Pyloric stenosis

disease
On this page

Also known as gastric outlet obstructionGOOpyloric stenosis (disease)

Summary

Pyloric stenosis (MONDO:0001561) is a disease with 29 cohort genes and 27 clinical trials. Top therapeutic interventions include acetaminophen.

At a glance

  • Cohort genes: 29
  • ClinVar variants: 34
  • Clinical trials: 27

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namepyloric stenosis
Mondo IDMONDO:0001561
EFOEFO:0009626
MeSHD011707, D017219
DOIDDOID:12639, DOID:3122
NCITC34966
SNOMED CT367403001
UMLSC0034194
MedGen18780
MedDRA10062499
Is cancer (heuristic)no

Also known as: gastric outlet obstruction · GOO · pyloric stenosis · pyloric stenosis (disease)

Data availability: 34 ClinVar variants · 1 HPO phenotype.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorderstomach disorderpyloric stenosis

Related subtypes (18): gastric ulcer, functional gastric disease, Dieulafoy lesion, pylorospasm, cascade stomach, gastric dilatation, stomach diverticulosis, gastritis, gastroesophageal reflux disease, hiatus hernia, stomach polyp, non-hypoproteinemic hypertrophic gastropathy, gastric neoplasm, angiodysplasia of stomach, achlorhydria, gastric intestinal metaplasia, gastric duplication, pyloric duplication

Subtypes (1): hypertrophic pyloric stenosis

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

34 retrieved; paginated sample, class counts are floors:

29 uncertain significance, 2 likely pathogenic, 1 likely benign, 1 pathogenic, 1 benign/likely benign

