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Atlas / Disease / Cystic fibrosis associated meconium ileus

Cystic fibrosis associated meconium ileus

disease
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Also known as cystic fibrosis associated meconium ileum

Summary

Cystic fibrosis associated meconium ileus (MONDO:0005413) is a disease with 6 cohort genes (21 GWAS associations across 4 studies).

At a glance

  • Cohort genes: 6
  • GWAS associations: 21

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namecystic fibrosis associated meconium ileus
Mondo IDMONDO:0005413
EFOEFO:0004608
UMLSC0546982
MedGen639765
Is cancer (heuristic)no

Also known as: cystic fibrosis associated meconium ileum

Data availability: 21 GWAS associations (4 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › intestinal obstruction › ileus › meconium ileus › cystic fibrosis associated meconium ileus

Related subtypes (1): intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency

Genetics & variants

GWAS landscape

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

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs37887662e-16RNU6-154P - SLC6A14T1.44
rs75491733e-11SLC26A9C1.37
rs619481084e-10ATP12AT1.55
rs20361001e-08SLC26A9?0.32
rs40774681e-07SLC26A9 - RAB7B?0.29
rs60958291e-07CEBPB - PELATON?0.29
rs17998862e-07TRBJ2-7 - TRBC2T1.33
rs28699632e-07CEBPB - PELATON?0.28
rs1398169843e-07TARS1 - TOMM40P3AAAAAAAAT1.35
rs37573773e-07TRBV29-1 - PRSS1T1.29
rs116998023e-07CEBPB - PELATON?0.28
rs20947165e-07CEBPB - PELATONA1.3

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST001468Sun L20123,7630Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis.
GCST007367Gong J20191,1155,655Genetic association and transcriptome integration identify contributing genes and tissues at cystic fibrosis modifier loci.
GCST90104458Aksit MA20229153,574Pleiotropic modifiers of age-related diabetes and neonatal intestinal obstruction in cystic fibrosis.
GCST90104459Aksit MA20228173,211Pleiotropic modifiers of age-related diabetes and neonatal intestinal obstruction in cystic fibrosis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory1
Tier 4: intronic/intergenic11

MAF distribution

BucketVariants
common (>=0.05)12
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intergenic_variant7
intron_variant4
regulatory_region_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs3788766X116435671G>A0.39intergenic_variantRNU6-154P - SLC6A142e-16Tier 4: intronic/intergenic
rs75491731205937769C>A,G,T0.39intron_variantSLC26A93e-11Tier 4: intronic/intergenic
rs619481081324708681C>T0.11intron_variantATP12A4e-10Tier 4: intronic/intergenic
rs20361001205938744C>G0.05intron_variantSLC26A91e-08Tier 4: intronic/intergenic
rs40774681205945629A>G0.05intergenic_variantSLC26A9 - RAB7B1e-07Tier 4: intronic/intergenic
rs60958292050214170A>C,T0.05intron_variantCEBPB - PELATON1e-07Tier 4: intronic/intergenic
rs17998867142800839T>C0.45intergenic_variantTRBJ2-7 - TRBC22e-07Tier 4: intronic/intergenic
rs28699632050218524T>A,C,G0.05intergenic_variantCEBPB - PELATON2e-07Tier 4: intronic/intergenic
rs139816984533470898AAAAAAAAT>A,AAAAAAAATAAAAAAAT0.05regulatory_region_variantTARS1 - TOMM40P33e-07Tier 3: regulatory
rs37573777142747687T>C,G0.39intergenic_variantTRBV29-1 - PRSS13e-07Tier 4: intronic/intergenic
rs116998022050215598C>T0.05intergenic_variantCEBPB - PELATON3e-07Tier 4: intronic/intergenic
rs20947162050218794A>C0.05intergenic_variantCEBPB - PELATON5e-07Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

GeneHGNCEvidence routes
SLC6A14SLC6A14GWAS, Orphanet
SLC26A9SLC26A9GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SLC6A14Orphanet:586Cystic fibrosis
TARS1Orphanet:33364Trichothiodystrophy
SLC26A9Orphanet:586Cystic fibrosis
PRSS1Orphanet:676Autosomal dominant hereditary chronic pancreatitis

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only6

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SLC6A14HGNC:11047ENSG00000268104Q9UN76Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)gwas
TARS1HGNC:11572ENSG00000113407P26639Threonine–tRNA ligase 1, cytoplasmicgwas
ATP12AHGNC:13816ENSG00000075673P54707Potassium-transporting ATPase alpha chain 2gwas
SLC26A9HGNC:14469ENSG00000174502Q7LBE3Solute carrier family 26 member 9gwas
CEBPBHGNC:1834ENSG00000172216P17676CCAAT/enhancer-binding protein betagwas
PRSS1HGNC:9475ENSG00000204983P07477Serine protease 1gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SLC6A14Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+)Amino acid transporter that plays an important role in the absorption of amino acids in the intestinal tract.
TARS1Threonine–tRNA ligase 1, cytoplasmicCatalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr).
ATP12APotassium-transporting ATPase alpha chain 2The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells.
SLC26A9Solute carrier family 26 member 9Ion transporter that can act both as an ion channel and anion exchanger.
CEBPBCCAAT/enhancer-binding protein betaImportant transcription factor regulating the expression of genes involved in immune and inflammatory responses.
PRSS1Serine protease 1Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33

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
Protease16.1×0.612
Enzyme (other)12.0×0.719
Transcription factor11.4×0.719
Other/Unknown30.9×0.758

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SLC6A14Other/UnknownnoNa/ntran_symport, SNS_sf
TARS1Enzyme (other)yes6.1.1.3aa-tRNA-synt_IIb, Thr-tRNA-ligase_IIa, TGS
ATP12ATranscription factorno7.2.2.19P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
SLC26A9Other/UnknownnoSLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom
CEBPBOther/UnknownnobZIP, C/EBP_chordates, C/EBP
PRSS1ProteaseyesTrypsin_dom, Peptidase_S1A, Peptidase_S1_PA

Expression context

Cohort genes with no expression data: 0.

6 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)6
unknown0

Top tissues across cohort

TissueCohort genes
nasal cavity epithelium2
nasal cavity mucosa1
palpebral conjunctiva1
adrenal tissue1
sural nerve1
tongue squamous epithelium1
olfactory segment of nasal mucosa1
trachea1
cardiac muscle of right atrium1
left ventricle myocardium1
parotid gland1
lower lobe of lung1
pericardium1
periodontal ligament1
body of pancreas1
islet of Langerhans1
pancreas1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SLC6A14146broadmarkerpalpebral conjunctiva, nasal cavity epithelium, nasal cavity mucosa
TARS1296ubiquitousmarkersural nerve, adrenal tissue, tongue squamous epithelium
ATP12A92tissue_specificmarkertrachea, nasal cavity epithelium, olfactory segment of nasal mucosa
SLC26A9151tissue_specificmarkerparotid gland, left ventricle myocardium, cardiac muscle of right atrium
CEBPB297ubiquitousmarkerlower lobe of lung, pericardium, periodontal ligament
PRSS1127tissue_specificmarkerbody of pancreas, pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CEBPB6,344
ATP12A3,743
TARS12,811
PRSS11,363
SLC26A91,212
SLC6A141,008

Intra-cohort edges

ABSources
SLC26A9SLC6A14string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CEBPBP1767616
PRSS1P0747712
TARS1P266395
SLC26A9Q7LBE31

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SLC6A14Q9UN7689.48
ATP12AP5470785.32

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 42. Enrichment computed across 6 evidence-associated genes (6 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 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Variant SLC6A14 may confer susceptibility towards obesity11903.3×0.016SLC6A14
R-HSA-425393243.3×0.016SLC6A14, SLC26A9
Transport of small molecules312.6×0.016SLC6A14, ATP12A, SLC26A9
Inorganic anion exchange by SLC26 transporters1211.5×0.037SLC26A9
Uptake of dietary cobalamins into enterocytes1190.3×0.037PRSS1
SLC-mediated transmembrane transport219.7×0.037SLC6A14, SLC26A9
PERK regulates gene expression1135.9×0.044CEBPB
Response of EIF2AK1 (HRI) to heme deficiency1119.0×0.044CEBPB
Cytosolic tRNA aminoacylation173.2×0.049TARS1
ATF4 activates genes in response to endoplasmic reticulum stress168.0×0.049CEBPB
SLC-mediated transport of neurotransmitters168.0×0.049SLC6A14
Unfolded Protein Response (UPR)159.5×0.049CEBPB
Nuclear events stimulated by ALK signaling in cancer154.4×0.049CEBPB
Activation of Matrix Metalloproteinases151.4×0.049PRSS1
Amino acid transport across the plasma membrane150.1×0.049SLC6A14
Developmental Lineage of Pancreatic Acinar Cells150.1×0.049PRSS1
tRNA Aminoacylation147.6×0.049TARS1
Signaling by ALK in cancer145.3×0.049CEBPB
Transcriptional Regulation by VENTX144.3×0.049CEBPB
Ion transport by P-type ATPases134.6×0.058ATP12A
SLC transporter disorders134.0×0.058SLC6A14
R-HSA-425366130.2×0.062SLC6A14
Cellular response to starvation127.6×0.065CEBPB
Adipogenesis126.1×0.066CEBPB
Signaling by ALK fusions and activated point mutants125.0×0.066CEBPB
Disorders of transmembrane transporters123.2×0.067SLC6A14
Cellular Senescence122.9×0.067CEBPB
Transcriptional regulation of white adipocyte differentiation121.6×0.068CEBPB
Transcriptional regulation of granulopoiesis120.9×0.068CEBPB
Response of EIF2AK4 (GCN2) to amino acid deficiency118.5×0.074CEBPB

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
beta-alanine transport11404.3×0.010SLC6A14
regulation of odontoblast differentiation11404.3×0.010CEBPB
granuloma formation1936.2×0.010CEBPB
threonyl-tRNA aminoacylation1936.2×0.010TARS1
T-helper 1 cell activation1936.2×0.010CEBPB
(R)-carnitine transmembrane transport1936.2×0.010SLC6A14
regulation of dendritic cell differentiation1936.2×0.010CEBPB
myeloid cell development1702.2×0.011CEBPB
positive regulation of sodium-dependent phosphate transport1702.2×0.011CEBPB
positive regulation of biomineral tissue development1468.1×0.014CEBPB
alanine transport1401.2×0.014SLC6A14
glycine import across plasma membrane1401.2×0.014SLC6A14
hepatocyte proliferation1351.1×0.015CEBPB
regulation of interleukin-6 production1280.9×0.016CEBPB
mammary gland epithelial cell proliferation1255.3×0.016CEBPB
regulation of osteoclast differentiation1255.3×0.016CEBPB
monoatomic anion transport1234.1×0.016SLC26A9
regulation of pH1234.1×0.016ATP12A
mammary gland epithelial cell differentiation1200.6×0.017CEBPB
sulfate transmembrane transport1200.6×0.017SLC26A9
sodium ion export across plasma membrane1175.5×0.017ATP12A
amino acid import across plasma membrane1175.5×0.017SLC6A14
intracellular potassium ion homeostasis1165.2×0.018ATP12A
embryonic placenta development1127.7×0.021CEBPB
intracellular sodium ion homeostasis1127.7×0.021ATP12A
amino acid transmembrane transport1122.1×0.021SLC6A14
integrated stress response signaling1117.0×0.021CEBPB
digestion1104.0×0.023PRSS1
positive regulation of interleukin-4 production193.6×0.025CEBPB
liver regeneration185.1×0.026CEBPB

Therapeutics

Drug target analysis

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

Druggability breadth: 5 of 6 evidence-associated genes (83%) 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
PRSS1ARGATROBAN

Top cohort targets by molecule count

SymbolMoleculesMax phase
PRSS1174
ATP12A12
SLC6A1400
TARS100
SLC26A900
CEBPB00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
ARGATROBAN4PRSS1
MELAGATRAN4PRSS1
SULFAGUANIDINE4PRSS1
BEROTRALSTAT4PRSS1
NAFAMOSTAT3PRSS1
OTAMIXABAN3PRSS1
CAMOSTAT3PRSS1
CAMOSTAT MESILATE3PRSS1
RUTIN3PRSS1
MILVEXIAN3PRSS1
DABIGATRAN3PRSS1
QUERCETIN3PRSS1
SILIBININ3PRSS1
ISTAROXIME2ATP12A
EFEGATRAN2PRSS1
SEPIMOSTAT2PRSS1
BAICALEIN2PRSS1
AZD-81651PRSS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
PRSS1674Binding:616, ADMET:51, Functional:7
TARS153Binding:53
ATP12A14Binding:13, Functional:1
SLC6A147Binding:6, ADMET:1
SLC26A94Binding:3, Functional:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
TARS16.1.1.3threonine-tRNA ligase
ATP12A7.2.2.19H+/K+-exchanging ATPase

Cohort genes with high screening signal

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

SymbolChEMBL assays
PRSS1674

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

18 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.

CompoundMax phaseCohort target (bioactivity)
ARGATROBAN4PRSS1
MELAGATRAN4PRSS1
SULFAGUANIDINE4PRSS1
BEROTRALSTAT4PRSS1
NAFAMOSTAT3PRSS1
OTAMIXABAN3PRSS1
CAMOSTAT3PRSS1
CAMOSTAT MESILATE3PRSS1
RUTIN3PRSS1
MILVEXIAN3PRSS1
DABIGATRAN3PRSS1
QUERCETIN3PRSS1
SILIBININ3PRSS1
ISTAROXIME2ATP12A
EFEGATRAN2PRSS1
SEPIMOSTAT2PRSS1
BAICALEIN2PRSS1
AZD-81651PRSS1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1PRSS1
BPhased (≥1) drug, not yet approved1ATP12A
CDruggable family + PDB, no drug1TARS1
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug3SLC6A14, SLC26A9, CEBPB

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SLC6A147—
TARS153—
SLC26A94—
CEBPB0—

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
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Sources 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot