CYBB

cytochrome b-245 beta chain

Basic information

Region (hg38): X:37780018-37813461

Previous symbols: [ "CGD" ]

Links

ENSG00000165168 ∙ NCBI:1536 ∙ OMIM:300481 ∙ HGNC:2578 ∙ Uniprot:P04839 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• granulomatous disease, chronic, X-linked (Definitive), mode of inheritance: XL
• chronic granulomatous disease (Supportive), mode of inheritance: AR
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency (Supportive), mode of inheritance: XL
• X-linked Mendelian susceptibility to mycobacterial diseases due to CYBB deficiency (Limited), mode of inheritance: Unknown
• granulomatous disease, chronic, X-linked (Strong), mode of inheritance: XL
• granulomatous disease, chronic, X-linked (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Granulomatous disease, chronic, X-linked; Immunodeficiency 34	XL	Allergy/Immunology/Infectious	In Immunodeficiency 34, BCG vacine should be avoided, and recognition may allow prompt diagnosis and treatment of infectious manifestations; In Chronic granulomatous disease, X-linked, 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	13430573; 13636694; 14258653; 4163887; 6021213; 4191616; 7273485; 6851217; 3011845; 2556453; 1710153; 8807090; 9454688; 9888386; 10914676; 11060536; 11259721; 11138621; 12802027; 17544093; 18762975; 21278736; 22236433; 22876374; 22924737; 23193493; 23826567; 23827747; 23859418; 23910690

ClinVar

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

• Granulomatous_disease,_chronic,_X-linked (611 variants)
• not_provided (158 variants)
• Chronic_granulomatous_disease (80 variants)
• not_specified (27 variants)
• Inborn_genetic_diseases (16 variants)
• CYBB-related_disorder (13 variants)
• X-linked_Mendelian_susceptibility_to_mycobacterial_diseases_due_to_CYBB_deficiency (11 variants)
• Granulomatous_disease,_chronic,_X-linked,_variant (7 variants)
• Recurrent_bronchitis (1 variants)
• Dynein_arm_defect_of_respiratory_motile_cilia (1 variants)
• Primary_ciliary_dyskinesia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYBB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000397.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	1	8	161	22	193
missense	35	26	158	32	7	258
nonsense	36	3	1			40
start loss	2					2
frameshift	46	7	2			55
splice donor/acceptor (+/-2bp)	27	5	2			34
Total	147	42	171	193	29

Highest pathogenic variant AF is 0.00000892507

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYBB	protein_coding	protein_coding	ENST00000378588	13	33451

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000959	125609	0	3	125612	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.19	125	215	0.580	0.0000161	3750
Missense in Polyphen		26	77.126	0.33711		1251
Synonymous	-0.482	85	79.5	1.07	0.00000588	1084
Loss of Function	4.40	1	24.5	0.0408	0.00000196	359

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000117	0.0000981
Ashkenazi Jewish	0.000134	0.0000993
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.
• Disease: DISEASE: Granulomatous disease, chronic, X-linked (CGD) [MIM:306400]: 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:10089913, ECO:0000269|PubMed:10914676, ECO:0000269|PubMed:11462241, ECO:0000269|PubMed:11997083, ECO:0000269|PubMed:12139950, ECO:0000269|PubMed:15338276, ECO:0000269|PubMed:1710153, ECO:0000269|PubMed:18773283, ECO:0000269|PubMed:22125116, ECO:0000269|PubMed:23910690, ECO:0000269|PubMed:2556453, ECO:0000269|PubMed:27666509, ECO:0000269|PubMed:7927345, ECO:0000269|PubMed:8101486, ECO:0000269|PubMed:8182143, ECO:0000269|PubMed:8916969, ECO:0000269|PubMed:9111587, ECO:0000269|PubMed:9585602, ECO:0000269|PubMed:9667376, ECO:0000269|PubMed:9794433, ECO:0000269|PubMed:9856476, ECO:0000269|PubMed:9888386}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Immunodeficiency 34 (IMD34) [MIM:300645]: A form of Mendelian susceptibility to mycobacterial disease, a rare condition characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. {ECO:0000269|PubMed:21278736}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Phagosome - Homo sapiens (human);Necroptosis - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Thyroid hormone synthesis;Microglia Pathogen Phagocytosis Pathway;HDAC6 interactions;Type II interferon signaling (IFNG);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;Signaling by Receptor Tyrosine Kinases;RAC1 signaling pathway (Consensus)

Recessive Scores

• pRec: 0.749

Intolerance Scores

• loftool: 0.0105
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.165
• hipred: Y
• hipred_score: 0.704
• ghis: 0.480

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cybb
• Phenotype: neoplasm; 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype; immune 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); digestive/alimentary phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: cybb
• Affected structure: respiratory burst
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: superoxide metabolic process;defense response;inflammatory response;electron transport chain;ion transmembrane transport;cellular response to oxidative stress;regulation of ion transmembrane transport;positive regulation of tumor necrosis factor biosynthetic process;superoxide anion generation;neutrophil degranulation;innate immune response;respiratory burst;positive regulation of angiogenesis;vascular endothelial growth factor receptor signaling pathway;hydrogen peroxide biosynthetic process;oxidation-reduction process;cellular response to cadmium ion;cellular response to ethanol;hypoxia-inducible factor-1alpha signaling pathway;response to aldosterone;cellular response to L-glutamine;response to angiotensin
• Cellular component: nuclear envelope;endoplasmic reticulum membrane;rough endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;dendrite;phagocytic vesicle membrane;specific granule membrane;NADPH oxidase complex;neuronal cell body;perinuclear region of cytoplasm;tertiary granule membrane
• Molecular function: voltage-gated ion channel activity;protein binding;electron transfer activity;superoxide-generating NADPH oxidase activity;heme binding;metal ion binding;protein heterodimerization activity;flavin adenine dinucleotide binding