CYB561D2

protein-coding

cytochrome b561 family member D2, the group of Cytochrome b561

Gene summary

Enables heme binding activity and transmembrane monodehydroascorbate reductase activity. Involved in ascorbate homeostasis. Predicted to be located in endoplasmic reticulum and vesicle. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001291284.2

Inheritance

—

ClinVar variants

U:21B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr3:50,350,845-50,358,460

External References & Databases

Ensembl (ENSG00000114395)

Transcript & Mutation Effects

hg38 • Region Span ~7.6 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 CYB561D2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001291284.2. 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 clinvar		2
missense			20 clinvar	1 clinvar		21
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	21	2	0	23

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001291284.2	RefSeq	NP_001278213.1	3	MANE Select
ENST00000425346.6	Ensembl	ENSP00000400454.1	3	MANE Select
NM_001414705.1	RefSeq	NP_001401634.1	3	Standard
NM_001414706.1	RefSeq	NP_001401635.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

oxidation-reduction process

Molecular Function

ferroxidase activity
heme binding
metal ion binding

Cellular Component

endoplasmic reticulum
integral component of membrane
vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000418577
Coding exons: 3
Length: 7766
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 125744
p: 0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.970	97	128	0.759	0.00000736	1366
Missense (PolyPhen)		21	38.981	0.53872		434
Synonymous	-0.451	66	61.5	1.07	0.00000346	537
Loss of Function	0.817	7	9.75	0.718	6.44e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.430
RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.925

Gene Damage Prediction

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