CYB5A

cytochrome b5 type A

Basic information

Region (hg38): 18:74250846-74291973

Previous symbols: [ "CYB5" ]

Links

ENSG00000166347 ∙ NCBI:1528 ∙ OMIM:613218 ∙ HGNC:2570 ∙ Uniprot:P00167 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 46,XY disorder of sex development due to isolated 17,20-lyase deficiency (Supportive), mode of inheritance: AR
• methemoglobinemia type 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Methemoglobinemia and ambiguous genitalia	AR	Endocrine; Oncologic; Genitourinary	Hormonal treatment (eg, with estrogen or testosterone) may be beneficial related to sexual characteristics; Due to risk of gonadal tumors, surgical removal may be indicated	Endocrine; Hematologic; Oncologic; Genitourinary	3951505; 8168836; 22170710

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYB5A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYB5A 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				1	1	2
missense		1	2	1		4
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					3	3
Total	0	2	2	2	4

Variants in CYB5A

This is a list of pathogenic ClinVar variants found in the CYB5A region.

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

Position	Type	Phenotype	Significance	ClinVar
18-74260915-C-T			Benign (Jan 25, 2024)
18-74260927-T-C			Likely benign (Jan 08, 2019)
18-74260963-G-C			Benign (Jun 30, 2023)
18-74263351-G-A		not specified	Uncertain significance (Nov 30, 2022)
18-74263366-T-C		not specified	Uncertain significance (Mar 03, 2022)
18-74263476-T-A		Methemoglobinemia type 4	Likely pathogenic (Oct 15, 2018)
18-74263479-T-C		Methemoglobinemia type 4	Pathogenic (Mar 20, 1986)
18-74263486-A-G		CYB5A-related disorder	Likely benign (Aug 22, 2024)
18-74263490-G-T			Benign (Jan 24, 2024)
18-74291736-C-A			Benign (Jan 24, 2024)
18-74291795-C-T		Methemoglobinemia type 4	Likely pathogenic (Oct 15, 2018)
18-74291797-A-C		not specified	Uncertain significance (Aug 10, 2024)
18-74291840-G-A			Benign (Jan 25, 2024)
18-74291851-C-A		CYB5A-related disorder	Likely benign (Oct 23, 2018)
18-74291863-A-C		not specified	Conflicting classifications of pathogenicity (Dec 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYB5A	protein_coding	protein_coding	ENST00000340533	5	38722

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00158	0.707	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0855	76	73.9	1.03	0.00000381	892
Missense in Polyphen		24	20.914	1.1476		274
Synonymous	-1.60	37	26.5	1.40	0.00000146	236
Loss of Function	0.784	5	7.28	0.687	3.11e-7	90

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytochrome b5 is a membrane bound hemoprotein which function as an electron carrier for several membrane bound oxygenases.
• Disease: DISEASE: Methemoglobinemia and ambiguous genitalia (METAG) [MIM:250790]: An autosomal recessive disorder characterized by sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve, male undermasculinization, absent or disturbed pubertal development, decreased levels of erythrocyte cytochrome B5, and excessive amounts of methemoglobin in blood cells resulting in cyanosis and hypoxia. {ECO:0000269|PubMed:20080843, ECO:0000269|PubMed:22170710, ECO:0000269|PubMed:8168836}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Methylene Blue Pathway, Pharmacodynamics;Oxidation by Cytochrome P450;Vitamin C (ascorbate) metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors (Consensus)

Recessive Scores

• pRec: 0.335

Intolerance Scores

• loftool: 0.354
• rvis_EVS: 0.08
• rvis_percentile_EVS: 59.76

Haploinsufficiency Scores

• pHI: 0.185
• hipred: Y
• hipred_score: 0.572
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.854

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyb5a
• Phenotype: homeostasis/metabolism phenotype

Gene ontology

• Biological process: L-ascorbic acid metabolic process;electron transport chain;response to cadmium ion;proton transmembrane transport
• Cellular component: mitochondrial outer membrane;endoplasmic reticulum membrane;cytosol;membrane;integral component of membrane;intracellular membrane-bounded organelle
• Molecular function: aldo-keto reductase (NADP) activity;cytochrome-c oxidase activity;enzyme binding;heme binding;metal ion binding