◎ Sugi Atlas

Atlas / Disease / Hereditary renal cell carcinoma

Hereditary renal cell carcinoma

disease
On this page

Also known as familial renal carcinomahereditary renal cell cancerhereditary renal cell carcinoma (disease)

Summary

Hereditary renal cell carcinoma (MONDO:0003008) is a cancer (an umbrella term covering 7 Mondo subtypes) with 4 cohort genes (3 CIViC-evidence somatic drivers; 4 ClinVar predisposition records). Molecularly, FH Deficient confers sensitivity to Bevacizumab + Erlotinib in Hereditary Renal Cell Carcinoma (CIViC Level B); 1 further subtype–drug associations are mapped below.

At a glance

  • Classification: Cancer
  • Umbrella term: 7 Mondo subtypes
  • Cohort genes: 4
  • ClinVar variants: 4
  • Precision-medicine evidence (CIViC): 2 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namehereditary renal cell carcinoma
Mondo IDMONDO:0003008
MeSHC536851
DOIDDOID:4455
NCITC39789
SNOMED CT717736007
UMLSC2608055
MedGen392857
GARD0023326
Is cancer (heuristic)yes

Also known as: familial renal carcinoma · hereditary renal cell cancer · hereditary renal cell carcinoma · hereditary renal cell carcinoma (disease)

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: human disease › 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

Related subtypes (8): childhood kidney cell carcinoma, sarcomatoid renal cell carcinoma, clear cell renal carcinoma, renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions, papillary renal cell carcinoma, chromophobe renal cell carcinoma, renal cell carcinoma associated with neuroblastoma, tubulocystic renal cell carcinoma

Subtypes (7): hereditary papillary renal cell carcinoma, 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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 benign

ClinVarVariant (HGVS)GeneClassificationReview
224947NM_004168.4(SDHA):c.133G>A (p.Ala45Thr)SDHAConflicting classifications of pathogenicitycriteria provided, conflicting classifications
347225NM_001963.6(EGF):c.47G>C (p.Ser16Thr)EGFUncertain significancecriteria provided, multiple submitters, no conflicts
496816NM_001618.4(PARP1):c.370A>G (p.Thr124Ala)PARP1Uncertain significanceno assertion criteria provided
496815NM_016292.3(TRAP1):c.1604C>G (p.Thr535Ser)DNASE1Benigncriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
SDHAActCHRCC,HCC,LGGNOSCIViC #5176
PARP1CIViC #199
EGFCIViC #1634

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SDHAOrphanet:139411Carney triad
SDHAOrphanet:154Familial isolated dilated cardiomyopathy
SDHAOrphanet:29072Hereditary pheochromocytoma-paraganglioma
SDHAOrphanet:3208Isolated succinate-CoQ reductase deficiency
SDHAOrphanet:44890Gastrointestinal stromal tumor
SDHAOrphanet:97286Carney-Stratakis syndrome
DNASE1Orphanet:300345Autosomal systemic lupus erythematosus
DNASE1Orphanet:536Systemic lupus erythematosus
EGFOrphanet:210159Adult hepatocellular carcinoma
EGFOrphanet:620368EGF-related primary hypomagnesemia with intellectual disability

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SDHAHGNC:10680ENSG00000073578P31040Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialclinvar
PARP1HGNC:270ENSG00000143799P09874Poly [ADP-ribose] polymerase 1clinvar
DNASE1HGNC:2956ENSG00000213918P24855Deoxyribonuclease-1clinvar
EGFHGNC:3229ENSG00000138798P01133Pro-epidermal growth factorclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SDHASuccinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrialFlavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
PARP1Poly [ADP-ribose] polymerase 1Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
DNASE1Deoxyribonuclease-1Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs.
EGFPro-epidermal growth factorEGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

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
Phosphatase121.0×0.141
Transcription factor12.1×0.605
Other/Unknown20.9×0.769

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SDHAOther/UnknownnoFRD_SDH_FAD_BS, FAD-dep_OxRdtase_2_FAD-bd, Succ_DH_flav_su_fwd
PARP1Transcription factorno2.4.2.30BRCT_dom, Znf_PARP, Poly(ADP-ribose)pol_reg_dom
DNASE1Phosphataseyes3.1.21.1Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS
EGFOther/UnknownnoLDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

Expression context

Cohort genes with no expression data: 0.

4 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)4
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart1
heart left ventricle1
mucosa of transverse colon1
ganglionic eminence1
primordial germ cell in gonad1
ventricular zone1
duodenum1
jejunal mucosa1
small intestine Peyer’s patch1
body of pancreas1
hindlimb stylopod muscle1
renal medulla1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SDHA143ubiquitousmarkerapex of heart, heart left ventricle, mucosa of transverse colon
PARP1292ubiquitousmarkerventricular zone, ganglionic eminence, primordial germ cell in gonad
DNASE1226ubiquitousmarkerduodenum, jejunal mucosa, small intestine Peyer’s patch
EGF215broadmarkerrenal medulla, body of pancreas, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PARP18,370
EGF8,267
SDHA6,141
DNASE11,051

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PARP1P09874106
EGFP0113313
SDHAP310405
DNASE1P248551

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
vRNA Synthesis13806.7×0.013PARP1
PLCG1 events in ERBB2 signaling1951.7×0.013EGF
POLB-Dependent Long Patch Base Excision Repair1423.0×0.013PARP1
Inhibition of Signaling by Overexpressed EGFR1423.0×0.013EGF
EGFR interacts with phospholipase C-gamma1380.7×0.013EGF
NFE2L2 regulating tumorigenic genes1317.2×0.013EGF
HDR through MMEJ (alt-NHEJ)1292.8×0.013PARP1
ERBB2 Activates PTK6 Signaling1271.9×0.013EGF
GRB2 events in EGFR signaling1253.8×0.013EGF
SHC1 events in EGFR signaling1237.9×0.013EGF
Constitutive Signaling by EGFRvIII1237.9×0.013EGF
ERBB2 Regulates Cell Motility1237.9×0.013EGF
PI3K events in ERBB2 signaling1223.9×0.013EGF
Signaling by ERBB2 ECD mutants1223.9×0.013EGF
GAB1 signalosome1211.5×0.013EGF
GRB2 events in ERBB2 signaling1211.5×0.013EGF
Developmental Lineage of Multipotent Pancreatic Progenitor Cells1200.3×0.013EGF
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1190.3×0.013EGF
Maturation of TCA enzymes and regulation of TCA cycle1190.3×0.013SDHA
Developmental Lineage of Mammary Gland Myoepithelial Cells1181.3×0.013EGF
SHC1 events in ERBB2 signaling1158.6×0.013EGF
NOTCH3 Activation and Transmission of Signal to the Nucleus1158.6×0.013EGF
Signaling by ERBB2 TMD/JMD mutants1158.6×0.013EGF
Developmental Lineage of Mammary Gland Luminal Epithelial Cells1152.3×0.013EGF
Estrogen-dependent nuclear events downstream of ESR-membrane signaling1146.4×0.013EGF
Citric acid cycle (TCA cycle)1141.0×0.013SDHA
Signaling by ERBB2 KD Mutants1141.0×0.013EGF
Downregulation of ERBB2 signaling1126.9×0.014EGF
Downregulation of SMAD2/3:SMAD4 transcriptional activity1122.8×0.014PARP1
Signaling by ERBB21115.3×0.014EGF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of myofibroblast differentiation14213.0×0.008PARP1
regulation of neutrophil mediated cytotoxicity12106.5×0.008DNASE1
regulation of base-excision repair12106.5×0.008PARP1
negative regulation of ATP biosynthetic process12106.5×0.008PARP1
DNA ADP-ribosylation11404.3×0.008PARP1
mitochondrial DNA metabolic process11404.3×0.008PARP1
regulation of circadian sleep/wake cycle, non-REM sleep11404.3×0.008PARP1
regulation of acute inflammatory response11053.2×0.008DNASE1
positive regulation of hyaluronan biosynthetic process11053.2×0.008EGF
ATP generation from poly-ADP-D-ribose11053.2×0.008PARP1
succinate metabolic process1842.6×0.008SDHA
mitochondrial electron transport, succinate to ubiquinone1842.6×0.008SDHA
positive regulation of cerebellar granule cell precursor proliferation1842.6×0.008EGF
negative regulation of secretion1842.6×0.008EGF
replication fork reversal1842.6×0.008PARP1
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway1842.6×0.008PARP1
positive regulation of necroptotic process1702.2×0.008PARP1
negative regulation of cholesterol efflux1702.2×0.008EGF
positive regulation of epithelial tube formation1702.2×0.008EGF
mitochondrial DNA repair1601.9×0.008PARP1
negative regulation of adipose tissue development1601.9×0.008PARP1
protein poly-ADP-ribosylation1526.6×0.008PARP1
regulation of calcium ion import1526.6×0.008EGF
neutrophil activation involved in immune response1468.1×0.008DNASE1
positive regulation of peptidyl-threonine phosphorylation1468.1×0.008EGF
ubiquitin-dependent endocytosis1468.1×0.008EGF
ERBB2-EGFR signaling pathway1421.3×0.008EGF
positive regulation of mitochondrial depolarization1421.3×0.008PARP1
positive regulation of protein localization to early endosome1421.3×0.008EGF
response to aldosterone1421.3×0.008PARP1