ClinVarVariant (HGVS)GeneClassificationReview
638688NM_005909.5(MAP1B):c.5368C>T (p.Arg1790Ter)MAP1BPathogeniccriteria provided, single submitter
523522NM_017780.4(CHD7):c.2867C>A (p.Ser956Ter)CHD7Likely pathogeniccriteria provided, single submitter
691346NM_017633.3(TENT5A):c.65C>G (p.Pro22Arg)TENT5ALikely pathogenicno assertion criteria provided
26786446;XY;t(2;13)(p25.2;q31.3)dnUncertain significancecriteria provided, single submitter
691340NM_001387011.1(AMBRA1):c.431C>T (p.Ala144Val)AMBRA1Uncertain significanceno assertion criteria provided
691412NM_152296.5(ATP1A3):c.1978C>A (p.Leu660Ile)ATP1A3Uncertain significanceno assertion criteria provided
691414NM_001130021.3(ATP6V0A1):c.1340G>A (p.Arg447Gln)ATP6V0A1Uncertain significanceno assertion criteria provided
691415NM_207322.3(C2CD4A):c.284A>C (p.His95Pro)C2CD4AUncertain significanceno assertion criteria provided
691416NM_000719.7(CACNA1C):c.5761C>T (p.Pro1921Ser)CACNA1CUncertain significanceno assertion criteria provided
691419NM_001256.6(CDC27):c.4A>G (p.Thr2Ala)CDC27Uncertain significanceno assertion criteria provided
691425NM_198390.3(CMIP):c.1478C>G (p.Thr493Ser)CMIPUncertain significanceno assertion criteria provided
691431NM_001382508.1(DROSHA):c.323G>A (p.Arg108Lys)DROSHAUncertain significanceno assertion criteria provided
691432NM_001389.5(DSCAM):c.4979T>A (p.Ile1660Asn)DSCAMUncertain significanceno assertion criteria provided
691344NM_001374736.1(DST):c.11993C>G (p.Ser3998Ter)DSTUncertain significanceno assertion criteria provided
691349NM_198904.4(GABRG2):c.155A>G (p.Asn52Ser)GABRG2Uncertain significanceno assertion criteria provided
691355NM_001007237.3(IGSF3):c.1841G>T (p.Arg614Leu)IGSF3Uncertain significanceno assertion criteria provided
691357NM_000208.4(INSR):c.3364G>A (p.Ala1122Thr)INSRUncertain significanceno assertion criteria provided
691359NM_002211.4(ITGB1):c.2252G>A (p.Trp751Ter)ITGB1Uncertain significanceno assertion criteria provided
691364NM_002235.5(KCNA6):c.233A>G (p.Asp78Gly)KCNA6Uncertain significanceno assertion criteria provided
691447NM_012216.4(MID2):c.1757T>C (p.Ile586Thr)LOC101928335Uncertain significanceno assertion criteria provided
691452NM_017617.5(NOTCH1):c.6032T>C (p.Leu2011Pro)LOC126860794Uncertain significanceno assertion criteria provided
691450NM_153006.3(NAGS):c.1378C>G (p.Leu460Val)NAGSUncertain significanceno assertion criteria provided
691367NM_001104631.2(PDE4D):c.1339T>C (p.Tyr447His)PDE4DUncertain significancecriteria provided, single submitter
691369NM_006622.4(PLK2):c.1049C>T (p.Thr350Ile)PLK2Uncertain significanceno assertion criteria provided
691374NM_001034853.2(RPGR):c.780G>T (p.Glu260Asp)RPGRUncertain significanceno assertion criteria provided
691381NM_006747.4(SIPA1):c.367A>G (p.Ser123Gly)SIPA1Uncertain significanceno assertion criteria provided
691386NM_001288718.2(STAT5A):c.1279G>A (p.Ala427Thr)STAT5AUncertain significanceno assertion criteria provided
691387NM_001395460.1(TENM2):c.4165C>A (p.Leu1389Met)TENM2Uncertain significanceno assertion criteria provided
691345NM_017633.3(TENT5A):c.64C>G (p.Pro22Ala)TENT5AUncertain significanceno assertion criteria provided
691347NM_017633.3(TENT5A):c.26C>G (p.Ala9Gly)TENT5AUncertain significanceno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
RPGROrphanet:1872Cone rod dystrophy
RPGROrphanet:244Primary ciliary dyskinesia
RPGROrphanet:247522Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGROrphanet:49382Achromatopsia
RPGROrphanet:791Retinitis pigmentosa
DSTOrphanet:314381Hereditary sensory and autonomic neuropathy type 6
DSTOrphanet:412181Epidermolysis bullosa simplex due to BP230 deficiency
TCF4Orphanet:171Primary sclerosing cholangitis
TCF4Orphanet:178469Autosomal dominant non-syndromic intellectual disability
TCF4Orphanet:2896Pitt-Hopkins syndrome
TCF4Orphanet:98974Fuchs endothelial corneal dystrophy
TERTOrphanet:146Differentiated thyroid carcinoma
TERTOrphanet:1501Adrenocortical carcinoma
TERTOrphanet:1775Dyskeratosis congenita
TERTOrphanet:2032Idiopathic pulmonary fibrosis
TERTOrphanet:2495Meningioma
TERTOrphanet:3322Hoyeraal-Hreidarsson syndrome
TERTOrphanet:457246Clear cell sarcoma of kidney
TERTOrphanet:618Familial melanoma
TERTOrphanet:88Idiopathic aplastic anemia
CACNA1COrphanet:101016Romano-Ward syndrome
CACNA1COrphanet:130Brugada syndrome
CACNA1COrphanet:528084Non-specific syndromic intellectual disability
CACNA1COrphanet:595098Timothy syndrome type 1
CACNA1COrphanet:595105Timothy syndrome type 2
CACNA1COrphanet:595109Atypical Timothy syndrome
NAGSOrphanet:927Hyperammonemia due to N-acetylglutamate synthase deficiency
TENT5AOrphanet:216812Osteogenesis imperfecta type 3
CHD7Orphanet:138CHARGE syndrome
CHD7Orphanet:39041Omenn syndrome
CHD7Orphanet:432Normosmic congenital hypogonadotropic hypogonadism
CHD7Orphanet:478Kallmann syndrome
GABRG2Orphanet:1945Self-limited epilepsy with centrotemporal spikes
GABRG2Orphanet:33069Dravet syndrome
GABRG2Orphanet:36387Genetic epilepsy with febrile seizure plus
GABRG2Orphanet:442835Non-specific early-onset epileptic encephalopathy
GABRG2Orphanet:64280Childhood absence epilepsy
IGSF3Orphanet:451612Familial congenital nasolacrimal duct obstruction
INSROrphanet:2297Insulin-resistance syndrome type A
INSROrphanet:263458Hyperinsulinism due to INSR deficiency
INSROrphanet:508Donohue syndrome
INSROrphanet:769Rabson-Mendenhall syndrome
KCNN3Orphanet:3473Zimmermann-Laband syndrome
MAP1BOrphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
MAP1BOrphanet:98892Periventricular nodular heterotopia
ATP1A3Orphanet:1171Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
ATP1A3Orphanet:2131Alternating hemiplegia of childhood
ATP1A3Orphanet:442835Non-specific early-onset epileptic encephalopathy
ATP1A3Orphanet:71517Rapid-onset dystonia-parkinsonism
ATP6V0A1Orphanet:528084Non-specific syndromic intellectual disability

Cohort genes → proteins

29 cohort genes, 29 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence29

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RPGRHGNC:10295ENSG00000156313Q92834X-linked retinitis pigmentosa GTPase regulatorclinvar
SIPA1HGNC:10885ENSG00000213445Q96FS4Signal-induced proliferation-associated protein 1clinvar
DSTHGNC:1090ENSG00000151914Q03001Dystoninclinvar
STAT5AHGNC:11366ENSG00000126561P42229Signal transducer and activator of transcription 5Aclinvar
TCF4HGNC:11634ENSG00000196628P15884Transcription factor 4clinvar
TERTHGNC:11730ENSG00000164362O14746Telomerase reverse transcriptaseclinvar
CACNA1CHGNC:1390ENSG00000151067Q13936Voltage-dependent L-type calcium channel subunit alpha-1Cclinvar
WDR13HGNC:14352ENSG00000101940Q9H1Z4WD repeat-containing protein 13clinvar
CDC27HGNC:1728ENSG00000004897P30260Cell division cycle protein 27 homologclinvar
DROSHAHGNC:17904ENSG00000113360Q9NRR4Ribonuclease 3clinvar
NAGSHGNC:17996ENSG00000161653Q8N159N-acetylglutamate synthase, mitochondrialclinvar
TENT5AHGNC:18345ENSG00000112773Q96IP4Terminal nucleotidyltransferase 5Aclinvar
PLK2HGNC:19699ENSG00000145632Q9NYY3Serine/threonine-protein kinase PLK2clinvar
CHD7HGNC:20626ENSG00000171316Q9P2D1ATP-dependent chromatin remodeler CHD7clinvar
CMIPHGNC:24319ENSG00000153815Q8IY22C-Maf-inducing proteinclinvar
AMBRA1HGNC:25990ENSG00000110497Q9C0C7Activating molecule in BECN1-regulated autophagy protein 1clinvar
TENM2HGNC:29943ENSG00000145934Q9NT68Teneurin-2clinvar
DSCAMHGNC:3039ENSG00000171587O60469Cell adhesion molecule DSCAMclinvar
C2CD4AHGNC:33627ENSG00000198535Q8NCU7C2 calcium-dependent domain-containing protein 4Aclinvar
GABRG2HGNC:4087ENSG00000113327P18507Gamma-aminobutyric acid receptor subunit gamma-2clinvar
IGSF3HGNC:5950ENSG00000143061O75054Immunoglobulin superfamily member 3clinvar
INSRHGNC:6091ENSG00000171105P06213Insulin receptorclinvar
ITGB1HGNC:6153ENSG00000150093P05556Integrin beta-1clinvar
KCNA6HGNC:6225ENSG00000151079P17658Potassium voltage-gated channel subfamily A member 6clinvar
KCNN3HGNC:6292ENSG00000143603Q9UGI6Small conductance calcium-activated potassium channel protein 3clinvar
MAP1BHGNC:6836ENSG00000131711P46821Microtubule-associated protein 1Bclinvar
ATP1A3HGNC:801ENSG00000105409P13637Sodium/potassium-transporting ATPase subunit alpha-3clinvar
ATP6V0A1HGNC:865ENSG00000033627Q93050V-type proton ATPase 116 kDa subunit a 1clinvar
PDE4DHGNC:8783ENSG00000113448Q084993’,5’-cyclic-AMP phosphodiesterase 4Dclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RPGRX-linked retinitis pigmentosa GTPase regulatorActs as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
SIPA1Signal-induced proliferation-associated protein 1GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state.
DSTDystoninCytoskeletal linker protein.
STAT5ASignal transducer and activator of transcription 5ACarries out a dual function: signal transduction and activation of transcription.
TCF4Transcription factor 4Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
TERTTelomerase reverse transcriptaseTelomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
CACNA1CVoltage-dependent L-type calcium channel subunit alpha-1CPore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CDC27Cell division cycle protein 27 homologComponent of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
DROSHARibonuclease 3Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis.
NAGSN-acetylglutamate synthase, mitochondrialPlays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPS1) activity.
TENT5ATerminal nucleotidyltransferase 5ACytoplasmic non-canonical poly(A) RNA polymerase that catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group and participates in the cytoplasmic polyadenylation.
PLK2Serine/threonine-protein kinase PLK2Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.
CHD7ATP-dependent chromatin remodeler CHD7ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
CMIPC-Maf-inducing proteinPlays a role in T-cell signaling pathway.
AMBRA1Activating molecule in BECN1-regulated autophagy protein 1Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy.
TENM2Teneurin-2Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
DSCAMCell adhesion molecule DSCAMCell adhesion molecule that plays a role in neuronal self-avoidance.
C2CD4AC2 calcium-dependent domain-containing protein 4AMay be involved in inflammatory process.
GABRG2Gamma-aminobutyric acid receptor subunit gamma-2Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
INSRInsulin receptorReceptor tyrosine kinase which mediates the pleiotropic actions of insulin.
ITGB1Integrin beta-1Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen.
KCNA6Potassium voltage-gated channel subfamily A member 6Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
KCNN3Small conductance calcium-activated potassium channel protein 3Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calci…
MAP1BMicrotubule-associated protein 1BFacilitates tyrosination of alpha-tubulin in neuronal microtubules.
ATP1A3Sodium/potassium-transporting ATPase subunit alpha-3This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.
ATP6V0A1V-type proton ATPase 116 kDa subunit a 1Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that transports protons across cellular membranes.
PDE4D3’,5’-cyclic-AMP phosphodiesterase 4DHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Protein-family classification

