NM_024996.5(GFM1):c.521A>G (p.Asn174Ser) AND Combined oxidative phosphorylation deficiency 1

Clinical significance:Pathogenic (Last evaluated: Nov 11, 2004)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_024996.5(GFM1):c.521A>G (p.Asn174Ser)]

NM_024996.5(GFM1):c.521A>G (p.Asn174Ser)

GFM1:G elongation factor mitochondrial 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_024996.5(GFM1):c.521A>G (p.Asn174Ser)
  • NC_000003.12:g.158646896A>G
  • NG_008441.1:g.7369A>G
  • NM_024996.5:c.521A>G
  • NP_079272.4:p.Asn174Ser
  • NC_000003.11:g.158364685A>G
  • Q96RP9:p.Asn174Ser
Protein change:
N174S; ASN174SER
UniProtKB: Q96RP9#VAR_021512; OMIM: 606639.0001; dbSNP: rs119470018
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_024996.5:c.521A>G - missense variant - [Sequence Ontology: SO:0001583]


Combined oxidative phosphorylation deficiency 1 (COXPD1)
MedGen: C1836797; OMIM: 609060

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000024549OMIMno assertion criteria providedPathogenic
(Nov 11, 2004)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency.

Coenen MJ, Antonicka H, Ugalde C, Sasarman F, Rossi R, Heister JG, Newbold RF, Trijbels FJ, van den Heuvel LP, Shoubridge EA, Smeitink JA.

N Engl J Med. 2004 Nov 11;351(20):2080-6.

PubMed [citation]

Details of each submission

From OMIM, SCV000024549.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In a brother and sister, born of first-cousin Lebanese parents, who died at an early age from progressive hepatoencephalopathy due to combined oxidative phosphorylation deficiency (COXPD1; 609060), Coenen et al. (2004) identified a 521A-G transition in the EFG1 gene, resulting in an asn174-to-ser (N174S) substitution of a conserved residue of the GTP-binding domain. The female sib showed intrauterine growth retardation and mild microcephaly. From day 10 of life, profound metabolic acidosis was evident, and liver dysfunction, progressing to full liver failure by day 12 and death on day 27, developed. Postmortem examination showed cholestasis and extensive necrosis of the liver. The brain showed hypoplasia of corpus callosum and symmetrical cystic lesions in the white matter in the area of the basal ganglia. The heart was normal, and histologic examination of skeletal muscle showed normal mitochondrial morphology and no ragged-red fibers. The activities of the oxidative phosphorylation complexes in fibroblasts were 40%, 69%, and 18% of the lowest control value with complex I, complex III, and complex IV, respectively. The male sib was born at 41 weeks' gestation. Lactic acidosis was found. Ultrasonography of the brain showed generalized atrophy and a small corpus callosum. He had extremely delayed growth and development, as well as increased muscle tone in the arms. Liver failure developed at week 7, leading to death at 5 months of age. As in the sister, the heart was normal. The activities of complex I and complex IV in fibroblasts were 13% and 31% of the lowest control value, respectively. Analysis of mtDNA by Southern blotting showed no rearrangements or reduction in mtDNA levels.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2019

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