Waardenburg syndrome type 2D

Summary

Waardenburg syndrome type 2D (MONDO:0012144) is a disease caused by SNAI2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SNAI2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Waardenburg syndrome type 2D
Mondo ID	MONDO:0012144
MeSH	C563839
OMIM	608890
DOID	DOID:0110952
UMLS	C1837203
MedGen	323102
Is cancer (heuristic)	no

Also known as: SNAI2 Waardenburg syndrome type 2 · Waardenburg syndrome type 2 caused by mutation in SNAI2 · Waardenburg syndrome type IID · Waardenburg syndrome, type 2D · WS2D

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Waardenburg syndrome › Waardenburg syndrome type 2 › Waardenburg syndrome type 2D

Related subtypes (4): Waardenburg syndrome type 2A, Waardenburg syndrome type 2B, Waardenburg syndrome type 2C, Waardenburg syndrome type 2E

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
7503	NG_012130.1:g.(?5165)(7623_?)del	SNAI2	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
SNAI2	Strong	Autosomal recessive	Waardenburg syndrome type 2D	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SNAI2	Orphanet:2884	Piebaldism
SNAI2	Orphanet:895	Waardenburg syndrome type 2

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
SNAI2	HGNC:11094	ENSG00000019549	O43623	Zinc finger protein SNAI2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SNAI2	Zinc finger protein SNAI2	Transcriptional repressor that modulates both activator-dependent and basal transcription.

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)
SNAI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_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
cartilage tissue	1
stromal cell of endometrium	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SNAI2	254	ubiquitous	marker	tibia, cartilage tissue, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SNAI2	3,657

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SNAI2	O43623	64.87

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. 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
PTEN Regulation	1	228.4×	0.016	SNAI2
Regulation of PTEN gene transcription	1	178.4×	0.016	SNAI2
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.016	SNAI2
Negative Regulation of CDH1 Gene Transcription	1	120.2×	0.016	SNAI2
MITF-M-regulated melanocyte development	1	114.2×	0.016	SNAI2
Intracellular signaling by second messengers	1	91.4×	0.016	SNAI2
PIP3 activates AKT signaling	1	66.8×	0.019	SNAI2
Developmental Biology	1	14.5×	0.078	SNAI2
Signal Transduction	1	10.2×	0.098	SNAI2

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
desmosome disassembly	1	16852.0×	0.001	SNAI2
negative regulation of vitamin D receptor signaling pathway	1	8426.0×	0.001	SNAI2
regulation of chemokine production	1	5617.3×	0.001	SNAI2
regulation of branching involved in salivary gland morphogenesis	1	5617.3×	0.001	SNAI2
negative regulation of hematopoietic stem cell proliferation	1	5617.3×	0.001	SNAI2
cell migration involved in endocardial cushion formation	1	4213.0×	0.001	SNAI2
negative regulation of cell adhesion involved in substrate-bound cell migration	1	4213.0×	0.001	SNAI2
negative regulation of vitamin D biosynthetic process	1	4213.0×	0.001	SNAI2
cartilage morphogenesis	1	3370.4×	0.001	SNAI2
myeloid cell apoptotic process	1	2106.5×	0.002	SNAI2
epithelium development	1	2106.5×	0.002	SNAI2
negative regulation of myeloid cell apoptotic process	1	1872.4×	0.002	SNAI2
regulation of bicellular tight junction assembly	1	1685.2×	0.002	SNAI2
epithelial to mesenchymal transition involved in endocardial cushion formation	1	1404.3×	0.002	SNAI2
negative regulation of cell adhesion mediated by integrin	1	1296.3×	0.002	SNAI2
regulation of osteoblast differentiation	1	1296.3×	0.002	SNAI2
negative regulation of DNA damage response, signal transduction by p53 class mediator	1	1123.5×	0.002	SNAI2
negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1	1123.5×	0.002	SNAI2
epithelial cell migration	1	936.2×	0.002	SNAI2
negative regulation of anoikis	1	887.0×	0.002	SNAI2
white fat cell differentiation	1	842.6×	0.002	SNAI2
neural crest cell development	1	802.5×	0.002	SNAI2
negative regulation of keratinocyte proliferation	1	702.2×	0.002	SNAI2
pigmentation	1	702.2×	0.002	SNAI2
negative regulation of chondrocyte differentiation	1	674.1×	0.002	SNAI2
hematopoietic stem cell proliferation	1	648.1×	0.002	SNAI2
aortic valve morphogenesis	1	432.1×	0.003	SNAI2
endothelial cell migration	1	411.0×	0.003	SNAI2
cellular response to ionizing radiation	1	411.0×	0.003	SNAI2
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	411.0×	0.003	SNAI2

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
SNAI2	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	SNAI2

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)
SNAI2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.