SURF1

SURF1 cytochrome c oxidase assembly factor

4 disorders 3 causative 1 no genetic record 9q34.2 gene with protein product

HGNC:11474 Monarch NCBI Gene 6834 ENSG00000148290 UniProt Q15526 OMIM 185620

Aliases: SHY1.

Normal function · from ai-gene-review (Q15526, commit 79fe13b38970) · AI-generated, not KB evidence

SURF1 (Surfeit locus protein 1) is a conserved mitochondrial inner membrane protein that functions as an assembly factor for cytochrome c oxidase (Complex IV, CIV). It is a component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, where it participates in early COX1-module assembly, likely facilitating heme a insertion into COX1 or stabilizing COX1 assembly intermediates. SURF1 is NOT a structural subunit of Complex IV itself. The protein contains two transmembrane helices with an intermembrane space-facing domain. Loss-of-function mutations in SURF1 are the most common nuclear gene cause of COX-deficient Leigh syndrome (MC4DN1), and SURF1 mutations also cause demyelinating Charcot-Marie-Tooth disease type 4K (CMT4K). SURF1 is the human ortholog of yeast Shy1. Interacts with the MITRAC component COA3/MITRAC12.

SURF1 functions as an assembly factor for mitochondrial cytochrome c oxidase (Complex IV), acting within the MITRAC complex during early COX1-module assembly. It may facilitate heme a insertion into COX1 or stabilize COX1 assembly intermediates. The precise molecular function is not yet fully characterized; evidence from bacterial models suggests a possible role as a heme insertion chaperone, but this has not been confirmed for the human protein.

directly involved in: mitochondrial respiratory chain complex IV assembly · locations: mitochondrial inner membrane · in complex: mitochondrial respiratory chain complex IV pre-assembly complex

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Charcot-Marie-Tooth Disease Type 4K	causative loss of function	mechanism: SURF1 Loss and Impaired Complex IV Assembly
Leigh Syndrome	causative germline CLINGEN: definitive	mechanism: Complex IV (cytochrome c oxidase) deficiency
SURF1-Related Leigh Syndrome	causative germline	mechanism: SURF1 Loss and Defective Complex IV Assembly
Charcot-Marie-Tooth Disease Type 4	no genetic record	subtype: CMT4K

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Leigh syndrome MONDO:0009723	AR	Definitive 2019-04-08	Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1 not named Leigh Syndrome causative
mitochondrial disease MONDO:0044970	AR	Definitive 2024-10-17	no dismech entry

Mechanism modules · computed from kb/

complex_iv_assembly_deficiency via SURF1-Related Leigh Syndrome

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.