CYB561

protein-coding

cytochrome b561, the group of Cytochrome b561

Gene summary

Predicted to enable transmembrane monodehydroascorbate reductase activity. Predicted to be involved in ascorbate homeostasis. Predicted to be located in chromaffin granule membrane. Predicted to be active in lysosomal membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001915.4

Inheritance

ClinVar variants

P:2U:34B:7

Top phenotype

Orthostatic hypotension 2

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr17:63,432,304-63,446,354

External References & Databases

Ensembl (ENSG00000008283)

Transcript & Mutation Effects

hg38 • Region Span ~14.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

orthostatic hypotension 2LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020751

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Orthostatic hypotension 2AR

Manifestation: Biochemical; Cardiovascular

Intervention: Biochemical; Cardiovascular

Rationale: The condition may involve early-onset severe orthostatic hypotension, and medical managment (eg, with L-dihydroxyphenylserine) has been reported as beneficial

Refs: 29343526

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CYB561 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 35

CYB561-related disorderTotal: 5

Orthostatic hypotension 2Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001915.4. 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				5 clinvar	1 clinvar	6
missense	1 clinvar		33 clinvar	1 clinvar		35
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	34	6	1	43

Highest pathogenic variant AF is 0.0000061954183

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001915.4	RefSeq	NP_001906.3	5	MANE Select
ENST00000360793.8	Ensembl	ENSP00000354028.3	5	MANE Select
NM_001017916.2	RefSeq	NP_001017916.1	5	Standard
NM_001017917.2	RefSeq	NP_001017917.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

electron transport chain

Molecular Function

ferric-chelate reductase activity
protein binding
oxidoreductase activity
metal ion binding

Cellular Component

lysosomal membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392976
Coding exons: 5
Length: 14075
Individuals with no LoFs: 125694
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125703
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.951	132	167	0.793	0.0000112	1589
Missense (PolyPhen)		44	61.3	0.71778		580
Synonymous	0.161	84	85.9	0.978	0.00000661	553
Loss of Function	2.61	2	11.6	0.173	5.81e-7	113

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Secretory vesicle-specific electron transport protein.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.556
RVIS EVS: -0.54
RVIS percentile EVS: 20.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.613

Gene Damage Prediction

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