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Atlas / Disease / Congenital heart defects, multiple types, 3

Congenital heart defects, multiple types, 3

disease
On this page

Also known as CHTD3

Summary

Congenital heart defects, multiple types, 3 (MONDO:0013988) is a disease with 1 cohort gene.

At a glance

  • Cohort genes: 1
  • ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecongenital heart defects, multiple types, 3
Mondo IDMONDO:0013988
OMIM614954
UMLSC3554194
MedGen767108
Is cancer (heuristic)no

Also known as: CHTD3 · congenital heart defects, multiple types, 3

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › congenital heart disease › congenital heart defects, multiple types › congenital heart defects, multiple types, 3

Related subtypes (7): congenital heart defects, multiple types, 6, congenital heart defects, multiple types, 2, congenital heart defects, multiple types, 4, congenital heart defects, multiple types, 5, MYH-6 related congenital heart defects, congenital heart defects, multiple types, 8, with or without heterotaxy, congenital heart defects, multiple types, 9

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
182452NM_007194.4(CHEK2):c.409C>T (p.Arg137Ter)CHEK2Pathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CHEK2Orphanet:1331Familial prostate cancer
CHEK2Orphanet:145Hereditary breast and/or ovarian cancer syndrome
CHEK2Orphanet:440437Familial colorectal cancer Type X
CHEK2Orphanet:524Li-Fraumeni syndrome
CHEK2Orphanet:668Osteosarcoma

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CHEK2HGNC:16627ENSG00000183765O96017Serine/threonine-protein kinase Chk2clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CHEK2Serine/threonine-protein kinase Chk2Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks.

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)
CHEK2Kinaseyes2.7.11.1FHA_dom, Prot_kinase_dom, Ser/Thr_kinase_AS

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
lower esophagus mucosa1
male germ line stem cell (sensu Vertebrata) in testis1
primordial germ cell in gonad1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CHEK2183ubiquitousmarkerprimordial germ cell in gonad, lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CHEK24,795

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CHEK2O9601738

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Stabilization of p531761.3×0.005CHEK2
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex1671.8×0.005CHEK2
Regulation of TP53 Activity through Methylation1543.8×0.005CHEK2
Regulation of TP53 Degradation1292.8×0.007CHEK2
Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A1203.9×0.008CHEK2
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks1146.4×0.008CHEK2
G2/M DNA damage checkpoint1120.2×0.008CHEK2
Regulation of TP53 Activity through Phosphorylation1117.7×0.008CHEK2

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 DNA damage checkpoint15617.3×0.003CHEK2
mitotic DNA damage checkpoint signaling14213.0×0.003CHEK2
cellular response to bisphenol A13370.4×0.003CHEK2
response to glycoside12407.4×0.003CHEK2
positive regulation of anoikis11872.4×0.003CHEK2
thymocyte apoptotic process11404.3×0.003CHEK2
regulation of autophagosome assembly11123.5×0.003CHEK2
replicative senescence1991.3×0.003CHEK2
mitotic intra-S DNA damage checkpoint signaling1936.2×0.003CHEK2
cellular response to stress1842.6×0.003CHEK2
regulation of protein catabolic process1842.6×0.003CHEK2
signal transduction in response to DNA damage1802.5×0.003CHEK2
cellular response to gamma radiation1601.9×0.004CHEK2
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator1495.6×0.004CHEK2
DNA damage checkpoint signaling1391.9×0.005CHEK2
regulation of signal transduction by p53 class mediator1383.0×0.005CHEK2
DNA damage response, signal transduction by p53 class mediator1358.6×0.005CHEK2
mitotic spindle assembly1343.9×0.005CHEK2
intrinsic apoptotic signaling pathway in response to DNA damage1324.1×0.005CHEK2
G2/M transition of mitotic cell cycle1312.1×0.005CHEK2
cellular response to xenobiotic stimulus1240.7×0.006CHEK2
protein catabolic process1237.3×0.006CHEK2
double-strand break repair1203.0×0.006CHEK2
protein autophosphorylation1145.3×0.009CHEK2
protein phosphorylation168.0×0.017CHEK2
protein stabilization166.9×0.017CHEK2
DNA damage response153.5×0.021CHEK2
cell division146.2×0.023CHEK2
regulation of DNA-templated transcription131.6×0.033CHEK2
positive regulation of DNA-templated transcription127.9×0.036CHEK2

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
CHEK2NERATINIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
CHEK2304

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
NERATINIB4CHEK2
BOSUTINIB4CHEK2
BRIGATINIB4CHEK2
SUNITINIB4CHEK2
GEFITINIB4CHEK2
FASUDIL3CHEK2
CEDIRANIB3CHEK2
DOVITINIB3CHEK2
LESTAURTINIB3CHEK2
RUBOXISTAURIN3CHEK2
DORAMAPIMOD2CHEK2
FORETINIB2CHEK2
SU-0148132CHEK2
CENISERTIB2CHEK2
ILORASERTIB2CHEK2
CEP-119812CHEK2
DEFOSBARASERTIB2CHEK2
PREXASERTIB2CHEK2
BI-25362CHEK2
UCN-012CHEK2
PF-005622711CHEK2
KW-24491CHEK2
RG-15301CHEK2
MLN-80541CHEK2
PF-037583091CHEK2
SRA-7371CHEK2
SNS-3141CHEK2
CYC-1161CHEK2
GSK-6906931CHEK2
AST-4871CHEK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
CHEK2690Binding:687, Functional:2, ADMET:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
CHEK22.7.11.1non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
CHEK2690

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).

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
NERATINIB4CHEK2
BOSUTINIB4CHEK2
BRIGATINIB4CHEK2
SUNITINIB4CHEK2
GEFITINIB4CHEK2
FASUDIL3CHEK2
CEDIRANIB3CHEK2
DOVITINIB3CHEK2
LESTAURTINIB3CHEK2
RUBOXISTAURIN3CHEK2
DORAMAPIMOD2CHEK2
FORETINIB2CHEK2
SU-0148132CHEK2
CENISERTIB2CHEK2
ILORASERTIB2CHEK2
CEP-119812CHEK2
DEFOSBARASERTIB2CHEK2
PREXASERTIB2CHEK2
BI-25362CHEK2
UCN-012CHEK2
PF-005622711CHEK2
KW-24491CHEK2
RG-15301CHEK2
MLN-80541CHEK2
PF-037583091CHEK2
SRA-7371CHEK2
SNS-3141CHEK2
CYC-1161CHEK2
GSK-6906931CHEK2
AST-4871CHEK2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CHEK2
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: 0.

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 67

This page pulls from 67 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot