intellectual disability, X-linked 93

Summary

intellectual disability, X-linked 93 (MONDO:0010393) is a disease caused by BRWD3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BRWD3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 187

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	intellectual disability, X-linked 93
Mondo ID	MONDO:0010393
MeSH	C567066
OMIM	300659
DOID	DOID:0112045
UMLS	C1970841
MedGen	410164
GARD	0024722
Is cancer (heuristic)	no

Also known as: BRWD3 non-syndromic X-linked intellectual disability · intellectual developmental disorder, X-linked 93, X-linked recessive · intellectual disability, X-linked 93 · intellectual disability, X-linked type 93 · mental retardation, X-linked 93 · mental retardation, X-linked type 93 · mental retardation, X-linked, with macrocephaly · MRX93 · non-syndromic X-linked intellectual disability caused by mutation in BRWD3

Data availability: 187 ClinVar variants · 4 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 93

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, 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

187 retrieved; paginated sample, class counts are floors:

89 uncertain significance, 40 benign, 20 likely pathogenic, 13 pathogenic, 11 conflicting classifications of pathogenicity, 9 benign/likely benign, 2 pathogenic/likely pathogenic, 2 likely benign, 1 vus-mid

ClinVar	Variant (HGVS)	Gene	Classification	Review
10802	NM_153252.5(BRWD3):c.3325+1G>T	BRWD3	Pathogenic	no assertion criteria provided
10803	NM_153252.5(BRWD3):c.946dup (p.Arg316fs)	BRWD3	Pathogenic	no assertion criteria provided
10804	NM_153252.5(BRWD3):c.4786A>G (p.Lys1596Glu)	BRWD3	Pathogenic	no assertion criteria provided
1526410	NM_153252.5(BRWD3):c.3976C>T (p.Arg1326Ter)	BRWD3	Pathogenic	criteria provided, single submitter
1526411	NM_153252.5(BRWD3):c.3413G>T (p.Trp1138Leu)	BRWD3	Pathogenic	no assertion criteria provided
235505	NM_153252.5(BRWD3):c.3718C>T (p.Arg1240Ter)	BRWD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2430139	NM_153252.5(BRWD3):c.828_829dup (p.Lys277fs)	BRWD3	Pathogenic	criteria provided, single submitter
2498284	NM_153252.5(BRWD3):c.2864C>G (p.Ala955Gly)	BRWD3	Pathogenic	no assertion criteria provided
3362784	NM_153252.5(BRWD3):c.665_666del (p.Ser222fs)	BRWD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3377339	NM_153252.5(BRWD3):c.2473G>T (p.Glu825Ter)	BRWD3	Pathogenic	criteria provided, single submitter
374258	NM_153252.5(BRWD3):c.568C>T (p.Arg190Ter)	BRWD3	Pathogenic	criteria provided, single submitter
3764597	NM_153252.5(BRWD3):c.263del (p.Pro88fs)	BRWD3	Pathogenic	criteria provided, single submitter
4531357	NM_153252.5(BRWD3):c.3119del (p.Tyr1040fs)	BRWD3	Pathogenic	criteria provided, single submitter
4531358	NM_153252.5(BRWD3):c.2620C>T (p.Gln874Ter)	BRWD3	Pathogenic	criteria provided, single submitter
623359	NM_153252.5(BRWD3):c.3200_3201del (p.Val1067fs)	BRWD3	Pathogenic	criteria provided, single submitter
1323983	NM_153252.5(BRWD3):c.1522-1G>C	BRWD3	Likely pathogenic	criteria provided, single submitter
1343196	NM_153252.5(BRWD3):c.3893T>A (p.Leu1298Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
1710421	NM_153252.5(BRWD3):c.144G>A (p.Trp48Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
2438769	NM_153252.5(BRWD3):c.2095C>T (p.Arg699Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
2442194	NM_153252.5(BRWD3):c.3899dup (p.Cys1300fs)	BRWD3	Likely pathogenic	criteria provided, single submitter
2582597	NM_153252.5(BRWD3):c.94dup (p.Leu32fs)	BRWD3	Likely pathogenic	criteria provided, single submitter
2584526	NM_153252.5(BRWD3):c.4006-1G>A	BRWD3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2920680	NM_153252.5(BRWD3):c.439dup (p.Thr147fs)	BRWD3	Likely pathogenic	criteria provided, single submitter
3375485	NM_153252.5(BRWD3):c.608T>G (p.Leu203Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
3376175	NM_153252.5(BRWD3):c.2T>C (p.Met1Thr)	BRWD3	Likely pathogenic	criteria provided, single submitter
3393443	NM_153252.5(BRWD3):c.4186del (p.Gln1396fs)	BRWD3	Likely pathogenic	criteria provided, single submitter
3572932	NM_153252.5(BRWD3):c.1150C>T (p.Arg384Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
3902006	NM_153252.5(BRWD3):c.824_827del (p.Ser275fs)	BRWD3	Likely pathogenic	criteria provided, single submitter
4073522	NM_153252.5(BRWD3):c.3373G>T (p.Glu1125Ter)	BRWD3	Likely pathogenic	criteria provided, single submitter
4292558	NM_153252.5(BRWD3):c.2955del (p.Phe985fs)	BRWD3	Likely pathogenic	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
BRWD3	Definitive	X-linked	intellectual disability, X-linked 93	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRWD3	Orphanet:528084	Non-specific syndromic intellectual disability

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
BRWD3	HGNC:17342	ENSG00000165288	Q6RI45	Bromodomain and WD repeat-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRWD3	Bromodomain and WD repeat-containing protein 3	Plays a role in the regulation of cell morphology and cytoskeletal organization.

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)
BRWD3	Scaffold/PPI	no		Bromodomain, WD40_rpt, WD40/YVTN_repeat-like_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
calcaneal tendon	1
epithelial cell of pancreas	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRWD3	223	ubiquitous	marker	tendon of biceps brachii, epithelial cell of pancreas, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRWD3	2,714

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BRWD3	Q6RI45	65.11

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
cytoskeleton organization	1	132.7×	0.012	BRWD3
regulation of cell shape	1	123.0×	0.012	BRWD3
regulation of transcription by RNA polymerase II	1	11.7×	0.086	BRWD3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRWD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
BRWD3	5	Binding:5

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	BRWD3

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)
BRWD3	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.