Familial adenomatous polyposis 1
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Also known as adenoma, periampullary, somaticadenomatous polyposis coliAPC-related adenomatous polyposisFAP1
Summary
Familial adenomatous polyposis 1 (MONDO:0021056) is a disease caused by APC (GenCC Definitive), with 7 cohort genes and 12 clinical trials. Top therapeutic interventions include guselkumab, sulindac, and celecoxib.
At a glance
- Causal gene: APC (GenCC Definitive)
- Cohort genes: 7
- ClinVar variants: 12,375
- Clinical trials: 12
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | familial adenomatous polyposis 1 |
| Mondo ID | MONDO:0021056 |
| OMIM | 175100 |
| DOID | DOID:0080409 |
| UMLS | C2713442 |
| MedGen | 398651 |
| GARD | 0025282 |
| Is cancer (heuristic) | no |
Also known as: adenoma, periampullary, somatic · adenomatous polyposis coli · APC-related adenomatous polyposis · familial adenomatous polyposis 1 · FAP1
Data availability: 12,375 ClinVar variants · 104 ClinGen variant curations · 4 GenCC gene-disease records.
Disease family
An umbrella term covering 1 Mondo subtype.
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › intestinal polyposis syndrome › classic or attenuated familial adenomatous polyposis › familial adenomatous polyposis 1
Related subtypes (7): familial adenomatous polyposis 2, familial adenomatous polyposis 3, attenuated familial adenomatous polyposis, AXIN2-related attenuated familial adenomatous polyposis, Polymerase proofreading-related adenomatous polyposis, classic familial adenomatous polyposis, familial adenomatous polyposis 4
Subtypes (1): APC-related attenuated familial adenomatous polyposis
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:
558 uncertain significance, 16 pathogenic, 11 conflicting classifications of pathogenicity, 6 benign/likely benign, 4 likely pathogenic, 3 pathogenic/likely pathogenic, 2 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1002757 | NM_001127511.3(APC):c.-40G>A | APC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1012188 | NM_000038.6(APC):c.1908_1909dup (p.Gly637fs) | APC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1012191 | NM_000038.6(APC):c.1490dup (p.Arg498fs) | APC | Pathogenic | criteria provided, single submitter |
| 1012192 | NM_000038.6(APC):c.1744G>T (p.Glu582Ter) | APC | Pathogenic | criteria provided, single submitter |
| 1012193 | NM_000038.6(APC):c.2510del (p.Ser836_Ser837insTer) | APC | Pathogenic | criteria provided, single submitter |
| 1048837 | NM_000038.6(APC):c.1742_1743del (p.Lys581fs) | APC | Pathogenic | no assertion criteria provided |
| 1049077 | NM_000038.6(APC):c.2893_2896del (p.Asn965fs) | APC | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1049123 | NM_000038.6(APC):c.5782del (p.Gln1928fs) | APC | Pathogenic | criteria provided, single submitter |
| 1049151 | NM_000038.6(APC):c.442del (p.Asp149fs) | APC | Pathogenic | no assertion criteria provided |
| 1049324 | NM_000038.6(APC):c.-2_135+1274del | APC | Pathogenic | no assertion criteria provided |
| 1049327 | NM_000038.6(APC):c.3411del (p.Asp1137fs) | APC | Pathogenic | no assertion criteria provided |
| 1049668 | NM_000038.6(APC):c.4945dup (p.Ile1649fs) | APC | Pathogenic | no assertion criteria provided |
| 1049772 | NM_000038.6(APC):c.1409-2del | APC | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1050064 | NM_000038.6(APC):c.841dup (p.Thr281fs) | APC | Pathogenic | criteria provided, single submitter |
| 1050121 | NM_000038.6(APC):c.3260_3263dup (p.Lys1088fs) | APC | Pathogenic | no assertion criteria provided |
| 1050316 | NM_000038.6(APC):c.2928_2929del (p.Gly977fs) | APC | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1050551 | NM_000038.6(APC):c.4606G>T (p.Glu1536Ter) | APC | Pathogenic | criteria provided, single submitter |
| 1050615 | NM_000038.6(APC):c.230T>A (p.Leu77Ter) | APC | Pathogenic | criteria provided, single submitter |
| 1050660 | NM_000038.6(APC):c.4161T>A (p.Cys1387Ter) | APC | Pathogenic | criteria provided, single submitter |
| 1012189 | NM_000038.6(APC):c.2743del (p.Cys914_Val915insTer) | APC | Likely pathogenic | criteria provided, single submitter |
| 1012190 | NM_000038.6(APC):c.3991A>T (p.Arg1331Ter) | APC | Likely pathogenic | criteria provided, single submitter |
| 1025291 | NM_000038.6(APC):c.933G>C (p.Lys311Asn) | APC | Likely pathogenic | reviewed by expert panel |
| 1050028 | NM_000038.6(APC):c.423-8A>G | APC | Likely pathogenic | reviewed by expert panel |
| 1004817 | NM_000038.6(APC):c.2186T>C (p.Leu729Pro) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1017874 | NM_000038.6(APC):c.531T>C (p.Asn177=) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1018693 | NM_000038.6(APC):c.5600T>A (p.Phe1867Tyr) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1023798 | NM_000038.6(APC):c.4475C>A (p.Ala1492Asp) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1025685 | NM_000038.6(APC):c.6481A>C (p.Ser2161Arg) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1036972 | NM_000038.6(APC):c.827A>G (p.Asn276Ser) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1041349 | NM_000038.6(APC):c.4021A>G (p.Ser1341Gly) | APC | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 15 · Orphanet: 10 · 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 |
|---|---|---|---|---|
| APC | Definitive | Autosomal dominant | familial adenomatous polyposis 1 | 15 |
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 |
| SRP19 | Orphanet:486 | Autosomal dominant severe congenital neutropenia |
| STK11 | Orphanet:2869 | Peutz-Jeghers syndrome |
| MUTYH | Orphanet:247798 | MUTYH-related polyposis |
| MUTYH | Orphanet:440437 | Familial colorectal cancer Type X |
| NTHL1 | Orphanet:454840 | NTHL1-related polyposis |
Cohort genes → proteins
7 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 7 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| APC | HGNC:583 | ENSG00000134982 | P25054 | Adenomatous polyposis coli protein | gencc,clinvar |
| SRP19 | HGNC:11300 | ENSG00000153037 | P09132 | Signal recognition particle 19 kDa protein | clinvar |
| STK11 | HGNC:11389 | ENSG00000118046 | Q15831 | Serine/threonine-protein kinase STK11 | clinvar |
| PCDHB16 | HGNC:14546 | ENSG00000272674 | Q9NRJ7 | Protocadherin beta-16 | clinvar |
| REEP5 | HGNC:30077 | ENSG00000129625 | Q00765 | Receptor expression-enhancing protein 5 | clinvar |
| MUTYH | HGNC:7527 | ENSG00000132781 | Q9UIF7 | Adenine DNA glycosylase | clinvar |
| NTHL1 | HGNC:8028 | ENSG00000065057 | P78549 | Endonuclease III-like protein 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| APC | Adenomatous polyposis coli protein | Tumor suppressor. |
| SRP19 | Signal recognition particle 19 kDa protein | Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). |
| STK11 | Serine/threonine-protein kinase STK11 | Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage… |
| PCDHB16 | Protocadherin beta-16 | Potential calcium-dependent cell-adhesion protein. |
| REEP5 | Receptor expression-enhancing protein 5 | Plays an essential role in heart function and development by regulating the organization and function of the sarcoplasmic reticulum in cardiomyocytes. |
| MUTYH | Adenine DNA glycosylase | Involved in oxidative DNA damage repair. |
| NTHL1 | Endonuclease III-like protein 1 | Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.29
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 |
|---|---|---|---|
| Kinase | 1 | 4.0× | 0.456 |
| Enzyme (other) | 1 | 1.7× | 0.456 |
| Other/Unknown | 5 | 1.3× | 0.456 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| APC | Other/Unknown | no | Armadillo, APC_rpt, SAMP | |
| SRP19 | Other/Unknown | no | Signal_recog_particle_SRP19, SRP19-like_sf | |
| STK11 | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf |
| PCDHB16 | Other/Unknown | no | Cadherin-like_dom, Cadherin_N, Cadherin-like_sf | |
| REEP5 | Other/Unknown | no | TB2_DP1_HVA22 | |
| MUTYH | Other/Unknown | no | NUDIX_hydrolase_dom, HhH_motif, HhH-GPD_domain | |
| NTHL1 | Enzyme (other) | yes | 4.2.99.18 | HhH_motif, HhH-GPD_domain, Endonuclease3_FeS-loop_motif |
Expression context
Cohort genes with no expression data: 0.
7 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) | 7 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| medial globus pallidus | 1 |
| substantia nigra pars compacta | 1 |
| substantia nigra pars reticulata | 1 |
| adenohypophysis | 1 |
| body of pancreas | 1 |
| islet of Langerhans | 1 |
| hindlimb stylopod muscle | 1 |
| left testis | 1 |
| right testis | 1 |
| caput epididymis | 1 |
| cauda epididymis | 1 |
| corpus epididymis | 1 |
| endothelial cell | 1 |
| lateral nuclear group of thalamus | 1 |
| middle temporal gyrus | 1 |
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| right hemisphere of cerebellum | 1 |
| apex of heart | 1 |
| mucosa of transverse colon | 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 |
| SRP19 | 169 | ubiquitous | marker | adenohypophysis, body of pancreas, islet of Langerhans |
| STK11 | 238 | ubiquitous | marker | left testis, right testis, hindlimb stylopod muscle |
| PCDHB16 | 191 | broad | marker | corpus epididymis, caput epididymis, cauda epididymis |
| REEP5 | 301 | ubiquitous | marker | middle temporal gyrus, lateral nuclear group of thalamus, endothelial cell |
| MUTYH | 134 | ubiquitous | marker | cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum |
| NTHL1 | 211 | ubiquitous | marker | right lobe of liver, apex of heart, mucosa of transverse colon |
Protein interactions among cohort
Intra-cohort edges: 4.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| STK11 | 5,146 |
| APC | 2,903 |
| SRP19 | 2,099 |
| NTHL1 | 1,994 |
| MUTYH | 1,815 |
| REEP5 | 1,764 |
| PCDHB16 | 489 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| APC | REEP5 | string_interaction |
| APC | SRP19 | string_interaction |
| MUTYH | NTHL1 | string_interaction |
| REEP5 | SRP19 | string_interaction |
Structural data
PDB: 5 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| APC | P25054 | 31 |
| SRP19 | P09132 | 9 |
| STK11 | Q15831 | 4 |
| MUTYH | Q9UIF7 | 3 |
| NTHL1 | P78549 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| PCDHB16 | Q9NRJ7 | 82.84 |
| REEP5 | Q00765 | 78.88 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 55. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Displacement of DNA glycosylase by APEX1 | 2 | 415.3× | 5e-04 | MUTYH, NTHL1 |
| APC truncation mutants are not K63 polyubiquitinated | 1 | 2284.0× | 0.004 | APC |
| Defective MUTYH substrate binding | 1 | 2284.0× | 0.004 | MUTYH |
| Defective MUTYH substrate processing | 1 | 2284.0× | 0.004 | MUTYH |
| Defective NTHL1 substrate processing | 1 | 2284.0× | 0.004 | NTHL1 |
| Defective NTHL1 substrate binding | 1 | 2284.0× | 0.004 | NTHL1 |
| AMPK inhibits chREBP transcriptional activation activity | 1 | 285.5× | 0.019 | STK11 |
| Signaling by AXIN mutants | 1 | 207.6× | 0.019 | APC |
| Signaling by CTNNB1 phospho-site mutants | 1 | 207.6× | 0.019 | APC |
| Signaling by APC mutants | 1 | 207.6× | 0.019 | APC |
| Signaling by AMER1 mutants | 1 | 207.6× | 0.019 | APC |
| APC truncation mutants have impaired AXIN binding | 1 | 163.1× | 0.019 | APC |
| AXIN missense mutants destabilize the destruction complex | 1 | 163.1× | 0.019 | APC |
| Truncations of AMER1 destabilize the destruction complex | 1 | 163.1× | 0.019 | APC |
| Signaling by GSK3beta mutants | 1 | 152.3× | 0.019 | APC |
| CTNNB1 S33 mutants aren’t phosphorylated | 1 | 152.3× | 0.019 | APC |
| CTNNB1 S37 mutants aren’t phosphorylated | 1 | 152.3× | 0.019 | APC |
| CTNNB1 S45 mutants aren’t phosphorylated | 1 | 152.3× | 0.019 | APC |
| CTNNB1 T41 mutants aren’t phosphorylated | 1 | 152.3× | 0.019 | APC |
| FOXO-mediated transcription of cell death genes | 1 | 142.8× | 0.019 | STK11 |
| Beta-catenin phosphorylation cascade | 1 | 134.3× | 0.019 | APC |
| Signaling by WNT in cancer | 1 | 120.2× | 0.021 | APC |
| Apoptotic cleavage of cellular proteins | 1 | 95.2× | 0.024 | APC |
| Apoptotic execution phase | 1 | 95.2× | 0.024 | APC |
| Energy dependent regulation of mTOR by LKB1-AMPK | 1 | 78.8× | 0.028 | STK11 |
| Disassembly of the destruction complex and recruitment of AXIN to the membrane | 1 | 71.4× | 0.029 | APC |
| FOXO-mediated transcription | 1 | 67.2× | 0.030 | STK11 |
| Ovarian tumor domain proteases | 1 | 55.7× | 0.035 | APC |
| MTOR signalling | 1 | 53.1× | 0.035 | STK11 |
| Deactivation of the beta-catenin transactivating complex | 1 | 46.6× | 0.039 | 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| positive regulation of vesicle transport along microtubule | 1 | 2407.4× | 0.018 | STK11 |
| SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition | 1 | 601.9× | 0.018 | SRP19 |
| depurination | 1 | 601.9× | 0.018 | MUTYH |
| base-excision repair, AP site formation | 1 | 481.5× | 0.018 | NTHL1 |
| regulation of microtubule-based movement | 1 | 401.2× | 0.018 | APC |
| negative regulation of epithelial cell proliferation involved in prostate gland development | 1 | 401.2× | 0.018 | STK11 |
| endoplasmic reticulum membrane organization | 1 | 343.9× | 0.018 | REEP5 |
| negative regulation of cell cycle G1/S phase transition | 1 | 343.9× | 0.018 | APC |
| positive regulation of protein localization to centrosome | 1 | 343.9× | 0.018 | APC |
| negative regulation of cyclin-dependent protein serine/threonine kinase activity | 1 | 300.9× | 0.018 | APC |
| Golgi localization | 1 | 300.9× | 0.018 | STK11 |
| epithelial cell proliferation involved in prostate gland development | 1 | 300.9× | 0.018 | STK11 |
| regulation of microtubule-based process | 1 | 267.5× | 0.018 | APC |
| depyrimidination | 1 | 267.5× | 0.018 | NTHL1 |
| cotranslational protein targeting to membrane | 1 | 240.7× | 0.018 | SRP19 |
| regulation of attachment of spindle microtubules to kinetochore | 1 | 240.7× | 0.018 | APC |
| dendrite extension | 1 | 240.7× | 0.018 | STK11 |
| heart valve development | 1 | 218.9× | 0.018 | APC |
| activation of protein kinase activity | 1 | 218.9× | 0.018 | STK11 |
| positive thymic T cell selection | 1 | 200.6× | 0.018 | STK11 |
| G1 to G0 transition | 1 | 200.6× | 0.018 | STK11 |
| cellular response to UV-B | 1 | 200.6× | 0.018 | STK11 |
| positive regulation of pseudopodium assembly | 1 | 185.2× | 0.018 | APC |
| anoikis | 1 | 185.2× | 0.018 | STK11 |
| negative regulation of canonical Wnt signaling pathway | 2 | 33.7× | 0.018 | APC, STK11 |
| vasculature development | 1 | 160.5× | 0.020 | STK11 |
| negative regulation of necroptotic process | 1 | 141.6× | 0.021 | MUTYH |
| DNA damage response | 2 | 15.3× | 0.021 | APC, STK11 |
| peptidyl-threonine phosphorylation | 1 | 126.7× | 0.022 | STK11 |
| regulation of Wnt signaling pathway | 1 | 126.7× | 0.022 | STK11 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 6
Druggability breadth: 6 of 7 evidence-associated genes (86%) 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 |
|---|---|
| STK11 | FEDRATINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| STK11 | 17 | 4 |
| APC | 0 | 0 |
| SRP19 | 0 | 0 |
| PCDHB16 | 0 | 0 |
| REEP5 | 0 | 0 |
| MUTYH | 0 | 0 |
| NTHL1 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | STK11 |
| PACRITINIB | 4 | STK11 |
| NINTEDANIB | 4 | STK11 |
| SUNITINIB | 4 | STK11 |
| MIDOSTAURIN | 4 | STK11 |
| DINACICLIB | 3 | STK11 |
| DOVITINIB | 3 | STK11 |
| LESTAURTINIB | 3 | STK11 |
| RUBOXISTAURIN | 3 | STK11 |
| AZD-1480 | 2 | STK11 |
| SU-014813 | 2 | STK11 |
| R-406 | 2 | STK11 |
| TOZASERTIB | 2 | STK11 |
| PF-00562271 | 1 | STK11 |
| KW-2449 | 1 | STK11 |
| PF-03758309 | 1 | STK11 |
| XL-228 | 1 | STK11 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| STK11 | 244 | Binding:244 |
| APC | 24 | Binding:24 |
| NTHL1 | 8 | Binding:7, Functional:1 |
| SRP19 | 2 | Binding:2 |
| REEP5 | 1 | Binding:1 |
| MUTYH | 1 | Functional:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| STK11 | 2.7.11.1 | non-specific serine/threonine protein kinase |
| NTHL1 | 4.2.99.18 | DNA-(apurinic or apyrimidinic site) lyase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| STK11 | 244 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
17 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) |
|---|---|---|
| FEDRATINIB | 4 | STK11 |
| PACRITINIB | 4 | STK11 |
| NINTEDANIB | 4 | STK11 |
| SUNITINIB | 4 | STK11 |
| MIDOSTAURIN | 4 | STK11 |
| DINACICLIB | 3 | STK11 |
| DOVITINIB | 3 | STK11 |
| LESTAURTINIB | 3 | STK11 |
| RUBOXISTAURIN | 3 | STK11 |
| AZD-1480 | 2 | STK11 |
| SU-014813 | 2 | STK11 |
| R-406 | 2 | STK11 |
| TOZASERTIB | 2 | STK11 |
| PF-00562271 | 1 | STK11 |
| KW-2449 | 1 | STK11 |
| PF-03758309 | 1 | STK11 |
| XL-228 | 1 | STK11 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | STK11 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | NTHL1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 5 | APC, SRP19, PCDHB16, REEP5, MUTYH |
Undrugged target profiles
6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| APC | 24 | — |
| SRP19 | 2 | — |
| PCDHB16 | 0 | — |
| REEP5 | 1 | — |
| MUTYH | 1 | — |
| NTHL1 | 8 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 12.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 4 |
| PHASE2 | 3 |
| PHASE1 | 3 |
| PHASE4 | 1 |
| PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00140894 | PHASE4 | TERMINATED | A Study of Rofecoxib in Familial Adenomatous Polyposis (FAP) (0966-205)(TERMINATED) |
| NCT00585312 | PHASE3 | TERMINATED | Trial In Pediatric Patients With Familial Adenomatous Polyposis (FAP) |
| NCT00319007 | PHASE2 | UNKNOWN | Influence of Sulindac and Probiotics on the Development of Pouch Adenomas in Patients With Familial Adenomatous Polyposis |
| NCT01187901 | PHASE2 | COMPLETED | A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients |
| NCT03095703 | PHASE2 | COMPLETED | Sirolimus and Familial Adenomatous Polyposis (FAP) |
| NCT02113202 | PHASE1 | COMPLETED | Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, Using Bevacizumab-IRDye800CW |
| NCT03649971 | PHASE1 | COMPLETED | A Study of Guselkumab in Participants With Familial Adenomatous Polyposis |
| NCT05014360 | PHASE1 | COMPLETED | A Study of JNJ-64251330 in Participants With Familial Adenomatous Polyposis |
| NCT06435533 | Not specified | RECRUITING | Cold Atmospheric Plasma for the Endoscopic Treatment of Duodenal Polyps in Patients With Familial Adenomatous Polyposis |
| NCT01604564 | Not specified | COMPLETED | Registry With Information About Colitis Ulcerosa and Familial Adenomatous Polyposis Patients |
| NCT03027401 | Not specified | WITHDRAWN | Clinical Sequencing of Cancer and Tissue Repository: OncoGenomics |
| NCT04948398 | Not specified | NO_LONGER_AVAILABLE | Post-Trial Access for Guselkumab in Participants With Familial Adenomatous Polyposis |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| GUSELKUMAB | 4 | 2 |
| SULINDAC | 4 | 2 |
| CELECOXIB | 4 | 1 |
| INULIN | 4 | 1 |