tooth agenesis, selective, X-linked, 1

Summary

tooth agenesis, selective, X-linked, 1 (MONDO:0010741) is a disease caused by EDA (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: EDA (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 24

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tooth agenesis, selective, X-linked, 1
Mondo ID	MONDO:0010741
MeSH	C567060
OMIM	313500
UMLS	C1970757
MedGen	410143
GARD	0018246
Is cancer (heuristic)	no

Also known as: EDA tooth agenesis · STHAGX1 · tooth agenesis caused by mutation in EDA · tooth agenesis, selective, X-linked 1, X-linked dominant · tooth agenesis, selective, X-linked, 1 · tooth agenesis, selective, X-linked, type 1

Data availability: 24 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › tooth agenesis › tooth agenesis, selective, X-linked, 1

Related subtypes (11): tooth agenesis, selective, 1, tooth agenesis, selective, 4, tooth agenesis, selective, 2, tooth agenesis, selective, 3, tooth agenesis, selective, 5, tooth agenesis, selective, 7, tooth agenesis, selective, 8, tooth agenesis, selective, 9, hypodontia/oligodontia with orofacial cleft, tooth agenesis, selective, with orofacial cleft, tooth agenesis, selective, 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

24 retrieved; paginated sample, class counts are floors:

10 pathogenic, 7 pathogenic/likely pathogenic, 3 uncertain significance, 2 likely pathogenic, 1 not provided, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11031	NM_001399.5(EDA):c.181T>C (p.Tyr61His)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11035	NM_001399.5(EDA):c.463C>T (p.Arg155Cys)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
11037	NM_001399.5(EDA):c.467G>A (p.Arg156His)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
11044	NM_001399.5(EDA):c.193C>G (p.Arg65Gly)	EDA	Pathogenic	no assertion criteria provided
11045	NM_001399.5(EDA):c.1072C>G (p.Gln358Glu)	EDA	Pathogenic	criteria provided, single submitter
11048	NM_001399.5(EDA):c.1013C>T (p.Thr338Met)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
1208540	NM_001399.5(EDA):c.800C>G (p.Ser267Ter)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
228257	NM_001399.5(EDA):c.866G>A (p.Arg289His)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253053	NM_001399.5(EDA):c.776C>A (p.Ala259Glu)	EDA	Pathogenic	no assertion criteria provided
253054	NM_001399.5(EDA):c.865C>T (p.Arg289Cys)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
418170	NM_001399.5(EDA):c.612_629del (p.202_204IPG[1])	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44185	NM_001399.5(EDA):c.1094T>C (p.Val365Ala)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44190	NM_001399.5(EDA):c.2T>C (p.Met1Thr)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
44197	NC_000023.11:g.70027876_70027911del	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
44200	NC_000023.11:g.70027902_70027919del	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
44213	NM_001399.5(EDA):c.895G>A (p.Gly299Ser)	EDA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
618616	NM_001399.5(EDA):c.252del (p.Gly85fs)	EDA	Pathogenic	criteria provided, multiple submitters, no conflicts
1482275	NM_001399.5(EDA):c.1093G>A (p.Val365Met)	EDA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4280124	NM_032581.4(HYCC1):c.175del (p.Gln59fs)	HYCC1	Likely pathogenic	criteria provided, single submitter
1398395	NM_001399.5(EDA):c.157C>T (p.Leu53Phe)	EDA	Uncertain significance	criteria provided, multiple submitters, no conflicts
1675183	NM_001399.5(EDA):c.480C>G (p.Ser160Arg)	EDA	Uncertain significance	criteria provided, single submitter
625527	NM_001399.5(EDA):c.956G>A (p.Ser319Asn)	EDA	Uncertain significance	criteria provided, single submitter
253055	NM_001399.5(EDA):c.1001G>A (p.Arg334His)	EDA	Benign	criteria provided, multiple submitters, no conflicts
127066	NM_001399.5(EDA):c.956G>T (p.Ser319Ile)	EDA	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
EDA	Definitive	X-linked	X-linked hypohidrotic ectodermal dysplasia	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EDA	Orphanet:181	X-linked hypohidrotic ectodermal dysplasia
EDA	Orphanet:99798	Oligodontia
HYCC1	Orphanet:85163	Hypomyelination-congenital cataract syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EDA	HGNC:3157	ENSG00000158813	Q92838	Ectodysplasin-A	gencc,clinvar
HYCC1	HGNC:24587	ENSG00000122591	Q9BYI3	Hyccin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EDA	Ectodysplasin-A	Cytokine which is involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs.
HYCC1	Hyccin	Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EDA	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_Ligand_Superfamily
HYCC1	Other/Unknown	no		Hyccin

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
tongue squamous epithelium	1
calcaneal tendon	1
endothelial cell	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EDA	175	broad	marker	tongue squamous epithelium, male germ line stem cell (sensu Vertebrata) in testis, oocyte
HYCC1	250	ubiquitous	marker	calcaneal tendon, endothelial cell, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EDA	792
HYCC1	700

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HYCC1	Q9BYI3	5
EDA	Q92838	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TNFs bind their physiological receptors	1	393.8×	0.003	EDA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
trachea gland development	1	4213.0×	0.004	EDA
salivary gland cavitation	1	1685.2×	0.004	EDA
hair follicle placode formation	1	1685.2×	0.004	EDA
regulation of non-canonical NF-kappaB signal transduction	1	766.0×	0.007	EDA
pigmentation	1	351.1×	0.011	EDA
odontogenesis	1	263.3×	0.012	EDA
phosphatidylinositol phosphate biosynthetic process	1	240.7×	0.012	HYCC1
odontogenesis of dentin-containing tooth	1	150.5×	0.016	EDA
positive regulation of non-canonical NF-kappaB signal transduction	1	127.7×	0.016	EDA
myelination	1	125.8×	0.016	HYCC1
cell-matrix adhesion	1	81.8×	0.020	EDA
positive regulation of canonical Wnt signaling pathway	1	77.3×	0.020	EDA
canonical Wnt signaling pathway	1	76.6×	0.020	EDA
cytokine-mediated signaling pathway	1	65.3×	0.022	EDA
protein localization to plasma membrane	1	54.4×	0.024	HYCC1
gene expression	1	39.9×	0.031	EDA
positive regulation of canonical NF-kappaB signal transduction	1	36.3×	0.032	EDA
immune response	1	23.5×	0.047	EDA
positive regulation of gene expression	1	19.4×	0.054	EDA
cell differentiation	1	14.6×	0.068	EDA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EDA	0	0
HYCC1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	EDA, HYCC1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
EDA	0	—
HYCC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.