Thyroid cancer, nonmedullary, 4

Summary

Thyroid cancer, nonmedullary, 4 (MONDO:0014681) is a cancer with 1 cohort gene.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thyroid cancer, nonmedullary, 4
Mondo ID	MONDO:0014681
OMIM	616534
UMLS	C4225293
MedGen	907624
GARD	0016132
Is cancer (heuristic)	yes

Also known as: FOXE1 thyroid cancer, nonmedullary · NMTC4 · thyroid cancer, nonmedullary caused by mutation in FOXE1 · thyroid cancer, nonmedullary, 4 · thyroid cancer, nonmedullary, type 4

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › thyroid tumor › thyroid cancer › thyroid gland carcinoma › differentiated thyroid carcinoma › thyroid gland follicular carcinoma › thyroid cancer, nonmedullary, 4

Related subtypes (6): trabecular follicular adenocarcinoma, thyroid gland papillary and follicular carcinoma, thyroid cancer, nonmedullary, 2, thyroid Hurthle cell carcinoma, thyroid cancer, nonmedullary, 5, medullary thyroid gland carcinoma

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
3362432	NM_004473.4(FOXE1):c.346C>A (p.Arg116Ser)	FOXE1	Likely pathogenic	criteria provided, single submitter
208453	NM_004473.4(FOXE1):c.743C>G (p.Ala248Gly)	FOXE1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3892377	NC_000005.10:g.101281019_101281030del		Uncertain significance	criteria provided, single submitter
3596018	NM_004473.4(FOXE1):c.608C>G (p.Pro203Arg)	FOXE1	Uncertain significance	criteria provided, single submitter
3892376	NM_004473.4(FOXE1):c.283A>C (p.Lys95Gln)	FOXE1	Uncertain significance	criteria provided, single submitter
522197	NM_004473.4(FOXE1):c.505GCC[7] (p.Ala176_Ala179del)	FOXE1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FOXE1	Orphanet:1226	Bamforth-Lazarus syndrome
FOXE1	Orphanet:146	Differentiated thyroid carcinoma
FOXE1	Orphanet:319487	Familial papillary or follicular thyroid carcinoma
FOXE1	Orphanet:95713	Athyreosis

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
FOXE1	HGNC:3806	ENSG00000178919	O00358	Forkhead box protein E1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FOXE1	Forkhead box protein E1	Transcription factor that binds consensus sites on a variety of gene promoters and activate their 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)
FOXE1	Transcription factor	no		Fork_head_dom, TF_fork_head_CS_1, TF_fork_head_CS_2

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FOXE1	94	tissue_specific	marker	right lobe of thyroid gland, left lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FOXE1	1,606

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FOXE1	O00358	62.02

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
chordate pharynx development	1	5617.3×	0.002	FOXE1
embryonic organ morphogenesis	1	4213.0×	0.002	FOXE1
soft palate development	1	3370.4×	0.002	FOXE1
hard palate development	1	1685.2×	0.002	FOXE1
thyroid hormone generation	1	991.3×	0.003	FOXE1
cranial skeletal system development	1	936.2×	0.003	FOXE1
thyroid gland development	1	543.6×	0.004	FOXE1
hair follicle morphogenesis	1	495.6×	0.004	FOXE1
thymus development	1	337.0×	0.005	FOXE1
cellular response to insulin stimulus	1	170.2×	0.009	FOXE1
anatomical structure morphogenesis	1	139.3×	0.010	FOXE1
cell migration	1	61.5×	0.022	FOXE1
cell differentiation	1	29.1×	0.041	FOXE1
positive regulation of DNA-templated transcription	1	27.9×	0.041	FOXE1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.060	FOXE1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	FOXE1

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
FOXE1	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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	FOXE1

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)
FOXE1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.