SURF1 Gene

HGNC Family	Mitochondrial respiratory chain complex assembly factors
Name	surfeit 1
Description	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]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSURF1 is a mitochondrial assembly factor essential for the biogenesis of cytochrome c oxidase (COX, complex IV). Analyses of patient fibroblasts carrying SURF1 mutations have revealed that defects in SURF1 function lead to an accumulation of specific COX assembly intermediates, suggesting that SURF1 normally facilitates the incorporation of COX subunits. In particular, studies indicate that in SURF1‐deficient cells, the association of subunit MTCO2 with an assembly intermediate comprising MTCO1, COX4, and COX5A is stalled, highlighting SURF1’s role in coordinating the sequential integration of nucleus‐ and mitochondrially encoded subunits during COX assembly."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther mechanistic insights come from studies using yeast models and investigations into mitochondrial copper homeostasis. Experiments with the yeast homolog (Shy1p) of human SURF1 demonstrate that SURF1 is involved in the proper insertion of heme a₃ into the active site of COX, a critical step for forming the catalytic heme a₃–Cu_B center required for efficient electron transfer. In parallel, research exploring the interplay between mitochondrial copper-binding proteins and SURF1 underscored a functional relationship among COX assembly factors, where loss of SURF1 disrupts the stability and maturation of COX subunits, thereby compromising complex IV function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, studies in mammalian models reveal that the dependence on SURF1 for the proper assembly and integration of COX into respiratory supercomplexes is more pronounced in humans than in mice, suggesting both species‐ and tissue-specific roles for SURF1 in mitochondrial function. This differential requirement may have important implications for understanding the variable clinical phenotypes observed in patients with SURF1 mutations, such as Leigh syndrome, where impaired COX assembly leads to severe bioenergetic deficits."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Siôn L Williams, Isabelle Valnot, Pierre Rustin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M309232200"}], "href": "https://doi.org/10.1074/jbc.M309232200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14607829"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14607829"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lukas Stiburek, Katerina Vesela, Hana Hansikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20050807"}], "href": "https://doi.org/10.1042/BJ20050807"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16083427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16083427"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Maciej J Zamek-Gliszczynski, Ken-ichi Nezasa, Xianbin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of the role of multidrug resistance-associated protein (Mrp) 3 and Mrp4 in hepatic basolateral excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in Abcc3-/- and Abcc4-/- mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.106.110106"}], "href": "https://doi.org/10.1124/jpet.106.110106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16988054"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16988054"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lukas Stiburek, Katerina Vesela, Hana Hansikova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of function of Sco1 and its interaction with cytochrome c oxidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00564.2008"}], "href": "https://doi.org/10.1152/ajpcell.00564.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19295170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19295170"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Megan Bestwick, Mi-Young Jeong, Oleh Khalimonchuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00228-10"}], "href": "https://doi.org/10.1128/MCB.00228-10"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20624914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20624914"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nikola Kovářová, Petr Pecina, Hana Nůsková, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2016.01.007"}], "href": "https://doi.org/10.1016/j.bbadis.2016.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26804654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26804654"}]}]}]}
Synonyms	CMT4K
Proteins	SURF1_HUMAN
NCBI Gene ID	6834
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

SURF1 has 6,367 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for SURF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

SURF1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SURF1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of SURF1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of SURF1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of SURF1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of SURF1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of SURF1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SURF1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of SURF1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of SURF1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of SURF1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of SURF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with SURF1 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SURF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of SURF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of SURF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with SURF1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with SURF1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of SURF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing SURF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing SURF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with SURF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with SURF1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with SURF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with SURF1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with SURF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of SURF1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by SURF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving SURF1 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving SURF1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with SURF1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with SURF1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with SURF1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with SURF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with SURF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at SURF1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of SURF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of SURF1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing SURF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with SURF1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with SURF1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.