023)
X-69616336-G-T		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Dec 30, 2023)
X-69616344-G-A		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Oct 30, 2023)
X-69616347-T-C		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Apr 10, 2022)
X-69616350-A-G		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Apr 10, 2022)
X-69616356-G-A		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Oct 09, 2021)
X-69616360-C-CTGCGA		Hypohidrotic X-linked ectodermal dysplasia	Likely pathogenic (Feb 23, 2023)
X-69616364-A-C		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Nov 11, 2023)
X-69616365-G-A		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Dec 12, 2023)
X-69616366-C-T		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Dec 15, 2021)
X-69616368-A-C		Hypohidrotic X-linked ectodermal dysplasia	Benign (Dec 19, 2023)
X-69616367-G-GAGGGAGCC		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Dec 19, 2023)
X-69616374-C-T		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Nov 13, 2021)
X-69616375-C-T		Hypohidrotic X-linked ectodermal dysplasia	Pathogenic (Nov 02, 2017)
X-69616398-C-A		Hypohidrotic X-linked ectodermal dysplasia	Likely benign (Mar 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EDA	protein_coding	protein_coding	ENST00000374552	8	423409

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.974	0.0261	102534	0	1	102535	0.00000488

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	96	159	0.602	0.0000120	2492
Missense in Polyphen		12	36.928	0.32496		553
Synonymous	0.725	57	64.4	0.885	0.00000484	833
Loss of Function	3.11	0	11.2	0.00	7.64e-7	201

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000389	0.0000389
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: 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;Cytokine Signaling in Immune system;Immune System;TNFs bind their physiological receptors (Consensus)

Recessive Scores

• pRec: 0.0995

Intolerance Scores

• rvis_EVS: 0.26
• rvis_percentile_EVS: 70.06

Haploinsufficiency Scores

• pHI: 0.371
• hipred: Y
• hipred_score: 0.786
• ghis: 0.508

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eda
• Phenotype: digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; renal/urinary system phenotype; skeleton phenotype; respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: eda
• Affected structure: lepidotrichium
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: immune response;cell-matrix adhesion;gene expression;positive regulation of gene expression;cell differentiation;tumor necrosis factor-mediated signaling pathway;odontogenesis of dentin-containing tooth;positive regulation of I-kappaB kinase/NF-kappaB signaling;pigmentation;positive regulation of NF-kappaB transcription factor activity;salivary gland cavitation;hair follicle placode formation;trachea gland development;positive regulation of canonical Wnt signaling pathway;positive regulation of NIK/NF-kappaB signaling
• Cellular component: extracellular region;collagen trimer;endoplasmic reticulum membrane;lipid droplet;cytoskeleton;plasma membrane;integral component of plasma membrane;membrane;integral component of membrane;intracellular membrane-bounded organelle;apical part of cell
• Molecular function: signaling receptor binding;tumor necrosis factor receptor binding;protein binding