Mutism

Summary

Mutism (MONDO:0002905) is a disease with 1 cohort gene and 2 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mutism
Mondo ID	MONDO:0002905
MeSH	D009155
DOID	DOID:4189
ICD-11	1275861519
UMLS	C0026884
MedGen	6476
Is cancer (heuristic)	no

Also known as: mutism · mutism (disease)

Data availability: 1 ClinVar variant · 1 HPO phenotype.

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 › mutism

Related subtypes (3): stutter disorder, articulation disorder, echolalia

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
397528	NC_000022.11:g.50721470dup	SHANK3	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SHANK3	Orphanet:662169	Phelan-McDermid syndrome due to 22q13.3 deletion
SHANK3	Orphanet:662172	Phelan-McDermid syndrome due to SHANK3 mutation

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
SHANK3	HGNC:14294	ENSG00000251322	Q9BYB0	SH3 and multiple ankyrin repeat domains protein 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SHANK3	SH3 and multiple ankyrin repeat domains protein 3	Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance.

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SHANK3	Scaffold/PPI	no		SH3_domain, PDZ, SAM

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SHANK3	246	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SHANK3	3,702

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SHANK3	Q9BYB0	3

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
guanylate kinase-associated protein clustering	1	8426.0×	0.001	SHANK3
positive regulation of synapse structural plasticity	1	5617.3×	0.001	SHANK3
striatal medium spiny neuron differentiation	1	4213.0×	0.001	SHANK3
negative regulation of cell volume	1	3370.4×	0.001	SHANK3
AMPA glutamate receptor clustering	1	3370.4×	0.001	SHANK3
NMDA glutamate receptor clustering	1	3370.4×	0.001	SHANK3
regulation of long-term synaptic depression	1	3370.4×	0.001	SHANK3
negative regulation of actin filament bundle assembly	1	2808.7×	0.001	SHANK3
vocal learning	1	2106.5×	0.001	SHANK3
positive regulation of long-term neuronal synaptic plasticity	1	1872.4×	0.001	SHANK3
postsynaptic density assembly	1	1872.4×	0.001	SHANK3
regulation of long-term synaptic potentiation	1	1532.0×	0.002	SHANK3
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.002	SHANK3
dendritic spine morphogenesis	1	887.0×	0.002	SHANK3
vocalization behavior	1	887.0×	0.002	SHANK3
regulation of dendritic spine morphogenesis	1	842.6×	0.002	SHANK3
positive regulation of dendritic spine development	1	766.0×	0.002	SHANK3
brain morphogenesis	1	732.7×	0.002	SHANK3
positive regulation of long-term synaptic potentiation	1	674.1×	0.002	SHANK3
positive regulation of synaptic transmission, glutamatergic	1	624.1×	0.002	SHANK3
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	SHANK3
associative learning	1	481.5×	0.003	SHANK3
adult behavior	1	468.1×	0.003	SHANK3
neuromuscular process controlling balance	1	330.4×	0.004	SHANK3
learning	1	280.9×	0.004	SHANK3
synapse organization	1	280.9×	0.004	SHANK3
social behavior	1	271.8×	0.004	SHANK3
synapse assembly	1	230.8×	0.005	SHANK3
memory	1	183.2×	0.006	SHANK3
MAPK cascade	1	153.2×	0.007	SHANK3

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
SHANK3	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	SHANK3

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)
SHANK3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02300766	Not specified	RECRUITING	Cerebellar Mutism Syndrome Study
NCT06080685	Not specified	COMPLETED	Efficacy of Character Strengths Intervention in Enhancing Character Strengths and Self-esteem Among Adolescents