amelogenesis imperfecta hypomaturation type 2A2

Summary

amelogenesis imperfecta hypomaturation type 2A2 (MONDO:0012926) is a disease caused by MMP20 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MMP20 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 70

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta hypomaturation type 2A2
Mondo ID	MONDO:0012926
MeSH	C567279
OMIM	612529
DOID	DOID:0110060
UMLS	C2675858
MedGen	436540
GARD	0015563
Is cancer (heuristic)	no

Also known as: AI2A2 · amelogenesis imperfecta caused by mutation in MMP20 · amelogenesis imperfecta, hypomaturation type, IIA2 · amelogenesis imperfecta, type IIA2 · MMP20 amelogenesis imperfecta

Data availability: 70 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 2A2

Related subtypes (6): amelogenesis imperfecta type 2A1, amelogenesis imperfecta type 1E, amelogenesis imperfecta hypomaturation type 2A3, 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

70 retrieved; paginated sample, class counts are floors:

42 uncertain significance, 8 pathogenic, 8 conflicting classifications of pathogenicity, 6 benign, 5 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1192505	NM_004771.4(MMP20):c.[1046C>T;911C>G]		Pathogenic	no assertion criteria provided
139624	NM_004771.4(MMP20):c.678T>A (p.His226Gln)	MMP20	Pathogenic	no assertion criteria provided
139625	NM_004771.4(MMP20):c.102G>A (p.Trp34Ter)	MMP20	Pathogenic	no assertion criteria provided
189295	NM_004771.4(MMP20):c.611A>G (p.His204Arg)	MMP20	Pathogenic	no assertion criteria provided
5428	NM_004771.4(MMP20):c.954-2A>T	MMP20	Pathogenic	criteria provided, multiple submitters, no conflicts
917991	NM_004771.4(MMP20):c.710C>A (p.Ser237Tyr)	MMP20	Pathogenic	no assertion criteria provided
917992	NM_004771.4(MMP20):c.1122A>C (p.Gln374His)	MMP20	Pathogenic	no assertion criteria provided
917993	NM_004771.4(MMP20):c.809_811+12delinsCCAG	MMP20	Pathogenic	no assertion criteria provided
2445440	NM_004771.4(MMP20):c.1362C>G (p.Tyr454Ter)	MMP20	Likely pathogenic	criteria provided, single submitter
2445441	NM_004771.4(MMP20):c.359dup (p.Asn120fs)	MMP20	Likely pathogenic	criteria provided, single submitter
2445443	NM_004771.4(MMP20):c.1126C>T (p.Gln376Ter)	MMP20	Likely pathogenic	criteria provided, single submitter
4845908	NM_004771.4(MMP20):c.566T>C (p.Leu189Pro)	MMP20	Likely pathogenic	criteria provided, single submitter
917990	NM_004771.4(MMP20):c.625G>C (p.Glu209Gln)	MMP20	Likely pathogenic	criteria provided, single submitter
301937	NM_004771.4(MMP20):c.1136C>T (p.Pro379Leu)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301942	NM_004771.4(MMP20):c.910G>A (p.Ala304Thr)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301955	NM_004771.4(MMP20):c.274A>G (p.Met92Val)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
301957	NM_004771.4(MMP20):c.92C>T (p.Pro31Leu)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
631643	NM_004771.4(MMP20):c.389C>T (p.Thr130Ile)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
770979	NM_004771.4(MMP20):c.1313G>C (p.Gly438Ala)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
781031	NM_004771.4(MMP20):c.870A>T (p.Pro290=)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878617	NM_004771.4(MMP20):c.103A>C (p.Arg35=)	MMP20	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2444100	NM_004771.4(MMP20):c.690T>G (p.His230Gln)	MMP20	Uncertain significance	criteria provided, single submitter
2445442	NM_004771.4(MMP20):c.530G>A (p.Gly177Glu)	MMP20	Uncertain significance	criteria provided, single submitter
301930	NM_004771.4(MMP20):c.*484T>C	MMP20	Uncertain significance	criteria provided, single submitter
301932	NM_004771.4(MMP20):c.*110A>T	MMP20	Uncertain significance	criteria provided, single submitter
301933	NM_004771.4(MMP20):c.1430C>G (p.Ser477Cys)	MMP20	Uncertain significance	criteria provided, single submitter
301934	NM_004771.4(MMP20):c.1422G>A (p.Val474=)	MMP20	Uncertain significance	criteria provided, single submitter
301935	NM_004771.4(MMP20):c.1247+8T>C	MMP20	Uncertain significance	criteria provided, single submitter
301936	NM_004771.4(MMP20):c.1219C>T (p.Leu407Phe)	MMP20	Uncertain significance	criteria provided, single submitter
301943	NM_004771.4(MMP20):c.883C>G (p.Leu295Val)	MMP20	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
MMP20	Strong	Autosomal recessive	amelogenesis imperfecta hypomaturation type 2A2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MMP20	Orphanet:100033	Hypomaturation amelogenesis imperfecta

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
MMP20	HGNC:7167	ENSG00000137674	O60882	Matrix metalloproteinase-20	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MMP20	Matrix metalloproteinase-20	Degrades amelogenin, the major protein component of the enamel matrix and two of the macromolecules characterizing the cartilage extracellular matrix: aggrecan and the cartilage oligomeric matrix protein (COMP).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MMP20	Protease	yes	3.4.24.B6	Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like

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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MMP20	56		marker	left testis, testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MMP20	503

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MMP20	O60882	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 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
Collagen formation	1	456.8×	0.009	MMP20
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.009	MMP20
Collagen degradation	1	175.7×	0.009	MMP20
Degradation of the extracellular matrix	1	117.7×	0.011	MMP20
Extracellular matrix organization	1	63.1×	0.016	MMP20

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
regulation of enamel mineralization	1	5617.3×	0.001	MMP20
amelogenesis	1	1404.3×	0.002	MMP20
collagen catabolic process	1	391.9×	0.005	MMP20
extracellular matrix disassembly	1	366.4×	0.005	MMP20
protein catabolic process	1	237.3×	0.006	MMP20
extracellular matrix organization	1	122.1×	0.010	MMP20
proteolysis	1	34.2×	0.029	MMP20

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MMP20	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MARIMASTAT	3	MMP20

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MMP20	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MMP20	3.4.24.B6

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
MARIMASTAT	3	MMP20

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	1	MMP20
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.