CYCS

cytochrome c, somatic

Basic information

Region (hg38): 7:25118656-25125260

Links

ENSG00000172115 ∙ NCBI:54205 ∙ OMIM:123970 ∙ HGNC:19986 ∙ Uniprot:P99999 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombocytopenia 4 (Moderate), mode of inheritance: AD
• thrombocytopenia 4 (Strong), mode of inheritance: AD
• autosomal thrombocytopenia with normal platelets (Supportive), mode of inheritance: AD
• thrombocytopenia 4 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia 4	AD	General	Reported clinical findings related to thrombocytopenia were absent or mild; 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	Hematologic	18345000; 22102269; 24326104; 30051457

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYCS 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				8		8
missense		4	12			16
nonsense						0
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			1	2	1	4
non coding			8	5		13
Total	0	4	22	13	0

Variants in CYCS

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

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

Position	Type	Phenotype	Significance	ClinVar
7-25118688-A-G		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25118695-ATT-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25118975-CTAT-C		Thrombocytopenia	Likely benign (Jun 14, 2016)
7-25119176-AT-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25120090-AT-A		Thrombocytopenia	Likely benign (Jun 14, 2016)
7-25120418-CT-C		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25121136-TAA-T		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25121862-G-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25121995-A-ATGTT		Thrombocytopenia	Likely benign (Jun 14, 2016)
7-25122022-C-CA		Thrombocytopenia	Likely benign (Jun 14, 2016)
7-25122022-C-CAAA		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25122078-AG-A		Thrombocytopenia	Uncertain significance (Jun 14, 2016)
7-25123702-T-G			Uncertain significance (Dec 15, 2020)
7-25123711-G-A		Thrombocytopenia • Thrombocytopenia 4	Conflicting classifications of pathogenicity (Jul 21, 2022)
7-25123714-GCTT-G			Uncertain significance (Dec 11, 2023)
7-25123715-CTTT-C		Thrombocytopenia 4	Pathogenic (Jan 16, 2019)
7-25123724-G-A		CYCS-related disorder	Likely pathogenic (Feb 16, 2023)
7-25123724-G-C		Thrombocytopenia	Likely pathogenic (-)
7-25123727-A-G		Thrombocytopenia 4	Uncertain significance (Sep 15, 2022)
7-25123729-G-T		Thrombocytopenia 4	Likely pathogenic (-)
7-25123740-T-C			Likely benign (Jul 27, 2023)
7-25123751-C-T			Uncertain significance (Jun 10, 2022)
7-25123758-CTTA-C			Uncertain significance (Dec 14, 2022)
7-25123767-G-A			Likely benign (Mar 19, 2023)
7-25123770-A-G			Likely benign (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYCS	protein_coding	protein_coding	ENST00000305786	2	5271

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.636	0.338	125640	0	1	125641	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	30	54.6	0.549	0.00000277	692
Missense in Polyphen		0	5.4301	0		81
Synonymous	-1.07	26	19.9	1.31	0.00000113	187
Loss of Function	1.67	0	3.25	0.00	1.38e-7	51

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.
• Disease: DISEASE: Thrombocytopenia 4 (THC4) [MIM:612004]: Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. {ECO:0000269|PubMed:18345000}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Influenza A - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Tuberculosis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Apoptosis - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Sulfur metabolism - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);Mitochondrial Electron Transport Chain;miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;Alzheimers Disease;AGE-RAGE pathway;Parkinsons Disease Pathway;Nanomaterial induced apoptosis;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Mitochondrial biogenesis;Apoptotic Signaling Pathway;Apoptosis Modulation by HSP70;Oxidative Damage;NO-cGMP-PKG mediated Neuroprotection;apoptotic signaling in response to dna damage;Chromosomal and microsatellite instability in colorectal cancer;DNA Damage Response;RAGE;Detoxification of Reactive Oxygen Species;Gene expression (Transcription);trefoil factors initiate mucosal healing;role of mitochondria in apoptotic signaling;hiv-1 nef: negative effector of fas and tnf;west nile virus;stress induction of hsp regulation;regulation of cell cycle progression by plk3;Generic Transcription Pathway;Fas;Cellular responses to stress;RNA Polymerase II Transcription;Respiratory electron transport;Release of apoptotic factors from the mitochondria;Formation of apoptosome;The citric acid (TCA) cycle and respiratory electron transport;Apoptotic factor-mediated response;Intrinsic Pathway for Apoptosis;Metabolism;Apoptosis;Programmed Cell Death;Activation of caspases through apoptosome-mediated cleavage;BCR;ceramide signaling pathway;TP53 Regulates Metabolic Genes;Cellular responses to external stimuli;Transcriptional Regulation by TP53;Transcriptional activation of mitochondrial biogenesis;Mitochondrial biogenesis;TNF;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.;Cytochrome c-mediated apoptotic response;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;mTOR signaling pathway;p75(NTR)-mediated signaling;Ceramide signaling pathway;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.988

Intolerance Scores

• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.43

Haploinsufficiency Scores

• pHI: 0.366
• hipred: N
• hipred_score: 0.386
• ghis: 0.620

Essentials

• essential_gene_CRISPR: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cycs
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system 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); immune system phenotype; skeleton phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: mitochondrial electron transport, ubiquinol to cytochrome c;mitochondrial electron transport, cytochrome c to oxygen;protein dephosphorylation;mitochondrion organization;activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c;cellular response to oxidative stress;cellular respiration;intrinsic apoptotic signaling pathway
• Cellular component: protein phosphatase type 2A complex;nucleus;mitochondrion;mitochondrial inner membrane;mitochondrial intermembrane space;cytosol;respirasome
• Molecular function: protein serine/threonine phosphatase activity;protein binding;heme binding;electron transporter, transferring electrons from CoQH2-cytochrome c reductase complex and cytochrome c oxidase complex activity;metal ion binding