Pulmonary hypertension, primary, 5

Summary

Pulmonary hypertension, primary, 5 (MONDO:0009935) is a disease caused by ATP13A3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP13A3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary hypertension, primary, 5
Mondo ID	MONDO:0009935
MeSH	C564862
OMIM	265400
UMLS	C5676877
MedGen	1802382
GARD	0024700
Is cancer (heuristic)	no

Also known as: PPH5 · pulmonary hypertension, primary, 5, autosomal recessive

Data availability: 9 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › heritable pulmonary arterial hypertension › pulmonary hypertension, primary, 5

Related subtypes (6): pulmonary hypertension, primary, 2, pulmonary hypertension, primary, 3, pulmonary hypertension, primary, 4, pulmonary hypertension, primary, 1, pulmonary hypertension, primary, 6, pulmonary hypertension, primary, 7

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

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 likely pathogenic, 2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1195990	NM_001367549.1(ATP13A3):c.2549dup (p.Met850fs)	ATP13A3	Pathogenic	criteria provided, multiple submitters, no conflicts
1195992	NM_001367549.1(ATP13A3):c.3079dup (p.Trp1027fs)	ATP13A3	Pathogenic	criteria provided, single submitter
1195989	NM_001367549.1(ATP13A3):c.2563G>A (p.Val855Met)	ATP13A3	Likely pathogenic	criteria provided, single submitter
1195991	NM_001367549.1(ATP13A3):c.2227C>T (p.Arg743Cys)	ATP13A3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1195993	NM_001367549.1(ATP13A3):c.3685G>T (p.Glu1229Ter)	ATP13A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2352566	NM_001367549.1(ATP13A3):c.2168A>G (p.Gln723Arg)	ATP13A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2431704	NM_001367549.1(ATP13A3):c.2009A>G (p.Asp670Gly)	ATP13A3	Uncertain significance	criteria provided, single submitter
3131395	NM_001367549.1(ATP13A3):c.1126G>A (p.Val376Ile)	ATP13A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
4280111	NM_001367549.1(ATP13A3):c.313_315del (p.Lys105del)	ATP13A3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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.

Gene	Classification	Inheritance	Disease	Records
ATP13A3	Definitive	Semidominant	pulmonary arterial hypertension	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP13A3	Orphanet:275777	Heritable pulmonary arterial hypertension

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATP13A3	HGNC:24113	ENSG00000133657	Q9H7F0	Polyamine-transporting ATPase 13A3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP13A3	Polyamine-transporting ATPase 13A3	ATP-driven pump involved in endocytosis-dependent polyamine transport.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP13A3	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_TPase_V

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
amniotic fluid	1
decidua	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP13A3	291	ubiquitous	marker	decidua, secondary oocyte, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP13A3	1,870

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP13A3	Q9H7F0	77.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
polyamine transmembrane transport	1	4213.0×	5e-04	ATP13A3
intracellular calcium ion homeostasis	1	145.3×	0.007	ATP13A3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP13A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	ATP13A3

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)
ATP13A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.