Beckwith-Wiedemann syndrome due to CDKN1C mutation

Summary

Beckwith-Wiedemann syndrome due to CDKN1C mutation (MONDO:0016476) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Beckwith-Wiedemann syndrome due to CDKN1C mutation
Mondo ID	MONDO:0016476
Orphanet	231120
UMLS	C5680918
MedGen	1826157
GARD	0017160
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 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 CDKN1C mutation

Related subtypes (7): Beckwith-Wiedemann syndrome due to imprinting defect of 11p15, Beckwith-Wiedemann syndrome due to 11p15 microdeletion, Beckwith-Wiedemann syndrome due to 11p15 translocation/inversion, Beckwith-Wiedemann syndrome due to NSD1 mutation, 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

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
404254	NM_001122630.2(CDKN1C):c.320C>T (p.Pro107Leu)	CDKN1C	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · 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
CDKN1C	Definitive	Autosomal dominant	Beckwith-Wiedemann syndrome	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDKN1C	Orphanet:231120	Beckwith-Wiedemann syndrome due to CDKN1C mutation
CDKN1C	Orphanet:397590	Silver-Russell syndrome due to a point mutation
CDKN1C	Orphanet:436144	Intrauterine growth restriction-short stature-early adult-onset diabetes syndrome
CDKN1C	Orphanet:85173	IMAGe 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
CDKN1C	HGNC:1786	ENSG00000129757	P49918	Cyclin-dependent kinase inhibitor 1C	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDKN1C	Cyclin-dependent kinase inhibitor 1C	Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2.

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)
CDKN1C	Other/Unknown	no		CDI_dom, CDI_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
C1 segment of cervical spinal cord	1
adrenal tissue	1
placenta	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDKN1C	134	ubiquitous	marker	placenta, adrenal tissue, C1 segment of cervical spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDKN1C	2,275

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CDKN1C	P49918	63.93

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	1	878.5×	0.005	CDKN1C
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	1	634.4×	0.005	CDKN1C
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	407.9×	0.005	CDKN1C
G1 Phase	1	393.8×	0.005	CDKN1C
Diseases of mitotic cell cycle	1	393.8×	0.005	CDKN1C
Cyclin D associated events in G1	1	233.1×	0.007	CDKN1C
Mitotic G1 phase and G1/S transition	1	184.2×	0.008	CDKN1C
Cell Cycle, Mitotic	1	48.2×	0.026	CDKN1C
Cell Cycle	1	36.0×	0.031	CDKN1C
Disease	1	13.1×	0.076	CDKN1C

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 lens fiber cell differentiation	1	8426.0×	0.002	CDKN1C
digestive system development	1	3370.4×	0.002	CDKN1C
embryonic placenta morphogenesis	1	3370.4×	0.002	CDKN1C
regulation of exit from mitosis	1	1203.7×	0.003	CDKN1C
genomic imprinting	1	991.3×	0.003	CDKN1C
neuron maturation	1	802.5×	0.003	CDKN1C
negative regulation of mitotic cell cycle	1	802.5×	0.003	CDKN1C
uterus development	1	802.5×	0.003	CDKN1C
adrenal gland development	1	674.1×	0.003	CDKN1C
myeloid cell differentiation	1	648.1×	0.003	CDKN1C
positive regulation of transforming growth factor beta receptor signaling pathway	1	526.6×	0.003	CDKN1C
camera-type eye development	1	358.6×	0.004	CDKN1C
negative regulation of epithelial cell proliferation	1	290.6×	0.005	CDKN1C
kidney development	1	140.4×	0.008	CDKN1C
multicellular organism growth	1	137.0×	0.008	CDKN1C
skeletal system development	1	125.8×	0.008	CDKN1C
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	CDKN1C

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
CDKN1C	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	CDKN1C

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)
CDKN1C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.