SURF1

SURF1 cytochrome c oxidase assembly factor, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 9:133351757-133356676

Links

ENSG00000148290 ∙ NCBI:6834 ∙ OMIM:185620 ∙ HGNC:11474 ∙ Uniprot:Q15526 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Definitive), mode of inheritance: AR
• Leigh syndrome with cardiomyopathy (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4K (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4K (Strong), mode of inheritance: AR
• Leigh syndrome (Strong), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease type 4K; Mitochondrial complex IV deficiency, nuclear type 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	9837813; 9843204; 10443880; 10556302; 10746561; 11317352; 11804207; 12538779; 14557577; 15214016; 16326995; 17908801; 18583168; 19780766; 21937992; 24027061

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SURF1 gene.

• Leigh syndrome (467 variants)
• not provided (110 variants)
• not specified (38 variants)
• Cytochrome-c oxidase deficiency disease (37 variants)
• Inborn genetic diseases (23 variants)
• Cytochrome-c oxidase deficiency disease;Charcot-Marie-Tooth disease type 4K (8 variants)
• Charcot-Marie-Tooth disease type 4K (8 variants)
• See cases (4 variants)
• Charcot-Marie-Tooth disease type 4K;Cytochrome-c oxidase deficiency disease (3 variants)
• Mitochondrial disease (2 variants)
• Cerebellar ataxia;Abnormal pyramidal sign;Dysarthria;Muscle weakness (1 variants)
• Charcot-Marie-Tooth disease type 4K;Leigh syndrome (1 variants)
• Charcot-Marie-Tooth disease type 4K;Leigh syndrome due to mitochondrial complex IV deficiency (1 variants)
• Abnormal pyramidal sign;Cerebellar ataxia;Dysarthria;Muscle weakness (1 variants)
• Leigh syndrome;Charcot-Marie-Tooth disease type 4K (1 variants)
• SURF1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SURF1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	86		87
missense	6	6	145	2		159
nonsense	12	5				17
start loss	2		3			5
frameshift	39	15	1			55
inframe indel	3	2	6			11
splice donor/acceptor (+/-2bp)	12	7				19
splice region		1	12	23	3	39
non coding			10	93	15	118
Total	74	35	166	181	15

Highest pathogenic variant AF is 0.000355

Variants in SURF1

This is a list of pathogenic ClinVar variants found in the SURF1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-133351795-A-G		Leigh syndrome	Benign (Jun 23, 2018)
9-133351820-G-A		Leigh syndrome	Uncertain significance (Jan 12, 2018)
9-133351866-C-T		Leigh syndrome	Conflicting classifications of pathogenicity (Jun 02, 2020)
9-133351913-T-A		Leigh syndrome	Uncertain significance (Feb 28, 2022)
9-133351913-T-C		Leigh syndrome	Uncertain significance (Apr 29, 2022)
9-133351913-TCACA-T		Mitochondrial complex IV deficiency, nuclear type 1	Likely pathogenic (Jan 31, 2023)
9-133351916-C-G		not specified • Leigh syndrome	Likely benign (Dec 09, 2023)
9-133351918-C-T		Inborn genetic diseases • Leigh syndrome	Uncertain significance (Jan 17, 2022)
9-133351918-CA-C		Leigh syndrome	Uncertain significance (Sep 01, 2022)
9-133351919-A-G		Leigh syndrome	Likely benign (May 13, 2023)
9-133351923-G-C		Leigh syndrome • Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
9-133351925-T-C		Leigh syndrome	Likely benign (Jan 25, 2024)
9-133351925-T-G		Leigh syndrome	Likely benign (Jan 26, 2024)
9-133351927-T-G		not specified • Leigh syndrome	Conflicting classifications of pathogenicity (Jun 14, 2022)
9-133351932-C-A		Leigh syndrome	Uncertain significance (May 26, 2023)
9-133351932-C-T		Leigh syndrome	Uncertain significance (Oct 18, 2022)
9-133351933-G-A		not specified • Leigh syndrome • SURF1-related disorder	Benign/Likely benign (Jan 31, 2024)
9-133351934-T-A		Leigh syndrome	Likely benign (Jun 09, 2023)
9-133351934-T-C		Leigh syndrome	Likely benign (Jan 13, 2020)
9-133351937-G-A		Leigh syndrome • SURF1-related disorder	Likely benign (Dec 14, 2023)
9-133351937-G-C		Leigh syndrome	Uncertain significance (Aug 06, 2022)
9-133351945-TA-T		Leigh syndrome	Pathogenic/Likely pathogenic (Mar 01, 2024)
9-133351945-T-TA		Inborn genetic diseases • Mitochondrial complex IV deficiency, nuclear type 1 • Leigh syndrome	Pathogenic (Jun 05, 2023)
9-133351949-C-T		Leigh syndrome	Pathogenic (Oct 11, 2021)
9-133351951-A-C		Leigh syndrome	Uncertain significance (Aug 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SURF1	protein_coding	protein_coding	ENST00000371974	9	4943

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.59e-13	0.00754	125648	0	100	125748	0.000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.680	177	153	1.15	0.00000886	1907
Missense in Polyphen		55	46.118	1.1926		553
Synonymous	-3.89	95	57.5	1.65	0.00000311	624
Loss of Function	-0.668	18	15.2	1.19	9.21e-7	169

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00124	0.00120
Ashkenazi Jewish	0.00	0.00
East Asian	0.000503	0.000489
Finnish	0.00	0.00
European (Non-Finnish)	0.000438	0.000431
Middle Eastern	0.000503	0.000489
South Asian	0.000395	0.000392
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. {ECO:0000269|PubMed:24027061, ECO:0000269|PubMed:9843204, ECO:0000305|PubMed:26321642}.
• Disease: DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:10647889, ECO:0000269|PubMed:10746561, ECO:0000269|PubMed:14564068, ECO:0000269|PubMed:21937992, ECO:0000269|PubMed:22410471, ECO:0000269|PubMed:22488715, ECO:0000269|PubMed:9843204}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Charcot-Marie-Tooth disease 4K (CMT4K) [MIM:616684]: An autosomal recessive, demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. CMT4K patients manifest upper and lower limbs involvement. Some affected individuals have nystagmus and late-onset cerebellar ataxia. {ECO:0000269|PubMed:24027061}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Electron Transport Chain;Type II diabetes mellitus;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.216

Intolerance Scores

• loftool: 0.384
• rvis_EVS: -0.16
• rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

• pHI: 0.114
• hipred: N
• hipred_score: 0.294
• ghis: 0.411

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.122

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Surf1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: surf1
• Affected structure: secondary motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: oxidative phosphorylation;respiratory chain complex IV assembly;aerobic respiration;electron transport chain;mitochondrial respiratory chain complex IV assembly;oxidation-reduction process;proton transmembrane transport
• Cellular component: mitochondrial respirasome;integral component of membrane
• Molecular function: cytochrome-c oxidase activity;protein binding