Thyroid cancer, nonmedullary, 5

Summary

Thyroid cancer, nonmedullary, 5 (MONDO:0014682) is a cancer with 1 cohort gene.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thyroid cancer, nonmedullary, 5
Mondo ID	MONDO:0014682
OMIM	616535
UMLS	C4225292
MedGen	895900
GARD	0016133
Is cancer (heuristic)	yes

Also known as: HABP2 thyroid cancer, nonmedullary · NMTC5 · thyroid cancer, nonmedullary caused by mutation in HABP2 · thyroid cancer, nonmedullary, 5 · thyroid cancer, nonmedullary, type 5

Data availability: 7 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, 5

Related subtypes (6): trabecular follicular adenocarcinoma, thyroid gland papillary and follicular carcinoma, thyroid cancer, nonmedullary, 2, thyroid Hurthle cell carcinoma, thyroid cancer, nonmedullary, 4, 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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 benign/likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
5974	NM_004132.5(HABP2):c.1601G>A (p.Gly534Glu)	HABP2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1683615	NM_004132.5(HABP2):c.1590C>T (p.Gly530=)	HABP2	Uncertain significance	criteria provided, single submitter
3233332	NM_004132.5(HABP2):c.1520G>T (p.Gly507Val)	HABP2	Uncertain significance	criteria provided, single submitter
3391142	NM_004132.5(HABP2):c.965C>T (p.Ala322Val)	HABP2	Uncertain significance	criteria provided, single submitter
3779725	NM_004132.5(HABP2):c.838+2T>C	HABP2	Uncertain significance	criteria provided, single submitter
298911	NM_004132.5(HABP2):c.947G>A (p.Gly316Glu)	HABP2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
877809	NM_004132.5(HABP2):c.364C>T (p.Arg122Trp)	HABP2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HABP2	Orphanet:319487	Familial papillary or follicular thyroid carcinoma

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
HABP2	HGNC:4798	ENSG00000148702	Q14520	Factor VII-activating protease	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HABP2	Factor VII-activating protease	Cleaves the alpha-chain at multiple sites and the beta-chain between ‘Lys-53’ and ‘Lys-54’ but not the gamma-chain of fibrinogen and therefore does not initiate the formation of the fibrin clot and does not cause the fibrinolysis directly.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HABP2	Protease	yes	3.4.21.B1	Kringle, EGF, Trypsin_dom

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
liver	1
pancreatic ductal cell	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HABP2	115	tissue_specific	marker	right lobe of liver, pancreatic ductal cell, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HABP2	4,008

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HABP2	Q14520	77.58

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
cell adhesion	1	37.5×	0.029	HABP2
proteolysis	1	34.2×	0.029	HABP2

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HABP2	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
HABP2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HABP2	3.4.21.B1

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	1	HABP2
E	Difficult family or no structure, no drug	0

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)
HABP2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.