ATPAF2

Chr 17AR

ATP synthase mitochondrial F1 complex assembly factor 2

Also known as: ATP12, ATP12p, LP3663, MC5DN1

NCBI Gene: 91647 ENSG00000171953 UniProt: Q8N5M1 OMIM: 608918

This protein functions as an assembly factor for the F1 component of mitochondrial ATP synthase, binding specifically to the F1 alpha subunit to prevent formation of nonproductive complexes during enzyme assembly. Mutations cause mitochondrial complex V (ATP synthase) deficiency with autosomal recessive inheritance. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with recessive disease requiring biallelic mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.441 OMIM phenotype

Clinical Summary— ATPAF2

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Gene-Disease Validity (ClinGen)

mitochondrial disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 150 VUS of 263 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.44LOEUF

pLI 0.000

Z-score 0.29

OE 0.92 (0.61–1.44)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.85 (0.74–0.98)

142 obs / 167.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.61–1.44)

0≤0.351.4

Missense OE?0.85 (0.74–0.98)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 14 / 15.2Missense obs/exp: 142 / 167.1Syn Z: 0.60

ClinVar Variant Classifications

263 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic3

VUS150

Likely Benign72

Benign18

Conflicting13

Likely Pathogenic

150

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	3	0	0	0	3
VUS	7	118	22	3	150
Likely Benign	0	6	36	30	72
Benign	0	1	16	1	18
Conflicting	—				13
Total	10	125	74	34	256

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

View in ClinVar →

116 pathogenic / likely-pathogenic (of 123) ClinVar copy-number / structural variants overlap ATPAF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →