amelogenesis imperfecta hypomaturation type 2A3

Summary

amelogenesis imperfecta hypomaturation type 2A3 (MONDO:0013181) is a disease caused by WDR72 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: WDR72 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 305

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta hypomaturation type 2A3
Mondo ID	MONDO:0013181
MeSH	C567706
OMIM	613211
DOID	DOID:0110061
UMLS	C2750771
MedGen	416381
GARD	0015630
Is cancer (heuristic)	no

Also known as: AI2A3 · amelogenesis imperfecta caused by mutation in WDR72 · amelogenesis imperfecta hypomaturation type 2A3 · amelogenesis imperfecta, hypomaturation type, IIA3 · amelogenesis imperfecta, type IIA3 · WDR72 amelogenesis imperfecta

Data availability: 305 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › amelogenesis imperfecta › amelogenesis imperfecta type 2 › amelogenesis imperfecta hypomaturation type 2A3

Related subtypes (6): amelogenesis imperfecta type 2A1, amelogenesis imperfecta type 1E, amelogenesis imperfecta hypomaturation type 2A2, amelogenesis imperfecta hypomaturation type 2A4, amelogenesis imperfecta hypomaturation type 2A5, amelogenesis imperfecta, hypomaturation type, IIa6

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

305 retrieved; paginated sample, class counts are floors:

234 uncertain significance, 30 likely pathogenic, 14 likely benign, 10 benign, 6 conflicting classifications of pathogenicity, 5 pathogenic, 4 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
161415	NM_182758.4(WDR72):c.1467_1468del (p.Val491fs)	WDR72	Pathogenic	criteria provided, single submitter
231	NM_182758.4(WDR72):c.2348C>G (p.Ser783Ter)	WDR72	Pathogenic	no assertion criteria provided
232	NM_182758.4(WDR72):c.2934G>A (p.Trp978Ter)	WDR72	Pathogenic	criteria provided, multiple submitters, no conflicts
233	NM_182758.4(WDR72):c.2857del (p.Ser953fs)	WDR72	Pathogenic	criteria provided, single submitter
3577445	NM_182758.4(WDR72):c.997A>T (p.Lys333Ter)	WDR72	Pathogenic	criteria provided, single submitter
517616	NM_182758.4(WDR72):c.88C>T (p.Arg30Ter)	WDR72	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
522610	NM_182758.4(WDR72):c.2686C>T (p.Arg896Ter)	WDR72	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2445427	NM_182758.4:c.-13+989_7del	WDR72	Likely pathogenic	criteria provided, single submitter
2445444	NM_182758.4(WDR72):c.118C>T (p.Gln40Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
2445445	NM_182758.4(WDR72):c.954+1_954+10del	WDR72	Likely pathogenic	criteria provided, single submitter
2445448	NM_182758.4(WDR72):c.2146del (p.Ala716fs)	WDR72	Likely pathogenic	criteria provided, single submitter
2445449	NM_182758.4(WDR72):c.2388del (p.Lys796fs)	WDR72	Likely pathogenic	criteria provided, single submitter
2504595	NM_182758.4(WDR72):c.2864T>G (p.Leu955Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
3064917	NM_182758.4(WDR72):c.858-1G>C	WDR72	Likely pathogenic	criteria provided, single submitter
3065340	NM_182758.4(WDR72):c.1348+1G>T	WDR72	Likely pathogenic	criteria provided, single submitter
3076032	NM_182758.4(WDR72):c.2019dup (p.Trp674fs)	WDR72	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382480	NM_182758.4(WDR72):c.2555del (p.Gly852fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577376	NM_182758.4(WDR72):c.2871_2872+7del	WDR72	Likely pathogenic	criteria provided, single submitter
3577395	NM_182758.4(WDR72):c.2473C>T (p.Gln825Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
3577398	NM_182758.4(WDR72):c.2383_2385delinsCC (p.Ala795fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577405	NM_182758.4(WDR72):c.2127dup (p.Gly710fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577409	NM_182758.4(WDR72):c.2078T>A (p.Leu693Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
3577416	NM_182758.4(WDR72):c.1862C>G (p.Ser621Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
3577418	NM_182758.4(WDR72):c.1777dup (p.Arg593fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577452	NM_182758.4(WDR72):c.868_880del (p.Lys290fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577454	NM_182758.4(WDR72):c.858-2A>G	WDR72	Likely pathogenic	criteria provided, single submitter
3577455	NM_182758.4(WDR72):c.733dup (p.Ser245fs)	WDR72	Likely pathogenic	criteria provided, single submitter
3577456	NM_182758.4(WDR72):c.711_711+1delinsTT	WDR72	Likely pathogenic	criteria provided, single submitter
3577459	NM_182758.4(WDR72):c.655C>T (p.Arg219Ter)	WDR72	Likely pathogenic	criteria provided, single submitter
3577461	NM_182758.4(WDR72):c.591+1G>C	WDR72	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · 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
WDR72	Strong	Autosomal recessive	amelogenesis imperfecta hypomaturation type 2A3	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
WDR72	Orphanet:100033	Hypomaturation amelogenesis imperfecta
WDR72	Orphanet:402041	Autosomal recessive distal renal tubular acidosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
WDR72	HGNC:26790	ENSG00000166415	Q3MJ13	WD repeat-containing protein 72	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
WDR72	WD repeat-containing protein 72	Plays a major role in formation of tooth enamel.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
WDR72	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
kidney epithelium	1
pancreatic ductal cell	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
WDR72	139	tissue_specific	marker	kidney epithelium, pancreatic ductal cell, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
WDR72	1,126

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WDR72	Q3MJ13	67.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
biomineral tissue development	1	648.1×	0.003	WDR72
protein localization to plasma membrane	1	108.7×	0.009	WDR72

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
WDR72	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	WDR72

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
WDR72	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.