CYB5R2

protein-coding

cytochrome b5 reductase 2

Gene summary

The protein encoded by this gene belongs to the flavoprotein pyridine nucleotide cytochrome reductase family of proteins. Cytochrome b-type NAD(P)H oxidoreductases are implicated in many processes including cholesterol biosynthesis, fatty acid desaturation and elongation, and respiratory burst in neutrophils and macrophages. Cytochrome b5 reductases have soluble and membrane-bound forms that are the product of alternative splicing. In animal cells, the membrane-bound form binds to the endoplasmic reticulum, where it is a member of a fatty acid desaturation complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

MANE transcript

NM_016229.5

Inheritance

—

ClinVar variants

U:65B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr11:7,665,100-7,677,222

External References & Databases

Ensembl (ENSG00000166394)

Transcript & Mutation Effects

hg38 • Region Span ~12.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYB5R2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 62

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016229.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			62 clinvar	2 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	65	2	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016229.5	RefSeq	NP_057313.2	8	MANE Select
ENST00000299498.11	Ensembl	ENSP00000299498.6	8	MANE Select
NM_001302826.2	RefSeq	NP_001289755.1	8	Standard
NM_001302827.1	RefSeq	NP_001289756.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

bicarbonate transport
sterol biosynthetic process
oxidation-reduction process

Molecular Function

cytochrome-b5 reductase activity, acting on NAD(P)H
protein binding
FAD binding

Cellular Component

nucleus
endoplasmic reticulum membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000533558
Coding exons: 8
Length: 12123
Individuals with no LoFs: 125630
Homozygous LoFs: 0
Heterozygous LoFs: 118
Defined: 125748
p: 0.000469

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.28	204	159	1.29	0.00000862	1814
Missense (PolyPhen)		67	61.929	1.0819		733
Synonymous	-1.83	81	62.6	1.29	0.00000377	518
Loss of Function	-0.0436	14	13.8	1.01	6.50e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00080	0.00080	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00068	0.00068	rare
South Asian	0.00065	0.00065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction (By similarity). Responsible for NADH-dependent lucigenin chemiluminescence in spermatozoa by reducing both lucigenin and 2-[4-iodophenyl]-3-[4-nitrophenyl]-5-[2,4- disulfophenyl]-2H tetrazolium monosodium salt (WST-1). {ECO:0000250, ECO:0000269|PubMed:15858218}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.250
RVIS EVS: 0.73
RVIS percentile EVS: 86.21

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.474

Gene Damage Prediction

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