Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Summary

Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism (MONDO:0007093) is a disease caused by DLX3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DLX3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 74

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism
Mondo ID	MONDO:0007093
MeSH	C566293
OMIM	104510
Orphanet	100034
DOID	DOID:0110053
UMLS	C1863012
MedGen	350816
GARD	0016932
Is cancer (heuristic)	no

Also known as: AI4 · AIHHT · amelogenesis imperfecta caused by mutation in DLX3 · amelogenesis imperfecta type 4 · amelogenesis imperfecta, type IV · DLX3 amelogenesis imperfecta

Data availability: 74 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 › hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism

Related subtypes (6): amelogenesis imperfecta type 1G, X-linked amelogenesis imperfecta hypoplastic/hypomaturation 2, amelogenesis imperfecta type 1, amelogenesis imperfecta type 2, amelogenesis imperfecta, IIa 1K, hypocalcified amelogenesis imperfecta

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

74 retrieved; paginated sample, class counts are floors:

33 uncertain significance, 25 benign, 5 likely benign, 4 conflicting classifications of pathogenicity, 4 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
430609	NM_005220.3(DLX3):c.476G>T (p.Arg159Leu)	DLX3	Pathogenic	no assertion criteria provided
9072	NM_005220.3(DLX3):c.571_574del (p.Gly191fs)	DLX3	Pathogenic	criteria provided, multiple submitters, no conflicts
9073	NM_005220.3(DLX3):c.561_562del (p.Tyr188fs)	DLX3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2445428	NM_005220.3(DLX3):c.537C>A (p.Asn179Lys)	DLX3	Likely pathogenic	criteria provided, single submitter
373912	NM_005220.3(DLX3):c.574dup (p.Glu192fs)	DLX3	Likely pathogenic	criteria provided, single submitter
3900721	NM_005220.3(DLX3):c.535A>C (p.Asn179His)	DLX3	Likely pathogenic	criteria provided, single submitter
430607	NM_005220.3(DLX3):c.574del (p.Glu192fs)	DLX3	Likely pathogenic	criteria provided, single submitter
193301	NM_005220.3(DLX3):c.90T>C (p.Pro30=)	DLX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
289857	NM_005220.3(DLX3):c.710A>G (p.Tyr237Cys)	DLX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
290750	NM_005220.3(DLX3):c.82G>T (p.Asp28Tyr)	DLX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
324021	NM_005220.3(DLX3):c.798G>A (p.Pro266=)	DLX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2445426	NM_005220.3(DLX3):c.92C>G (p.Thr31Ser)	DLX3	Uncertain significance	criteria provided, single submitter
323999	NM_005220.3(DLX3):c.*1505G>A	DLX3	Uncertain significance	criteria provided, single submitter
324003	NM_005220.3(DLX3):c.*1272T>C	DLX3	Uncertain significance	criteria provided, single submitter
324004	NM_005220.3(DLX3):c.*1252C>G	DLX3	Uncertain significance	criteria provided, single submitter
324007	NM_005220.3(DLX3):c.*1205A>C	DLX3	Uncertain significance	criteria provided, single submitter
324011	NM_005220.3(DLX3):c.*988G>A	DLX3	Uncertain significance	criteria provided, single submitter
324014	NM_005220.3(DLX3):c.*821C>A	DLX3	Uncertain significance	criteria provided, single submitter
324015	NM_005220.3(DLX3):c.*714C>T	DLX3	Uncertain significance	criteria provided, single submitter
324018	NM_005220.3(DLX3):c.*124C>A	DLX3	Uncertain significance	criteria provided, single submitter
324019	NM_005220.3(DLX3):c.*83G>A	DLX3	Uncertain significance	criteria provided, single submitter
324020	NM_005220.3(DLX3):c.846C>A (p.Asn282Lys)	DLX3	Uncertain significance	criteria provided, multiple submitters, no conflicts
324022	NM_005220.3(DLX3):c.698C>T (p.Pro233Leu)	DLX3	Uncertain significance	criteria provided, multiple submitters, no conflicts
324026	NM_005220.3(DLX3):c.140A>G (p.Gln47Arg)	DLX3	Uncertain significance	criteria provided, multiple submitters, no conflicts
324029	NM_005220.3(DLX3):c.-131C>G	DLX3	Uncertain significance	criteria provided, single submitter
324030	NM_005220.3(DLX3):c.-131C>A	DLX3	Uncertain significance	criteria provided, single submitter
324031	NM_005220.3(DLX3):c.-132C>A	DLX3	Uncertain significance	criteria provided, single submitter
324033	NM_005220.3(DLX3):c.-135C>T	DLX3	Uncertain significance	criteria provided, single submitter
324035	NM_005220.3(DLX3):c.-190C>T	DLX3	Uncertain significance	criteria provided, single submitter
324036	NM_005220.3(DLX3):c.-225G>A	DLX3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
DLX3	Strong	Autosomal dominant	hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DLX3	Orphanet:100034	Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism
DLX3	Orphanet:3352	Tricho-dento-osseous syndrome

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
DLX3	HGNC:2916	ENSG00000064195	O60479	Homeobox protein DLX-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DLX3	Homeobox protein DLX-3	Transcriptional activator.

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DLX3	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf

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
skin of abdomen	1
skin of leg	1
zone of skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DLX3	133	broad	marker	skin of leg, skin of abdomen, zone of skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DLX3	1,382

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DLX3	O60479	1

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
hair follicle cell proliferation	1	16852.0×	8e-04	DLX3
hair cell differentiation	1	2106.5×	0.002	DLX3
odontoblast differentiation	1	2106.5×	0.002	DLX3
hair follicle morphogenesis	1	495.6×	0.005	DLX3
placenta development	1	443.5×	0.005	DLX3
embryonic skeletal system development	1	391.9×	0.005	DLX3
blood vessel development	1	374.5×	0.005	DLX3
odontogenesis of dentin-containing tooth	1	300.9×	0.006	DLX3
BMP signaling pathway	1	200.6×	0.008	DLX3
epithelial cell differentiation	1	175.5×	0.008	DLX3
Wnt signaling pathway	1	99.7×	0.013	DLX3
gene expression	1	79.9×	0.015	DLX3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.072	DLX3
regulation of transcription by RNA polymerase II	1	11.7×	0.086	DLX3

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
DLX3	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	DLX3

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)
DLX3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.