Sigmoid colon cancer

Summary

Sigmoid colon cancer (MONDO:0001464) is a cancer with 3 cohort genes (3 CIViC-evidence somatic drivers; 3 ClinVar predisposition records) and 5 clinical trials. Top therapeutic interventions include udenafil.

At a glance

• Classification: Cancer
• Cohort genes: 3
• ClinVar variants: 3
• Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	sigmoid colon cancer
Mondo ID	MONDO:0001464
DOID	DOID:12192
ICD-10-CM	C18.7
ICD-11	1717786596
SNOMED CT	363410008
UMLS	C0153436
MedGen	509292
Anatomy (UBERON)	UBERON:0001159
Is cancer (heuristic)	yes

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

Data availability: 3 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 › sigmoid neoplasm › sigmoid colon cancer

Related subtypes (1): rectosigmoid junction neoplasm

Subtypes (1): rectosigmoid junction 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

3 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
91239	NM_000251.3(MSH2):c.892C>T (p.Gln298Ter)	MSH2	Pathogenic	reviewed by expert panel
559946	NM_000038.6(APC):c.6994G>A (p.Gly2332Ser)	APC	Uncertain significance	criteria provided, multiple submitters, no conflicts
89518	NM_000179.3(MSH6):c.4068_4071dup (p.Lys1358delinsAspTer)	MSH6	Likely benign	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · 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
MSH6			CIViC #2478

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
MSH6	Orphanet:144	Lynch syndrome
MSH6	Orphanet:252202	Constitutional mismatch repair deficiency syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

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
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	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).
MSH6	DNA mismatch repair protein Msh6	Component of the post-replicative DNA mismatch repair system (MMR).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

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
MSH6	Other/Unknown	no		PWWP_dom, DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
medial globus pallidus	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1
oocyte	1
secondary oocyte	1
embryo	1
ganglionic eminence	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
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSH2	4,537
MSH6	4,091
APC	2,903

Intra-cohort edges

A	B	Sources
MSH2	MSH6	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APC	P25054	31
MSH2	P43246	30
MSH6	P52701	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 3 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective Mismatch Repair Associated With MSH6	2	3806.7×	2e-06	MSH2, MSH6
Defective Mismatch Repair Associated With MSH2	2	2537.8×	3e-06	MSH2, MSH6
Mismatch Repair	2	1903.3×	3e-06	MSH2, MSH6
Diseases of Mismatch Repair (MMR)	2	1903.3×	3e-06	MSH2, MSH6
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	2	543.8×	4e-05	MSH2, MSH6
Diseases of DNA repair	2	380.7×	7e-05	MSH2, MSH6
APC truncation mutants are not K63 polyubiquitinated	1	3806.7×	0.002	APC
DNA Repair	2	65.6×	0.002	MSH2, MSH6
Disease	3	13.1×	0.002	APC, MSH2, MSH6
Defective Mismatch Repair Associated With MSH3	1	1903.3×	0.002	MSH2
Signaling by AXIN mutants	1	346.1×	0.008	APC
Signaling by CTNNB1 phospho-site mutants	1	346.1×	0.008	APC
Signaling by APC mutants	1	346.1×	0.008	APC
Signaling by AMER1 mutants	1	346.1×	0.008	APC
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	1	271.9×	0.008	MSH2
APC truncation mutants have impaired AXIN binding	1	271.9×	0.008	APC
AXIN missense mutants destabilize the destruction complex	1	271.9×	0.008	APC
Truncations of AMER1 destabilize the destruction complex	1	271.9×	0.008	APC
Signaling by GSK3beta mutants	1	253.8×	0.008	APC
CTNNB1 S33 mutants aren’t phosphorylated	1	253.8×	0.008	APC
CTNNB1 S37 mutants aren’t phosphorylated	1	253.8×	0.008	APC
CTNNB1 S45 mutants aren’t phosphorylated	1	253.8×	0.008	APC
CTNNB1 T41 mutants aren’t phosphorylated	1	253.8×	0.008	APC
Beta-catenin phosphorylation cascade	1	223.9×	0.008	APC
Signaling by WNT in cancer	1	200.3×	0.009	APC
Apoptotic cleavage of cellular proteins	1	158.6×	0.010	APC
Apoptotic execution phase	1	158.6×	0.010	APC
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	119.0×	0.013	APC
Ovarian tumor domain proteases	1	92.8×	0.017	APC
Deactivation of the beta-catenin transactivating complex	1	77.7×	0.019	APC

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
somatic recombination of immunoglobulin gene segments	2	2808.7×	8e-06	MSH2, MSH6
negative regulation of DNA recombination	2	749.0×	5e-05	MSH2, MSH6
somatic hypermutation of immunoglobulin genes	2	702.2×	5e-05	MSH2, MSH6
isotype switching	2	561.7×	6e-05	MSH2, MSH6
mismatch repair	2	432.1×	8e-05	MSH2, MSH6
determination of adult lifespan	2	288.1×	2e-04	MSH2, MSH6
meiotic mismatch repair	1	5617.3×	0.001	MSH6
somatic recombination of immunoglobulin genes involved in immune response	1	5617.3×	0.001	MSH2
B cell mediated immunity	1	1404.3×	0.004	MSH2
DNA repair	2	42.6×	0.004	MSH2, MSH6
maintenance of DNA repeat elements	1	1123.5×	0.005	MSH2
mitotic recombination	1	936.2×	0.005	MSH2
positive regulation of isotype switching to IgA isotypes	1	936.2×	0.005	MSH2
regulation of microtubule-based movement	1	936.2×	0.005	APC
negative regulation of cell cycle G1/S phase transition	1	802.5×	0.005	APC
positive regulation of protein localization to centrosome	1	802.5×	0.005	APC
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	702.2×	0.005	APC
response to UV-B	1	624.1×	0.005	MSH2
regulation of microtubule-based process	1	624.1×	0.005	APC
DNA damage tolerance	1	561.7×	0.005	MSH2
regulation of attachment of spindle microtubules to kinetochore	1	561.7×	0.005	APC
heart valve development	1	510.7×	0.005	APC
positive regulation of isotype switching to IgG isotypes	1	510.7×	0.005	MSH2
oxidative phosphorylation	1	468.1×	0.005	MSH2
positive regulation of pseudopodium assembly	1	432.1×	0.006	APC
mitotic intra-S DNA damage checkpoint signaling	1	312.1×	0.007	MSH2
response to X-ray	1	295.6×	0.008	MSH2
endocardial cushion morphogenesis	1	280.9×	0.008	APC
mitotic spindle assembly checkpoint signaling	1	187.2×	0.011	APC
cell fate specification	1	175.5×	0.011	APC

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 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
MSH6	1	2
APC	0	0
MSH2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	MSH6

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
MSH6	10	Binding:10
MSH2	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	MSH6

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	1	MSH6
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: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00607282	PHASE2	COMPLETED	Efficacy of Udenafil After Radical Resection for Sigmoid Colon and Rectal Cancer
NCT05943041	PHASE1	COMPLETED	Live Biotherapeutic Product GB104 Phase 1 Study in Colorectal Cancer
NCT03259828	Not specified	COMPLETED	Sigmoid Colon Organ Motion in Radiotherapy
NCT03531606	Not specified	COMPLETED	The Effects of Mechnikov Probiotics on Symptom and Surgical Outcome
NCT07423130	Not specified	COMPLETED	Indocyanine Green Fluorescence Angiography in Laparoscopic Sigmoid and Rectal Cancer Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
UDENAFIL	3	1