Pyloric stenosis, infantile hypertrophic, 1

Summary

Pyloric stenosis, infantile hypertrophic, 1 (MONDO:0008355) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pyloric stenosis, infantile hypertrophic, 1
Mondo ID	MONDO:0008355
OMIM	179010
UMLS	C1867403
MedGen	357978
Is cancer (heuristic)	no

Also known as: IHPS1 · pyloric stenosis, infantile hypertrophic 1, multifactorial · pyloric stenosis, infantile hypertrophic, 1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › stomach disorder › pyloric stenosis › hypertrophic pyloric stenosis › inherited hypertrophic pyloric stenosis › pyloric stenosis, infantile hypertrophic, 1

Related subtypes (5): pyloric stenosis, infantile hypertrophic, 4, pyloric stenosis, infantile hypertrophic, 2, pyloric stenosis, infantile hypertrophic, 3, pyloric stenosis, infantile hypertrophic, 5, intellectual disability-hypotonia-brachycephaly-pyloric stenosis-cryptorchidism syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
14012	NC_000012.12:g.117439680C>T	NOS1	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NANOS1	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
NOS1	Orphanet:930	Idiopathic achalasia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NANOS1	HGNC:23044	ENSG00000188613	Q8WY41	Nanos homolog 1	clinvar
NOS1	HGNC:7872	ENSG00000089250	P29475	Nitric oxide synthase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NANOS1	Nanos homolog 1	May act as a translational repressor which regulates translation of specific mRNAs by forming a complex with PUM2 that associates with the 3’-UTR of mRNA targets.
NOS1	Nitric oxide synthase 1	Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 0 · Druggable fraction: 0.0

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
Scaffold/PPI	1	8.6×	0.225
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NANOS1	Transcription factor	no		Nanos/Xcar2, Znf_nanos-typ, Nanos_sf
NOS1	Scaffold/PPI	no	1.14.13.39	Flavdoxin-like, OxRdtase_FAD/NAD-bd, PDZ

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skeletal muscle tissue of biceps brachii	2
oocyte	1
secondary oocyte	1
biceps brachii	1
body of tongue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NANOS1	199	ubiquitous	yes	secondary oocyte, oocyte, skeletal muscle tissue of biceps brachii
NOS1	167	broad	marker	body of tongue, biceps brachii, skeletal muscle tissue of biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOS1	2,835
NANOS1	1,112

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NOS1	P29475	121
NANOS1	Q8WY41	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Nitric oxide stimulates guanylate cyclase	1	815.7×	0.004	NOS1
ROS and RNS production in phagocytes	1	335.9×	0.004	NOS1
Ion homeostasis	1	203.9×	0.005	NOS1

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 term	Cohort genes	Fold	FDR	Sample cohort genes
synaptic signaling by nitric oxide	1	8426.0×	0.003	NOS1
positive regulation of sodium ion transmembrane transport	1	8426.0×	0.003	NOS1
negative regulation of serotonin uptake	1	2808.7×	0.003	NOS1
positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential	1	2808.7×	0.003	NOS1
regulation of postsynaptic membrane potential	1	2106.5×	0.003	NOS1
cerebellar neuron development	1	2106.5×	0.003	NANOS1
negative regulation of calcium ion transport into cytosol	1	1685.2×	0.003	NOS1
positive regulation of the force of heart contraction	1	1685.2×	0.003	NOS1
L-arginine catabolic process	1	1404.3×	0.003	NOS1
positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	1404.3×	0.003	NOS1
negative regulation of potassium ion transport	1	936.2×	0.004	NOS1
negative regulation of calcium ion transport	1	842.6×	0.004	NOS1
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel	1	842.6×	0.004	NOS1
obsolete nitric oxide mediated signal transduction	1	648.1×	0.004	NOS1
regulation of cardiac muscle contraction by calcium ion signaling	1	648.1×	0.004	NOS1
multicellular organismal response to stress	1	648.1×	0.004	NOS1
regulation of sodium ion transport	1	468.1×	0.005	NOS1
epithelial cell migration	1	468.1×	0.005	NANOS1
regulation of cardiac muscle contraction	1	443.5×	0.005	NOS1
striated muscle contraction	1	421.3×	0.005	NOS1
nitric oxide biosynthetic process	1	351.1×	0.006	NOS1
mRNA destabilization	1	337.0×	0.006	NANOS1
post-transcriptional regulation of gene expression	1	324.1×	0.006	NANOS1
negative regulation of blood pressure	1	324.1×	0.006	NOS1
myoblast fusion	1	300.9×	0.006	NOS1
tissue homeostasis	1	280.9×	0.006	NANOS1
xenobiotic catabolic process	1	280.9×	0.006	NOS1
response to hormone	1	216.1×	0.007	NOS1
response to heat	1	210.7×	0.007	NOS1
regulation of neurogenesis	1	200.6×	0.007	NOS1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
NOS1	SAPROPTERIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NOS1	10	4
NANOS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
SAPROPTERIN	4	NOS1
CHLORZOXAZONE	4	NOS1
TILARGININE	3	NOS1
GW-274150	2	NOS1
KD7040	2	NOS1
PIMAGEDINE	2	NOS1
AMINOTHIAZOLE	2	NOS1
PRAXADINE	2	NOS1
L-NAME	2	NOS1
NITROARGININE	1	NOS1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
NOS1	238	Binding:234, Functional:2, Unclassified:1, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
NOS1	1.14.13.39	nitric-oxide synthase (NADPH)

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NOS1	238

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).

Chemical tractability of cohort targets

10 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)
SAPROPTERIN	4	NOS1
CHLORZOXAZONE	4	NOS1
TILARGININE	3	NOS1
GW-274150	2	NOS1
KD7040	2	NOS1
PIMAGEDINE	2	NOS1
AMINOTHIAZOLE	2	NOS1
PRAXADINE	2	NOS1
L-NAME	2	NOS1
NITROARGININE	1	NOS1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NOS1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	NANOS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NANOS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.