Beckwith-Wiedemann syndrome due to NSD1 mutation

Summary

Beckwith-Wiedemann syndrome due to NSD1 mutation (MONDO:0016547) is a disease caused by NSD1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: NSD1 (GenCC Definitive)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Beckwith-Wiedemann syndrome due to NSD1 mutation
Mondo ID	MONDO:0016547
Orphanet	238613
UMLS	C5680933
MedGen	1825953
GARD	0017178
Is cancer (heuristic)	no

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › Beckwith-Wiedemann syndrome › Beckwith-Wiedemann syndrome due to NSD1 mutation

Related subtypes (7): Beckwith-Wiedemann syndrome due to imprinting defect of 11p15, Beckwith-Wiedemann syndrome due to CDKN1C mutation, Beckwith-Wiedemann syndrome due to 11p15 microdeletion, Beckwith-Wiedemann syndrome due to 11p15 translocation/inversion, Beckwith-Wiedemann syndrome due to 11p15 microduplication, Beckwith-Wiedemann syndrome due to paternal uniparental disomy of chromosome 11, Franceschini Vardeu Guala syndrome

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
NSD1	Definitive	Autosomal dominant	Beckwith-Wiedemann syndrome due to NSD1 mutation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NSD1	Orphanet:1627	Deletion 5q35 syndrome
NSD1	Orphanet:228415	5q35 microduplication syndrome
NSD1	Orphanet:3447	Weaver syndrome
NSD1	Orphanet:821	Sotos 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
NSD1	HGNC:14234	ENSG00000165671	Q96L73	Histone-lysine N-methyltransferase, H3 lysine-36 specific	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NSD1	Histone-lysine N-methyltransferase, H3 lysine-36 specific	Histone methyltransferase that dimethylates Lys-36 of histone H3 (H3K36me2).

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NSD1	Transcription factor	no	2.1.1.357	PWWP_dom, SET_dom, Znf_PHD

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
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NSD1	235	ubiquitous	marker	sural nerve, colonic epithelium, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NSD1	2,979

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NSD1	Q96L73	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
PKMTs methylate histone lysines	1	160.8×	0.006	NSD1

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 peptidyl-serine phosphorylation	1	16852.0×	2e-04	NSD1
regulation of RNA polymerase II regulatory region sequence-specific DNA binding	1	16852.0×	2e-04	NSD1
methylation	1	170.2×	0.012	NSD1
regulation of DNA-templated transcription	1	31.6×	0.043	NSD1
positive regulation of DNA-templated transcription	1	27.9×	0.043	NSD1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	NSD1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
NSD1	VENETOCLAX

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NSD1	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
SURAMIN	3	NSD1
SINEFUNGIN	2	NSD1
PF-03882845	1	NSD1
PLUMBAGIN	1	NSD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NSD1	90	Binding:90

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NSD1	2.1.1.357, 2.1.1.362	[histone H3]-lysine36 N-dimethyltransferase, [histone H4]-N-methyl-L-lysine20 N-methyltransferase

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

7 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.

Compound	Max phase	Cohort target (bioactivity)
VENETOCLAX	4	NSD1
PRIMAQUINE	4	NSD1
CHLOROQUINE PHOSPHATE	4	NSD1
SURAMIN	3	NSD1
SINEFUNGIN	2	NSD1
PF-03882845	1	NSD1
PLUMBAGIN	1	NSD1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NSD1
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.