◎ Sugi Atlas

Atlas / Disease / Hereditary papillary renal cell carcinoma

Hereditary papillary renal cell carcinoma

disease
On this page

Also known as familial renal papillary carcinomahereditary kidney papillary carcinomahereditary papillary carcinoma of kidneyhereditary papillary carcinoma of the kidneyhereditary papillary renal carcinomahereditary papillary renal cell cancerrenal cell carcinoma, papillaryrenal cell carcinoma, papillary, 1, familial and somatic

Summary

Hereditary papillary renal cell carcinoma (MONDO:0003789) is a cancer caused by MET (GenCC Definitive), with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include pamiparib.

At a glance

  • Classification: Cancer
  • Causal gene: MET (GenCC Definitive)
  • Cohort genes: 1
  • ClinVar variants: 9
  • Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namehereditary papillary renal cell carcinoma
Mondo IDMONDO:0003789
OMIM605074
Orphanet47044
DOIDDOID:6163
NCITC9222
SNOMED CT715561008
UMLSC0879257
MedGen163907
GARD0013157
Is cancer (heuristic)yes

Also known as: familial renal papillary carcinoma · hereditary kidney papillary carcinoma · hereditary papillary carcinoma of kidney · hereditary papillary carcinoma of the kidney · hereditary papillary renal carcinoma · hereditary papillary renal cell cancer · hereditary papillary renal cell carcinoma · renal cell carcinoma, papillary · renal cell carcinoma, papillary, 1, familial and somatic

Data availability: 9 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › renal cell carcinoma › renal cell adenocarcinoma › hereditary renal cell carcinoma › hereditary papillary renal cell carcinoma

Related subtypes (6): adrenocortical carcinoma, hereditary, renal cell carcinoma, Xp11-associated, aniridia 2, aniridia 3, hereditary clear cell renal cell carcinoma, PAX6-related ocular dysgenesis

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

9 retrieved; paginated sample, class counts are floors:

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

ClinVarVariant (HGVS)GeneClassificationReview
13881NM_000245.4(MET):c.3392T>C (p.Met1131Thr)METPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1367069NM_000245.4(MET):c.232C>T (p.Leu78Phe)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
167292NM_000245.4(MET):c.901A>G (p.Thr301Ala)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
188364NM_000245.4(MET):c.1132G>A (p.Val378Ile)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
485733NM_000245.4(MET):c.2547G>C (p.Met849Ile)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
582091NM_000245.4(MET):c.2554A>G (p.Met852Val)METConflicting classifications of pathogenicitycriteria provided, conflicting classifications
1511567NM_000245.4(MET):c.395G>T (p.Ser132Ile)METUncertain significancecriteria provided, multiple submitters, no conflicts
3294308NM_000245.4(MET):c.3010C>T (p.Arg1004Ter)METUncertain significancecriteria provided, multiple submitters, no conflicts
454250NM_000245.4(MET):c.3997C>G (p.Leu1333Val)METUncertain significancecriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 5 · 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.

GeneClassificationInheritanceDiseaseRecords
METDefinitiveAutosomal dominanthereditary papillary renal cell carcinoma14

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
METOrphanet:319298Papillary renal cell carcinoma
METOrphanet:33402Pediatric hepatocellular carcinoma
METOrphanet:47044Hereditary papillary renal cell carcinoma
METOrphanet:488265Osteofibrous dysplasia
METOrphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
METHGNC:7029ENSG00000105976P08581Hepatocyte growth factor receptorgencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
METHepatocyte growth factor receptorReceptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.

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.

FamilyGenesFoldFDR
Kinase127.7×0.036

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
METKinaseyes2.7.10.1Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Semap_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)

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

Top tissues across cohort

TissueCohort genes
cartilage tissue1
germinal epithelium of ovary1
pigmented layer of retina1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
MET270ubiquitousmarkerpigmented layer of retina, germinal epithelium of ovary, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
MET5,823

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
METP08581130

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Drug-mediated inhibition of MET activation15710.0×0.004MET
MET activates STAT313806.7×0.004MET
MET activates PTPN1112284.0×0.004MET
MET interacts with TNS proteins12284.0×0.004MET
MET Receptor Activation11903.3×0.004MET
MET activates PI3K/AKT signaling11903.3×0.004MET
Sema4D mediated inhibition of cell attachment and migration11427.5×0.004MET
MET receptor recycling11142.0×0.004MET
MET activates RAS signaling11038.2×0.004MET
MET activates RAP1 and RAC111038.2×0.004MET
Listeria monocytogenes entry into host cells11038.2×0.004MET
InlB-mediated entry of Listeria monocytogenes into host cell1761.3×0.005MET
Sema4D in semaphorin signaling1671.8×0.005MET
MET promotes cell motility1601.0×0.005MET
MECP2 regulates neuronal receptors and channels1601.0×0.005MET
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation1571.0×0.005MET
Negative regulation of MET activity1519.1×0.005MET
Semaphorin interactions1393.8×0.006MET
MET activates PTK2 signaling1380.7×0.006MET
PI3K/AKT Signaling in Cancer1368.4×0.006MET
Bacterial Infection Pathways1335.9×0.006MET
Signaling by MET1317.2×0.006MET
Transcriptional Regulation by MECP21317.2×0.006MET
Negative regulation of the PI3K/AKT network1278.5×0.007MET
MITF-M-dependent gene expression1181.3×0.010MET
MAPK1/MAPK3 signaling1131.3×0.013MET
Constitutive Signaling by Aberrant PI3K in Cancer1126.9×0.013MET
MITF-M-regulated melanocyte development1114.2×0.014MET
MAPK family signaling cascades1102.9×0.015MET
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling196.8×0.015MET

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 termCohort genesFoldFDRSample cohort genes
negative regulation of hydrogen peroxide-mediated programmed cell death14213.0×0.003MET
hepatocyte growth factor receptor signaling pathway12106.5×0.003MET
endothelial cell morphogenesis11053.2×0.003MET
positive regulation of endothelial cell chemotaxis1991.3×0.003MET
positive chemotaxis1802.5×0.003MET
branching morphogenesis of an epithelial tube1732.7×0.003MET
pancreas development1674.1×0.003MET
excitatory postsynaptic potential1443.5×0.004MET
semaphorin-plexin signaling pathway1401.2×0.004MET
negative regulation of autophagy1259.3×0.006MET
liver development1221.7×0.006MET
cell surface receptor protein tyrosine kinase signaling pathway1173.7×0.007MET
neuron differentiation1100.3×0.012MET
cell surface receptor signaling pathway164.1×0.017MET
positive regulation of transcription by RNA polymerase II114.9×0.067MET

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
METAFATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
MET954

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
AFATINIB4MET
FEDRATINIB4MET
TIVOZANIB4MET
AXITINIB4MET
SORAFENIB4MET
NERATINIB4MET
INFIGRATINIB PHOSPHATE4MET
INFIGRATINIB4MET
PALBOCICLIB4MET
ENTRECTINIB4MET
DABRAFENIB4MET
CABOZANTINIB S-MALATE4MET
AFATINIB DIMALEATE4MET
CABOZANTINIB4MET
CERITINIB4MET
VANDETANIB4MET
BOSUTINIB4MET
CAPMATINIB4MET
TEPOTINIB4MET
BRIGATINIB4MET
ENSARTINIB4MET
PAZOPANIB4MET
NINTEDANIB4MET
SUNITINIB4MET
ERLOTINIB4MET
CRIZOTINIB4MET
MIDOSTAURIN4MET
GEFITINIB4MET
LINSITINIB3MET
RIGOSERTIB3MET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
MET2,015Binding:2005, Functional:6, ADMET:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
MET2.7.10.1receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
MET2,015

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

30 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)
AFATINIB4MET
FEDRATINIB4MET
TIVOZANIB4MET
AXITINIB4MET
SORAFENIB4MET
NERATINIB4MET
INFIGRATINIB PHOSPHATE4MET
INFIGRATINIB4MET
PALBOCICLIB4MET
ENTRECTINIB4MET
DABRAFENIB4MET
CABOZANTINIB S-MALATE4MET
AFATINIB DIMALEATE4MET
CABOZANTINIB4MET
CERITINIB4MET
VANDETANIB4MET
BOSUTINIB4MET
CAPMATINIB4MET
TEPOTINIB4MET
BRIGATINIB4MET
ENSARTINIB4MET
PAZOPANIB4MET
NINTEDANIB4MET
SUNITINIB4MET
ERLOTINIB4MET
CRIZOTINIB4MET
MIDOSTAURIN4MET
GEFITINIB4MET
LINSITINIB3MET
RIGOSERTIB3MET

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1MET
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04603365PHASE2WITHDRAWNPamiparib and Temozolomide for the Treatment of Hereditary Leiomyomatosis and Renal Cell Cancer

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
PAMIPARIB31
CHEMBL391953301
CHEMBL422879401

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
v1.1.2
BioBTree
v2.0.2

Sources 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot