Stuttering, familial persistent, 1

Summary

Stuttering, familial persistent, 1 (MONDO:0008483) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	stuttering, familial persistent, 1
Mondo ID	MONDO:0008483
OMIM	184450
UMLS	C3489627
MedGen	483580
Is cancer (heuristic)	no

Also known as: STUT1 · stuttering, familial persistent, 1

Data availability: 27 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › specific developmental disorder › communication disorder › speech disorder › stutter disorder › stuttering, familial persistent, 1

Related subtypes (3): stuttering, familial persistent, 2, stuttering, familial persistent, 3, stuttering, familial persistent, 4

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

27 retrieved; paginated sample, class counts are floors:

9 benign, 9 benign/likely benign, 6 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
224506	NM_007347.4(AP4E1):c.[1549G>A;2401G>A]		Pathogenic	no assertion criteria provided
548459	NM_007347.5(AP4E1):c.2234_2235dup (p.Thr746Ter)	AP4E1	Likely pathogenic	criteria provided, single submitter
128402	NM_007347.5(AP4E1):c.613C>A (p.His205Asn)	AP4E1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1383328	NM_007347.5(AP4E1):c.382C>T (p.His128Tyr)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3577352	NM_007347.5(AP4E1):c.2731A>G (p.Thr911Ala)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
434233	NM_007347.5(AP4E1):c.1675A>C (p.Thr559Pro)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
458249	NM_007347.5(AP4E1):c.2149C>T (p.Pro717Ser)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
931303	NM_007347.5(AP4E1):c.617T>C (p.Ile206Thr)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
931304	NM_007347.5(AP4E1):c.2813A>G (p.Asp938Gly)	AP4E1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1243701	NM_007347.5(AP4E1):c.1967-91A>G	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
1245233	NM_007347.5(AP4E1):c.3096-57dup	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
1277493	NM_007347.5(AP4E1):c.222+48_222+49insT	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
1278582	NM_007347.5(AP4E1):c.1316+44_1316+54del	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
128392	NM_007347.5(AP4E1):c.1085A>G (p.Tyr362Cys)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128393	NM_007347.5(AP4E1):c.1283A>G (p.Asn428Ser)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128395	NM_007347.5(AP4E1):c.2429C>T (p.Thr810Ile)	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
128398	NM_007347.5(AP4E1):c.2755A>G (p.Met919Val)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
128399	NM_007347.5(AP4E1):c.2905-8A>G	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
1286033	NM_007347.5(AP4E1):c.346+50G>C	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
210198	NM_007347.5(AP4E1):c.1177-9T>C	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
434237	NM_007347.5(AP4E1):c.3117C>T (p.Asp1039=)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
508250	NM_007347.5(AP4E1):c.3079C>T (p.Leu1027=)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
508353	NM_007347.5(AP4E1):c.2346+10C>T	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
677999	NM_007347.5(AP4E1):c.150+33A>G	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
678150	NM_007347.5(AP4E1):c.1066+51T>C	AP4E1	Benign	criteria provided, multiple submitters, no conflicts
680002	NM_007347.5(AP4E1):c.542+11T>G	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
695562	NM_007347.5(AP4E1):c.171G>A (p.Gln57=)	AP4E1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AP4E1	Orphanet:280763	Severe intellectual disability and progressive spastic paraplegia

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
AP4E1	HGNC:573	ENSG00000081014	Q9UPM8	AP-4 complex subunit epsilon-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AP4E1	AP-4 complex subunit epsilon-1	Component of the adaptor protein complex 4 (AP-4).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AP4E1	Other/Unknown	no		Clathrin/coatomer_adapt-like_N, ARM-like, ARM-type_fold

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
esophagus squamous epithelium	1
gingival epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AP4E1	262	ubiquitous	yes	gingival epithelium, esophagus squamous epithelium, buccal mucosa cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AP4E1	2,108

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AP4E1	Q9UPM8	4

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
Lysosome Vesicle Biogenesis	1	326.3×	0.008	AP4E1
trans-Golgi Network Vesicle Budding	1	253.8×	0.008	AP4E1
Golgi Associated Vesicle Biogenesis	1	200.3×	0.008	AP4E1
Membrane Trafficking	1	37.1×	0.029	AP4E1
Vesicle-mediated transport	1	34.8×	0.029	AP4E1

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
protein targeting	1	366.4×	0.011	AP4E1
intracellular protein localization	1	104.7×	0.014	AP4E1
vesicle-mediated transport	1	96.3×	0.014	AP4E1
intracellular protein transport	1	64.8×	0.015	AP4E1

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
AP4E1	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	AP4E1

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)
AP4E1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.