intellectual disability, X-linked 90

Summary

intellectual disability, X-linked 90 (MONDO:0010452) is a disease caused by DLG3 (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: DLG3 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 64

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 90
Mondo ID	MONDO:0010452
OMIM	300850
DOID	DOID:0112041
UMLS	C3275443
MedGen	477074
GARD	0022690
Is cancer (heuristic)	no

Also known as: DLG3 non-syndromic X-linked intellectual disability · intellectual developmental disorder, X-linked 90, X-linked recessive · intellectual disability, X-linked 90 · intellectual disability, X-linked type 90 · mental retardation, X-linked 90 · mental retardation, X-linked type 90 · MRX90 · non-syndromic X-linked intellectual disability caused by mutation in DLG3

Data availability: 64 ClinVar variants · 3 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 90

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 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 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

64 retrieved; paginated sample, class counts are floors:

31 uncertain significance, 12 likely pathogenic, 10 pathogenic, 8 conflicting classifications of pathogenicity, 1 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11519	NM_021120.4(DLG3):c.1302+1G>A	DLG3	Pathogenic	no assertion criteria provided
127193	NM_021120.4(DLG3):c.357+1G>C	DLG3	Pathogenic	no assertion criteria provided
127194	NM_021120.4(DLG3):c.985+1G>C	DLG3	Pathogenic	no assertion criteria provided
1319664	NM_021120.4(DLG3):c.2266C>T (p.Arg756Ter)	DLG3	Pathogenic	criteria provided, multiple submitters, no conflicts
2576624	NM_021120.4(DLG3):c.-8dup	DLG3	Pathogenic	criteria provided, single submitter
29942	NM_021120.4(DLG3):c.1092dup (p.Thr365fs)	DLG3	Pathogenic	no assertion criteria provided
29943	NM_021120.4(DLG3):c.1373C>G (p.Ser458Ter)	DLG3	Pathogenic	criteria provided, single submitter
3393533	NM_021120.4(DLG3):c.649C>T (p.Arg217Ter)	DLG3	Pathogenic	criteria provided, multiple submitters, no conflicts
3598422	NM_021120.4(DLG3):c.1669C>T (p.Gln557Ter)	DLG3	Pathogenic	criteria provided, single submitter
3770157	NM_021120.4(DLG3):c.1349_1350del (p.Ala450fs)	DLG3	Pathogenic	criteria provided, single submitter
817679	NM_021120.4(DLG3):c.159del (p.Tyr54fs)	DLG3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
11518	NM_021120.4(DLG3):c.985+5G>A	DLG3	Likely pathogenic	criteria provided, single submitter
1334574	NM_021120.4(DLG3):c.1447C>T (p.Gln483Ter)	DLG3	Likely pathogenic	criteria provided, single submitter
2429999	NM_021120.4(DLG3):c.1819+1del	DLG3	Likely pathogenic	criteria provided, single submitter
2626899	NM_021120.4(DLG3):c.116dup (p.Tyr39Ter)	DLG3	Likely pathogenic	criteria provided, single submitter
3770137	NM_021120.4(DLG3):c.131dup (p.Asn45fs)	DLG3	Likely pathogenic	criteria provided, single submitter
3770138	NC_000023.11:g.(70500990_70502096)(70502336?)del	DLG3	Likely pathogenic	criteria provided, single submitter
3770144	NM_021120.4(DLG3):c.691A>T (p.Lys231Ter)	DLG3	Likely pathogenic	criteria provided, single submitter
3770153	NM_021120.4(DLG3):c.1015dup (p.Ser339fs)	DLG3	Likely pathogenic	criteria provided, single submitter
3770156	NM_021120.4(DLG3):c.1302+5G>A	DLG3	Likely pathogenic	criteria provided, single submitter
3770158	NM_021120.4(DLG3):c.1462dup (p.Ser488fs)	DLG3	Likely pathogenic	criteria provided, single submitter
3770159	NM_021120.4(DLG3):c.1619_1628del (p.Asp540fs)	DLG3	Likely pathogenic	criteria provided, single submitter
3770160	NM_021120.4(DLG3):c.2371G>T (p.Glu791Ter)	DLG3	Likely pathogenic	criteria provided, single submitter
1299587	NM_021120.4(DLG3):c.251C>T (p.Pro84Leu)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1805626	NM_021120.4(DLG3):c.575C>T (p.Ser192Leu)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
224095	NM_021120.4(DLG3):c.1721G>A (p.Arg574Gln)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2440804	NM_021120.4(DLG3):c.593G>A (p.Arg198Gln)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3024274	NM_021120.4(DLG3):c.1972+1G>A	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931628	NM_021120.4(DLG3):c.341G>C (p.Arg114Pro)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
985614	NM_021120.4(DLG3):c.128G>T (p.Gly43Val)	DLG3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
DLG3	Definitive	X-linked	intellectual disability, X-linked 90	4
MPP3	Definitive	X-linked	intellectual disability, X-linked 90	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DLG3	Orphanet:777	X-linked non-syndromic intellectual disability

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DLG3	HGNC:2902	ENSG00000082458	Q92796	Disks large homolog 3	gencc,clinvar
MPP3	HGNC:7221	ENSG00000161647	Q13368	MAGUK p55 subfamily member 3	gencc,clinvar
DLG3-AS1	HGNC:40182	ENSG00000231651		DLG3 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DLG3	Disks large homolog 3	Required for learning most likely through its role in synaptic plasticity following NMDA receptor signaling.
MPP3	MAGUK p55 subfamily member 3	Participates in cell spreading through the phosphoinositide-3-kinase (PI3K) pathway by connecting CADM1 to DLG1 and the regulatory subunit of phosphoinositide-3-kinase (PI3K).

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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
Kinase	2	18.5×	0.008
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DLG3	Kinase	yes		SH3_domain, PDZ, Guanylate_kin-like_dom
MPP3	Kinase	yes		SH3_domain, PDZ, L27_dom
DLG3-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
buccal mucosa cell	1
cortical plate	1
apex of heart	1
cerebellar hemisphere	1
right atrium auricular region	1
epithelial cell of pancreas	1
nasal cavity epithelium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DLG3	276	ubiquitous	marker	cortical plate, body of pancreas, buccal mucosa cell
MPP3	193	ubiquitous	marker	apex of heart, right atrium auricular region, cerebellar hemisphere
DLG3-AS1	155		yes	pancreatic ductal cell, nasal cavity epithelium, epithelial cell of pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DLG3	3,967
MPP3	2,216
DLG3-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DLG3	Q92796	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MPP3	Q13368	78.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 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
NrCAM interactions	1	1631.4×	0.003	DLG3
Activation of Ca-permeable Kainate Receptor	1	1142.0×	0.003	DLG3
Ras activation upon Ca2+ influx through NMDA receptor	1	571.0×	0.003	DLG3
Unblocking of NMDA receptors, glutamate binding and activation	1	543.8×	0.003	DLG3
Synaptic adhesion-like molecules	1	543.8×	0.003	DLG3
Negative regulation of NMDA receptor-mediated neuronal transmission	1	543.8×	0.003	DLG3
Long-term potentiation	1	475.8×	0.003	DLG3
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.005	DLG3
Neurexins and neuroligins	1	196.9×	0.006	DLG3
RAF/MAP kinase cascade	1	61.1×	0.016	DLG3

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
receptor localization to synapse	1	2106.5×	0.003	DLG3
establishment of planar polarity	1	1053.2×	0.003	DLG3
protein localization to synapse	1	766.0×	0.003	DLG3
receptor clustering	1	624.1×	0.003	DLG3
establishment or maintenance of epithelial cell apical/basal polarity	1	581.1×	0.003	DLG3
regulation of postsynaptic membrane neurotransmitter receptor levels	1	495.6×	0.003	DLG3
cell-cell adhesion	1	101.5×	0.014	DLG3
chemical synaptic transmission	1	77.3×	0.016	DLG3
nervous system development	1	45.9×	0.024	DLG3
negative regulation of cell population proliferation	1	42.1×	0.024	DLG3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 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
DLG3	0	0
MPP3	0	0
DLG3-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	DLG3
D	Druggable family + AlphaFold only, no drug	1	MPP3
E	Difficult family or no structure, no drug	1	DLG3-AS1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DLG3	0	—
MPP3	0	—
DLG3-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.