amelogenesis imperfecta type 1F

Summary

amelogenesis imperfecta type 1F (MONDO:0014560) is a disease caused by AMBN (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: AMBN (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta type 1F
Mondo ID	MONDO:0014560
OMIM	616270
DOID	DOID:0110065
UMLS	C4225394
MedGen	898597
GARD	0016076
Is cancer (heuristic)	no

Also known as: AI1F · AMBN amelogenesis imperfecta · amelogenesis imperfecta caused by mutation in AMBN · amelogenesis imperfecta, type IF

Data availability: 13 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 1 › amelogenesis imperfecta type 1F

Related subtypes (5): amelogenesis imperfecta type 1B, amelogenesis imperfecta type 1A, amelogenesis imperfecta type 1C, amelogenesis imperfecta type 1H, amelogenesis imperfecta, type 1J

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

13 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 pathogenic, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
183689	NM_016519.6(AMBN):c.294+140_531+479del	AMBN	Pathogenic	no assertion criteria provided
2501301	NM_016519.6(AMBN):c.539dup (p.Val181fs)	AMBN	Pathogenic	no assertion criteria provided
372171	NM_016519.6(AMBN):c.532-1G>C	AMBN	Pathogenic	no assertion criteria provided
2501302	NM_016519.6(AMBN):c.76G>A (p.Ala26Thr)	AMBN	Likely pathogenic	no assertion criteria provided
2444856	NM_016519.6(AMBN):c.571-1G>C	AMBN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1702585	NM_016519.6(AMBN):c.209C>G (p.Ser70Ter)	AMBN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2233469	NM_016519.6(AMBN):c.295T>C (p.Tyr99His)	AMBN	Uncertain significance	criteria provided, single submitter
2445235	NM_016519.6(AMBN):c.15+1G>A	AMBN	Uncertain significance	criteria provided, single submitter
2445418	NM_016519.6(AMBN):c.577G>T (p.Gly193Ter)	AMBN	Uncertain significance	criteria provided, single submitter
3779438	NM_016519.6(AMBN):c.1267_1268del (p.Leu423fs)	AMBN	Uncertain significance	criteria provided, single submitter
4277969	NM_018303.6(EXOC2):c.196C>A (p.Gln66Lys)	EXOC2	Uncertain significance	criteria provided, single submitter
4278066	NM_018303.6(EXOC2):c.1310G>A (p.Arg437Gln)	EXOC2	Uncertain significance	criteria provided, single submitter
780465	NM_016519.6(AMBN):c.882C>A (p.His294Gln)	AMBN	Benign/Likely benign	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
AMBN	Strong	Autosomal recessive	amelogenesis imperfecta type 1F	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AMBN	Orphanet:100031	Hypoplastic amelogenesis imperfecta

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
AMBN	HGNC:452	ENSG00000178522	Q9NP70	Ameloblastin	gencc,clinvar
EXOC2	HGNC:24968	ENSG00000112685	Q96KP1	Exocyst complex component 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AMBN	Ameloblastin	Involved in the mineralization and structural organization of enamel.
EXOC2	Exocyst complex component 2	Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Antibody/Immunoglobulin	1	14.6×	0.135
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AMBN	Other/Unknown	no		Amelin
EXOC2	Antibody/Immunoglobulin	yes		IPT_dom, Ig-like_fold, Ig_E-set

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	2
diaphragm	1
periodontal ligament	1
cortical plate	1
middle temporal gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AMBN	32	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, periodontal ligament, diaphragm
EXOC2	255	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, middle temporal gyrus, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EXOC2	2,587
AMBN	1,348

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EXOC2	Q96KP1	80.82
AMBN	Q9NP70	44.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
VxPx cargo-targeting to cilium	1	259.6×	0.015	EXOC2
Insulin processing	1	228.4×	0.015	EXOC2
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	77.2×	0.030	EXOC2
Post-translational protein phosphorylation	1	50.1×	0.032	AMBN
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.032	AMBN
Post-translational protein modification	1	9.6×	0.118	AMBN
Metabolism of proteins	1	6.2×	0.155	AMBN

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
regulation of entry of bacterium into host cell	1	1685.2×	0.006	EXOC2
obsolete vesicle tethering involved in exocytosis	1	936.2×	0.006	EXOC2
obsolete vesicle docking involved in exocytosis	1	337.0×	0.009	EXOC2
biomineral tissue development	1	324.1×	0.009	AMBN
Golgi to plasma membrane transport	1	280.9×	0.009	EXOC2
membrane fission	1	205.5×	0.010	EXOC2
odontogenesis of dentin-containing tooth	1	150.5×	0.011	AMBN
mitotic cytokinesis	1	129.6×	0.012	EXOC2
exocytosis	1	75.9×	0.018	EXOC2
regulation of cell population proliferation	1	57.7×	0.021	AMBN
protein transport	1	21.9×	0.049	EXOC2
cell adhesion	1	18.7×	0.053	AMBN

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
AMBN	0	0
EXOC2	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	1	EXOC2
E	Difficult family or no structure, no drug	1	AMBN

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)
AMBN	0	—
EXOC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.