intellectual disability, X-linked 50

Summary

intellectual disability, X-linked 50 (MONDO:0010251) is a disease caused by SYN1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SYN1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 50
Mondo ID	MONDO:0010251
MeSH	C564713
OMIM	300115
DOID	DOID:0112029
UMLS	C1848087
MedGen	376278
GARD	0022668
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 50 · intellectual disability, X-linked 50 · mental retardation, X-linked 50 · MRX50

Data availability: 19 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › neurodevelopmental disorder › intellectual disability › non-syndromic intellectual disability › non-syndromic X-linked intellectual disability › intellectual disability, X-linked 50

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 21, intellectual disability, X-linked 58, intellectual disability, X-linked 72, intellectual disability, X-linked 53, intellectual disability, X-linked 73, intellectual disability, X-linked 42, intellectual disability, X-linked 63, intellectual disability, X-linked, with or without seizures, ARX-related, intellectual disability, X-linked 2, intellectual disability, X-linked 81, intellectual disability, X-linked 46, intellectual disability, X-linked 77, intellectual disability, X-linked 45, intellectual disability, X-linked 84, intellectual disability, X-linked 82, intellectual disability, X-linked 30, intellectual disability, X-linked 91, intellectual disability, X-linked 93, chromosome Xp11.22 duplication syndrome, intellectual disability, X-linked 95, intellectual disability, X-linked 96, intellectual disability, X-linked 97, intellectual disability, X-linked 19, intellectual disability, X-linked 89, intellectual disability, X-linked 41, intellectual disability, X-linked 90, intellectual disability, X-linked 92, intellectual disability, X-linked 88, intellectual disability, X-linked 99, intellectual disability, X-linked 100, intellectual disability, X-linked 101, intellectual disability, X-linked 102, intellectual disability, X-linked 61, intellectual disability, X-linked 103, intellectual disability, X-linked 104, intellectual disability, X-linked 105, intellectual disability, X-linked 1, methylmalonic acidemia with homocystinuria, type cblX, FRAXE intellectual disability, intellectual disability, X-linked 9, intellectual developmental disorder, X-linked 108, intellectual disability, X-linked 106, intellectual disability, X-linked 107, intellectual developmental disorder, X-linked 110, intellectual developmental disorder, X-linked 111, intellectual developmental disorder, X-linked 112, intellectual developmental disorder, X-linked 113, intellectual developmental disorder, X-linked 114

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

19 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 pathogenic, 4 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1068662	NM_006950.3(SYN1):c.700C>T (p.Arg234Ter)	SYN1	Pathogenic	criteria provided, multiple submitters, no conflicts
1700043	NM_006950.3(SYN1):c.980+43_981del	SYN1	Pathogenic	criteria provided, single submitter
3220893	NM_006950.3(SYN1):c.218dup (p.Gly74fs)	SYN1	Pathogenic	criteria provided, single submitter
981406	NM_006950.3(SYN1):c.745C>T (p.Gln249Ter)	SYN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
997017	NM_006950.3(SYN1):c.236C>G (p.Ser79Trp)	SYN1	Pathogenic	no assertion criteria provided
1319815	NM_006950.3(SYN1):c.1259G>A (p.Arg420Gln)	SYN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3598323	NM_006950.3(SYN1):c.616C>T (p.Gln206Ter)	SYN1	Likely pathogenic	criteria provided, single submitter
1994692	NM_006950.3(SYN1):c.1647_1650dup (p.Ser551fs)	SYN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
207472	NM_006950.3(SYN1):c.1372C>G (p.Gln458Glu)	SYN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41890	NM_006950.3(SYN1):c.1699A>G (p.Thr567Ala)	SYN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
932913	NM_006950.3(SYN1):c.986C>T (p.Thr329Met)	SYN1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1484946	NM_006950.3(SYN1):c.1110C>G (p.Cys370Trp)	SYN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1696673	NM_006950.3(SYN1):c.435G>A (p.Gln145=)	SYN1	Uncertain significance	criteria provided, single submitter
1700041	NM_006950.3(SYN1):c.1121C>T (p.Ala374Val)	SYN1	Uncertain significance	criteria provided, single submitter
2665059	NM_006950.3(SYN1):c.1158+8C>T	SYN1	Uncertain significance	criteria provided, single submitter
3899869	NM_006950.3(SYN1):c.967T>C (p.Tyr323His)	SYN1	Uncertain significance	criteria provided, single submitter
520609	NM_006950.3(SYN1):c.635G>T (p.Ser212Ile)	SYN1	Uncertain significance	criteria provided, single submitter
954219	NM_006950.3(SYN1):c.1972C>T (p.Pro658Ser)	SYN1	Uncertain significance	criteria provided, multiple submitters, no conflicts
96364	NM_006950.3(SYN1):c.510T>C (p.Asn170=)	SYN1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
SYN1	Strong	X-linked	epilepsy, X-linked 1, with variable learning disabilities and behavior disorders	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYN1	Orphanet:85294	X-linked epilepsy-learning disabilities-behavior disorders syndrome

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
SYN1	HGNC:11494	ENSG00000008056	P17600	Synapsin-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYN1	Synapsin-1	Neuronal phosphoprotein that coats synaptic vesicles, and binds to the cytoskeleton.

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)
SYN1	Other/Unknown	no		Synapsin, ATP_grasp_subdomain_1, PreATP-grasp_dom_sf

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
prefrontal cortex	1
right frontal lobe	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYN1	190	broad	marker	right frontal lobe, right hemisphere of cerebellum, prefrontal cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYN1	3,188

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SYN1	P17600	69.86

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Serotonin Neurotransmitter Release Cycle	1	634.4×	0.006	SYN1
Dopamine Neurotransmitter Release Cycle	1	496.5×	0.006	SYN1
Neurotransmitter release cycle	1	439.2×	0.006	SYN1
Sensory processing of sound	1	308.6×	0.006	SYN1
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.010	SYN1
Sensory Perception	1	95.2×	0.014	SYN1
Transmission across Chemical Synapses	1	76.1×	0.015	SYN1
Neuronal System	1	44.3×	0.023	SYN1

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
synaptic vesicle clustering	1	1404.3×	0.003	SYN1
regulation of synaptic vesicle cycle	1	1123.5×	0.003	SYN1
regulation of neurotransmitter secretion	1	766.0×	0.003	SYN1
neurotransmitter secretion	1	702.2×	0.003	SYN1
regulation of synaptic vesicle exocytosis	1	455.5×	0.004	SYN1
synapse organization	1	280.9×	0.004	SYN1
neuron development	1	255.3×	0.004	SYN1
chemical synaptic transmission	1	77.3×	0.013	SYN1

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
SYN1	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	SYN1

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)
SYN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.