CYB5R4

cytochrome b5 reductase 4

Basic information

Region (hg38): 6:83859656-83967423

Previous symbols: [ "NCB5OR" ]

Links

ENSG00000065615 ∙ NCBI:51167 ∙ OMIM:608343 ∙ HGNC:20147 ∙ Uniprot:Q7L1T6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYB5R4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYB5R4 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						0
missense			23	2	1	26
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	2	1

Variants in CYB5R4

This is a list of pathogenic ClinVar variants found in the CYB5R4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-83859810-C-T		not specified	Uncertain significance (Jul 06, 2024)
6-83859819-A-G		not specified	Uncertain significance (Apr 27, 2022)
6-83859844-G-C		not specified	Uncertain significance (Jun 11, 2021)
6-83864245-G-A		not specified	Uncertain significance (Apr 20, 2023)
6-83864271-A-G		not specified	Uncertain significance (Nov 14, 2024)
6-83864299-A-G		not specified	Uncertain significance (Aug 06, 2024)
6-83893573-A-G		not specified	Uncertain significance (May 30, 2023)
6-83909009-G-T		not specified	Uncertain significance (Jan 05, 2022)
6-83909015-C-T		not specified	Uncertain significance (Dec 08, 2023)
6-83909036-A-G		not specified	Uncertain significance (Sep 22, 2023)
6-83909052-T-A		not specified	Uncertain significance (Dec 21, 2023)
6-83918008-T-C		not specified	Uncertain significance (Nov 25, 2024)
6-83921083-A-G		not specified	Uncertain significance (Apr 13, 2022)
6-83921085-A-G		not specified	Uncertain significance (Oct 25, 2024)
6-83921089-A-G		not specified	Uncertain significance (Sep 22, 2023)
6-83921092-T-C		not specified	Uncertain significance (Jan 22, 2024)
6-83921100-A-G		not specified	Likely benign (May 24, 2023)
6-83921106-G-A		not specified	Uncertain significance (Mar 22, 2023)
6-83921134-C-A		not specified	Uncertain significance (Aug 11, 2024)
6-83921151-G-A		not specified	Uncertain significance (Jun 14, 2022)
6-83924475-G-T		not specified	Uncertain significance (Aug 01, 2022)
6-83924488-T-C		not specified	Uncertain significance (Apr 11, 2023)
6-83924488-T-G		not specified	Uncertain significance (Dec 06, 2024)
6-83924518-A-C		not specified	Uncertain significance (Feb 10, 2022)
6-83924572-T-C		not specified	Uncertain significance (Dec 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYB5R4	protein_coding	protein_coding	ENST00000369681	16	107782

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.62e-9	0.900	125718	0	26	125744	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.739	224	257	0.870	0.0000120	3428
Missense in Polyphen		73	97.489	0.7488		1276
Synonymous	-0.0420	87	86.5	1.01	0.00000403	930
Loss of Function	1.80	18	28.4	0.635	0.00000127	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000310	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.000177	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000177	0.000163
South Asian	0.000143	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway. Plays a critical role in protecting pancreatic beta-cells against oxidant stress, possibly by protecting the cell from excess buildup of reactive oxygen species (ROS). Reduces a variety of substrates in vitro, such as cytochrome c, feericyanide and methemoglobin.
• Pathway: Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Oxidation by Cytochrome P450;O2/CO2 exchange in erythrocytes;Transport of small molecules;Erythrocytes take up carbon dioxide and release oxygen (Consensus)

Intolerance Scores

• loftool: 0.335
• rvis_EVS: 0.28
• rvis_percentile_EVS: 71.41

Haploinsufficiency Scores

• pHI: 0.223
• hipred: N
• hipred_score: 0.495
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.700

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyb5r4
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: detection of oxygen;generation of precursor metabolites and energy;superoxide metabolic process;bicarbonate transport;insulin secretion;glucose homeostasis;response to antibiotic;cell development;oxidation-reduction process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;perinuclear region of cytoplasm
• Molecular function: cytochrome-b5 reductase activity, acting on NAD(P)H;NAD(P)H oxidase activity;oxidoreductase activity, acting on NAD(P)H, heme protein as acceptor;heme binding;metal ion binding