Therapeutics

Drug target analysis

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

Druggability breadth: 4 of 4 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
SDHALINEZOLID
PARP1NIRAPARIB
DNASE1GENTIAN VIOLET

Top cohort targets by molecule count

SymbolMoleculesMax phase
PARP1244
SDHA14
DNASE114
EGF00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
LINEZOLID4SDHA
NIRAPARIB4PARP1
RUCAPARIB4PARP1
PALBOCICLIB4PARP1
TALAZOPARIB4PARP1
RUCAPARIB CAMSYLATE4PARP1
OLAPARIB4PARP1
AMITRIPTYLINE4PARP1
GENTIAN VIOLET4DNASE1
INIPARIB3PARP1
FLUZOPARIB3PARP1
PAMIPARIB3PARP1
VELIPARIB3PARP1
SARUPARIB3PARP1
CHLORTHENOXAZINE2PARP1
LUTEOLIN2PARP1
FLAVONE2PARP1
E-70162PARP1
2X-1212PARP1
AMELPARIB2PARP1
NESUPARIB2PARP1
RUCAPARIB PHOSPHATE1PARP1
AZD24611PARP1
CEP-97221PARP1
ATAMPARIB1PARP1
AZD-95741PARP1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
PARP1825Binding:814, Functional:8, ADMET:3
EGF5Binding:5
DNASE14Binding:4
SDHA3Binding:3

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PARP12.4.2.30NAD+ ADP-ribosyltransferase
DNASE13.1.21.1deoxyribonuclease I

Cohort genes with high screening signal

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

SymbolChEMBL assays
PARP1825

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

26 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)
LINEZOLID4SDHA
NIRAPARIB4PARP1
RUCAPARIB4PARP1
PALBOCICLIB4PARP1
TALAZOPARIB4PARP1
RUCAPARIB CAMSYLATE4PARP1
OLAPARIB4PARP1
AMITRIPTYLINE4PARP1
GENTIAN VIOLET4DNASE1
INIPARIB3PARP1
FLUZOPARIB3PARP1
PAMIPARIB3PARP1
VELIPARIB3PARP1
SARUPARIB3PARP1
CHLORTHENOXAZINE2PARP1
LUTEOLIN2PARP1
FLAVONE2PARP1
E-70162PARP1
2X-1212PARP1
AMELPARIB2PARP1
NESUPARIB2PARP1
RUCAPARIB PHOSPHATE1PARP1
AZD24611PARP1
CEP-97221PARP1
ATAMPARIB1PARP1
AZD-95741PARP1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3SDHA, PARP1, DNASE1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1EGF

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
EGF5—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 2 predictive associations from 2 curated evidence items.

Molecular subtypeTherapyEffectLevelCIViC
FH DeficientBevacizumab + ErlotinibSensitivity/ResponseCIViC BEID12939
SDHB MutationVandetanib + MetforminSensitivity/ResponseCIViC BEID7959

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