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IEMbase 0738: ATPAF2-related mitochondrial ATP synthase assembly factor deficiency

Scope

Field Value
IEMbase ID 738
Nosology 7.5.02.01
Nosology code IEM1151
Gene ATPAF2
External IDs OMIM:604273; ORPHA:254913
Generated mapping CANDIDATE; fuzzy SURF1-Related_Leigh_Syndrome.yaml
Candidate DisMech targets Broad complex V context only; no exact ATPAF2 target identified
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents autosomal recessive ATPAF2-related mitochondrial ATP synthase F1 assembly factor 2 deficiency, also labeled mitochondrial complex V deficiency, nuclear type 1. The phenotype rows are neonatal/infantile and multisystem: urinary 3-methylglutaconic and fumaric acid elevations, CSF, plasma, and urinary lactate elevation, basal ganglia abnormalities, corpus callosum abnormalities, cortical and subcortical atrophy, developmental delay, feeding difficulty, failure to thrive, hepatomegaly, hypertonia, seizures, renal hypoplasia, perinatal death, and multiple dysmorphology prompts including frontal bossing, micrognathia, low-set ears, hypospadias, large mouth, prominent nasal bridge, and rocker-bottom feet.

DisMech phenotype coverage

No exact ATPAF2 target was identified in DisMech.

The generated SURF1-Related_Leigh_Syndrome.yaml candidate is a false positive for this record. SURF1 is a complex IV assembly-factor Leigh syndrome entry, whereas ATPAF2 is a nuclear complex V assembly factor. Both can involve lactate and basal ganglia/Leigh-like neuroimaging, but the gene, respiratory-chain complex, and disease identity differ. NARP_syndrome.yaml, Myopathy_Lactic_Acidosis_and_Sideroblastic_Anemia.yaml, and the prior TMEM70 note provide complex V context only.

Concordance and completeness

Judgement: true ATPAF2 complex V local gap. Reject the SURF1 candidate as exact coverage.

IEMbase is relatively complete for initial phenotype seeding, especially for neonatal lactate and organic-acid abnormalities, neuroimaging, seizures, renal/hepatic involvement, dysmorphology, feeding/FTT, and early lethality. DisMech currently lacks the ATPAF2-specific complex V assembly disease entity.

Curation actions

  • Add ATPAF2-related mitochondrial complex V deficiency, nuclear type 1, to the complex V backlog.
  • Reject SURF1-Related_Leigh_Syndrome.yaml as exact coverage.
  • Preserve neonatal organic-acid, lactate, neuroimaging, renal, hepatic, dysmorphology, seizure, feeding, FTT, and perinatal-death prompts.