Lynch syndrome

Summary

Lynch syndrome (MONDO:0005835) is a disease (an umbrella term covering 5 Mondo subtypes) caused by variants in EPCAM, MLH1, MSH2, and 2 other genes, with 15 cohort genes and 106 clinical trials. The dominant Reactome pathway is Mismatch Repair (4 cohort genes). Top therapeutic interventions include aspirin, atezolizumab, and leucovorin.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal genes: EPCAM (GenCC Definitive), MLH1 (GenCC Definitive), MSH2 (GenCC Definitive), MSH6 (GenCC Definitive) (+1 more)
• Umbrella term: 5 Mondo subtypes
• Cohort genes: 15
• ClinVar variants: 5,589
• Phenotypes (HPO): 62
• Clinical trials: 106

Clinical features

Signs & symptoms

Clinical features (HPO)

62 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0002019	Constipation	Very frequent (80-99%)
HP:0002024	Malabsorption	Very frequent (80-99%)
HP:0002027	Abdominal pain	Very frequent (80-99%)
HP:0002239	Gastrointestinal hemorrhage	Very frequent (80-99%)
HP:0008069	Neoplasm of the skin	Very frequent (80-99%)
HP:0009720	Adenoma sebaceum	Very frequent (80-99%)
HP:0012174	Glioblastoma multiforme	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0003003	Colon cancer	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0000737	Irritability	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001522	Death in infancy	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002076	Migraine	Frequent (30-79%)
HP:0002516	Increased intracranial pressure	Frequent (30-79%)
HP:0006753	Neoplasm of the stomach	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0100613	Death in early adulthood	Frequent (30-79%)
HP:0100743	Neoplasm of the rectum	Frequent (30-79%)
HP:0000505	Visual impairment	Occasional (5-29%)
HP:0000738	Hallucinations	Occasional (5-29%)
HP:0001123	Visual field defect	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001288	Gait disturbance	Occasional (5-29%)
HP:0001371	Flexion contracture	Occasional (5-29%)
HP:0001402	Hepatocellular carcinoma	Occasional (5-29%)
HP:0002167	Abnormality of speech or vocalization	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002376	Developmental regression	Occasional (5-29%)
HP:0002671	Basal cell carcinoma	Occasional (5-29%)
HP:0002893	Pituitary adenoma	Occasional (5-29%)
HP:0002894	Neoplasm of the pancreas	Occasional (5-29%)
HP:0002896	Neoplasm of the liver	Occasional (5-29%)
HP:0003002	Breast carcinoma	Occasional (5-29%)
HP:0003006	Neuroblastoma	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)
HP:0004374	Hemiplegia/hemiparesis	Occasional (5-29%)
HP:0004377	Hematological neoplasm	Occasional (5-29%)
HP:0006725	Pancreatic adenocarcinoma	Occasional (5-29%)
HP:0006758	Malignant genitourinary tract tumor	Occasional (5-29%)
HP:0007256	Abnormal pyramidal sign	Occasional (5-29%)
HP:0009726	Renal neoplasm	Occasional (5-29%)
HP:0010524	Agnosia	Occasional (5-29%)
HP:0010526	Dysgraphia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Lynch syndrome
Mondo ID	MONDO:0005835
Orphanet	144
DOID	DOID:3883
NCIT	C8494
SNOMED CT	716318002
UMLS	C4552100
MedGen	1633554
MedDRA	10051981
NORD	1386
Is cancer (heuristic)	no

Also known as: familial non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2) · Hereditary colorectal endometrial cancer syndrome · hereditary defective mismatch repair syndrome · Hereditary non-polyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2) · Hereditary nonpolyposis colon cancer (hMSH2, hMLH1, hPMS1, hPMS2) · Lynch syndrome

Data availability: 5,589 ClinVar variants · 16 ClinGen variant curations · 13 GenCC gene-disease records · 24 cell lines.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Lynch syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

Subtypes (5): Lynch syndrome 1, Lynch syndrome 2, Lynch syndrome 8, Lynch syndrome 4, Lynch syndrome 5

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

600 retrieved; paginated sample, class counts are floors:

275 conflicting classifications of pathogenicity, 149 uncertain significance, 53 benign/likely benign, 52 pathogenic, 31 likely benign, 24 pathogenic/likely pathogenic, 9 likely pathogenic, 7 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1049646	NM_000249.4(MLH1):c.546-2_589-59del	MLH1	Pathogenic	no assertion criteria provided
1070239	NM_000249.4(MLH1):c.22del (p.Ile8fs)	MLH1	Pathogenic	criteria provided, multiple submitters, no conflicts
141132	NM_000249.4(MLH1):c.207+5G>C	MLH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
141177	NM_000249.4(MLH1):c.971dup (p.Arg325fs)	MLH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
142856	NM_000249.4(MLH1):c.117-2A>G	MLH1	Pathogenic	reviewed by expert panel
17079	NM_000249.4(MLH1):c.131C>T (p.Ser44Phe)	MLH1	Pathogenic	reviewed by expert panel
17080	NM_000249.4(MLH1):c.1846AAG[2] (p.Lys618del)	MLH1	Pathogenic	reviewed by expert panel
17085	NM_000249.4(MLH1):c.986A>C (p.His329Pro)	MLH1	Pathogenic	reviewed by expert panel
17087	NM_000249.4(MLH1):c.676C>T (p.Arg226Ter)	MLH1	Pathogenic	reviewed by expert panel
17088	NM_000249.4(MLH1):c.199G>T (p.Gly67Trp)	MLH1	Pathogenic	reviewed by expert panel
17094	NM_000249.4(MLH1):c.350C>T (p.Thr117Met)	MLH1	Pathogenic	reviewed by expert panel
17097	NM_000249.4(MLH1):c.1942C>T (p.Pro648Ser)	MLH1	Pathogenic	reviewed by expert panel
17098	NM_000249.4(MLH1):c.806C>G (p.Ser269Ter)	MLH1	Pathogenic	reviewed by expert panel
17099	NM_000249.4(MLH1):c.2041G>A (p.Ala681Thr)	MLH1	Pathogenic	reviewed by expert panel
17105	NM_000249.4(MLH1):c.104_105delinsAC (p.Met35Asn)	MLH1	Pathogenic	reviewed by expert panel
17106	NM_000249.4(MLH1):c.200G>A (p.Gly67Glu)	MLH1	Pathogenic	reviewed by expert panel
1752723	NM_000249.4(MLH1):c.121del (p.Asp41fs)	MLH1	Pathogenic	criteria provided, multiple submitters, no conflicts
1773361	NM_000249.4(MLH1):c.1039-1G>T	MLH1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1779952	NM_000249.4(MLH1):c.177del (p.Gln60fs)	MLH1	Pathogenic	criteria provided, multiple submitters, no conflicts
1048814	NM_000251.3(MSH2):c.459del (p.Ala154fs)	MSH2	Pathogenic	criteria provided, single submitter
1049201	NM_000251.3(MSH2):c.1277-2_1386+1del	MSH2	Pathogenic	no assertion criteria provided
1049573	NM_000251.3(MSH2):c.367-2_645+432del	MSH2	Pathogenic	no assertion criteria provided
1049937	NM_000251.3(MSH2):c.367-2_645+742del	MSH2	Pathogenic	no assertion criteria provided
142708	NM_000251.3(MSH2):c.211G>C (p.Gly71Arg)	MSH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1753	NM_000251.3(MSH2):c.1865C>T (p.Pro622Leu)	MSH2	Pathogenic	reviewed by expert panel
1755	NM_000251.3(MSH2):c.1216C>T (p.Arg406Ter)	MSH2	Pathogenic	reviewed by expert panel
1756	NM_000251.3(MSH2):c.1915C>T (p.His639Tyr)	MSH2	Pathogenic	reviewed by expert panel
1757	NM_000251.3(MSH2):c.1786_1788del (p.Asn596del)	MSH2	Pathogenic	reviewed by expert panel
1758	NM_000251.3(MSH2):c.1801C>T (p.Gln601Ter)	MSH2	Pathogenic	reviewed by expert panel
1760	NM_000251.3(MSH2):c.2113del (p.Val705fs)	MSH2	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 92 · Orphanet: 21 · 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.

Gene	Classification	Inheritance	Disease	Records
EPCAM	Definitive	Autosomal dominant	Lynch syndrome 8	11
MLH1	Definitive	Autosomal dominant	Lynch syndrome 2	19
MSH2	Definitive	Autosomal dominant	Lynch syndrome 1	17
MSH6	Definitive	Autosomal dominant	Lynch syndrome 5	17
PMS2	Definitive	Autosomal dominant	Lynch syndrome	15
FAN1	Supportive	Autosomal dominant	Lynch syndrome	6
MSH3	Disputed Evidence	Autosomal dominant	Lynch syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EPCAM	Orphanet:144	Lynch syndrome
EPCAM	Orphanet:92050	Congenital tufting enteropathy
MLH1	Orphanet:144	Lynch syndrome
MLH1	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
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
PMS2	Orphanet:144	Lynch syndrome
PMS2	Orphanet:252202	Constitutional mismatch repair deficiency syndrome
FAN1	Orphanet:401996	Karyomegalic interstitial nephritis
MSH3	Orphanet:480536	MSH3-related polyposis
RPS20	Orphanet:124	Diamond-Blackfan anemia
RPS20	Orphanet:440437	Familial colorectal cancer Type X
TGFBR2	Orphanet:144	Lynch syndrome
TGFBR2	Orphanet:284973	Marfan syndrome type 2
TGFBR2	Orphanet:60030	Loeys-Dietz syndrome
TGFBR2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TGFBR2	Orphanet:99977	Squamous cell carcinoma of the esophagus
FBXO11	Orphanet:528084	Non-specific syndromic intellectual disability
PMS1	Orphanet:144	Lynch syndrome

Cohort genes → proteins

15 cohort genes, 15 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	15

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
EPCAM	HGNC:11529	ENSG00000119888	P16422	Epithelial cell adhesion molecule	gencc,clinvar,civic_evidence
MLH1	HGNC:7127	ENSG00000076242	P40692	DNA mismatch repair protein Mlh1	gencc,clinvar
MSH2	HGNC:7325	ENSG00000095002	P43246	DNA mismatch repair protein Msh2	gencc,clinvar
MSH6	HGNC:7329	ENSG00000116062	P52701	DNA mismatch repair protein Msh6	gencc,clinvar
PMS2	HGNC:9122	ENSG00000122512	P54278	Mismatch repair endonuclease PMS2	gencc,clinvar
FAN1	HGNC:29170	ENSG00000198690	Q9Y2M0	Fanconi-associated nuclease 1	gencc
MSH3	HGNC:7326	ENSG00000113318	P20585	DNA mismatch repair protein Msh3	gencc
RPS20	HGNC:10405	ENSG00000008988	P60866	Small ribosomal subunit protein uS10	clinvar
TGFBR2	HGNC:11773	ENSG00000163513	P37173	TGF-beta receptor type-2	clinvar
FBXO11	HGNC:13590	ENSG00000138081	Q86XK2	F-box only protein 11	clinvar
AIMP2	HGNC:20609	ENSG00000106305	Q13155	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	clinvar
STPG4	HGNC:26850	ENSG00000239605	Q8N801	Protein STPG4	clinvar
LRRFIP2	HGNC:6703	ENSG00000093167	Q9Y608	Leucine-rich repeat flightless-interacting protein 2	clinvar
MLH3	HGNC:7128	ENSG00000119684	Q9UHC1	DNA mismatch repair protein Mlh3	clinvar
PMS1	HGNC:9121	ENSG00000064933	P54277	PMS1 protein homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EPCAM	Epithelial cell adhesion molecule	May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosa…
MLH1	DNA mismatch repair protein Mlh1	Heterodimerizes with PMS2 to form MutL alpha, a component of the post-replicative DNA mismatch repair system (MMR).
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).
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
FAN1	Fanconi-associated nuclease 1	Nuclease required for the repair of DNA interstrand cross-links (ICL) recruited at sites of DNA damage by monoubiquitinated FANCD2.
MSH3	DNA mismatch repair protein Msh3	Component of the post-replicative DNA mismatch repair system (MMR).
RPS20	Small ribosomal subunit protein uS10	Component of the small ribosomal subunit.
TGFBR2	TGF-beta receptor type-2	Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3.
FBXO11	F-box only protein 11	Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6, SNAI1 and PRDM1/BLI…
AIMP2	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2	Required for assembly and stability of the aminoacyl-tRNA synthase complex.
STPG4	Protein STPG4	Maternal factor that plays a role in epigenetic chromatin reprogramming during early development of the zygote.
LRRFIP2	Leucine-rich repeat flightless-interacting protein 2	May function as activator of the canonical Wnt signaling pathway, in association with DVL3, upstream of CTNNB1/beta-catenin.
MLH3	DNA mismatch repair protein Mlh3	Probably involved in the repair of mismatches in DNA.
PMS1	PMS1 protein homolog 1	Probably involved in the repair of mismatches in DNA.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 12 · Druggable fraction: 0.13

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	12	1.4×	0.193
Kinase	1	1.9×	0.848
Enzyme (other)	1	0.8×	0.856
Transcription factor	1	0.6×	0.856

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
EPCAM	Enzyme (other)	yes	2.4.1.37	Thyroglobulin_1, Thyroglobulin_1_sf, EpCAM_N
MLH1	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
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
PMS2	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
FAN1	Other/Unknown	no		Rad18_UBZ4, tRNA_endonuc-like_dom_sf, VRR_NUC
MSH3	Other/Unknown	no		DNA_mismatch_repair_MutS_C, DNA_mismatch_repair_MutS-lik_N, DNA_mismatch_repair_MutS_core
RPS20	Other/Unknown	no		Ribosomal_uS10, Ribosomal_uS10_euk/arc, Ribosomal_uS10_CS
TGFBR2	Kinase	yes	2.7.10.2	TGFB_receptor, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
FBXO11	Transcription factor	no		F-box_dom, Znf_UBR, PbH1
AIMP2	Other/Unknown	no		GST_C, AIMP2_LysRS-bd, Glutathione-S-Trfase_C_sf
STPG4	Other/Unknown	no		SHIPPO-rpt
LRRFIP2	Other/Unknown	no		LRRFIP1/2
MLH3	Other/Unknown	no		MutL/Mlh/PMS, DNA_mismatch_S5_2-like, Ribsml_uS5_D2-typ_fold_subgr
PMS1	Other/Unknown	no		MutL/Mlh/PMS, HMG_box_dom, DNA_mismatch_S5_2-like

Expression context

Cohort genes with no expression data: 0.

13 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)	15
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	3
oocyte	2
secondary oocyte	2
ganglionic eminence	2
male germ line stem cell (sensu Vertebrata) in testis	2
buccal mucosa cell	2
left testis	2
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1
deltoid	1
skeletal muscle tissue of rectus abdominis	1
tibialis anterior	1
embryo	1
prefrontal cortex	1
thymus	1
gastrocnemius	1
pancreatic ductal cell	1
right hemisphere of cerebellum	1
bronchial epithelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EPCAM	253	broad	marker	jejunal mucosa, colonic mucosa, mucosa of sigmoid colon
MLH1	296	ubiquitous	marker	tibialis anterior, skeletal muscle tissue of rectus abdominis, deltoid
MSH2	278	ubiquitous	marker	secondary oocyte, oocyte, ventricular zone
MSH6	293	ubiquitous	marker	ventricular zone, embryo, ganglionic eminence
PMS2	143	ubiquitous	marker	thymus, prefrontal cortex, male germ line stem cell (sensu Vertebrata) in testis
FAN1	214	ubiquitous	yes	pancreatic ductal cell, right hemisphere of cerebellum, gastrocnemius
MSH3	287	ubiquitous	marker	buccal mucosa cell, bronchial epithelial cell, mucosa of paranasal sinus
RPS20	311	ubiquitous	marker	adult organism, left ovary, lymph node
TGFBR2	289	ubiquitous	marker	pericardium, tibia, parietal pleura
FBXO11	287	ubiquitous	marker	cortical plate, ganglionic eminence, ventricular zone
AIMP2	297	ubiquitous	marker	oocyte, secondary oocyte, vastus lateralis
STPG4	130	tissue_specific	yes	primordial germ cell in gonad, left testis, male germ line stem cell (sensu Vertebrata) in testis
LRRFIP2	286	ubiquitous	marker	buccal mucosa cell, calcaneal tendon, tendon
MLH3	270	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
PMS1	286	ubiquitous	marker	sperm, male germ cell, left testis

Protein interactions among cohort

Intra-cohort edges: 25.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TGFBR2	5,777
MSH2	4,537
MLH1	4,435
MSH6	4,091
EPCAM	3,359
AIMP2	2,867
PMS2	2,658
MSH3	2,276
PMS1	2,238
FBXO11	2,000

Intra-cohort edges

A	B	Sources
EPCAM	MLH1	string_interaction
EPCAM	MSH2	string_interaction
EPCAM	MSH6	string_interaction
EPCAM	PMS1	string_interaction
EPCAM	PMS2	string_interaction
FAN1	MLH1	biogrid_interaction, intact, string_interaction
FAN1	PMS1	biogrid_interaction, intact, string_interaction
FAN1	PMS2	biogrid_interaction, string_interaction
FBXO11	MSH6	string_interaction
MLH1	MLH3	biogrid_interaction, intact
MLH1	MSH2	string_interaction
MLH1	MSH3	biogrid_interaction, intact, string_interaction
MLH1	MSH6	string_interaction
MLH1	PMS1	biogrid_interaction, intact, string_interaction
MLH1	PMS2	biogrid_interaction, intact, string_interaction
MSH2	MSH3	intact, string_interaction
MSH2	MSH6	biogrid_interaction, intact, string_interaction
MSH2	PMS1	string_interaction
MSH2	PMS2	string_interaction
MSH3	MSH6	string_interaction
MSH3	PMS1	string_interaction
MSH3	PMS2	string_interaction
MSH6	PMS1	string_interaction
MSH6	PMS2	string_interaction
PMS1	PMS2	string_interaction

Structural data

PDB: 12 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS20	P60866	199
MSH2	P43246	30
MSH3	P20585	24
TGFBR2	P37173	22
FAN1	Q9Y2M0	18
AIMP2	Q13155	13
PMS2	P54278	9
MSH6	P52701	8
MLH1	P40692	7
EPCAM	P16422	2
FBXO11	Q86XK2	1
PMS1	P54277	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRFIP2	Q9Y608	68.23
STPG4	Q8N801	67.29
MLH3	Q9UHC1	56.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 106. Enrichment computed across 15 evidence-associated genes (13 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 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Mismatch Repair	4	878.5×	5e-11	MLH1, MSH2, MSH6, MSH3
Diseases of Mismatch Repair (MMR)	4	878.5×	5e-11	MLH1, MSH2, MSH6, MSH3
Defective Mismatch Repair Associated With MSH2	3	878.5×	2e-08	MSH2, MSH6, MSH3
Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)	4	251.0×	2e-08	MLH1, MSH2, MSH6, PMS2
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)	4	251.0×	2e-08	MLH1, MSH2, PMS2, MSH3
Diseases of DNA repair	4	175.7×	9e-08	MLH1, MSH2, MSH6, MSH3
Defective Mismatch Repair Associated With MLH1	2	878.5×	1e-05	MLH1, PMS2
Defective Mismatch Repair Associated With MSH3	2	878.5×	1e-05	MSH2, MSH3
Defective Mismatch Repair Associated With MSH6	2	878.5×	1e-05	MSH2, MSH6
Defective Mismatch Repair Associated With PMS2	2	878.5×	1e-05	MLH1, PMS2
DNA Repair	4	30.3×	6e-05	MLH1, MSH2, MSH6, MSH3
TP53 Regulates Transcription of DNA Repair Genes	3	41.8×	4e-04	MLH1, MSH2, PMS2
Disease	6	6.0×	0.002	MLH1, MSH2, MSH6, RPS20, TGFBR2, MSH3
Meiosis	2	43.9×	0.007	MLH1, MLH3
Selenoamino acid metabolism	2	30.3×	0.013	RPS20, AIMP2
Reproduction	2	29.3×	0.014	MLH1, MLH3
TGFBR2 MSI Frameshift Mutants in Cancer	1	439.2×	0.014	TGFBR2
Loss of Function of TGFBR2 in Cancer	1	292.8×	0.019	TGFBR2
TGFBR2 Kinase Domain Mutants in Cancer	1	292.8×	0.019	TGFBR2
TGFBR1 LBD Mutants in Cancer	1	219.6×	0.023	TGFBR2
Meiotic recombination	2	20.0×	0.023	MLH1, MLH3
Loss of Function of TGFBR1 in Cancer	1	175.7×	0.027	TGFBR2
Loss of Function of SMAD2/3 in Cancer	1	146.4×	0.028	TGFBR2
Signaling by TGF-beta Receptor Complex in Cancer	1	146.4×	0.028	TGFBR2
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	146.4×	0.028	TGFBR2
TGFBR1 KD Mutants in Cancer	1	146.4×	0.028	TGFBR2
TGFBR3 regulates TGF-beta signaling	1	109.8×	0.036	TGFBR2
Metabolism of amino acids and derivatives	2	10.4×	0.058	RPS20, AIMP2
Developmental Lineage of Mammary Stem Cells	1	58.6×	0.060	EPCAM
Maternal to zygotic transition (MZT)	1	54.9×	0.060	STPG4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 15 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mismatch repair	7	302.5×	7e-15	MLH1, MSH2, MSH6, PMS2, MLH3, MSH3, PMS1
somatic recombination of immunoglobulin gene segments	4	1123.5×	3e-11	MSH2, MSH6, PMS2, MSH3
somatic hypermutation of immunoglobulin genes	4	280.9×	3e-08	MLH1, MSH2, MSH6, PMS2
positive regulation of isotype switching to IgA isotypes	3	561.7×	4e-07	MLH1, MSH2, PMS2
positive regulation of isotype switching to IgG isotypes	3	306.4×	3e-06	MLH1, MSH2, PMS2
negative regulation of DNA recombination	3	224.7×	6e-06	MSH2, MSH6, MSH3
isotype switching	3	168.5×	1e-05	MLH1, MSH2, MSH6
maintenance of DNA repeat elements	2	449.4×	1e-04	MSH2, MSH3
mitotic recombination	2	374.5×	2e-04	MSH2, MSH3
DNA repair	4	17.0×	9e-04	MSH2, MSH6, FAN1, MSH3
determination of adult lifespan	2	57.6×	0.007	MSH2, MSH6
meiotic mismatch repair	1	1123.5×	0.007	MSH6
somatic recombination of immunoglobulin genes involved in immune response	1	1123.5×	0.007	MSH2
positive regulation of tolerance induction to self antigen	1	1123.5×	0.007	TGFBR2
positive regulation of B cell tolerance induction	1	1123.5×	0.007	TGFBR2
meiotic metaphase I homologous chromosome alignment	1	1123.5×	0.007	MLH1
pyrimidine-containing compound catabolic process	1	1123.5×	0.007	STPG4
inferior endocardial cushion morphogenesis	1	1123.5×	0.007	TGFBR2
intrinsic apoptotic signaling pathway in response to DNA damage	2	43.2×	0.007	MLH1, MSH6
response to xenobiotic stimulus	3	13.8×	0.008	PMS2, TGFBR2, PMS1
meiotic spindle midzone assembly	1	561.7×	0.010	MLH1
bronchus morphogenesis	1	561.7×	0.010	TGFBR2
mammary gland morphogenesis	1	561.7×	0.010	TGFBR2
male meiosis chromosome segregation	1	374.5×	0.014	MLH1
negative regulation of mitotic recombination	1	374.5×	0.014	MLH1
miRNA transport	1	374.5×	0.014	TGFBR2
positive regulation of T cell tolerance induction	1	280.9×	0.015	TGFBR2
female meiosis chromosome segregation	1	280.9×	0.015	MLH1
B cell mediated immunity	1	280.9×	0.015	MSH2
epigenetic programing of male pronucleus	1	280.9×	0.015	STPG4

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 12

Druggability breadth: 8 of 15 evidence-associated genes (53%) 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.

Symbol	Example approved molecule
RPS20	GENTAMICIN SULFATE
TGFBR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TGFBR2	22	4
MSH6	1	2
RPS20	1	4
EPCAM	0	0
MLH1	0	0
MSH2	0	0
PMS2	0	0
FAN1	0	0
MSH3	0	0
FBXO11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPS20
PONATINIB	4	TGFBR2
VEMURAFENIB	4	TGFBR2
FEDRATINIB	4	TGFBR2
SORAFENIB	4	TGFBR2
DABRAFENIB	4	TGFBR2
TOVORAFENIB	4	TGFBR2
PAZOPANIB	4	TGFBR2
DASATINIB	4	TGFBR2
CANERTINIB	3	TGFBR2
ALVOCIDIB	3	TGFBR2
LESTAURTINIB	3	TGFBR2
MOLIBRESIB	2	MSH6
GALUNISERTIB	2	TGFBR2
SCH-900776	2	TGFBR2
DANUSERTIB	2	TGFBR2
TG100-801	2	TGFBR2
R-406	2	TGFBR2
ENMD-2076	2	TGFBR2
AT-9283	2	TGFBR2
BMS-387032	1	TGFBR2
RGB-286638	1	TGFBR2
CYC-116	1	TGFBR2
AST-487	1	TGFBR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
TGFBR2	188	Binding:188
RPS20	90	Binding:90
AIMP2	23	Binding:21, ADMET:2
MSH6	10	Binding:10
MSH2	9	Binding:9
FBXO11	2	Binding:2
EPCAM	1	Binding:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
EPCAM	2.4.1.37, 2.4.1.40	fucosylgalactoside 3-alpha-galactosyltransferase, glycoprotein-fucosylgalactoside alpha-N-acetylgalactosaminyltransferase
TGFBR2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TGFBR2	188

Pharmacogenomics

Cohort genes with a PharmGKB record: 15; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

24 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.

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPS20
PONATINIB	4	TGFBR2
VEMURAFENIB	4	TGFBR2
FEDRATINIB	4	TGFBR2
SORAFENIB	4	TGFBR2
DABRAFENIB	4	TGFBR2
TOVORAFENIB	4	TGFBR2
PAZOPANIB	4	TGFBR2
DASATINIB	4	TGFBR2
CANERTINIB	3	TGFBR2
ALVOCIDIB	3	TGFBR2
LESTAURTINIB	3	TGFBR2
MOLIBRESIB	2	MSH6
GALUNISERTIB	2	TGFBR2
SCH-900776	2	TGFBR2
DANUSERTIB	2	TGFBR2
TG100-801	2	TGFBR2
R-406	2	TGFBR2
ENMD-2076	2	TGFBR2
AT-9283	2	TGFBR2
BMS-387032	1	TGFBR2
RGB-286638	1	TGFBR2
CYC-116	1	TGFBR2
AST-487	1	TGFBR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	RPS20, TGFBR2
B	Phased (≥1) drug, not yet approved	1	MSH6
C	Druggable family + PDB, no drug	1	EPCAM
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	11	MLH1, MSH2, PMS2, FAN1, MSH3, FBXO11, AIMP2, STPG4, LRRFIP2, MLH3 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MLH1	0	MSH6
PMS2	1	MSH6
FBXO11	2	MSH6
PMS1	0	MSH6
EPCAM	1	—
MSH2	9	—
FAN1	0	—
MSH3	0	—
AIMP2	23	—
STPG4	0	—
LRRFIP2	0	—
MLH3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 106.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	85
PHASE3	6
PHASE2	5
EARLY_PHASE1	4
PHASE1	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02000089	PHASE3	RECRUITING	The Cancer of the Pancreas Screening-5 CAPS5)Study
NCT02813824	PHASE3	ACTIVE_NOT_RECRUITING	Effect of Chemoprevention by Low-dose Aspirin of New or Recurrent Colorectal Adenomas in Patients With Lynch Syndrome
NCT02912559	PHASE3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT07609901	PHASE3	NOT_YET_RECRUITING	Preventive Dendritic Cell Vaccination for Lynch Syndrome Carriers
NCT00566644	PHASE3	TERMINATED	Intrauterine Levonorgestrel and Observation or Observation Alone in Preventing Atypical Endometrial Hyperplasia and Endometrial Cancer in Women With Hereditary Non-Polyposis Colorectal Cancer or Lynch Syndrome
NCT04711434	PHASE3	UNKNOWN	PD-1 Antibody for The Prevention of Adenomatous Polyps and Second Primary Tumors in Lynch Syndrome Patients
NCT04920149	PHASE2	RECRUITING	Mesalamine for Colorectal Cancer Prevention Program in Lynch Syndrome
NCT05078866	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Cancer Preventive Vaccine Nous-209 for Lynch Syndrome Patients
NCT05411718	PHASE2	RECRUITING	A Phase IIa Randomized, Double-Blinded Clinical Trial of Naproxen or Aspirin for Cancer Immune Interception in Lynch Syndrome
NCT05419011	PHASE2	ACTIVE_NOT_RECRUITING	Testing a Combination of Vaccines for Cancer Prevention in Lynch Syndrome
NCT07412197	PHASE1/PHASE2	NOT_YET_RECRUITING	Preventive Dendritic Cell Vaccination for Lynch Syndrome
NCT03631641	PHASE2	TERMINATED	Nivolumab in Preventing Colon Adenomas in Participants With Lynch Syndrome and a History of Partial Colectomy
NCT03831698	PHASE2	UNKNOWN	Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE)
NCT02359565	PHASE1	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma
NCT07163403	PHASE1	RECRUITING	First in Human Pilot Study to Assess the Safety and Efficacy of Dendritic Cells Loaded With Frameshift Derived Neopeptides for the Prevention of Cancer in of Lynch Syndrome Carriers
NCT02052908	PHASE1	COMPLETED	Naproxen in Preventing DNA Mismatch Repair Deficient Colorectal Cancer in Patients With Lynch Syndrome
NCT04500548	PHASE1	WITHDRAWN	Testing the Combination of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) in Children, Adolescent, and Young Adult Patients With Relapsed/Refractory Cancers That Have an Increased Number of Genetic Changes, The 3CI Study
NCT00898768	EARLY_PHASE1	COMPLETED	Capsule Endoscopy to Screen for Small Bowel Neoplasia in Lynch Syndrome
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT04379999	EARLY_PHASE1	COMPLETED	Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
NCT04906382	EARLY_PHASE1	TERMINATED	Tislelizumab for the Treatment of Recurrent Mismatch Repair Deficient Endometrial Cancer
NCT00582296	Not specified	ACTIVE_NOT_RECRUITING	Multi-Organ Screening Recommendations in Patients With Lynch Syndrome
NCT02012699	Not specified	RECRUITING	Integrated Cancer Repository for Cancer Research
NCT02194387	Not specified	ACTIVE_NOT_RECRUITING	Energy Balance Interventions in Increasing Physical Activity in Breast Cancer Gene Positive Patients, Lynch Syndrome-Positive Patients, CLL Survivors or High-Risk Family Members
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02371135	Not specified	ACTIVE_NOT_RECRUITING	Metagenomic Evaluation of the Gut Microbiome in Patients With Lynch Syndrome and Other Hereditary Colonic Polyposis Syndromes
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03303833	Not specified	RECRUITING	The GEOLynch Cohort Study
NCT03702309	Not specified	RECRUITING	Liquid Biopsy Evaluation and Repository Development at Princess Margaret
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04494945	Not specified	RECRUITING	Identifying and Caring for Individuals With Inherited Cancer Syndrome
NCT05129605	Not specified	RECRUITING	Prostate Cancer Genetic Risk Evaluation and Screening Study
NCT05410977	Not specified	RECRUITING	Collecting Blood and Stool Samples to Detect Colorectal Cancer or Advanced Neoplasia in Lynch Syndrome Patients
NCT05495776	Not specified	RECRUITING	Prospective Multicenter Registry Study to Assess the Frequency of Lynch Syndrome Among Patients With Colorectal Cancer
NCT05677048	Not specified	ACTIVE_NOT_RECRUITING	Feasibility Study: IGNITE-TX (Identifying Individuals for Genetic Testing & Treatment) Intervention
NCT05692596	Not specified	ACTIVE_NOT_RECRUITING	The Pancreas Interception Center (PIC) for Early Detection, Prevention, and Novel Therapeutics
NCT05704010	Not specified	RECRUITING	Videocapsule Endoscopy in Lynch Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	1
ATEZOLIZUMAB	4	1
LEUCOVORIN	4	1
MESALAMINE	4	1
SECRETIN	4	1
NOGAPENDEKIN ALFA	3	1
CHEMBL5412235	0	1