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Atlas / Disease / Small intestine neuroendocrine neoplasm

Small intestine neuroendocrine neoplasm

disease
On this page

Also known as NET of the small intestineneuroendocrine neoplasm of small intestineneuroendocrine neoplasm of the small intestineneuroendocrine tumor of small bowelneuroendocrine tumour of small bowelneuroendocrine tumour of the small intestinesmall intestinal neuroendocrine neoplasmsmall intestine NETsmall intestine neuroendocrine tumorsmall intestine neuroendocrine tumor, well differentiated, low or intermediate gradesmall intestine neuroendocrine tumour

Summary

Small intestine neuroendocrine neoplasm (MONDO:0018510) is a cancer with 2 cohort genes (7 GWAS associations across 2 studies).

At a glance

  • Classification: Cancer
  • Cohort genes: 2
  • GWAS associations: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namesmall intestine neuroendocrine neoplasm
Mondo IDMONDO:0018510
EFOEFO:1001928
Orphanet423975
DOIDDOID:4434
NCITC5803
UMLSC1336005
MedGen233453
GARD0021765
Anatomy (UBERON)UBERON:0002108
Is cancer (heuristic)yes

Also known as: NET of the small intestine · neuroendocrine neoplasm of small intestine · neuroendocrine neoplasm of the small intestine · neuroendocrine tumor of small bowel · neuroendocrine tumour of small bowel · neuroendocrine tumour of the small intestine · small intestinal neuroendocrine neoplasm · small intestine NET · small intestine neuroendocrine neoplasm · small intestine neuroendocrine tumor · small intestine neuroendocrine tumor, well differentiated, low or intermediate grade · small intestine neuroendocrine tumour

Data availability: 7 GWAS associations (2 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › intestinal neoplasm › intestinal neuroendocrine neoplasm › small intestine neuroendocrine neoplasm

Related subtypes (3): colon neuroendocrine neoplasm, rectum neuroendocrine neoplasm, intestinal neuroendocrine tumor G1

Subtypes (3): small intestine neuroendocrine tumor, well differentiated, low or intermediate grade, hereditary neuroendocrine tumor of small intestine, duodenal neuroendocrine neoplasm

Genetics & variants

GWAS landscape

7 GWAS associations across 2 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1931949213e-13TMEM19 - RAB21?2.14
rs26608583e-11RN7SL88P - LINC02452?0.45
rs23285471e-09CDKAL1?0.61
rs25405133e-09YPEL5P3 - RN7SL88P?1.87
rs80096339e-09FERMT2?0.42
rs10198663792e-08LINC00992?4.44
rs60438732e-08KIF16B?0.38

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90316496Giri AK2023307287,137Genome wide association study identifies 4 novel risk loci for small intestinal neuroendocrine tumors including a missense mutation in LGR5.
GCST003786Du Y20162934,542Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic7

MAF distribution

BucketVariants
common (>=0.05)5
low_freq (0.01-0.05)0
rare (<0.01)0
unknown2

Functional consequences

ConsequenceCount
intron_variant5
intergenic_variant2

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1931949211271725768A>Gintergenic_variantTMEM19 - RAB213e-13Tier 4: intronic/intergenic
rs26608581296111563A>C,G,T0.05intron_variantRN7SL88P - LINC024523e-11Tier 4: intronic/intergenic
rs2328547620716339A>G,T0.05intron_variantCDKAL11e-09Tier 4: intronic/intergenic
rs25405131296098670A>G0.05intron_variantYPEL5P3 - RN7SL88P3e-09Tier 4: intronic/intergenic
rs80096331452920118G>C0.05intron_variantFERMT29e-09Tier 4: intronic/intergenic
rs10198663795117573124T>Aintergenic_variantLINC009922e-08Tier 4: intronic/intergenic
rs60438732016292557G>A,C,T0.05intron_variantKIF16B2e-08Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
ELK3HGNC:3325ENSG00000111145P41970ETS domain-containing protein Elk-3gwas
LTA4HHGNC:6710ENSG00000111144P09960Leukotriene A-4 hydrolasegwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
ELK3ETS domain-containing protein Elk-3May be a negative regulator of transcription, but can activate transcription when coexpressed with Ras, Src or Mos.
LTA4HLeukotriene A-4 hydrolaseBifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Protease118.3×0.108
Other/Unknown10.9×0.805

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
ELK3Other/UnknownnoEts_dom, WH-like_DNA-bd_sf, WH_DNA-bd_sf
LTA4HProteaseyes3.3.2.6Peptidase_M1, LTA4H, Peptidase_M1_dom

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
amniotic fluid1
bronchial epithelial cell1
synovial joint1
leukocyte1
monocyte1
mononuclear cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
ELK3286ubiquitousmarkerbronchial epithelial cell, synovial joint, amniotic fluid
LTA4H302ubiquitousmarkermonocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
LTA4H2,031
ELK3490

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
LTA4HP0996077

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
ELK3P4197060.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 16. Enrichment computed across 2 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
Biosynthesis of aspirin-triggered D-series resolvins13806.7×0.001LTA4H
Biosynthesis of D-series resolvins12855.0×0.001LTA4H
Biosynthesis of EPA-derived SPMs12855.0×0.001LTA4H
Biosynthesis of protectins12855.0×0.001LTA4H
Biosynthesis of E-series 18(R)-resolvins12855.0×0.001LTA4H
Biosynthesis of E-series 18(S)-resolvins12284.0×0.001LTA4H
Biosynthesis of DHA-derived SPMs11903.3×0.001LTA4H
Biosynthesis of specialized proresolving mediators (SPMs)11903.3×0.001LTA4H
Synthesis of Leukotrienes (LT) and Eoxins (EX)1571.0×0.003LTA4H
Arachidonate metabolism1571.0×0.003LTA4H
Fatty acid metabolism1131.3×0.011LTA4H
Metabolism of lipids131.6×0.042LTA4H
Innate Immune System125.5×0.048LTA4H
Neutrophil degranulation123.1×0.050LTA4H
Immune System113.0×0.082LTA4H
Metabolism111.6×0.086LTA4H

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 termCohort genesFoldFDRSample cohort genes
type I pneumocyte differentiation1766.0×0.009LTA4H
leukotriene biosynthetic process1648.1×0.009LTA4H
peptide catabolic process1526.6×0.009LTA4H
response to zinc ion1312.1×0.011LTA4H
response to peptide hormone1195.9×0.014LTA4H
wound healing1113.9×0.020ELK3
lipid metabolic process145.8×0.043LTA4H
angiogenesis131.2×0.056ELK3
proteolysis117.1×0.090LTA4H
cell differentiation114.6×0.095ELK3
negative regulation of transcription by RNA polymerase II18.9×0.140ELK3
signal transduction18.0×0.140ELK3
positive regulation of transcription by RNA polymerase II17.4×0.140ELK3
regulation of transcription by RNA polymerase II15.8×0.164ELK3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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
LTA4HCAPTOPRIL

Top cohort targets by molecule count

SymbolMoleculesMax phase
LTA4H84
ELK300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
CAPTOPRIL4LTA4H
ZILEUTON4LTA4H
VORINOSTAT4LTA4H
RESVERATROL3LTA4H
TOSEDOSTAT2LTA4H
TESMILIFENE2LTA4H
UBENIMEX2LTA4H
ACEBILUSTAT2LTA4H

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
LTA4H159Binding:154, Functional:3, ADMET:2
ELK32Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
LTA4H3.3.2.6, 3.4.11.6leukotriene-A4 hydrolase, aminopeptidase B

Cohort genes with high screening signal

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

SymbolChEMBL assays
LTA4H159

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

8 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.

CompoundMax phaseCohort target (bioactivity)
CAPTOPRIL4LTA4H
ZILEUTON4LTA4H
VORINOSTAT4LTA4H
RESVERATROL3LTA4H
TOSEDOSTAT2LTA4H
TESMILIFENE2LTA4H
UBENIMEX2LTA4H
ACEBILUSTAT2LTA4H

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1LTA4H
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1ELK3

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
ELK32—

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
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Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptuberonufeatureumlsuniprot