mitochondrial complex V (ATP synthase) deficiency, nuclear type 3

Summary

mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 (MONDO:0013547) is a disease caused by ATP5F1E (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ATP5F1E (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

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 3
Mondo ID	MONDO:0013547
OMIM	614053
DOID	DOID:0060332
UMLS	C3279708
MedGen	481338
GARD	0018666
Is cancer (heuristic)	no

Also known as: ATP5F1E mitochondrial proton-transporting ATP synthase complex deficiency · MC5DN3 · mitochondrial complex V (ATP synthase) deficiency, nuclear type 3 · mitochondrial proton-transporting ATP synthase complex deficiency caused by mutation in ATP5F1E

Data availability: 2 ClinVar variants · 3 GenCC gene-disease records.

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 › mitochondrial respiratory chain complex deficiency › mitochondrial complex V (ATP synthase) deficiency, nuclear type 3

Related subtypes (8): mitochondrial complex V (ATP synthase) deficiency, nuclear type 1, mitochondrial complex V (ATP synthase) deficiency, nuclear type 2, mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B, mitochondrial complex III deficiency, mitochondrial complex V (ATP synthase) deficiency, nuclear type 5, mitochondrial complex IV deficiency, nuclear-type, mitochondrial complex I deficiency, SDHC-related Mitochondrial Disease

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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
30551	NM_006886.4(ATP5F1E):c.35A>G (p.Tyr12Cys)	ATP5F1E	Pathogenic	no assertion criteria provided
3065807	NM_006886.4(ATP5F1E):c.151G>T (p.Glu51Ter)	ATP5F1E	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ATP5F1E	Strong	Autosomal recessive	mitochondrial complex V (ATP synthase) deficiency, nuclear type 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP5F1E	Orphanet:254913	Isolated ATP synthase deficiency

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
ATP5F1E	HGNC:838	ENSG00000124172	P56381	ATP synthase F(1) complex subunit epsilon, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP5F1E	ATP synthase F(1) complex subunit epsilon, mitochondrial	Subunit epsilon, 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…

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)
ATP5F1E	Other/Unknown	no		ATP_synth_F1_esu_mt, ATP_synth_F1_esu_sf_mt

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
cranial nerve II	1
renal medulla	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP5F1E	296	ubiquitous	marker	renal medulla, cranial nerve II, substantia nigra pars reticulata

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP5F1E	1,742

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATP5F1E	P56381	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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×	0.009	ATP5F1E
Cristae formation	1	346.1×	0.009	ATP5F1E
Mitochondrial biogenesis	1	167.9×	0.012	ATP5F1E
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	ATP5F1E
Organelle biogenesis and maintenance	1	66.0×	0.018	ATP5F1E
Metabolism	1	11.6×	0.086	ATP5F1E

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
proton motive force-driven ATP synthesis	1	802.5×	0.002	ATP5F1E
proton motive force-driven mitochondrial ATP synthesis	1	263.3×	0.004	ATP5F1E

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
ATP5F1E	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	ATP5F1E

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)
ATP5F1E	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.