Druggable: 11 · Difficult: 7 · Unknown: 11 · Druggable fraction: 0.38

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
Ion channel311.5×0.015
Kinase32.9×0.199
Scaffold/PPI42.4×0.199
Antibody/Immunoglobulin22.0×0.458
Enzyme (other)31.2×0.616
Transcription factor30.8×0.816
Other/Unknown110.7×0.983

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RPGROther/UnknownnoReg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
SIPA1Scaffold/PPInoRap/Ran_GAP_dom, PDZ, Rap/Ran-GAP_sf
DSTScaffold/PPInoPlectin_repeat, SH3_domain, Actinin_actin-bd_CS
STAT5ATranscription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
TCF4Transcription factorno7.6.2.3bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TERTOther/UnknownnoRT_dom, Telomerase_RT, Telomerase_RBD
CACNA1CIon channelyesVDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
WDR13Scaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
CDC27Other/UnknownnoTPR-like_helical_dom_sf, TPR_rpt
DROSHAEnzyme (other)yes3.1.26.3RNase_III_dom, RNase_III, dsRBD_dom
NAGSKinaseyes2.3.1.1GNAT_dom, Asp/Glu/Uridylate_kinase, Vertebrate-like_GNAT_dom
TENT5AEnzyme (other)yes2.7.7.19TET5
PLK2Kinaseyes2.7.11.21Prot_kinase_dom, POLO_box_dom, Ser/Thr_kinase_AS
CHD7Other/UnknownnoSNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
CMIPOther/UnknownnoLRR_dom_sf, CMIP, PH_CMIP
AMBRA1Scaffold/PPInoWD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TENM2Other/UnknownnoEGF, EGF-like_Ca-bd_dom, YD
DSCAMAntibody/ImmunoglobulinyesIg_sub2, Ig_sub, FN3_dom
C2CD4AOther/UnknownnoC2_dom, C2_domain_sf, C2_Ca-dependent_4
GABRG2Other/UnknownnoGABRG-1/4, GABBAg2_rcpt, GABAA/Glycine_rcpt
IGSF3Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, Ig-like_dom
INSRKinaseyes2.7.10.1Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ITGB1Other/UnknownnoIntegrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell
KCNA6Ion channelyesBTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
KCNN3Ion channelyesCaM-bd_dom, K_chnl_dom, K_chnl_Ca-activ_SK
MAP1BOther/UnknownnoMAP1B_neuraxin, MAP1, MAP1B/S_N
ATP1A3Transcription factornoP_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
ATP6V0A1Other/UnknownnoV-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
PDE4DEnzyme (other)yes3.1.4.53PDEase_catalytic_dom, PDEase, PDEase_CS

Expression context

Cohort genes with no expression data: 0.

27 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)29
unknown0

Top tissues across cohort

TissueCohort genes
cortical plate5
apex of heart3
secondary oocyte3
right uterine tube2
granulocyte2
spleen2
medial globus pallidus2
endothelial cell2
pericardium2
buccal mucosa cell2
oocyte2
ileal mucosa2
middle temporal gyrus2
lateral nuclear group of thalamus2
superior frontal gyrus2
visceral pleura2
substantia nigra pars reticulata2
bronchial epithelial cell1
sperm1
lower esophagus mucosa1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RPGR281ubiquitousmarkersperm, bronchial epithelial cell, right uterine tube
SIPA1191ubiquitousmarkergranulocyte, spleen, lower esophagus mucosa
DST305ubiquitousmarkercorpus callosum, calcaneal tendon, medial globus pallidus
STAT5A190ubiquitousmarkergranulocyte, monocyte, leukocyte
TCF4292ubiquitousmarkerendothelial cell, skin of hip, pericardium
TERT105broadyesstromal cell of endometrium, type B pancreatic cell, olfactory bulb
CACNA1C134broadmarkerapex of heart, right coronary artery, muscle layer of sigmoid colon
WDR13292ubiquitousmarkerbody of pancreas, apex of heart, right uterine tube
CDC27293ubiquitousmarkersecondary oocyte, buccal mucosa cell, oocyte
DROSHA283ubiquitousmarkerendothelial cell, ventricular zone, germinal epithelium of ovary
NAGS160broadmarkerileal mucosa, right lobe of liver, jejunal mucosa
TENT5A270ubiquitousmarkerparotid gland, tibia, pericardium
PLK2289ubiquitousmarkerspleen, apex of heart, cortical plate
CHD7269ubiquitousmarkersecondary oocyte, cerebellar vermis, sural nerve
CMIP247ubiquitousmarkerkidney epithelium, pancreatic ductal cell, ileal mucosa
AMBRA1279ubiquitousmarkeroocyte, secondary oocyte, cervix squamous epithelium
TENM2207broadmarkerleft ventricle myocardium, cardiac muscle of right atrium, middle temporal gyrus
DSCAM83broadmarkerendometrium epithelium, cortical plate, lateral nuclear group of thalamus
C2CD4A126broadmarkerislet of Langerhans, epithelial cell of pancreas, cartilage tissue
GABRG2174tissue_specificmarkermiddle temporal gyrus, Brodmann (1909) area 23, superior frontal gyrus
IGSF3265ubiquitousmarkercortical plate, tongue squamous epithelium, gingival epithelium
INSR296ubiquitousmarkerbuccal mucosa cell, palpebral conjunctiva, visceral pleura
ITGB1303ubiquitousmarkervisceral pleura, seminal vesicle, pleura
KCNA6123tissue_specificyescortical plate, male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex
KCNN3227broadmarkerlateral globus pallidus, substantia nigra pars reticulata, medial globus pallidus
MAP1B299ubiquitousmarkerlateral nuclear group of thalamus, substantia nigra pars compacta, substantia nigra pars reticulata
ATP1A3129broadmarkersuperior frontal gyrus, primary visual cortex, cortical plate
ATP6V0A1287ubiquitousmarkerright frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere
PDE4D283ubiquitousmarkergluteal muscle, biceps brachii, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
DROSHA6,846
TERT5,717
ITGB15,325
CDC275,006
CHD74,819
INSR4,446
AMBRA14,380
STAT5A4,153
ATP1A33,876
MAP1B3,724

Intra-cohort edges

ABSources
CACNA1CCMIPintact
DSCAMDSTbiogrid_interaction
DSCAMWDR13intact
INSRTENT5Aintact

Structural data

PDB: 21 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PDE4DQ08499122
INSRP0621388
GABRG2P1850775
CACNA1CQ1393633
CDC27P3026025
TERTO1474623
ITGB1P0555622
DROSHAQ9NRR412
PLK2Q9NYY37
ATP6V0A1Q930507
STAT5AP422295
TCF4P158845
ATP1A3P136375
RPGRQ928343
CHD7Q9P2D13
DSTQ030012
TENT5AQ96IP42
AMBRA1Q9C0C72
TENM2Q9NT682
NAGSQ8N1591
DSCAMO604691

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
IGSF3O7505481.81
WDR13Q9H1Z479.85
CMIPQ8IY2279.52
KCNA6P1765875.42
SIPA1Q96FS472.20
KCNN3Q9UGI668.54
C2CD4AQ8NCU759.36
MAP1BP4682146.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 221. Enrichment computed across 29 evidence-associated genes (22 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 22 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
NAGS variants cause NAGS deficiency1519.1×0.126NAGS
Localization of the PINCH-ILK-PARVIN complex to focal adhesions1129.8×0.126ITGB1
DSCAM interactions1103.8×0.126DSCAM
IRS activation1103.8×0.126INSR
MET interacts with TNS proteins1103.8×0.126ITGB1
Erythropoietin activates STAT5174.2×0.126STAT5A
STAT5 Activation174.2×0.126STAT5A
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence174.2×0.126TERT
CHL1 interactions157.7×0.126ITGB1
Interleukin-9 signaling157.7×0.126STAT5A
Ca2+ activated K+ channels151.9×0.126KCNN3
FGFR1 mutant receptor activation151.9×0.126STAT5A
Interleukin-21 signaling151.9×0.126STAT5A
CD163 mediating an anti-inflammatory response151.9×0.126PLK2
Signaling by KIT in disease151.9×0.126STAT5A
FLT3 signaling in disease151.9×0.126STAT5A
STAT5 activation downstream of FLT3 ITD mutants151.9×0.126STAT5A
Signaling by Leptin147.2×0.126STAT5A
Type I hemidesmosome assembly147.2×0.126DST
Signal attenuation147.2×0.126INSR
Signaling by Erythropoietin147.2×0.126STAT5A
Interleukin-2 signaling143.3×0.126STAT5A
Urea cycle139.9×0.126NAGS
Signaling by Insulin receptor139.9×0.126INSR
Kidney development137.1×0.126ITGB1
Insulin receptor recycling234.6×0.126INSR, ATP6V0A1
Prolactin receptor signaling134.6×0.126STAT5A
Phase 2 - plateau phase134.6×0.126CACNA1C
Interleukin-15 signaling134.6×0.126STAT5A
Signaling by FLT3 ITD and TKD mutants134.6×0.126STAT5A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 29 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
RNA-templated transcription1581.1×0.042TERT
right ventricular compact myocardium morphogenesis1581.1×0.042CHD7
developmental maturation1581.1×0.042MAP1B
DNA strand elongation1581.1×0.042TERT
myoblast fate specification1581.1×0.042ITGB1
induction of synaptic plasticity by chemical substance1581.1×0.042MAP1B
siRNA transcription1581.1×0.042TERT
positive regulation of transdifferentiation1581.1×0.042TERT
RNA-templated DNA biosynthetic process1290.6×0.042TERT
regulation of collagen catabolic process1290.6×0.042ITGB1
positive regulation of hair cycle1290.6×0.042TERT
positive regulation of meiotic cell cycle1290.6×0.042INSR
positive regulation of glutamate uptake involved in transmission of nerve impulse1290.6×0.042ITGB1
post-embryonic retina morphogenesis in camera-type eye1290.6×0.042DSCAM
positive regulation of mast cell differentiation1290.6×0.042STAT5A
cardiac cell fate specification1290.6×0.042ITGB1
establishment of monopolar cell polarity1290.6×0.042MAP1B
negative regulation of relaxation of cardiac muscle1290.6×0.042PDE4D
positive regulation of free ubiquitin chain polymerization1290.6×0.042AMBRA1
regulation of female gonad development1290.6×0.042INSR
regulation of vascular permeability involved in acute inflammatory response1193.7×0.042C2CD4A
L-arginine biosynthetic process1193.7×0.042NAGS
cranial nerve development1193.7×0.042CHD7
olfactory nerve development1193.7×0.042CHD7
negative regulation of intracellular transport1193.7×0.042MAP1B
negative regulation of mast cell apoptotic process1193.7×0.042STAT5A
cellular response to water deprivation1193.7×0.042SIPA1
development of animal secondary female sexual characteristics1193.7×0.042STAT5A
development of animal secondary male sexual characteristics1193.7×0.042STAT5A
regulation of growth hormone secretion1193.7×0.042CHD7

Therapeutics

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 10 · Phased (≥1): 11 · Undrugged: 18

Druggability breadth: 13 of 29 evidence-associated genes (45%) 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
STAT5AMOMELOTINIB
TERTBERBERINE
CACNA1CREMIFENTANIL
PLK2FEDRATINIB
GABRG2ENZALUTAMIDE
INSRFEDRATINIB
KCNN3DEQUALINIUM CHLORIDE
ATP1A3OMEPRAZOLE
PDE4DINAMRINONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
PDE4D2694
CACNA1C854
GABRG2554
INSR364
PLK2124
TERT104
ATP1A354
STAT5A44
ITGB143
KCNN324

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
MOMELOTINIB4STAT5A
BERBERINE4TERT
DOXORUBICIN4TERT
REMIFENTANIL4CACNA1C
BEPRIDIL4CACNA1C
CLOTRIMAZOLE4CACNA1C
PROPIVERINE4CACNA1C
DIBUCAINE4CACNA1C
IMIPRAMINE4CACNA1C
DULOXETINE4CACNA1C
QUINIDINE4CACNA1C
ESTRADIOL4CACNA1C
TOLTERODINE4CACNA1C
PIMOZIDE4CACNA1C
NIMODIPINE4CACNA1C, PDE4D
NICARDIPINE4CACNA1C
AMLODIPINE4CACNA1C
VARDENAFIL4CACNA1C, PDE4D
CLEMASTINE4CACNA1C
ISRADIPINE4CACNA1C, PDE4D
TERFENADINE4CACNA1C
NISOLDIPINE4CACNA1C, PDE4D
SOLIFENACIN4CACNA1C
PINAVERIUM4CACNA1C
SILDENAFIL4CACNA1C, PDE4D
NIFEDIPINE4CACNA1C
XANOMELINE4CACNA1C
DILTIAZEM4CACNA1C
PRENYLAMINE4CACNA1C
OLICERIDINE4CACNA1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

SymbolAssaysType breakdown
GABRG21,155Binding:940, Functional:201, ADMET:10, Toxicity:4
INSR954Binding:900, Functional:49, ADMET:4, Toxicity:1
PDE4D863Binding:805, Functional:33, ADMET:23, Toxicity:2
CACNA1C575Binding:319, Functional:211, Toxicity:26, ADMET:19
ITGB1409Binding:376, Functional:32, ADMET:1
TERT391Binding:389, Functional:2
PLK2270Binding:268, ADMET:1, Functional:1
STAT5A199Binding:199
KCNN351Binding:51
ATP1A345Binding:45
TCF431Binding:31
KCNA629Binding:24, Functional:3, Toxicity:1, ADMET:1
MAP1B10Binding:6, Functional:4

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
TCF47.6.2.3ABC-type glutathione-S-conjugate transporter
DROSHA3.1.26.3ribonuclease III
NAGS2.3.1.1amino-acid N-acetyltransferase
TENT5A2.7.7.19polynucleotide adenylyltransferase
PLK22.7.11.21polo kinase
INSR2.7.10.1receptor protein-tyrosine kinase
PDE4D3.1.4.533’,5’-cyclic-AMP phosphodiesterase

Cohort genes with high screening signal

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

SymbolChEMBL assays
STAT5A199
TERT391
CACNA1C575
PLK2270
GABRG21,155
INSR954
ITGB1409
PDE4D863

Pharmacogenomics

Cohort genes with a PharmGKB record: 29; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
MOMELOTINIB4STAT5A
BERBERINE4TERT
DOXORUBICIN4TERT
REMIFENTANIL4CACNA1C
BEPRIDIL4CACNA1C
CLOTRIMAZOLE4CACNA1C
PROPIVERINE4CACNA1C
DIBUCAINE4CACNA1C
IMIPRAMINE4CACNA1C
DULOXETINE4CACNA1C
QUINIDINE4CACNA1C
ESTRADIOL4CACNA1C
TOLTERODINE4CACNA1C
PIMOZIDE4CACNA1C
NIMODIPINE4CACNA1C, PDE4D
NICARDIPINE4CACNA1C
AMLODIPINE4CACNA1C
VARDENAFIL4CACNA1C, PDE4D
CLEMASTINE4CACNA1C
ISRADIPINE4CACNA1C, PDE4D
TERFENADINE4CACNA1C
NISOLDIPINE4CACNA1C, PDE4D
SOLIFENACIN4CACNA1C
PINAVERIUM4CACNA1C
SILDENAFIL4CACNA1C, PDE4D
NIFEDIPINE4CACNA1C
XANOMELINE4CACNA1C
DILTIAZEM4CACNA1C
PRENYLAMINE4CACNA1C
OLICERIDINE4CACNA1C

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)9STAT5A, TERT, CACNA1C, PLK2, GABRG2, INSR, KCNN3, ATP1A3, PDE4D
BPhased (≥1) drug, not yet approved2TCF4, ITGB1
CDruggable family + PDB, no drug4DROSHA, NAGS, TENT5A, DSCAM
DDruggable family + AlphaFold only, no drug2IGSF3, KCNA6
EDifficult family or no structure, no drug12RPGR, SIPA1, DST, WDR13, CDC27, CHD7, CMIP, AMBRA1, TENM2, C2CD4A (+2 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
RPGR0
SIPA10
DST0
WDR130
CDC270
DROSHA0
NAGS0
TENT5A0
CHD70
CMIP0
AMBRA10
TENM20
DSCAM0
C2CD4A0
IGSF30
KCNA629
MAP1B10
ATP6V0A10

Clinical trials & evidence

Clinical trials

Clinical trials: 27.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified24
PHASE41
PHASE2/PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00556283PHASE4COMPLETEDRCT: STARR vs Biofeedback
NCT03223480PHASE2/PHASE3COMPLETEDEUS - Guided Balloon-occluded Gastrojejunostomy Bypass
NCT01139853EARLY_PHASE1COMPLETEDPost-Operative Impact of Nasogastric Tubes on Rates of Emesis in Infants Diagnosed With Pyloric Stenosis
NCT04813055Not specifiedRECRUITINGProspective Registry Of Therapeutic EndoscopiC ulTrasound
NCT05548114Not specifiedACTIVE_NOT_RECRUITINGRandomized Trial of EUS-guided Gastrojejunostomy and Surgical Gastrojejunostomy in Gastric Outlet Obstruction
NCT05640947Not specifiedRECRUITINGEndoscopic Ultrasound-guided Large Diameter Lumen-apposing Metal Stent Gastro-gastrostomy for Bypass Reversal in Patients With Roux-en-y Gastric Bypass
NCT06071507Not specifiedRECRUITINGManagement of Malignant Gastric Outlet Obstruction Between Surgery and Endoscopy
NCT07161856Not specifiedNOT_YET_RECRUITINGNovel Balloon-Assisted vs Direct Technique in EUS-Guided Gastroenterostomy
NCT07317076Not specifiedRECRUITINGGT Metabolic Magnet System in Adults With Gastrointestinal Disorders
NCT07609511Not specifiedNOT_YET_RECRUITINGMagnet System Gastric Outlet Obstruction Study
NCT00144924Not specifiedTERMINATEDOpen vs Laparoscopic Pyloromyotomy for Pyloric Stenosis
NCT00409734Not specifiedCOMPLETEDFrequency of Formula Change Prior to the Accurate Diagnosis of Pyloric Stenosis
NCT00487552Not specifiedTERMINATEDMagnetic Anastomosis Device Relief of Malignant Gastric Outlet Obstruction
NCT00991614Not specifiedCOMPLETEDEVOLUTION® Duodenal Stent for Duodenal or Gastric Outlet Obstruction Caused by Malignant Neoplasms
NCT01839292Not specifiedCOMPLETEDComVi and D-type Stent in Malignant GOO
NCT02299258Not specifiedCOMPLETEDGastric Outlet Obstructions Tailored Covered Stents for GOO
NCT02359305Not specifiedCOMPLETEDInstitutional Audit of the Use of Intravenous Acetaminophen in Infants Undergoing Pyloromyotomy
NCT02775214Not specifiedTERMINATEDConventional Direct Laryngoscopy Vs. Video Laryngoscopy With The C-MAC For Pyloromyotomy
NCT03259763Not specifiedCOMPLETEDEUS-GE vs ES for Palliation of Gastric Outlet Obstruction
NCT03650842Not specifiedCOMPLETEDChanges in Cerebral Oxygenation During Laparoscopic Pyloromyotomy
NCT03823690Not specifiedCOMPLETEDEPASS Versus Uncovered Duodenal Stent for Unresectable Malignant Gastric Outlet Obstruction.
NCT04660695Not specifiedCOMPLETEDNasobiliary Drain Assisted EUS-guided Gastroenterostomies in Unresectable Malignant Gastric Outlet Obstruction
NCT05041608Not specifiedUNKNOWNEndoscopic Surgery for Gastrointestinal Disorders: A Multicenter Registry Study
NCT05561907Not specifiedUNKNOWNEnteral Anastomosis for the Treatment of Gastric Outlet Obstruction: A Randomized Controlled Study Comparing Endoscopic Versus Surgical Gastrojejunostomy
NCT05605327Not specifiedUNKNOWNEUS-guided Versus Laparoscopic Gastrojejunostomy for Malignant Gastric Outlet Obstruction
NCT05644951Not specifiedCOMPLETEDClinical Trial of EPASS With Hot AXIOS System
NCT06174805Not specifiedSUSPENDEDAXIOS™ Gastroenterostomy for Gastric Outlet Obstruction IDE

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
ACETAMINOPHEN41