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Atlas / Disease / Thyroid cancer

Thyroid cancer

disease
On this page

Also known as cancer of thyroid glandmalignant neoplasm of the thyroidmalignant neoplasm of the thyroid glandmalignant neoplasm of thyroidmalignant neoplasm of thyroid glandmalignant thyroid gland neoplasmmalignant thyroid gland tumormalignant thyroid gland tumourmalignant thyroid neoplasmmalignant thyroid tumormalignant thyroid tumourmalignant tumor of the thyroidmalignant tumor of the thyroid glandmalignant tumor of thyroidmalignant tumor of thyroid glandmalignant tumour of the thyroidmalignant tumour of the thyroid glandmalignant tumour of thyroidmalignant tumour of thyroid glandneoplasm of thyroid gland

Summary

Thyroid cancer (MONDO:0002108) is a cancer with 10 cohort genes (33 GWAS associations across 16 studies; 8 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 439 clinical trials. Molecularly, RET Fusion confers sensitivity to Pralsetinib in Thyroid Cancer (CIViC Level A); 13 further subtype–drug associations are mapped below. Top therapeutic interventions include dabrafenib, levothyroxine, and cabozantinib.

At a glance

  • Classification: Cancer
  • Cohort genes: 10
  • GWAS associations: 33
  • ClinVar variants: 2
  • Clinical trials: 439
  • Precision-medicine evidence (CIViC): 14 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namethyroid cancer
Mondo IDMONDO:0002108
DOIDDOID:1781
ICD-10-CMC73
ICD-11447433352
NCITC7510
SNOMED CT363478007
UMLSC0007115
MedGen2869
Anatomy (UBERON)UBERON:0002046
Is cancer (heuristic)yes

Also known as: cancer of thyroid gland · malignant neoplasm of the thyroid · malignant neoplasm of the thyroid gland · malignant neoplasm of thyroid · malignant neoplasm of thyroid gland · malignant thyroid gland neoplasm · malignant thyroid gland tumor · malignant thyroid gland tumour · malignant thyroid neoplasm · malignant thyroid tumor · malignant thyroid tumour · malignant tumor of the thyroid · malignant tumor of the thyroid gland · malignant tumor of thyroid · malignant tumor of thyroid gland · malignant tumour of the thyroid · malignant tumour of the thyroid gland · malignant tumour of thyroid · malignant tumour of thyroid gland · neoplasm of thyroid gland (+2 more)

Data availability: 2 ClinVar variants · 33 GWAS associations (16 studies) · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › endocrine gland neoplasm › thyroid tumor › thyroid cancer

Related subtypes (4): thyroid hyalinizing trabecular adenoma, TSH producing pituitary tumor, benign thyroid gland neoplasm, familial thyroglossal duct cyst

Subtypes (3): thyroid sarcoma, thyroid gland carcinoma, thyroid lymphoma

Genetics & variants

GWAS landscape

33 GWAS associations across 16 studies. Top hits map to 16 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
chr9:977853456e-129C0.48
rs168576091e-57DIRC3T0.32
rs132902581e-47PTCSC2C0.4
chr9:1005384704e-45A0.43
rs38021602e-40NRG1G0.25
rs1169093745e-32LINC00609 - MBIPT0.56
chr2:2182942175e-23C0.32
rs70270306e-22PTCSC2?0.69
rs80204816e-21LINC00609C0.26
rs574814459e-21DIRC3A0.28
rs732274981e-18EPB41L4AT0.25
rs99717701e-18MSRB3-AS1?
chr14:365582664e-18A0.26
rs77349924e-17TERTC0.17
rs96427274e-17NRG1A0.23
chr10:1039167075e-14A0.21
chr15:671494129e-14A0.17
rs3697138688e-13LINC01117C2.16
rs71452112e-12LINC00609?1.31
chr8:324132404e-12T0.21
rs5378766326e-12ZNF765C2.4
rs107867741e-11STN1G0.28
rs1427007233e-11LINC00861A2.73
rs1916437494e-11PGAP1 - ANKRD44A2.69
rs9254895e-11PTCSC2T
rs121305592e-10PCNX2C0.15
rs1395662103e-10LINC02082 - LINC01997T0.3
rs1491286373e-09RNU6-1249P - TMEM100T1.72
rs177679046e-09LINC01229, MAFTRRA0.12
rs787529387e-08ACSS3C1.15

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90399736Zhou W20226,0151,333,754Global Biobank Meta-analysis Initiative: Powering genetic discovery across human disease.
GCST90475600Verma A20242,370448,487Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651189Liu TY20251,164234,488Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90079118Backman JD202154673,684Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083104Backman JD202154673,684Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90043902Jiang L2021506455,842A generalized linear mixed model association tool for biobank-scale data.
GCST90479815Verma A2024450121,343Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481522Verma A2024450121,343Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST008371Zhou W2018358407,399Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90481521Verma A202428359,586Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic32

MAF distribution

BucketVariants
common (>=0.05)23
low_freq (0.01-0.05)5
rare (<0.01)4
unknown0

Functional consequences

ConsequenceCount
intron_variant18
unknown7
intergenic_variant5
non_coding_transcript_exon_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
chr9:977853450.2996e-129Tier 4: intronic/intergenic
rs168576092217431785C>T0.321intron_variantDIRC31e-57Tier 4: intronic/intergenic
rs13290258997796811C>A,G,T0.36intron_variantPTCSC21e-47Tier 4: intronic/intergenic
chr9:1005384700.3424e-45Tier 4: intronic/intergenic
rs3802160832547111A>G,T0.429intron_variantNRG12e-40Tier 4: intronic/intergenic
rs1169093741436269155C>T0.038non_coding_transcript_exon_variantLINC00609 - MBIP5e-32Tier 4: intronic/intergenic
chr2:2182942170.2765e-23Tier 4: intronic/intergenic
rs7027030997788173A>C,G,T0.05non_coding_transcript_exon_variantPTCSC26e-22Tier 4: intronic/intergenic
rs80204811436092939C>T0.47intron_variantLINC006096e-21Tier 4: intronic/intergenic
rs574814452217431651A>G0.252intron_variantDIRC39e-21Tier 4: intronic/intergenic
rs732274985112150207A>T0.12intergenic_variantEPB41L4A1e-18Tier 4: intronic/intergenic
rs99717701265639270G>A,C,T0.05intron_variantMSRB3-AS11e-18Tier 4: intronic/intergenic
chr14:365582660.4734e-18Tier 4: intronic/intergenic
rs773499251280013T>A,C0.423intron_variantTERT4e-17Tier 4: intronic/intergenic
rs9642727832556514A>C0.406intron_variantNRG14e-17Tier 4: intronic/intergenic
chr10:1039167070.1125e-14Tier 4: intronic/intergenic
chr15:671494120.2069e-14Tier 4: intronic/intergenic
rs3697138682176878031C>A,T0.001intron_variantLINC011178e-13Tier 4: intronic/intergenic
rs71452111436089060A>T0.05intron_variantLINC006092e-12Tier 4: intronic/intergenic
chr8:324132400.4694e-12Tier 4: intronic/intergenic
rs5378766321953422440C>T0.001intron_variantZNF7656e-12Tier 4: intronic/intergenic
rs1078677410103884565G>A,C,T0.108intron_variantSTN11e-11Tier 4: intronic/intergenic
rs1427007238126154871A>G0.001intron_variantLINC008613e-11Tier 4: intronic/intergenic
rs1916437492196964205A>G0intergenic_variantPGAP1 - ANKRD444e-11Tier 4: intronic/intergenic
rs925489997784318C>A,G,T0.332intron_variantPTCSC25e-11Tier 4: intronic/intergenic
rs121305591233276358T>C0.201intron_variantPCNX22e-10Tier 4: intronic/intergenic
rs1395662103168959780TA>T,TAA0.05intergenic_variantLINC02082 - LINC019973e-10Tier 4: intronic/intergenic
rs1491286371755651796A>T0.012intron_variantRNU6-1249P - TMEM1003e-09Tier 4: intronic/intergenic
rs177679041679716078G>A0.299intron_variantLINC01229, MAFTRR6e-09Tier 4: intronic/intergenic
rs787529381281007727T>C0.039intergenic_variantACSS37e-08Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVarVariant (HGVS)GeneClassificationReview
185440NM_000051.4(ATM):c.7654C>A (p.His2552Asn)ATMUncertain significancecriteria provided, multiple submitters, no conflicts
186956NM_000465.4(BARD1):c.632T>C (p.Leu211Ser)BARD1Uncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 80 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
BRAFActBLCA,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,WDTCCIViC #5
TERTActPRCCCIViC #79
KRASActALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTCCIViC #30
PIK3CAActACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTCCIViC #37
PTENLoFANGS,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,WDTCCIViC #41
RETActANGS,MEL,NSCLC,PGNG,SOFT_TISSUE,WDTCCIViC #42
ATMLoFBLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTCCIViC #69
BARD1ActPRADCIViC #549

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.

GeneClassificationInheritanceDiseaseRecords
TGStrongAutosomal recessivethyroid dyshormonogenesis 34
TIMM44LimitedAutosomal dominantthyroid cancer

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
BRAFOrphanet:1340Cardiofaciocutaneous syndrome
BRAFOrphanet:146Differentiated thyroid carcinoma
BRAFOrphanet:251615Pilomyxoid astrocytoma
BRAFOrphanet:389Langerhans cell histiocytosis
BRAFOrphanet:500Noonan syndrome with multiple lentigines
BRAFOrphanet:54595Craniopharyngioma
BRAFOrphanet:58017Classic hairy cell leukemia
BRAFOrphanet:626Large/giant congenital melanocytic nevus
BRAFOrphanet:648Noonan syndrome
BRAFOrphanet:840Syringocystadenoma papilliferum
BRAFOrphanet:96253Cushing disease
TERTOrphanet:146Differentiated thyroid carcinoma
TERTOrphanet:1501Adrenocortical carcinoma
TERTOrphanet:1775Dyskeratosis congenita
TERTOrphanet:2032Idiopathic pulmonary fibrosis
TERTOrphanet:2495Meningioma
TERTOrphanet:3322Hoyeraal-Hreidarsson syndrome
TERTOrphanet:457246Clear cell sarcoma of kidney
TERTOrphanet:618Familial melanoma
TERTOrphanet:88Idiopathic aplastic anemia
TGOrphanet:95716Familial thyroid dyshormonogenesis
KRASOrphanet:1333Familial pancreatic carcinoma
KRASOrphanet:1340Cardiofaciocutaneous syndrome
KRASOrphanet:144Lynch syndrome
KRASOrphanet:146Differentiated thyroid carcinoma
KRASOrphanet:2396Encephalocraniocutaneous lipomatosis
KRASOrphanet:251615Pilomyxoid astrocytoma
KRASOrphanet:2612Linear nevus sebaceus syndrome
KRASOrphanet:268114RAS-associated autoimmune leukoproliferative disease
KRASOrphanet:3339Oculoectodermal syndrome
KRASOrphanet:648Noonan syndrome
KRASOrphanet:86834Juvenile myelomonocytic leukemia
PIK3CAOrphanet:140944CLOVES syndrome
PIK3CAOrphanet:144Lynch syndrome
PIK3CAOrphanet:168984CLAPO syndrome
PIK3CAOrphanet:201Cowden syndrome
PIK3CAOrphanet:210159Adult hepatocellular carcinoma
PIK3CAOrphanet:221061Familial cerebral cavernous malformation
PIK3CAOrphanet:2495Meningioma
PIK3CAOrphanet:276280Hemihyperplasia-multiple lipomatosis syndrome
PIK3CAOrphanet:295239Macrodactyly of fingers, unilateral
PIK3CAOrphanet:295243Macrodactyly of toes, unilateral
PIK3CAOrphanet:314662Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CAOrphanet:60040Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CAOrphanet:714737Diffuse capillary malformation with overgrowth
PIK3CAOrphanet:90308Capillary-lymphatic-venous malformation with segmental distribution
PIK3CAOrphanet:99802Hemimegalencephaly
PTENOrphanet:109Bannayan-Riley-Ruvalcaba syndrome
PTENOrphanet:137608Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTENOrphanet:145Hereditary breast and/or ovarian cancer syndrome

Cohort genes → proteins

10 cohort genes, 10 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only6
multi_evidence4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
BRAFHGNC:1097ENSG00000157764P15056Serine/threonine-protein kinase B-rafcivic_evidence
TERTHGNC:11730ENSG00000164362O14746Telomerase reverse transcriptasecivic_evidence
TGHGNC:11764ENSG00000042832P01266Thyroglobulingencc
TIMM44HGNC:17316ENSG00000104980O43615Mitochondrial import inner membrane translocase subunit TIM44gencc
KRASHGNC:6407ENSG00000133703P01116GTPase KRascivic_evidence
PIK3CAHGNC:8975ENSG00000121879P42336Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformcivic_evidence
PTENHGNC:9588ENSG00000171862P60484Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENcivic_evidence
RETHGNC:9967ENSG00000165731P07949Proto-oncogene tyrosine-protein kinase receptor Retcivic_evidence
ATMHGNC:795ENSG00000149311Q13315Serine-protein kinase ATMclinvar
BARD1HGNC:952ENSG00000138376Q99728BRCA1-associated RING domain protein 1clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
BRAFSerine/threonine-protein kinase B-rafProtein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
TERTTelomerase reverse transcriptaseTelomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TGThyroglobulinActs as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
TIMM44Mitochondrial import inner membrane translocase subunit TIM44Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner.
KRASGTPase KRasRas proteins bind GDP/GTP and possess intrinsic GTPase activity.
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoformPhosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
PTENPhosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTENDual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
RETProto-oncogene tyrosine-protein kinase receptor RetReceptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
ATMSerine-protein kinase ATMSerine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.
BARD1BRCA1-associated RING domain protein 1E3 ubiquitin-protein ligase.

Protein-family classification

Druggable: 6 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.6

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.

FamilyGenesFoldFDR
Kinase411.1×0.001
Phosphatase18.4×0.283
Enzyme (other)11.2×0.906
Transcription factor10.8×0.906
Other/Unknown30.5×0.976

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
BRAFKinaseyes2.7.10.2Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
TERTOther/UnknownnoRT_dom, Telomerase_RT, Telomerase_RBD
TGOther/UnknownnoThyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
TIMM44Other/UnknownnoTim44-like_dom, Tim44, NTF2-like_dom_sf
KRASEnzyme (other)yes3.6.5.2Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
PIK3CAKinaseyes2.7.1.137PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
PTENPhosphataseyes3.1.3.16Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
RETKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
ATMKinaseyes2.7.11.1PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_dom
BARD1Transcription factorno2.3.2.27BRCT_dom, Znf_RING, Ankyrin_rpt

Expression context

Cohort genes with no expression data: 0.

9 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)10
unknown0

Top tissues across cohort

TissueCohort genes
calcaneal tendon4
colonic epithelium2
buccal mucosa cell1
olfactory bulb1
stromal cell of endometrium1
type B pancreatic cell1
left lobe of thyroid gland1
right lobe of thyroid gland1
thyroid gland1
apex of heart1
gastrocnemius1
right hemisphere of cerebellum1
nipple1
pylorus1
trigeminal ganglion1
adrenal tissue1
tendon1
endothelial cell1
sperm1
dorsal root ganglion1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
BRAF265ubiquitousmarkerbuccal mucosa cell, colonic epithelium, calcaneal tendon
TERT105broadyesstromal cell of endometrium, type B pancreatic cell, olfactory bulb
TG169tissue_specificmarkerright lobe of thyroid gland, left lobe of thyroid gland, thyroid gland
TIMM44263ubiquitousmarkerapex of heart, gastrocnemius, right hemisphere of cerebellum
KRAS298ubiquitousmarkertrigeminal ganglion, pylorus, nipple
PIK3CA284ubiquitousmarkercalcaneal tendon, adrenal tissue, tendon
PTEN256ubiquitousmarkersperm, endothelial cell, calcaneal tendon
RET193broadmarkersubstantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
ATM286ubiquitousmarkercalcaneal tendon, colonic epithelium, corpus callosum
BARD1271ubiquitousmarkersecondary oocyte, oocyte, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

SymbolInteractor count
KRAS14,509
PTEN11,626
BRAF7,394
ATM7,383
TERT5,717
PIK3CA5,157
BARD14,230
RET4,203
TIMM442,221
TG1,493

