amelogenesis imperfecta, type 1J

Summary

amelogenesis imperfecta, type 1J (MONDO:0015008) is a disease caused by ACP4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ACP4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amelogenesis imperfecta, type 1J
Mondo ID	MONDO:0015008
EFO	EFO:0009302
OMIM	617297
DOID	DOID:0080953
UMLS	C4310630
MedGen	934597
GARD	0016220
Is cancer (heuristic)	no

Also known as: AI1J · amelogenesis imperfecta, type 1J

Data availability: 15 ClinVar variants · 1 GenCC gene-disease record.

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 1J

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

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

15 retrieved; paginated sample, class counts are floors:

8 pathogenic, 3 uncertain significance, 3 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
374863	NM_033068.3(ACP4):c.331C>T (p.Arg111Cys)	ACP4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
374864	NM_033068.3(ACP4):c.226C>T (p.Arg76Cys)	ACP4	Pathogenic	no assertion criteria provided
374865	NM_033068.3(ACP4):c.382G>C (p.Ala128Pro)	ACP4	Pathogenic	no assertion criteria provided
374866	NM_033068.3(ACP4):c.397G>A (p.Glu133Lys)	ACP4	Pathogenic	no assertion criteria provided
375694	NM_033068.3(ACP4):c.746C>T (p.Pro249Leu)	ACP4	Pathogenic	criteria provided, single submitter
375700	NM_033068.3(ACP4):c.428C>T (p.Thr143Met)	ACP4	Pathogenic	no assertion criteria provided
4687880	NM_033068.3(ACP4):c.254T>C (p.Leu85Pro)	ACP4	Pathogenic	criteria provided, single submitter
4687881	NM_033068.3(ACP4):c.435del (p.Val146fs)	ACP4	Pathogenic	criteria provided, single submitter
4687882	NM_033068.3(ACP4):c.845T>C (p.Met282Thr)	ACP4	Pathogenic	criteria provided, single submitter
2445430	NM_033068.3(ACP4):c.645+1G>A	ACP4	Likely pathogenic	criteria provided, single submitter
2445431	NM_033068.3(ACP4):c.736G>A (p.Val246Met)	ACP4	Likely pathogenic	criteria provided, single submitter
4849306	NM_033068.3(ACP4):c.984_986+1del	ACP4	Likely pathogenic	criteria provided, single submitter
2445429	NM_033068.3(ACP4):c.1199C>A (p.Ala400Asp)	ACP4	Uncertain significance	criteria provided, single submitter
2445595	NM_033068.3(ACP4):c.626T>C (p.Leu209Pro)	ACP4	Uncertain significance	criteria provided, single submitter
374862	NM_033068.3(ACP4):c.713C>T (p.Ser238Leu)	ACP4	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
ACP4	Strong	Autosomal recessive	amelogenesis imperfecta, type 1J	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ACP4	Orphanet:100031	Hypoplastic 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
ACP4	HGNC:14376	ENSG00000142513	Q9BZG2	Testicular acid phosphatase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ACP4	Testicular acid phosphatase	May dephosphorylate receptor tyrosine-protein kinase ERBB4 and inhibits its ligand-induced proteolytic cleavage.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ACP4	Phosphatase	yes		His_Pase_clade-2, His_PPase_superfam, Acid_Pase_AS

Expression context

Cohort genes with no expression data: 0.

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
buccal mucosa cell	1
tendon of biceps brachii	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ACP4	99		yes	tendon of biceps brachii, buccal mucosa cell, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ACP4	649

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACP4	Q9BZG2	88.30

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
negative regulation of ERBB4 signaling pathway	1	16852.0×	2e-04	ACP4
peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity	1	16852.0×	2e-04	ACP4
negative regulation of protein processing	1	1123.5×	0.002	ACP4
regulation of neuronal synaptic plasticity	1	674.1×	0.002	ACP4
odontogenesis	1	526.6×	0.002	ACP4
negative regulation of neuron projection development	1	237.3×	0.004	ACP4

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
ACP4	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	1	ACP4
E	Difficult family or no structure, no drug	0

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)
ACP4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.