CYB561A3

protein-coding

cytochrome b561 family member A3, the group of Cytochrome b561

Gene summary

Predicted to enable transmembrane ascorbate ferrireductase activity. Predicted to be involved in intracellular iron ion homeostasis. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

CYBASC3

MANE transcript

NM_153611.6

Inheritance

—

ClinVar variants

U:29B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr11:61,348,754-61,362,283

External References & Databases

Ensembl (ENSG00000162144)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 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 CYB561A3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 29

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_153611.6. 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						0
missense			27 clinvar	2 clinvar		29
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	29	2	0	31

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_153611.6	RefSeq	NP_705839.3	5	MANE Select
ENST00000294072.9	Ensembl	ENSP00000294072.4	5	MANE Select
NM_001161452.2	RefSeq	NP_001154924.1	5	Standard
NM_001161454.1	RefSeq	NP_001154926.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

oxidation-reduction process

Molecular Function

protein binding
oxidoreductase activity
metal ion binding

Cellular Component

lysosomal membrane
integral component of membrane
late endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000426130
Coding exons: 6
Length: 13555
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125746
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.898	122	153	0.796	0.00000886	1674
Missense (PolyPhen)		44	58.687	0.74973		677
Synonymous	0.0202	67	67.2	0.997	0.00000418	546
Loss of Function	1.81	5	11.7	0.429	4.98e-7	124

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000090	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Ferric-chelate reductase that reduces Fe(3+) to Fe(2+) before its transport from the endosome to the cytoplasm. Probably uses ascorbate as electron donor (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

RVIS EVS: -0.34
RVIS percentile EVS: 30.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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