mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6

disease

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Also known as MC5DN6

Summary

mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6 (MONDO:0032869) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6
Mondo ID	MONDO:0032869
OMIM	618683
DOID	DOID:0111749
UMLS	C5231461
MedGen	1684729
GARD	0018673
Is cancer (heuristic)	no

Also known as: MC5DN6

Data availability: 5 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 5 (ATP synthase) deficiency, nuclear type 6

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

5 retrieved; paginated sample, class counts are floors:

1 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4294000	NM_001206427.2(ATP5MK):c.87+1G>A	ATP5MK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
694833	NM_001206427.2(ATP5MK):c.87+1G>C	ATP5MK	Pathogenic	no assertion criteria provided
981119	NM_001206427.2(ATP5MK):c.87+2dup	ATP5MK	Likely pathogenic	criteria provided, single submitter
4277760	NM_001206427.2(ATP5MK):c.-9-1G>T	ATP5MK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030054	NM_001206427.2(ATP5MK):c.59A>G (p.Asn20Ser)	ATP5MK	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
ATP5MK	Moderate	Autosomal recessive	mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATP5MK	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
ATP5MK	HGNC:30889	ENSG00000173915	Q96IX5	ATP synthase F(0) complex subunit k, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATP5MK	ATP synthase F(0) complex subunit k, mitochondrial	Subunit k, 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 th…

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)
ATP5MK	Other/Unknown	no		ATPMK

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
heart left ventricle	1
primary visual cortex	1
quadriceps femoris	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATP5MK	138	ubiquitous	marker	quadriceps femoris, heart left ventricle, primary visual cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATP5MK	1,709

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATP5MK	Q96IX5	77.03

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	ATP5MK
Cristae formation	1	346.1×	0.009	ATP5MK
Mitochondrial biogenesis	1	167.9×	0.012	ATP5MK
Aerobic respiration and respiratory electron transport	1	88.5×	0.017	ATP5MK
Organelle biogenesis and maintenance	1	66.0×	0.018	ATP5MK
Metabolism	1	11.6×	0.086	ATP5MK

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
proton motive force-driven ATP synthesis	1	802.5×	0.001	ATP5MK

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
ATP5MK	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
ATP5MK	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	ATP5MK

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)
ATP5MK	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: ATP5MK