ATP5MK

Chr 10AR

ATP synthase membrane subunit k

Also known as: AGP, ATP5MD, DAPIT, HCVFTP2, MC5DN6, USMG5, bA792D24.4

NCBI Gene: 84833 ENSG00000173915 UniProt: Q96IX5 OMIM: 615204

The ATP5MK protein is a subunit of mitochondrial ATP synthase (Complex V) that is required for dimerization of the enzyme complex and regulation of ATP synthesis from ADP using the proton gradient generated by the respiratory chain. Mutations cause mitochondrial complex V deficiency nuclear type 6, which is inherited in an autosomal recessive pattern. This gene has relatively low constraint against loss-of-function variants (LOEUF 1.69), and a GeneReviews entry is available for additional clinical guidance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be involved in proton motive force-driven ATP synthesis. Located in mitochondrion. Part of proton-transporting ATP synthase complex. Implicated in mitochondrial complex V (ATP synthase) deficiency nuclear type 6. [provided by Alliance of Genome Resources, Jul 2025]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 1.691 OMIM phenotype

Clinical Summary— ATP5MK

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Gene-Disease Validity (ClinGen)

Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 8 VUS of 20 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — ATP5MK

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.048

Z-score 0.63

OE 0.62 (0.25–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.09Z-score

OE missense 0.95 (0.70–1.32)

27 obs / 28.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.25–1.69)

0≤0.351.4

Missense OE?0.95 (0.70–1.32)

0≤0.61.4

Synonymous OE?1.44

0≤1.21.6

LoF obs/exp: 2 / 3.2Missense obs/exp: 27 / 28.3Syn Z: -1.16

This gene — mechanism propensity

0.7131th %ile

GOF

0.6052th %ile

LOF

0.3842th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

20 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic2

VUS8

Likely Benign2

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	0	0	0	2
VUS	0	8	0	0	8
Likely Benign	0	1	0	1	2
Benign	0	0	0	0	0
Conflicting	—				1
Total	3	9	0	1	14

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap ATP5MK — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →