SURF1

Chr 9AR

SURF1 cytochrome c oxidase assembly factor

Also known as: CMT4K, MC4DN1, SHY1

NCBI Gene: 6834 ENSG00000148290 UniProt: Q15526 OMIM: 185620

The SURF1 protein localizes to the inner mitochondrial membrane and is involved in the biogenesis of cytochrome c oxidase (complex IV). Mutations cause autosomal recessive mitochondrial complex IV deficiency leading to Leigh syndrome and Charcot-Marie-Tooth disease type 4K through loss of function. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern where biallelic mutations are required for disease.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein localized to the inner mitochondrial membrane and thought to be involved in the biogenesis of the cytochrome c oxidase complex. The protein is a member of the SURF1 family, which includes the related yeast protein SHY1 and rickettsial protein RP733. The gene is located in the surfeit gene cluster, a group of very tightly linked genes that do not share sequence similarity, where it shares a bidirectional promoter with SURF2 on the opposite strand. Defects in this gene are a cause of Leigh syndrome, a severe neurological disorder that is commonly associated with systemic cytochrome c oxidase deficiency. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 4KMIM #616684

Mitochondrial complex IV deficiency, nuclear type 1MIM #220110

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.72

LOEUF

LOF

Mechanism· G2P

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GeneReview available — SURF1