SURF1

Chr 9AR

SURF1 cytochrome c oxidase assembly factor

Also known as: CMT4K, MC4DN1, SHY1

NCBI Gene: 6834ENSG00000148290UniProt: Q15526

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]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 4KMIM #616684
AR
Mitochondrial complex IV deficiency, nuclear type 1MIM #220110
AR
858
ClinVar variants
96
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SURF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
96 Pathogenic / Likely Pathogenic· 109 VUS of 858 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.72LOEUF
pLI 0.000
Z-score -0.67
OE 1.19 (0.82–1.72)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.68Z-score
OE missense 1.15 (1.02–1.31)
177 obs / 153.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.19 (0.82–1.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.02–1.31)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.65
0≤1.21.6
LoF obs/exp: 18 / 15.2Missense obs/exp: 177 / 153.3Syn Z: -3.89

ClinVar Variant Classifications

858 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55
Likely Pathogenic41
VUS109
Likely Benign161
Benign13
Conflicting12
55
Pathogenic
41
Likely Pathogenic
109
VUS
161
Likely Benign
13
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
5
22
1
55
Likely Pathogenic
20
14
7
0
41
VUS
0
92
15
2
109
Likely Benign
0
1
78
82
161
Benign
0
1
12
0
13
Conflicting
—12
Total4711313485391

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SURF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SURF1-related Leigh syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SURFEIT 1; SURF1
MIM #185620 · *

Charcot-Marie-Tooth disease, type 4K

MIM #616684

Molecular basis of disorder known

Autosomal recessive

Mitochondrial complex IV deficiency, nuclear type 1

MIM #220110

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Leigh Syndrome: A Study of 209 Patients at the Beijing Children's Hospital.
Stenton SL et al.·Ann Neurol
2022Cohort
SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype.
Kayani S et al.·Am J Med Genet A
2025
Genetic variants affecting mitochondrial function provide further insights for kidney disease.
Cañadas-Garre M et al.·BMC Genomics
2024
Natural History of SURF1 Deficiency: A Retrospective Chart Review.
Khan TR et al.·Pediatr Neurol
2023Review
Clinical manifestations and pathogenesis of mitochondrial dysfunction in short stature.
Jiang Y et al.·World J Pediatr
2025Review
Hypertrophic olivary degeneration on magnetic resonance imaging in mitochondrial syndromes associated with POLG and SURF1 mutations.
Kinghorn KJ et al.·J Neurol
2013Review
SURF1 knockout cloned pigs: Early onset of a severe lethal phenotype.
Quadalti C et al.·Biochim Biophys Acta Mol Basis Dis
2018
A colorimetric biosensor for ultrasensitive detection of the SURF1 gene based on a dual DNA-induced cascade hybridization reaction.
Yu T et al.·Anal Methods
2021
Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations.
Sonam K et al.·Brain Dev
2014Case report
Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency.
Darin N et al.·Neuropediatrics
2003Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools