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Atlas / Disease / Niemann-Pick disease type C, severe perinatal form

Niemann-Pick disease type C, severe perinatal form

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Summary

Niemann-Pick disease type C, severe perinatal form (MONDO:0016306) is a disease with 2 cohort genes.

At a glance

  • Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameNiemann-Pick disease type C, severe perinatal form
Mondo IDMONDO:0016306
Orphanet216972
UMLSC5680866
MedGen1842349
GARD0020504
Is cancer (heuristic)no

Data availability: 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › lymphoid system disorder › lymphatic system disorder › histiocytosis › non-Langerhans cell histiocytosis › Niemann-Pick disease › Niemann-Pick disease type C › Niemann-Pick disease type C, severe perinatal form

Related subtypes (6): Niemann-Pick disease, type C1, Niemann-Pick disease, type C2, Niemann-Pick disease type C, severe early infantile neurologic onset, Niemann-Pick disease type C, late infantile neurologic onset, Niemann-Pick disease type C, juvenile neurologic onset, Niemann-Pick disease type C, adult neurologic onset

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · 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.

GeneClassificationInheritanceDiseaseRecords
NPC1DefinitiveAutosomal recessiveNiemann-Pick disease, type C110
NPC2DefinitiveAutosomal recessiveNiemann-Pick disease, type C211

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
NPC2Orphanet:216972Niemann-Pick disease type C, severe perinatal form
NPC2Orphanet:216975Niemann-Pick disease type C, severe early infantile neurologic onset
NPC2Orphanet:216978Niemann-Pick disease type C, late infantile neurologic onset
NPC2Orphanet:216981Niemann-Pick disease type C, juvenile neurologic onset
NPC2Orphanet:216986Niemann-Pick disease type C, adult neurologic onset
NPC1Orphanet:216972Niemann-Pick disease type C, severe perinatal form
NPC1Orphanet:216975Niemann-Pick disease type C, severe early infantile neurologic onset
NPC1Orphanet:216978Niemann-Pick disease type C, late infantile neurologic onset
NPC1Orphanet:216981Niemann-Pick disease type C, juvenile neurologic onset
NPC1Orphanet:216986Niemann-Pick disease type C, adult neurologic onset

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence2

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
NPC2HGNC:14537ENSG00000119655P61916NPC intracellular cholesterol transporter 2gencc
NPC1HGNC:7897ENSG00000141458O15118NPC intracellular cholesterol transporter 1gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
NPC2NPC intracellular cholesterol transporter 2Intracellular cholesterol transporter which acts in concert with NPC1 and plays an important role in the egress of cholesterol from the lysosomal compartment.
NPC1NPC intracellular cholesterol transporter 1Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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.

FamilyGenesFoldFDR
Other/Unknown21.8×0.312

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
NPC2Other/UnknownnoML_dom, Ig_E-set, ML_Npc2-like
NPC1Other/UnknownnoSSD, NPC1-like, NPC1_N

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
cauda epididymis1
corpus epididymis1
epididymis1
adrenal tissue1
oocyte1
secondary oocyte1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
NPC2296ubiquitousmarkercorpus epididymis, cauda epididymis, epididymis
NPC1292ubiquitousmarkersecondary oocyte, oocyte, adrenal tissue

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

SymbolInteractor count
NPC12,648
NPC21,706

Intra-cohort edges

ABSources
NPC1NPC2intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
NPC1O1511820
NPC2P619162

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
LDL clearance2543.8×6e-06NPC2, NPC1
Neutrophil degranulation111.5×0.085NPC2

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
cholesterol storage22407.4×5e-06NPC2, NPC1
intracellular cholesterol transport21296.3×1e-05NPC2, NPC1
cholesterol transport2732.7×2e-05NPC2, NPC1
cholesterol efflux2526.6×3e-05NPC2, NPC1
cholesterol metabolic process2195.9×2e-04NPC2, NPC1
cholesterol homeostasis2156.0×2e-04NPC2, NPC1
regulation of isoprenoid metabolic process18426.0×5e-04NPC2
cyclodextrin metabolic process18426.0×5e-04NPC1
gene expression279.9×6e-04NPC2, NPC1
intracellular lipid transport12808.7×0.001NPC1
glycolipid transport12808.7×0.001NPC2
membrane raft organization11685.2×0.002NPC1
intracellular sterol transport11685.2×0.002NPC2
sterol transport11404.3×0.002NPC1
establishment of protein localization to membrane1936.2×0.003NPC1
intestinal cholesterol absorption1702.2×0.003NPC1
programmed cell death1648.1×0.003NPC1
negative regulation of epithelial cell apoptotic process1601.9×0.003NPC1
negative regulation of macroautophagy1561.7×0.003NPC1
cellular response to steroid hormone stimulus1526.6×0.003NPC1
bile acid metabolic process1495.6×0.003NPC1
cellular response to low-density lipoprotein particle stimulus1443.5×0.004NPC1
response to cadmium ion1366.4×0.004NPC1
lysosomal transport1351.1×0.004NPC1
phospholipid transport1351.1×0.004NPC2
adult walking behavior1247.8×0.006NPC1
symbiont entry into host cell1200.6×0.007NPC1
glycoprotein biosynthetic process1168.5×0.008NPC1
negative regulation of TORC1 signaling1162.0×0.008NPC1
macroautophagy1120.4×0.010NPC1

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.

SymbolExample approved molecule
NPC1NABUMETONE

Top cohort targets by molecule count

SymbolMoleculesMax phase
NPC1904
NPC200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
NABUMETONE4NPC1
PHENELZINE4NPC1
AMLEXANOX4NPC1
IDARUBICIN4NPC1
RABEPRAZOLE SODIUM4NPC1
NITAZOXANIDE4NPC1
NICLOSAMIDE4NPC1
NITROXOLINE4NPC1
NICARDIPINE4NPC1
DAUNORUBICIN HYDROCHLORIDE4NPC1
INDOPROFEN4NPC1
CYCLOSPORINE4NPC1
TERFENADINE4NPC1
DIGOXIN4NPC1
PRAZOSIN4NPC1
MAPROTILINE4NPC1
DIGITOXIN4NPC1
HYDRALAZINE4NPC1
EBASTINE4NPC1
DEQUALINIUM4NPC1
DOXORUBICIN HYDROCHLORIDE4NPC1
VINBLASTINE SULFATE4NPC1
FLUOXETINE4NPC1
DITHIAZANINE IODIDE4NPC1
TRIFLUOPERAZINE4NPC1
PACLITAXEL4NPC1
NORTRIPTYLINE4NPC1
MIBEFRADIL4NPC1
FLUSPIRILENE4NPC1
KETOROLAC4NPC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
NPC118Binding:13, Functional:5

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

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)
NABUMETONE4NPC1
PHENELZINE4NPC1
AMLEXANOX4NPC1
IDARUBICIN4NPC1
RABEPRAZOLE SODIUM4NPC1
NITAZOXANIDE4NPC1
NICLOSAMIDE4NPC1
NITROXOLINE4NPC1
NICARDIPINE4NPC1
DAUNORUBICIN HYDROCHLORIDE4NPC1
INDOPROFEN4NPC1
CYCLOSPORINE4NPC1
TERFENADINE4NPC1
DIGOXIN4NPC1
PRAZOSIN4NPC1
MAPROTILINE4NPC1
DIGITOXIN4NPC1
HYDRALAZINE4NPC1
EBASTINE4NPC1
DEQUALINIUM4NPC1
DOXORUBICIN HYDROCHLORIDE4NPC1
VINBLASTINE SULFATE4NPC1
FLUOXETINE4NPC1
DITHIAZANINE IODIDE4NPC1
TRIFLUOPERAZINE4NPC1
PACLITAXEL4NPC1
NORTRIPTYLINE4NPC1
MIBEFRADIL4NPC1
FLUSPIRILENE4NPC1
KETOROLAC4NPC1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1NPC1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1NPC2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
NPC20NPC1

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
v1.1.4
BioBTree
v2.0.2

Sources 67

This page pulls from 67 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot