Thyroid cancer, nonmedullary, 2

Summary

Thyroid cancer, nonmedullary, 2 (MONDO:0008566) is a cancer with 7 cohort genes (4 CIViC-evidence somatic drivers; 42 ClinVar predisposition records) and 5 clinical trials. Top therapeutic interventions include copanlisib, dabrafenib, and spartalizumab.

At a glance

• Classification: Cancer
• Cohort genes: 7
• ClinVar variants: 42
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thyroid cancer, nonmedullary, 2
Mondo ID	MONDO:0008566
MeSH	C572845
OMIM	188470
UMLS	C4225426
MedGen	904175
GARD	0005206
Is cancer (heuristic)	yes

Also known as: FTC · NMTC2 · thyroid cancer, follicular · thyroid cancer, nonmedullary, 2 · thyroid cancer, nonmedullary, 2, autosomal dominant, somatic mutation · thyroid cancer, nonmedullary, type 2 · thyroid carcinoma, follicular · thyroid carcinoma, follicular, autosomal dominant, somatic mutation · thyroid carcinoma, follicular, somatic

Data availability: 42 ClinVar variants · 2 GenCC gene-disease records.

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, 2

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

42 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 11 pathogenic, 3 benign, 2 likely benign, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 likely benign; risk factor, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
13966	NM_004333.6(BRAF):c.1801A>G (p.Lys601Glu)	BRAF	Pathogenic	criteria provided, single submitter
12601	NM_005343.4(HRAS):c.181C>A (p.Gln61Lys)	HRAS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12603	NM_005343.4(HRAS):c.35G>C (p.Gly12Ala)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12604	NM_005343.4(HRAS):c.38G>A (p.Gly13Asp)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
12606	NM_005343.4(HRAS):c.37G>T (p.Gly13Cys)	HRAS	Pathogenic	reviewed by expert panel
12613	NM_005343.4(HRAS):c.34G>T (p.Gly12Cys)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
391700	NM_005343.4(HRAS):c.179G>T (p.Gly60Val)	HRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
5021	NM_004897.5(MINPP1):c.122C>T (p.Ser41Leu)	MINPP1	Pathogenic	no assertion criteria provided
5022	NM_004897.5(MINPP1):c.809A>G (p.Gln270Arg)	MINPP1	Pathogenic	no assertion criteria provided
13900	NM_002524.5(NRAS):c.182A>G (p.Gln61Arg)	NRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
560358	NM_000314.8(PTEN):c.672del (p.Tyr225fs)	PTEN	Pathogenic	criteria provided, single submitter
208457	NM_020762.4(SRGAP1):c.823G>A (p.Ala275Thr)	SRGAP1	Pathogenic	no assertion criteria provided
160364	NM_005343.4(HRAS):c.182A>G (p.Gln61Arg)	HRAS	Likely pathogenic	criteria provided, multiple submitters, no conflicts
208458	NM_020762.4(SRGAP1):c.1849C>T (p.Arg617Cys)	SRGAP1	Likely benign; risk factor	no assertion criteria provided
240138	NM_005343.4(HRAS):c.546G>A (p.Met182Ile)	HRAS	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
177918	NM_005343.4(HRAS):c.505C>T (p.Arg169Trp)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
180851	NM_005343.4(HRAS):c.367C>T (p.Arg123Cys)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
180856	NM_005343.4(HRAS):c.506G>A (p.Arg169Gln)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
3599788	NM_005343.4(HRAS):c.550T>G (p.Cys184Gly)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
40447	NM_005343.4(HRAS):c.508A>T (p.Lys170Ter)	HRAS	Uncertain significance	reviewed by expert panel
409949	NM_005343.4(HRAS):c.391C>T (p.Gln131Ter)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
45304	NM_005343.4(HRAS):c.412G>A (p.Gly138Ser)	HRAS	Uncertain significance	reviewed by expert panel
503537	NM_005343.4(HRAS):c.11A>G (p.Tyr4Cys)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
644041	NM_005343.4(HRAS):c.481C>T (p.Arg161Cys)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
835903	NM_005343.4(HRAS):c.410A>C (p.Tyr137Ser)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
850426	NM_005343.4(HRAS):c.491G>C (p.Arg164Pro)	HRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts
3891662	NM_004897.5(MINPP1):c.1063C>T (p.Gln355Ter)	MINPP1	Uncertain significance	criteria provided, single submitter
3891663	NM_004897.5(MINPP1):c.125C>T (p.Ser42Leu)	MINPP1	Uncertain significance	criteria provided, single submitter
3891664	NM_004897.5(MINPP1):c.991A>G (p.Ile331Val)	MINPP1	Uncertain significance	criteria provided, single submitter
477662	NM_002524.5(NRAS):c.25G>A (p.Val9Ile)	NRAS	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 40 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
HRAS	Act	ANGS,BLCA,BRCA,COADREAD,CSCC,HNSC,LUSC,NPC,PGNG,PRAD,PROSTATE,THYM,UTUC,WDTC	CIViC #2747
NRAS	Act	ALL,AML,ANGS,CHOL,CLLSLL,COAD,COADREAD,GBM,HCC,LGGNOS,LUAD,LUSC,MEL,MGCT,NPC,OVT,PCM,PROSTATE,SKCM,THYM,UCEC,WDTC	CIViC #36
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41

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
MINPP1	No Known Disease Relationship	Unknown	thyroid cancer, nonmedullary, 2	4
SRGAP1	No Known Disease Relationship	Autosomal dominant	thyroid cancer, nonmedullary, 2	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MINPP1	Orphanet:284339	Pontocerebellar hypoplasia type 7
MINPP1	Orphanet:319487	Familial papillary or follicular thyroid carcinoma
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
LRRC56	Orphanet:244	Primary ciliary dyskinesia
HRAS	Orphanet:146	Differentiated thyroid carcinoma
HRAS	Orphanet:2612	Linear nevus sebaceus syndrome
HRAS	Orphanet:2874	Phakomatosis pigmentokeratotica
HRAS	Orphanet:3071	Costello syndrome
HRAS	Orphanet:79414	Woolly hair nevus
NRAS	Orphanet:146	Differentiated thyroid carcinoma
NRAS	Orphanet:2612	Linear nevus sebaceus syndrome
NRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
NRAS	Orphanet:389	Langerhans cell histiocytosis
NRAS	Orphanet:626	Large/giant congenital melanocytic nevus
NRAS	Orphanet:648	Noonan syndrome
NRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SRGAP1	HGNC:17382	ENSG00000196935	Q7Z6B7	SLIT-ROBO Rho GTPase-activating protein 1	gencc,clinvar
MINPP1	HGNC:7102	ENSG00000107789	Q9UNW1	Multiple inositol polyphosphate phosphatase 1	gencc,clinvar
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	clinvar
LRRC56	HGNC:25430	ENSG00000161328	Q8IYG6	Leucine-rich repeat-containing protein 56	clinvar
HRAS	HGNC:5173	ENSG00000174775	P01112	GTPase HRas	clinvar
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SRGAP1	SLIT-ROBO Rho GTPase-activating protein 1	GTPase-activating protein for RhoA and Cdc42 small GTPases.
MINPP1	Multiple inositol polyphosphate phosphatase 1	Multiple inositol polyphosphate phosphatase that hydrolyzes 1D-myo-inositol 1,3,4,5,6-pentakisphosphate (InsP5[2OH]) and 1D-myo-inositol hexakisphosphate (InsP6) to a range of less phosphorylated inositol phosphates.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
LRRC56	Leucine-rich repeat-containing protein 56	Required for the assembly of dynein arms.
HRAS	GTPase HRas	Involved in the activation of Ras protein signal transduction.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.57

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
Phosphatase	1	12.0×	0.275
Enzyme (other)	2	3.4×	0.275
Kinase	1	4.0×	0.378
Scaffold/PPI	1	2.5×	0.426
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SRGAP1	Scaffold/PPI	no		RhoGAP_dom, FCH_dom, SH3_domain
MINPP1	Enzyme (other)	yes	3.1.3.62	His_Pase_clade-2, Histidine_acid_Pase_euk, His_PPase_superfam
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
LRRC56	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_4, LRR_dom_sf
HRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

7 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
calcaneal tendon	2
cortical plate	1
medial globus pallidus	1
adrenal tissue	1
tibia	1
trabecular bone tissue	1
colonic epithelium	1
left testis	1
right testis	1
right uterine tube	1
skin of abdomen	1
skin of leg	1
zone of skin	1
epithelium of nasopharynx	1
gingival epithelium	1
secondary oocyte	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SRGAP1	236	ubiquitous	marker	buccal mucosa cell, cortical plate, medial globus pallidus
MINPP1	275	ubiquitous	marker	trabecular bone tissue, tibia, adrenal tissue
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
LRRC56	129	broad	marker	right uterine tube, right testis, left testis
HRAS	139	ubiquitous	marker	skin of abdomen, skin of leg, zone of skin
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626
HRAS	8,064
NRAS	7,598
BRAF	7,394
SRGAP1	1,122
LRRC56	914
MINPP1	821

Intra-cohort edges

A	B	Sources
BRAF	HRAS	intact, string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
MINPP1	PTEN	string_interaction
NRAS	PTEN	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HRAS	P01112	246
BRAF	P15056	131
NRAS	P01111	35
PTEN	P60484	12

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MINPP1	Q9UNW1	90.42
SRGAP1	Q7Z6B7	73.49
LRRC56	Q8IYG6	56.07

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 125. Enrichment computed across 7 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by RAS GAP mutants	2	1268.9×	1e-05	HRAS, NRAS
Signaling by RAS GTPase mutants	2	1268.9×	1e-05	HRAS, NRAS
RAF activation	3	167.9×	1e-05	BRAF, HRAS, NRAS
Signaling by high-kinase activity BRAF mutants	3	158.6×	1e-05	BRAF, HRAS, NRAS
MAP2K and MAPK activation	3	142.8×	1e-05	BRAF, HRAS, NRAS
Signaling by RAF1 mutants	3	139.3×	1e-05	BRAF, HRAS, NRAS
Negative regulation of MAPK pathway	3	132.8×	1e-05	BRAF, HRAS, NRAS
Signaling by moderate kinase activity BRAF mutants	3	126.9×	1e-05	BRAF, HRAS, NRAS
Paradoxical activation of RAF signaling by kinase inactive BRAF	3	126.9×	1e-05	BRAF, HRAS, NRAS
Signaling downstream of RAS mutants	3	126.9×	1e-05	BRAF, HRAS, NRAS
Activation of RAS in B cells	2	761.3×	3e-05	HRAS, NRAS
Signaling by BRAF and RAF1 fusions	3	85.2×	4e-05	BRAF, HRAS, NRAS
RAS signaling downstream of NF1 loss-of-function variants	2	543.8×	4e-05	HRAS, NRAS
Estrogen-stimulated signaling through PRKCZ	2	543.8×	4e-05	HRAS, NRAS
SOS-mediated signalling	2	475.8×	5e-05	HRAS, NRAS
Activated NTRK3 signals through RAS	2	423.0×	6e-05	HRAS, NRAS
EGFR Transactivation by Gastrin	2	380.7×	7e-05	HRAS, NRAS
SHC-related events triggered by IGF1R	2	380.7×	7e-05	HRAS, NRAS
Activated NTRK2 signals through RAS	2	380.7×	7e-05	HRAS, NRAS
MET activates RAS signaling	2	346.1×	8e-05	HRAS, NRAS
Signaling by FGFR4 in disease	2	317.2×	8e-05	HRAS, NRAS
Activated NTRK2 signals through FRS2 and FRS3	2	317.2×	8e-05	HRAS, NRAS
Constitutive Signaling by Overexpressed ERBB2	2	317.2×	8e-05	HRAS, NRAS
p38MAPK events	2	292.8×	9e-05	HRAS, NRAS
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	292.8×	9e-05	HRAS, NRAS
Signaling by PDGFRA extracellular domain mutants	2	292.8×	9e-05	HRAS, NRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases	2	271.9×	1e-04	HRAS, NRAS
GRB2 events in EGFR signaling	2	253.8×	1e-04	HRAS, NRAS
Erythropoietin activates RAS	2	253.8×	1e-04	HRAS, NRAS
Signaling by FLT3 ITD and TKD mutants	2	253.8×	1e-04	HRAS, NRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
MAPK cascade	3	65.7×	0.001	BRAF, HRAS, NRAS
negative regulation of synaptic vesicle clustering	1	1203.7×	0.018	PTEN
CD4-positive or CD8-positive, alpha-beta T cell lineage commitment	1	802.5×	0.018	BRAF
negative regulation of keratinocyte migration	1	802.5×	0.018	PTEN
positive regulation of miRNA metabolic process	1	802.5×	0.018	HRAS
rhythmic synaptic transmission	1	601.9×	0.018	PTEN
positive regulation of axon regeneration	1	481.5×	0.018	BRAF
negative regulation of synaptic vesicle exocytosis	1	481.5×	0.018	BRAF
central nervous system myelin maintenance	1	401.2×	0.018	PTEN
CD4-positive, alpha-beta T cell differentiation	1	401.2×	0.018	BRAF
myeloid progenitor cell differentiation	1	343.9×	0.018	BRAF
oncogene-induced cell senescence	1	343.9×	0.018	HRAS
negative regulation of cell cycle G1/S phase transition	1	343.9×	0.018	PTEN
negative regulation of wound healing, spreading of epidermal cells	1	343.9×	0.018	PTEN
positive regulation of D-glucose transmembrane transport	1	300.9×	0.018	BRAF
head morphogenesis	1	300.9×	0.018	BRAF
spindle assembly involved in female meiosis	1	267.5×	0.018	PTEN
central nervous system neuron axonogenesis	1	267.5×	0.018	PTEN
T-helper 1 type immune response	1	267.5×	0.018	HRAS
establishment of protein localization to membrane	1	267.5×	0.018	BRAF
postsynaptic density assembly	1	267.5×	0.018	PTEN
neuron-neuron synaptic transmission	1	240.7×	0.018	PTEN
negative regulation of peptidyl-serine phosphorylation	1	240.7×	0.018	PTEN
negative regulation of cell size	1	240.7×	0.018	PTEN
presynaptic membrane assembly	1	240.7×	0.018	PTEN
Ras protein signal transduction	2	58.7×	0.018	HRAS, NRAS
animal organ morphogenesis	2	54.7×	0.018	BRAF, HRAS
T cell receptor signaling pathway	2	43.4×	0.018	BRAF, HRAS
regulation of cell population proliferation	2	33.0×	0.018	BRAF, HRAS
negative regulation of cell migration	2	31.9×	0.018	SRGAP1, PTEN

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 7 evidence-associated genes (57%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRAF	VEMURAFENIB
HRAS	LONAFARNIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRAF	48	4
HRAS	4	4
NRAS	1	1
SRGAP1	0	0
MINPP1	0	0
LRRC56	0	0
PTEN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
LONAFARNIB	4	HRAS
MASITINIB	3	BRAF
AVUTOMETINIB	3	BRAF
NAPORAFENIB	3	BRAF
QUERCETIN	3	BRAF
MOTESANIB	3	BRAF
DORAMAPIMOD	2	BRAF
FORETINIB	2	BRAF
REBASTINIB	2	BRAF
CEP-32496	2	BRAF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
HRAS	48	Binding:45, Functional:3
NRAS	18	Binding:18
PTEN	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MINPP1	3.1.3.62	multiple inositol-polyphosphate phosphatase
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
HRAS	3.6.5.2	small monomeric GTPase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
BRAF	1,442

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

29 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.

Compound	Max phase	Cohort target (bioactivity)
VEMURAFENIB	4	BRAF
PONATINIB	4	BRAF
FEDRATINIB	4	BRAF
SORAFENIB	4	BRAF
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	BRAF
INFIGRATINIB PHOSPHATE	4	BRAF
INFIGRATINIB	4	BRAF
REGORAFENIB	4	BRAF
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ABEMACICLIB	4	BRAF
ENCORAFENIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	BRAF
DASATINIB	4	BRAF
ERLOTINIB	4	BRAF
GEFITINIB	4	BRAF
IMATINIB	4	BRAF
LONAFARNIB	4	HRAS
MASITINIB	3	BRAF
AVUTOMETINIB	3	BRAF
NAPORAFENIB	3	BRAF
QUERCETIN	3	BRAF
MOTESANIB	3	BRAF
DORAMAPIMOD	2	BRAF
FORETINIB	2	BRAF
REBASTINIB	2	BRAF
CEP-32496	2	BRAF

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	BRAF, HRAS
B	Phased (≥1) drug, not yet approved	1	NRAS
C	Druggable family + PDB, no drug	1	PTEN
D	Druggable family + AlphaFold only, no drug	1	MINPP1
E	Difficult family or no structure, no drug	2	SRGAP1, LRRC56

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SRGAP1	0	—
MINPP1	0	—
LRRC56	0	—
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04544111	PHASE2	ACTIVE_NOT_RECRUITING	PDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer
NCT04462471	PHASE1	COMPLETED	Vemurafenib Plus Copanlisib in Radioiodine-Refractory (RAIR) Thyroid Cancers
NCT06730321	Not specified	RECRUITING	Surgical Competency for Robot-Assisted Thyroidectomy: Construction and Validation of a Robotic Thyroidectomy Assessment Score (RTAS)
NCT07122557	Not specified	NOT_YET_RECRUITING	Real World Effectiveness of Bictegravir/Emtricitabine/Tenofovir Alafenamide(BIC/FTC/TAF) in PLWH in Precarity Settings in France -IMEA073
NCT05796960	Not specified	UNKNOWN	European Multicenter Study on Surgical Management of Advanced Thyroid Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
COPANLISIB	4	1
DABRAFENIB	4	1
SPARTALIZUMAB	3	1
CHEMBL5433950	0	1