Intra-cohort edges

ABSources
ATMBARD1string_interaction
BRAFKRASbiogrid_interaction, intact, string_interaction
BRAFPIK3CAbiogrid_interaction, string_interaction
BRAFPTENbiogrid_interaction, string_interaction
BRAFTGstring_interaction
KRASPIK3CAstring_interaction
KRASPTENstring_interaction
PIK3CAPTENstring_interaction

Structural data

PDB: 10 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
KRASP01116511
PIK3CAP42336135
BRAFP15056131
RETP0794934
TERTO1474623
ATMQ1331514
PTENP6048412
BARD1Q9972811
TGP012663
TIMM44O436151

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 233. Enrichment computed across 10 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Signaling by FGFR4 in disease2211.5×0.002KRAS, PIK3CA
Defective homologous recombination repair (HRR) due to PALB2 loss of function2211.5×0.002ATM, BARD1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants2195.2×0.002KRAS, PIK3CA
Signaling by PDGFRA extracellular domain mutants2195.2×0.002KRAS, PIK3CA
Diseases of DNA Double-Strand Break Repair2181.3×0.002ATM, BARD1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function2181.3×0.002ATM, BARD1
Signaling by FLT3 ITD and TKD mutants2169.2×0.002KRAS, PIK3CA
Constitutive Signaling by EGFRvIII2158.6×0.002KRAS, PIK3CA
Signaling by ERBB2 ECD mutants2149.3×0.002KRAS, PIK3CA
Resolution of D-Loop Structures2141.0×0.002ATM, BARD1
Tie2 Signaling2133.6×0.002KRAS, PIK3CA
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants2126.9×0.002KRAS, PIK3CA
Diseases of DNA repair2126.9×0.002ATM, BARD1
Signaling by FLT3 fusion proteins2126.9×0.002KRAS, PIK3CA
RAF/MAP kinase cascade427.1×0.002BRAF, KRAS, PIK3CA, RET
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants2115.3×0.002KRAS, PIK3CA
Signaling by FGFR3 in disease2110.3×0.002KRAS, PIK3CA
DNA Double Strand Break Response2105.7×0.002ATM, BARD1
Impaired BRCA2 binding to PALB22101.5×0.002ATM, BARD1
Signaling by ERBB2 KD Mutants294.0×0.002KRAS, PIK3CA
Defective homologous recombination repair (HRR) due to BRCA1 loss of function294.0×0.002ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function294.0×0.002ATM, BARD1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function294.0×0.002ATM, BARD1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)287.5×0.002ATM, BARD1
Downstream signal transduction284.6×0.002KRAS, PIK3CA
Homologous DNA Pairing and Strand Exchange284.6×0.002ATM, BARD1
DAP12 signaling281.9×0.002KRAS, PIK3CA
FLT3 Signaling276.9×0.002KRAS, PIK3CA
Signaling by CSF1 (M-CSF) in myeloid cells276.9×0.002KRAS, PIK3CA
RAF activation274.6×0.002BRAF, KRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
negative regulation of neuron apoptotic process444.4×4e-04BRAF, TERT, KRAS, PIK3CA
replicative senescence2198.3×0.004TERT, ATM
MAPK cascade346.0×0.004BRAF, KRAS, RET
positive regulation of gene expression415.5×0.006BRAF, KRAS, ATM, RET
negative regulation of cellular senescence2129.6×0.006TERT, PTEN
thyroid gland development2108.7×0.007BRAF, TG
negative regulation of endothelial cell apoptotic process299.1×0.008BRAF, TERT
heart development323.6×0.009TERT, ATM, PTEN
RNA-templated transcription11685.2×0.010TERT
response to muscle inactivity11685.2×0.010PIK3CA
DNA strand elongation11685.2×0.010TERT
negative regulation of mRNA 3’-end processing11685.2×0.010BARD1
response to mineralocorticoid11685.2×0.010KRAS
siRNA transcription11685.2×0.010TERT
response to butyrate11685.2×0.010PIK3CA
positive regulation of transdifferentiation11685.2×0.010TERT
thymus development267.4×0.010BRAF, ATM
visual learning261.3×0.010BRAF, KRAS
telomere maintenance253.5×0.010TERT, ATM
epidermal growth factor receptor signaling pathway249.6×0.011BRAF, PIK3CA
cellular response to retinoic acid246.8×0.011ATM, RET
embryonic epithelial tube formation1842.6×0.012RET
RNA-templated DNA biosynthetic process1842.6×0.012TERT
posterior midgut development1842.6×0.012RET
positive regulation of hair cycle1842.6×0.012TERT
establishment of RNA localization to telomere1842.6×0.012ATM
establishment of protein-containing complex localization to telomere1842.6×0.012ATM
positive regulation of telomerase catalytic core complex assembly1842.6×0.012ATM
negative regulation of synaptic vesicle clustering1842.6×0.012PTEN
liver development244.4×0.012KRAS, PIK3CA

Therapeutics

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 4

Druggability breadth: 8 of 10 evidence-associated genes (80%) 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.

SymbolExample approved molecule
BRAFVEMURAFENIB
TERTBERBERINE
KRASVEMURAFENIB
PIK3CAIDELALISIB
RETPONATINIB
ATMAMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
RET1354
PIK3CA674
BRAF484
ATM354
KRAS114
TERT104
TG00
TIMM4400
PTEN00
BARD100

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
VEMURAFENIB4BRAF, KRAS, RET
PONATINIB4BRAF, RET
FEDRATINIB4BRAF, PIK3CA, RET
SORAFENIB4BRAF, RET
DASATINIB ANHYDROUS4BRAF, RET
RUXOLITINIB4BRAF, RET
INFIGRATINIB PHOSPHATE4BRAF, RET
INFIGRATINIB4BRAF, RET
REGORAFENIB4BRAF, RET
DABRAFENIB4BRAF, KRAS
COBIMETINIB4BRAF
NILOTINIB4BRAF, RET
ABEMACICLIB4BRAF
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF, RET
DASATINIB4BRAF, PIK3CA, RET
ERLOTINIB4BRAF, RET
GEFITINIB4BRAF, RET
IMATINIB4BRAF
BERBERINE4TERT
DOXORUBICIN4TERT
LONAFARNIB4KRAS
SOTORASIB4KRAS
ADAGRASIB4KRAS
IDELALISIB4PIK3CA
ALPELISIB4PIK3CA
DUVELISIB4PIK3CA
COPANLISIB4PIK3CA
ROMIDEPSIN4PIK3CA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
PIK3CA2,034Binding:2009, ADMET:19, Toxicity:4, Functional:2
RET1,586Binding:1573, Functional:10, ADMET:3
BRAF1,442Binding:1400, Functional:37, ADMET:5
KRAS861Binding:829, Functional:32
TERT391Binding:389, Functional:2
ATM240Binding:233, Functional:5, ADMET:2
PTEN8Binding:8
TIMM441Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BRAF2.7.10.2, 2.7.11.1non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
KRAS3.6.5.2small monomeric GTPase
PIK3CA2.7.1.137, 2.7.1.153, 2.7.11.1phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
PTEN3.1.3.16, 3.1.3.67protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
RET2.7.10.1receptor protein-tyrosine kinase
ATM2.7.11.1non-specific serine/threonine protein kinase
BARD12.3.2.27RING-type E3 ubiquitin transferase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BRAF1,442
TERT391
KRAS861
PIK3CA2,034
RET1,586
ATM240

Pharmacogenomics

Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

24 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.

CompoundMax phaseCohort target (bioactivity)
VEMURAFENIB4BRAF, KRAS, RET
PONATINIB4BRAF, RET
FEDRATINIB4BRAF, PIK3CA, RET
DASATINIB ANHYDROUS4BRAF, RET
RUXOLITINIB4BRAF, RET
INFIGRATINIB PHOSPHATE4BRAF, RET
INFIGRATINIB4BRAF, RET
COBIMETINIB4BRAF
NILOTINIB4BRAF, RET
ENCORAFENIB4BRAF
TOVORAFENIB4BRAF
PAZOPANIB4BRAF, RET
DASATINIB4BRAF, PIK3CA, RET
ERLOTINIB4BRAF, RET
GEFITINIB4BRAF, RET
IMATINIB4BRAF
BERBERINE4TERT
DOXORUBICIN4TERT
LONAFARNIB4KRAS
SOTORASIB4KRAS
ADAGRASIB4KRAS
IDELALISIB4PIK3CA
ALPELISIB4PIK3CA
DUVELISIB4PIK3CA

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)6BRAF, TERT, KRAS, PIK3CA, RET, ATM
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug1PTEN
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug3TG, TIMM44, BARD1

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
TG0—
TIMM441—
PTEN8—
BARD10—

Clinical trials & evidence

Clinical trials

Clinical trials: 439.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified274
PHASE287
PHASE131
PHASE1/PHASE218
PHASE314
PHASE48
PHASE2/PHASE34
EARLY_PHASE13

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07600580PHASE4ACTIVE_NOT_RECRUITINGThe Association Between Bilateral Intermediate Cervical Plexus Block During Total Thyroidectomy and Surgical Stress Response
NCT00604318PHASE4COMPLETEDQuality of Life, Recombinant TSH (Thyrogen) and Thyroid Cancer
NCT01496313PHASE4COMPLETEDTo Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer
NCT02946918PHASE4TERMINATEDLevothyroxine Replacement With Liquid Gel Capsules vs Tablets Post-thyroidectomy
NCT03065218PHASE4TERMINATED99mTc Sestamibi Scans In Thyroglobulin Positive Scan Negative Differentiated Thyroid Cancer (DTC) Patients
NCT03469310PHASE4COMPLETEDMinimizing Narcotic Analgesics After Endocrine Surgery
NCT03969108PHASE4COMPLETEDDiagnostic Accuracy Study of Indocyanine Green for Parathyroid Perfusion Assessment
NCT06697782PHASE4COMPLETEDAprepitant and Ondansetron Monotherapy or Combination for Postoperative Nausea and Vomiting in Thyroid Cancer
NCT01398085PHASE2/PHASE3ACTIVE_NOT_RECRUITINGIoN- Is Ablative Radio-iodine Necessary for Low Risk Differentiated Thyroid Cancer Patients
NCT03570021PHASE3ACTIVE_NOT_RECRUITINGESTIMation of the ABiLity of Prophylactic Central Compartment Neck Dissection to Modify Outcomes in Low-risk Differentiated Thyroid Cancer
NCT04290663PHASE3RECRUITINGSystematic Radioiodine Administration Versus Decision of Radioiodine Treatment Guided by a Post-operative Work-up
NCT05999630PHASE3RECRUITINGArtificial Tears to Prevent Nasolacrimal Duct Obstruction in Patients Treated With Radioactive Iodine for Thyroid Cancer
NCT06082180PHASE3RECRUITINGA Prospective, Open-label, Multicenter, Randomized Controlled Phase III Study of Prophylactic Central Neck Dissection in Low-risk Papillary Thyroid Cancer
NCT06554652PHASE3RECRUITINGSelective Neck Dissection Versus Modified Neck Dissection in PTC
NCT06558981PHASE3RECRUITINGAdjuvant Radiotherapy in High Risk Locally Advanced DTC
NCT06851663PHASE2/PHASE3RECRUITINGTrop2-targeted immunoPET Imaging of Solid Tumors
NCT06860971PHASE3RECRUITINGA Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma
NCT00410761PHASE3COMPLETEDAn Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer
NCT00435851PHASE3UNKNOWNMedico-Economic Comparison of Four Strategies of Radioiodine Ablation in Thyroid Carcinoma Patients
NCT00704730PHASE3COMPLETEDEfficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer
NCT00794053PHASE3COMPLETEDThe Usefulness of Staining Lymph Nodes During Operations for Cancer Thyroid in Detecting the Nodes That Have Cancer
NCT00795782PHASE3COMPLETEDProphylactic Central Lymph Node Dissection in Papillary Thyroid Microcarcinoma
NCT01083550PHASE2/PHASE3COMPLETEDDecision Making on Radioactive Iodine Treatment for Papillary Thyroid Cancer
NCT01321554PHASE3COMPLETEDA Multicenter, Randomized, Double-Blind, Placebo-Controlled, Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC)
NCT01616316PHASE2/PHASE3COMPLETEDEfficacy of Subfascial Approach in Thyroidectomy to Quality of Life in Thyroid Disease Patients
NCT05468554PHASE3UNKNOWNEvaluation of Metformin Effect on the Fertility of Women Treated With 131I for Thyroid Cancer
NCT01141309PHASE2ACTIVE_NOT_RECRUITINGEvaluating the Combination of Everolimus and Sorafenib in the Treatment of Thyroid Cancer
NCT01709292PHASE2ACTIVE_NOT_RECRUITINGVemurafenib Neoadjuvant Trial in Locally Advanced Thyroid Cancer
NCT02628067PHASE2ACTIVE_NOT_RECRUITINGStudy of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)
NCT02657551PHASE2ACTIVE_NOT_RECRUITINGA Study Using Regorafenib as Second or Third Line Therapy in Metastatic Medullary Thyroid Cancer
NCT03099356PHASE2RECRUITINGCyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer
NCT03175224PHASE2RECRUITINGAPL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
NCT03360890PHASE2ACTIVE_NOT_RECRUITINGPembrolizumab With Chemotherapy for Poorly Chemo-responsive Thyroid and Salivary Gland Tumors
NCT03841617PHASE2RECRUITINGThe Use of 124-I-PET/CT Whole Body and Lesional Dosimetry in Differentiated Thyroid Cancer
NCT04238624PHASE2ACTIVE_NOT_RECRUITINGStudy of Cemiplimab Combined With Dabrafenib and Trametinib in People With Anaplastic Thyroid Cancer
NCT04544111PHASE2ACTIVE_NOT_RECRUITINGPDR001 Combination Therapy for Radioiodine-Refractory Thyroid Cancer
NCT04623801PHASE2ACTIVE_NOT_RECRUITINGLaser Ablation of Papillary Thyroid Microcarcinoma
NCT04759911PHASE2ACTIVE_NOT_RECRUITINGSelpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer
NCT05119296PHASE2ACTIVE_NOT_RECRUITINGPhase II Trial of Pembrolizumab in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer
NCT05275374PHASE1/PHASE2NOT_YET_RECRUITINGXP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
DABRAFENIB46
LEVOTHYROXINE46
CABOZANTINIB45
SORAFENIB45
VANDETANIB45
LENVATINIB44
LIOTHYRONINE43
ONDANSETRON43
SELPERCATINIB43
THYROTROPIN ALFA43
FLUDEOXYGLUCOSE F 1842
INDOCYANINE GREEN ACID FORM42
ABEMACICLIB41
APREPITANT41
BEXAROTENE41
BRODALUMAB41
CEMIPLIMAB41
COPANLISIB41
DACARBAZINE41
DECITABINE41
LITHIUM CARBONATE41
PASIREOTIDE41
PAZOPANIB HYDROCHLORIDE41
PERFLUTREN41
REGORAFENIB41
ROMIDEPSIN41
SACITUZUMAB GOVITECAN41
SODIUM IODIDE I 13141
SUNITINIB MALATE41
TECHNETIUM TC 99M SESTAMIBI41

