CYBA

cytochrome b-245 alpha chain

Basic information

Region (hg38): 16:88643275-88651083

Links

ENSG00000051523 ∙ NCBI:1535 ∙ OMIM:608508 ∙ HGNC:2577 ∙ Uniprot:P13498 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (Strong), mode of inheritance: AR
• chronic granulomatous disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Granulomatous disease, chronic, autosomal recessive, 4	AR	Allergy/Immunology/Infectious	Surveillance for infections and infectious complications is indicated, and preventive measures (eg, antibacterial/antifungal prophylaxis, interferon gamma) may be beneficial; To treat fungal infections, specific antifungal drugs may be beneficial, and longer treatment courses (as well as specific considerations including coadministration with corticosteroids) may be indicated in individuals with CGD; In some instances, HSCT may be beneficial; Certain agents should be avoided, including material that would allow fungal spore inhalation	Allergy/Immunology/Infectious	4384563; 2770793; 3368442; 2713485; 2243141; 1415254; 11060536; 12073015; 18422995; 10759707; 20407811; 22336310; 22562447; 22876374; 22924696; 23910690

ClinVar

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

• Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative (30 variants)
• Chronic granulomatous disease (6 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYBA 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			2	132	4	138
missense	3	6	96	6	2	113
nonsense	12	1	1			14
start loss			2			2
frameshift	10	4	6			20
inframe indel	1	1	2			4
splice donor/acceptor (+/-2bp)	4	7				11
splice region	1		8	16	1	26
non coding	1		1	74	17	93
Total	31	19	110	212	23

Highest pathogenic variant AF is 0.0000263

Variants in CYBA

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

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

Position	Type	Phenotype	Significance	ClinVar
16-88643304-A-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • not specified	Benign (Jan 24, 2024)
16-88643329-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • not specified	Benign (Jan 24, 2024)
16-88643358-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Chronic granulomatous disease	Uncertain significance (Sep 01, 2021)
16-88643359-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Sep 19, 2023)
16-88643364-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Uncertain significance (Sep 08, 2021)
16-88643365-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Granulomatous disease, chronic, X-linked	Likely benign (Jan 24, 2024)
16-88643367-C-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Uncertain significance (Feb 05, 2022)
16-88643367-C-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Chronic granulomatous disease	Uncertain significance (Nov 05, 2021)
16-88643367-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Inborn genetic diseases	Uncertain significance (Aug 16, 2022)
16-88643368-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Nov 17, 2023)
16-88643371-C-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Jan 02, 2023)
16-88643374-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Chronic granulomatous disease • CYBA-related disorder	Likely benign (Jan 11, 2024)
16-88643375-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Inborn genetic diseases	Uncertain significance (Jul 05, 2023)
16-88643375-G-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Apr 25, 2022)
16-88643377-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • CYBA-related disorder	Likely benign (Jan 16, 2024)
16-88643377-G-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Feb 04, 2020)
16-88643380-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (May 27, 2019)
16-88643383-G-A		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Jan 06, 2023)
16-88643386-G-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Mar 02, 2021)
16-88643388-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Chronic granulomatous disease	Uncertain significance (Aug 31, 2021)
16-88643389-C-T		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Aug 17, 2023)
16-88643392-G-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Jun 12, 2023)
16-88643393-G-C		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Uncertain significance (Aug 31, 2021)
16-88643398-T-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Likely benign (Jun 19, 2023)
16-88643400-C-G		Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative • Inborn genetic diseases	Uncertain significance (May 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYBA	protein_coding	protein_coding	ENST00000261623	6	7870

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000887	0.334	125594	0	25	125619	0.0000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.215	123	130	0.947	0.00000947	1188
Missense in Polyphen		56	58.359	0.95958		511
Synonymous	-0.622	66	59.9	1.10	0.00000482	404
Loss of Function	0.206	8	8.65	0.925	3.71e-7	97

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000931	0.0000912
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000235	0.000231
European (Non-Finnish)	0.000133	0.000132
Middle Eastern	0.00	0.00
South Asian	0.000102	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide. {ECO:0000269|PubMed:15824103}.
• Disease: DISEASE: Granulomatous disease, chronic, cytochrome-b-negative, autosomal recessive (ARCGD) [MIM:233690]: A disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections. {ECO:0000269|PubMed:10759707, ECO:0000269|PubMed:10910929, ECO:0000269|PubMed:10914676, ECO:0000269|PubMed:1415254, ECO:0000269|PubMed:1763037, ECO:0000269|PubMed:18422995, ECO:0000269|PubMed:2243141, ECO:0000269|PubMed:23910690, ECO:0000269|PubMed:7964505, ECO:0000269|PubMed:8168815}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phagosome - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;NOD-like receptor signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Thyroid hormone synthesis;TNF alpha Signaling Pathway;Microglia Pathogen Phagocytosis Pathway;Oxidative Stress;Neutrophil degranulation;Signal Transduction;Detoxification of Reactive Oxygen Species;VEGFA-VEGFR2 Pathway;Cellular responses to stress;ROS, RNS production in phagocytes;Innate Immune System;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Cellular responses to external stimuli;RHO GTPases Activate NADPH Oxidases;RHO GTPase Effectors;Signaling by Rho GTPases;Cross-presentation of particulate exogenous antigens (phagosomes);Signaling by VEGF;TNFalpha;Signaling by Receptor Tyrosine Kinases;RAC1 signaling pathway (Consensus)

Recessive Scores

• pRec: 0.418

Haploinsufficiency Scores

• pHI: 0.227
• hipred: Y
• hipred_score: 0.672

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.940

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyba
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; hearing/vestibular/ear 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); digestive/alimentary phenotype; vision/eye phenotype; 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

Gene ontology

• Biological process: response to hypoxia;positive regulation of endothelial cell proliferation;negative regulation of glomerular filtration by angiotensin;superoxide metabolic process;inflammatory response;response to activity;smooth muscle hypertrophy;cytochrome complex assembly;electron transport chain;positive regulation of cell growth;positive regulation of interleukin-6 production;positive regulation of tumor necrosis factor production;positive regulation of superoxide anion generation;positive regulation of NAD(P)H oxidase activity;positive regulation of toll-like receptor 2 signaling pathway;cellular response to oxidative stress;superoxide anion generation;neutrophil degranulation;innate immune response;respiratory burst;vascular endothelial growth factor receptor signaling pathway;positive regulation of smooth muscle cell proliferation;hydrogen peroxide biosynthetic process;positive regulation of phagocytosis;regulation of release of sequestered calcium ion into cytosol;oxidation-reduction process;positive regulation of mucus secretion;response to interleukin-1;cellular response to mechanical stimulus;cellular response to glucose stimulus;cellular response to tumor necrosis factor;cellular response to organic cyclic compound;cellular response to gamma radiation;positive regulation of defense response to bacterium;positive regulation of reactive oxygen species biosynthetic process;response to aldosterone;cellular response to angiotensin;cellular response to L-glutamine
• Cellular component: stress fiber;nucleus;endosome;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;focal adhesion;membrane;apical plasma membrane;secretory granule;dendrite;phagocytic vesicle membrane;specific granule membrane;NADPH oxidase complex;neuronal cell body;tertiary granule membrane;perinuclear endoplasmic reticulum
• Molecular function: protein binding;electron transfer activity;superoxide-generating NADPH oxidase activity;SH3 domain binding;heme binding;metal ion binding;protein heterodimerization activity