intellectual disability, X-linked 96

Summary

intellectual disability, X-linked 96 (MONDO:0010429) is a disease caused by SYP (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: SYP (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 96
Mondo ID	MONDO:0010429
OMIM	300802
DOID	DOID:0112035
UMLS	C3275408
MedGen	477039
GARD	0022685
Is cancer (heuristic)	no

Also known as: intellectual developmental disorder, X-linked 96, X-linked recessive · intellectual disability, X-linked 96 · intellectual disability, X-linked type 96 · mental retardation, X-linked 96 · mental retardation, X-linked type 96 · MRX96 · non-syndromic X-linked intellectual disability caused by mutation in SYP · SYP non-syndromic X-linked intellectual disability

Data availability: 22 ClinVar variants · 5 GenCC gene-disease records.

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 96

Related subtypes (51): intellectual disability, X-linked 23, intellectual disability, X-linked 20, intellectual disability, X-linked 14, intellectual disability, X-linked 50, 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 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

22 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 5 likely pathogenic, 4 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3393445	NM_003179.3(SYP):c.583_584del (p.Asp195fs)	SYP	Pathogenic	criteria provided, single submitter
9863	NM_003179.3(SYP):c.274dup (p.Thr92fs)	SYP	Pathogenic	no assertion criteria provided
9864	NM_003179.3(SYP):c.177_178delinsGT (p.Asn59_Lys60delinsLysTer)	SYP	Pathogenic	no assertion criteria provided
9866	NM_003179.3(SYP):c.649G>C (p.Gly217Arg)	SYP	Pathogenic	no assertion criteria provided
3024328	NM_003179.3(SYP):c.615+2T>C	SYP	Likely pathogenic	criteria provided, single submitter
4531323	NM_003179.3(SYP):c.103-1G>A	SYP	Likely pathogenic	criteria provided, single submitter
4819717	NM_003179.3(SYP):c.277A>T (p.Lys93Ter)	SYP	Likely pathogenic	criteria provided, single submitter
987397	NM_003179.3(SYP):c.829_832del (p.Asp277fs)	SYP	Likely pathogenic	criteria provided, single submitter
1339647	NM_003179.3(SYP):c.2T>C (p.Met1Thr)	SYP-AS1	Likely pathogenic	criteria provided, single submitter
1030635	NM_003179.3(SYP):c.526A>G (p.Ile176Val)	SYP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1699249	NM_003179.3(SYP):c.367G>A (p.Ala123Thr)	SYP	Uncertain significance	criteria provided, single submitter
1705715	NM_003179.3(SYP):c.214G>T (p.Glu72Ter)	SYP	Uncertain significance	criteria provided, single submitter
1709598	NM_003179.3(SYP):c.786C>G (p.Tyr262Ter)	SYP	Uncertain significance	criteria provided, single submitter
2436915	NM_003179.3(SYP):c.787G>A (p.Gly263Arg)	SYP	Uncertain significance	criteria provided, single submitter
3064753	NM_003179.3(SYP):c.882C>G (p.Asp294Glu)	SYP	Uncertain significance	criteria provided, single submitter
3376337	NM_003179.3(SYP):c.654C>A (p.Asn218Lys)	SYP	Uncertain significance	criteria provided, single submitter
4076237	NM_003179.3(SYP):c.905del (p.Pro302fs)	SYP	Uncertain significance	criteria provided, single submitter
4819661	NM_003179.3(SYP):c.115T>C (p.Phe39Leu)	SYP	Uncertain significance	criteria provided, single submitter
982860	NM_003179.3(SYP):c.103G>A (p.Val35Ile)	SYP	Uncertain significance	criteria provided, single submitter
2664186	NM_003179.3(SYP):c.49G>A (p.Gly17Ser)	SYP-AS1	Uncertain significance	criteria provided, single submitter
2672138	NM_003179.3(SYP):c.61G>A (p.Val21Met)	SYP-AS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3062057	NM_003179.3(SYP):c.54G>C (p.Gln18His)	SYP-AS1	Uncertain significance	criteria provided, single submitter

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
SYP	Definitive	X-linked	intellectual disability, X-linked 96	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYP	Orphanet:777	X-linked non-syndromic intellectual disability

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SYP	HGNC:11506	ENSG00000102003	P08247	Synaptophysin	gencc,clinvar
SYP-AS1	HGNC:40571	ENSG00000237341		SYP antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYP	Synaptophysin	Possibly involved in structural functions as organizing other membrane components or in targeting the vesicles to the plasma membrane.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SYP	Other/Unknown	no		Synaptophysin/porin, Marvel
SYP-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
bone marrow	1
male germ line stem cell (sensu Vertebrata) in testis	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYP	206	broad	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SYP-AS1	103		yes	male germ line stem cell (sensu Vertebrata) in testis, bone marrow, thymus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYP	3,655
SYP-AS1	0

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SYP	P08247	77.92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Sensory processing of sound	1	308.6×	0.009	SYP
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.009	SYP
Sensory Perception	1	95.2×	0.011	SYP

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
regulation of opioid receptor signaling pathway	1	5617.3×	0.001	SYP
synaptic vesicle membrane organization	1	3370.4×	0.001	SYP
synaptic vesicle maturation	1	1872.4×	0.001	SYP
regulation of synaptic vesicle priming	1	1685.2×	0.001	SYP
regulation of short-term neuronal synaptic plasticity	1	1123.5×	0.001	SYP
regulation of long-term neuronal synaptic plasticity	1	991.3×	0.001	SYP
regulation of neuronal synaptic plasticity	1	674.1×	0.002	SYP
endocytosis	1	95.2×	0.011	SYP

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
SYP	0	0
SYP-AS1	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	2	SYP, SYP-AS1

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)
SYP	0	—
SYP-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.