mitochondrial complex V (ATP synthase) deficiency, nuclear type 7

Summary

mitochondrial complex V (ATP synthase) deficiency, nuclear type 7 (MONDO:0957255) is a disease caused by ATP5PO (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP5PO (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex V (ATP synthase) deficiency, nuclear type 7
Mondo ID	MONDO:0957255
OMIM	620359
DOID	DOID:0070464
UMLS	C5830482
MedGen	1841118
GARD	0026799
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › combined oxidative phosphorylation deficiency › mitochondrial proton-transporting ATP synthase complex deficiency › mitochondrial complex V (ATP synthase) deficiency, nuclear type 7

Related subtypes (7): mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, mitochondrial complex V (ATP synthase) deficiency, nuclear type 3, mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B, combined oxidative phosphorylation deficiency 22, mitochondrial complex 5 (ATP synthase) deficiency, mitochondrial type 1, mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6, mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A

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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1804019	NM_001697.3(ATP5PO):c.329-20A>G	ATP5PO	Pathogenic	criteria provided, single submitter
1804024	NM_001697.3(ATP5PO):c.34C>T (p.Gln12Ter)	ATP5PO	Pathogenic	criteria provided, single submitter
977787	NM_001697.3(ATP5PO):c.87+3A>G	ATP5PO	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
ATP5PO	Strong	Autosomal recessive	mitochondrial complex V (ATP synthase) deficiency, nuclear type 7

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
ATP5PO	HGNC:850	ENSG00000241837	P48047	ATP synthase peripheral stalk subunit OSCP, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP5PO	ATP synthase peripheral stalk subunit OSCP, mitochondrial	Subunit OSCP, of the mitochondrial membrane ATP synthase complex (F(1)F(0) ATP synthase or Complex V) that produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATP5PO	Other/Unknown	no		ATPase_OSCP/dsu, ATPase_OSCP/d_CS, ATP_synth_OSCP/delta_N_sf

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
apex of heart	1
heart left ventricle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP5PO	149	ubiquitous	marker	heart left ventricle, apex of heart, right atrium auricular region

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP5PO	3,811

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP5PO	P48047	9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 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
Formation of ATP by chemiosmotic coupling	1	571.0×	0.012	ATP5PO
Cristae formation	1	346.1×	0.012	ATP5PO
Mitochondrial biogenesis	1	167.9×	0.016	ATP5PO
Mitochondrial protein degradation	1	114.2×	0.018	ATP5PO
Aerobic respiration and respiratory electron transport	1	88.5×	0.018	ATP5PO
Organelle biogenesis and maintenance	1	66.0×	0.020	ATP5PO
Metabolism of proteins	1	12.4×	0.086	ATP5PO
Metabolism	1	11.6×	0.086	ATP5PO

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
ATP biosynthetic process	1	991.3×	0.004	ATP5PO
proton motive force-driven ATP synthesis	1	802.5×	0.004	ATP5PO
cellular response to cytokine stimulus	1	543.6×	0.004	ATP5PO
proton transmembrane transport	1	312.1×	0.004	ATP5PO
cellular response to cAMP	1	290.6×	0.004	ATP5PO
proton motive force-driven mitochondrial ATP synthesis	1	263.3×	0.004	ATP5PO

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATP5PO	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ATP5PO	1	Binding:1

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	ATP5PO

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)
ATP5PO	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.