Waardenburg syndrome 2F

Summary

Waardenburg syndrome 2F (MONDO:0030983) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Waardenburg syndrome 2F
Mondo ID	MONDO:0030983
OMIM	619947
UMLS	C5677013
MedGen	1809587
GARD	0025672
Is cancer (heuristic)	no

Also known as: WS2F

Data availability: 6 ClinVar variants · 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 2F

Related subtypes (4): Waardenburg syndrome type 3, Waardenburg syndrome type 1, Waardenburg syndrome type 2, Waardenburg-Shah 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

6 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1693554	NM_000899.5(KITLG):c.94C>T (p.Arg32Cys)	KITLG	Pathogenic	no assertion criteria provided
1693555	NM_000899.5(KITLG):c.443T>C (p.Ile148Thr)	KITLG	Pathogenic	no assertion criteria provided
1693556	NM_000899.5(KITLG):c.550_551del (p.Met184fs)	KITLG	Pathogenic	no assertion criteria provided
3767214	NM_139242.4(MTFMT):c.1022del (p.Thr341fs)	MTFMT	Likely pathogenic	criteria provided, single submitter
2504286	NM_000899.5(KITLG):c.715-2A>G	KITLG	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2504592	NM_000899.5(KITLG):c.15+6T>C	KITLG	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 6 · 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
KITLG	Strong	Autosomal dominant	Waardenburg syndrome	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KITLG	Orphanet:280628	Familial progressive hyper- and hypopigmentation
KITLG	Orphanet:363494	Non-seminomatous germ cell tumor of testis
KITLG	Orphanet:79146	Familial progressive hyperpigmentation
KITLG	Orphanet:895	Waardenburg syndrome type 2
KITLG	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MTFMT	Orphanet:319524	Combined oxidative phosphorylation defect type 15

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KITLG	HGNC:6343	ENSG00000049130	P21583	Kit ligand	gencc,clinvar
MTFMT	HGNC:29666	ENSG00000103707	Q96DP5	Methionyl-tRNA formyltransferase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KITLG	Kit ligand	Ligand for the receptor-type protein-tyrosine kinase KIT.
MTFMT	Methionyl-tRNA formyltransferase, mitochondrial	Methionyl-tRNA formyltransferase that formylates methionyl-tRNA in mitochondria and is crucial for translation initiation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KITLG	Other/Unknown	no		SCF, 4_helix_cytokine-like_core
MTFMT	Enzyme (other)	yes	2.1.2.9	Formyl_transf_N, Formyl_trans_C, Fmt

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardia of stomach	1
lower lobe of lung	1
visceral pleura	1
buccal mucosa cell	1
cardiac muscle of right atrium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KITLG	262	ubiquitous	marker	visceral pleura, cardia of stomach, lower lobe of lung
MTFMT	245	ubiquitous	marker	left ventricle myocardium, buccal mucosa cell, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KITLG	3,075
MTFMT	2,143

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KITLG	P21583	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MTFMT	Q96DP5	86.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Regulation of KIT signaling	1	300.5×	0.025	KITLG
Signaling by SCF-KIT	1	124.1×	0.025	KITLG
Transcriptional and post-translational regulation of MITF-M expression and activity	1	89.2×	0.025	KITLG
Constitutive Signaling by Aberrant PI3K in Cancer	1	63.4×	0.025	KITLG
Mitochondrial translation initiation	1	63.4×	0.025	MTFMT
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	48.4×	0.027	KITLG
PIP3 activates AKT signaling	1	33.4×	0.032	KITLG
RAF/MAP kinase cascade	1	30.5×	0.032	KITLG

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
conversion of methionyl-tRNA to N-formyl-methionyl-tRNA	1	8426.0×	0.001	MTFMT
positive regulation of myeloid leukocyte differentiation	1	4213.0×	0.001	KITLG
myeloid leukocyte differentiation	1	2808.7×	0.001	KITLG
negative regulation of mast cell apoptotic process	1	2808.7×	0.001	KITLG
melanocyte migration	1	2808.7×	0.001	KITLG
mast cell migration	1	2808.7×	0.001	KITLG
positive regulation of hematopoietic progenitor cell differentiation	1	2808.7×	0.001	KITLG
mast cell apoptotic process	1	2106.5×	0.001	KITLG
positive regulation of melanocyte differentiation	1	1685.2×	0.001	KITLG
mast cell proliferation	1	1685.2×	0.001	KITLG
positive regulation of mast cell proliferation	1	1685.2×	0.001	KITLG
positive regulation of hematopoietic stem cell proliferation	1	936.2×	0.002	KITLG
positive regulation of leukocyte migration	1	495.6×	0.004	KITLG
embryonic hemopoiesis	1	495.6×	0.004	KITLG
positive regulation of Ras protein signal transduction	1	443.5×	0.004	KITLG
ectopic germ cell programmed cell death	1	421.3×	0.004	KITLG
extrinsic apoptotic signaling pathway in absence of ligand	1	234.1×	0.007	KITLG
ovarian follicle development	1	195.9×	0.007	KITLG
T cell proliferation	1	191.5×	0.007	KITLG
neural crest cell migration	1	168.5×	0.008	KITLG
positive regulation of T cell proliferation	1	129.6×	0.010	KITLG
hematopoietic progenitor cell differentiation	1	118.7×	0.010	KITLG
Ras protein signal transduction	1	102.8×	0.011	KITLG
male gonad development	1	78.0×	0.014	KITLG
cell adhesion	1	18.7×	0.055	KITLG
positive regulation of cell population proliferation	1	16.8×	0.059	KITLG

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KITLG	0	0
MTFMT	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KITLG	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MTFMT	2.1.2.9	methionyl-tRNA formyltransferase

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	0
D	Druggable family + AlphaFold only, no drug	1	MTFMT
E	Difficult family or no structure, no drug	1	KITLG

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KITLG	1	—
MTFMT	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.