SURF1

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

Basic information

Region (hg38): 9:133351758-133356676

Links

ENSG00000148290

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

Phenotypes

GenCC

Source: genCC

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
mitochondrial complex IV deficiency, nuclear type 1 (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 (633 variants)
not_provided (112 variants)
Mitochondrial_complex_IV_deficiency,_nuclear_type_1 (86 variants)
Inborn_genetic_diseases (55 variants)
Charcot-Marie-Tooth_disease_type_4K (51 variants)
not_specified (50 variants)
SURF1-related_disorder (14 variants)
See_cases (4 variants)
Abnormal_pyramidal_sign (2 variants)
Cerebellar_ataxia (2 variants)
Mitochondrial_disease (2 variants)
Dysarthria (2 variants)
Muscle_weakness (2 variants)
Leigh_syndrome_due_to_mitochondrial_complex_IV_deficiency (1 variants)
Cardioencephalomyopathy,_fatal_infantile,_due_to_cytochrome_c_oxidase_deficiency_2 (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. These statistics are base on transcript: NM_000003172.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		3 clinvar	168 clinvar		172
missense	8 clinvar	23 clinvar	175 clinvar	9 clinvar		215
nonsense	14 clinvar	7 clinvar				21
start loss	3	2				5
frameshift	47 clinvar	34 clinvar	1 clinvar			82
splice donor/acceptor (+/-2bp)	16 clinvar	13 clinvar				29
Total	89	79	179	177	0

Highest pathogenic variant AF is 0.000580917

Loading clinvar variants...

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