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 14 predictive associations from 15 curated evidence items; also 3 diagnostic, 3 oncogenic, 1 predisposing, 1 prognostic.

Molecular subtypeTherapyEffectLevelCIViC
RET FusionPralsetinibSensitivity/ResponseCIViC AEID11234
RET FusionSelpercatinibSensitivity/ResponseCIViC AEID8852
RET Fusion OR RET MutationPralsetinibSensitivity/ResponseCIViC AEID11267
TPR::NTRK1 FusionLarotrectinibSensitivity/ResponseCIViC CEID11748
BRAF V600EPonatinib + PLX4720Sensitivity/ResponseCIViC DEID8033 +1
BRAF V600EMEK Inhibitor CI-1040Sensitivity/ResponseCIViC DEID2136
BRAF V600ERDEA 119Sensitivity/ResponseCIViC DEID2139
BRAF V600ESorafenibSensitivity/ResponseCIViC DEID2142
BRAF V600EVemurafenibSensitivity/ResponseCIViC DEID3760
KRAS G12RDasatinibSensitivity/ResponseCIViC DEID3997
PIK3CA E542KPerifosine + TemsirolimusSensitivity/ResponseCIViC DEID1626
PIK3CA H1047RPerifosine + TemsirolimusSensitivity/ResponseCIViC DEID1625
PIK3CA MutationAkt Inhibitor MK2206Sensitivity/ResponseCIViC DEID12720
PTEN R130*Perifosine + TemsirolimusSensitivity/ResponseCIViC DEID1627

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 76

This page pulls from 76 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmicd11intactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot