CYC1

cytochrome c1, the group of Apoptosome|Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Basic information

Region (hg38): 8:144095039-144097525

Links

ENSG00000179091 ∙ NCBI:1537 ∙ OMIM:123980 ∙ HGNC:2579 ∙ Uniprot:P08574 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex III deficiency nuclear type 6 (Definitive), mode of inheritance: AR
• mitochondrial complex III deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex III deficiency nuclear type 6 (Limited), mode of inheritance: Unknown
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex III deficiency, nuclear, type 6	AR	Biochemical	Individuals may present with episodes of acute metabolic decompensation, including hyperlactatemia, hyperammonemia, ketoacidosis and glucose instability, and awareness may allow rapid treatment, including with IV rehydration (and insulin therapy as required), as well as other biochemical interventions (eg, arginine and sodium benzoate)	Biochemical	23910460

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYC1 gene.

• not_provided (101 variants)
• not_specified (62 variants)
• CYC1-related_disorder (8 variants)
• Mitochondrial_complex_III_deficiency_nuclear_type_6 (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYC1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001916.5. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	28	2	33
missense	2		81	3		86
nonsense						0
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	2	0	86	31	2

Highest pathogenic variant AF is 0.000001368195

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYC1	protein_coding	protein_coding	ENST00000318911	7	2499

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.139	0.858	125717	0	29	125746	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.127	169	174	0.973	0.00000981	2039
Missense in Polyphen		55	63.278	0.86918		735
Synonymous	-2.33	99	73.6	1.35	0.00000425	699
Loss of Function	2.53	4	14.3	0.279	7.91e-7	157

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000363
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000275	0.000231
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000167	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: This is the heme-containing component of the cytochrome b-c1 complex, which accepts electrons from Rieske protein and transfers electrons to cytochrome c in the mitochondrial respiratory chain.
• Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 6 (MC3DN6) [MIM:615453]: An autosomal recessive disorder caused by mitochondrial dysfunction. It is characterized by onset in early childhood of episodic acute lactic acidosis, ketoacidosis, and insulin-responsive hyperglycemia, usually associated with infection. Laboratory studies show decreased activity of mitochondrial complex III. Psychomotor development is normal. {ECO:0000269|PubMed:23910460}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Metabolism of proteins;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Mitochondrial protein import;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.214
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.400
• hipred: Y
• hipred_score: 0.704
• ghis: 0.507

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.869

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyc1

Gene ontology

• Biological process: mitochondrial electron transport, ubiquinol to cytochrome c;response to glucagon;mitochondrial ATP synthesis coupled proton transport
• Cellular component: nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex III;membrane;integral component of membrane
• Molecular function: heme binding;electron transporter, transferring electrons within CoQH2-cytochrome c reductase complex activity;electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity;metal ion binding