Ascending colon cancer

Summary

Ascending colon cancer (MONDO:0002238) is a cancer with 2 cohort genes (2 CIViC-evidence somatic drivers; 2 ClinVar predisposition records) and 3 clinical trials.

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 2
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ascending colon cancer
Mondo ID	MONDO:0002238
DOID	DOID:218
ICD-10-CM	C18.2
ICD-11	74144027
SNOMED CT	363412000
UMLS	C0153439
MedGen	509293
Anatomy (UBERON)	UBERON:0001156
Is cancer (heuristic)	yes

Also known as: ascending colon cancer · cancer of ascending colon · malignant ascending colon neoplasm · malignant neoplasm of ascending colon · malignant tumour of ascending colon

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › large intestine disorder › colonic disorder › colonic neoplasm › malignant colon neoplasm › ascending colon cancer

Related subtypes (8): descending colon cancer, sigmoid colon cancer, colon carcinoma, cecum cancer, colon lymphoma, transverse colon cancer, colon sarcoma, metastasis from malignant tumor of colon

Subtypes (1): hepatic flexure cancer

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
36572	NM_000251.3(MSH2):c.2038C>T (p.Arg680Ter)	MSH2	Pathogenic	reviewed by expert panel
411410	NM_000038.6(APC):c.6553A>G (p.Ser2185Gly)	APC	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
MSH2			CIViC #3628

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
APC	Orphanet:220460	Attenuated familial adenomatous polyposis
APC	Orphanet:261584	5q22 microdeletion syndrome
APC	Orphanet:314022	Gastric adenocarcinoma and proximal polyposis of the stomach
APC	Orphanet:3258	Cenani-Lenz syndrome
APC	Orphanet:873	Desmoid tumor
MSH2	Orphanet:144	Lynch syndrome
MSH2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APC	Adenomatous polyposis coli protein	Tumor suppressor.
MSH2	DNA mismatch repair protein Msh2	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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.

Family	Genes	Fold	FDR
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
MSH2	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
oocyte	1
secondary oocyte	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APC	297	ubiquitous	marker	substantia nigra pars compacta, substantia nigra pars reticulata, medial globus pallidus
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH2	4,537
APC	2,903

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APC	P25054	31
MSH2	P43246	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
APC truncation mutants are not K63 polyubiquitinated	1	5710.0×	0.005	APC
Defective Mismatch Repair Associated With MSH3	1	2855.0×	0.005	MSH2
Defective Mismatch Repair Associated With MSH6	1	2855.0×	0.005	MSH2
Defective Mismatch Repair Associated With MSH2	1	1903.3×	0.005	MSH2
Mismatch Repair	1	1427.5×	0.005	MSH2
Diseases of Mismatch Repair (MMR)	1	1427.5×	0.005	MSH2
Signaling by AXIN mutants	1	519.1×	0.006	APC
Signaling by CTNNB1 phospho-site mutants	1	519.1×	0.006	APC
Signaling by APC mutants	1	519.1×	0.006	APC
Signaling by AMER1 mutants	1	519.1×	0.006	APC
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	1	407.9×	0.006	MSH2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	407.9×	0.006	MSH2
APC truncation mutants have impaired AXIN binding	1	407.9×	0.006	APC
AXIN missense mutants destabilize the destruction complex	1	407.9×	0.006	APC
Truncations of AMER1 destabilize the destruction complex	1	407.9×	0.006	APC
Signaling by GSK3beta mutants	1	380.7×	0.006	APC
CTNNB1 S33 mutants aren’t phosphorylated	1	380.7×	0.006	APC
CTNNB1 S37 mutants aren’t phosphorylated	1	380.7×	0.006	APC
CTNNB1 S45 mutants aren’t phosphorylated	1	380.7×	0.006	APC
CTNNB1 T41 mutants aren’t phosphorylated	1	380.7×	0.006	APC
Beta-catenin phosphorylation cascade	1	335.9×	0.006	APC
Signaling by WNT in cancer	1	300.5×	0.007	APC
Diseases of DNA repair	1	285.5×	0.007	MSH2
Apoptotic cleavage of cellular proteins	1	237.9×	0.008	APC
Apoptotic execution phase	1	237.9×	0.008	APC
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	178.4×	0.010	APC
Disease	2	13.1×	0.010	APC, MSH2
Ovarian tumor domain proteases	1	139.3×	0.012	APC
Deactivation of the beta-catenin transactivating complex	1	116.5×	0.013	APC
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.017	MSH2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin genes involved in immune response	1	8426.0×	0.004	MSH2
somatic recombination of immunoglobulin gene segments	1	2106.5×	0.004	MSH2
B cell mediated immunity	1	2106.5×	0.004	MSH2
maintenance of DNA repeat elements	1	1685.2×	0.004	MSH2
mitotic recombination	1	1404.3×	0.004	MSH2
positive regulation of isotype switching to IgA isotypes	1	1404.3×	0.004	MSH2
regulation of microtubule-based movement	1	1404.3×	0.004	APC
negative regulation of cell cycle G1/S phase transition	1	1203.7×	0.004	APC
positive regulation of protein localization to centrosome	1	1203.7×	0.004	APC
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	1053.2×	0.004	APC
response to UV-B	1	936.2×	0.004	MSH2
regulation of microtubule-based process	1	936.2×	0.004	APC
DNA damage tolerance	1	842.6×	0.004	MSH2
regulation of attachment of spindle microtubules to kinetochore	1	842.6×	0.004	APC
heart valve development	1	766.0×	0.004	APC
positive regulation of isotype switching to IgG isotypes	1	766.0×	0.004	MSH2
oxidative phosphorylation	1	702.2×	0.005	MSH2
positive regulation of pseudopodium assembly	1	648.1×	0.005	APC
negative regulation of DNA recombination	1	561.7×	0.005	MSH2
somatic hypermutation of immunoglobulin genes	1	526.6×	0.005	MSH2
mitotic intra-S DNA damage checkpoint signaling	1	468.1×	0.005	MSH2
response to X-ray	1	443.5×	0.005	MSH2
endocardial cushion morphogenesis	1	421.3×	0.005	APC
isotype switching	1	421.3×	0.005	MSH2
mismatch repair	1	324.1×	0.007	MSH2
mitotic spindle assembly checkpoint signaling	1	280.9×	0.008	APC
cell fate specification	1	263.3×	0.008	APC
negative regulation of microtubule depolymerization	1	247.8×	0.008	APC
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	247.8×	0.008	MSH2
pattern specification process	1	234.1×	0.008	APC

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
APC	0	0
MSH2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
APC	24	Binding:24
MSH2	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	APC, MSH2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
APC	24	—
MSH2	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07207317	Not specified	RECRUITING	LIRRH Trial for the Right-sided Colon Cancer
NCT02309931	Not specified	COMPLETED	ISOperistaltic Versus ANTIperistaltic Anastomosis After Laparoscopic Right Colectomy for Cancer
NCT02949440	Not specified	UNKNOWN	A Study of Laparoscopic Right Hemicolectomy Using the Caudal-to-cranial Approach