Details for: CYB561

Gene ID: 1534

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CYB561

Ensembl ID: ENSG00000008283

Description: cytochrome b561

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ciliated epithelial cell CL0000067
    CSI 11.53
    rCSI 10.14%
    PRS 72.56
  • lung ciliated cell CL1000271
    CSI 7.21
    rCSI 8.34%
    PRS 75.58
  • duct epithelial cell CL0000068
    CSI 6.14
    rCSI 8.98%
    PRS 87.29
  • tracheobronchial serous cell CL0019001
    CSI 3.49
    rCSI 15.07%
    PRS 88.47
  • choroid plexus epithelial cell CL0000706
    CSI 3.33
    rCSI 5.46%
    PRS 72.9
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.1
    rCSI 2.23%
    PRS 93.77
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 3.04
    rCSI 17.9%
    PRS 66.27
  • secretory cell CL0000151
    CSI 3.03
    rCSI 3.16%
    PRS 82.07
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3
    rCSI 2.33%
    PRS 86.39
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 2.87
    rCSI 10.32%
    PRS 63.63
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.81
    rCSI 1.9%
    PRS 93.88
  • intestine goblet cell CL0019031
    CSI 2.81
    rCSI 2.49%
    PRS 80.59
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.55
    rCSI 5.82%
    PRS 76.35
  • acinar cell CL0000622
    CSI 2.5
    rCSI 3.67%
    PRS 90.91
  • mucus secreting cell CL0000319
    CSI 2.49
    rCSI 3.95%
    PRS 90.13
  • ciliated cell CL0000064
    CSI 2.47
    rCSI 4%
    PRS 77.65
  • epithelial cell of lung CL0000082
    CSI 2.43
    rCSI 2.01%
    PRS 83.86
  • pancreatic D cell CL0000173
    CSI 2.34
    rCSI 2.3%
    PRS 85.08
  • colon epithelial cell CL0011108
    CSI 2.33
    rCSI 2.44%
    PRS 80.3
  • pancreatic A cell CL0000171
    CSI 2.28
    rCSI 2.39%
    PRS 85.79
  • intestinal epithelial cell CL0002563
    CSI 2.23
    rCSI 2.34%
    PRS 80.43
  • multi-ciliated epithelial cell CL0005012
    CSI 2.22
    rCSI 2.22%
    PRS 76.89
  • group 3 innate lymphoid cell CL0001071
    CSI 2.21
    rCSI 1.66%
    PRS 88.12
  • nasal mucosa goblet cell CL0002480
    CSI 2.15
    rCSI 2.49%
    PRS 86.02
  • blood vessel endothelial cell CL0000071
    CSI 2.13
    rCSI 4.43%
    PRS 79.82
  • lung secretory cell CL1000272
    CSI 2.12
    rCSI 5.25%
    PRS 82.94
  • goblet cell CL0000160
    CSI 2.12
    rCSI 2%
    PRS 81.2
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 2.11
    rCSI 7.98%
    PRS 66.29
  • respiratory hillock cell CL4030023
    CSI 2.1
    rCSI 3.74%
    PRS 90.09
  • respiratory suprabasal cell CL4033048
    CSI 2.07
    rCSI 2.65%
    PRS 85.64
  • fallopian tube secretory epithelial cell CL4030006
    CSI 2.05
    rCSI 1.97%
    PRS 82.28
  • colon goblet cell CL0009039
    CSI 2.04
    rCSI 4.85%
    PRS 86.91
  • enteroendocrine cell CL0000164
    CSI 1.98
    rCSI 2.7%
    PRS 82.31
  • ependymal cell CL0000065
    CSI 1.97
    rCSI 4%
    PRS 62.04
  • stem cell CL0000034
    CSI 1.95
    rCSI 1.88%
    PRS 76.94
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.92
    rCSI 2.38%
    PRS 63.6
  • conjunctival epithelial cell CL1000432
    CSI 1.9
    rCSI 2.91%
    PRS 82.84
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.87
    rCSI 3.01%
    PRS 67.07
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.85
    rCSI 3.36%
    PRS 91.36
  • lung neuroendocrine cell CL1000223
    CSI 1.84
    rCSI 2.72%
    PRS 86.07
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.83
    rCSI 2.18%
    PRS 65.78
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.75
    rCSI 2.25%
    PRS 66.87
  • medium spiny neuron CL1001474
    CSI 1.74
    rCSI 14.99%
    PRS 71.47
  • cerebral cortex neuron CL0010012
    CSI 1.71
    rCSI 6.96%
    PRS 74.74
  • mucous neck cell CL0000651
    CSI 1.71
    rCSI 2.46%
    PRS 88.51
  • squamous epithelial cell CL0000076
    CSI 1.68
    rCSI 3.98%
    PRS 82.37
  • transit amplifying cell of colon CL0009011
    CSI 1.66
    rCSI 1.95%
    PRS 84.31
  • pancreatic acinar cell CL0002064
    CSI 1.64
    rCSI 2.18%
    PRS 87.74
  • glandular epithelial cell CL0000150
    CSI 1.55
    rCSI 4.09%
    PRS 92.59
  • club cell CL0000158
    CSI 1.54
    rCSI 2.25%
    PRS 77.66
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.5
    rCSI 2.52%
    PRS 65.71
  • mammary gland epithelial cell CL0002327
    CSI 1.4
    rCSI 4.9%
    PRS 89.66
  • pulmonary artery endothelial cell CL1001568
    CSI 1.35
    rCSI 1.83%
    PRS 90.28
  • pancreatic ductal cell CL0002079
    CSI 1.29
    rCSI 2.51%
    PRS 85.72
  • deuterosomal cell CL4033044
    CSI 1.29
    rCSI 4.35%
    PRS 79.55
  • tracheal goblet cell CL1000329
    CSI 1.17
    rCSI 2.56%
    PRS 88.61
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.17
    rCSI 2.07%
    PRS 65.25
  • neuroendocrine cell CL0000165
    CSI 1.17
    rCSI 4.52%
    PRS 89.84
  • foveolar cell of stomach CL0002179
    CSI 1.11
    rCSI 2.37%
    PRS 87.94
  • type B pancreatic cell CL0000169
    CSI 1.09
    rCSI 2.42%
    PRS 82.21
  • small intestine goblet cell CL1000495
    CSI 1.08
    rCSI 2.37%
    PRS 87.33
  • luminal cell of prostate epithelium CL0002340
    CSI 0.97
    rCSI 5.24%
    PRS 89.41
  • retinal ganglion cell CL0000740
    CSI 0.88
    rCSI 1.95%
    PRS 69.32
  • bronchial goblet cell CL1000312
    CSI 0.88
    rCSI 3.52%
    PRS 89.42
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.86
    rCSI 2.1%
    PRS 63.65
  • podocyte CL0000653
    CSI 0.78
    rCSI 3.49%
    PRS 83.42
  • respiratory goblet cell CL0002370
    CSI 0.78
    rCSI 8.44%
    PRS 89.27
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.65
    rCSI 2.04%
    PRS 67.39
  • pancreatic PP cell CL0002275
    CSI 0.59
    rCSI 2.34%
    PRS 88.8
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.57
    rCSI 1.77%
    PRS 69.65
  • peptic cell CL0000155
    CSI 0.33
    rCSI 3.27%
    PRS 91.2
  • acinar cell of salivary gland CL0002623
    CSI 0.23
    rCSI 5.36%
    PRS 92.23

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CYB561](/details-gene/1534) encodes Cytochrome b561, a transmembrane oxidoreductase crucial for electron transport across cellular membranes. Its primary function is linked to ascorbate (Vitamin C) regeneration, which is essential for maintaining cellular redox balance and serving as a cofactor for various enzymes. The gene's function is reflected in its expression profile; **Overall**, it shows exceptionally high significance in metabolically active epithelial and secretory cells, most notably `[ciliated epithelial cell](/details-cell/CL0000067)`. Clinically, loss-of-function mutations in [CYB561](/details-gene/1534) are associated with a novel orthostatic hypotension syndrome ([Link](https://doi.org/10.1161/circresaha.117.311949)), highlighting its vital role in neuroendocrine function and cardiovascular homeostasis (OMIM: [600019](https://omim.org/entry/600019)). ## Cellular Roles and Expression Landscape The expression landscape of [CYB561](/details-gene/1534) points to a fundamental role in epithelial and secretory tissues that are either exposed to the external environment or involved in high-volume synthesis and secretion. **Overall**, the gene's significance is most pronounced in cells of the respiratory tract, including `[ciliated epithelial cell](/details-cell/CL0000067)` (CSI: 11.53), `[lung ciliated cell](/details-cell/CL1000271)` (CSI: 7.21), and `[tracheobronchial serous cell](/details-cell/CL0019001)` (CSI: 3.49). This pattern extends to other secretory and barrier cells such as `[duct epithelial cell](/details-cell/CL0000068)`, `[intestine goblet cell](/details-cell/CL0019031)`, and `[acinar cell](/details-cell/CL0000622)`. This specific expression pattern suggests a critical function in maintaining the integrity and function of mucosal surfaces, likely by protecting these high-turnover cells from oxidative stress. Beyond mucosal barriers, [CYB561](/details-gene/1534) is also significant in specialized neuro-epithelial cells like `[choroid plexus epithelial cell](/details-cell/CL0000706)`, which form the blood-cerebrospinal fluid barrier, and in specific neuronal populations such as `[corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013)`. A moderate but consistent signal is also observed in subsets of memory T lymphocytes, including `[CD4-positive, alpha-beta memory T cell](/details-cell/CL0000897)` and `[central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907)`, which may reflect the metabolic demands of long-lived immune cells. ## Pathways and Molecular Function The functions of [CYB561](/details-gene/1534) are tightly linked to its role as a transmembrane electron transporter, which is critical for several interconnected cellular processes. * **Ascorbate Homeostasis and Redox Regulation:** The gene's most well-defined molecular function is its transmembrane monodehydroascorbate reductase activity ([GO:0140575](https://www.ebi.ac.uk/QuickGO/term/GO:0140575)), which regenerates ascorbate from its oxidized form. This is central to ascorbate homeostasis ([GO:0140576](https://www.ebi.ac.uk/QuickGO/term/GO:0140576)) and is vital for protecting cells from oxidative damage. This function is particularly relevant in the highly expressive `[ciliated epithelial cell](/details-cell/CL0000067)` of the lung, which is constantly exposed to environmental oxidants. * **Electron Transport and Metal Ion Binding:** As a cytochrome, [CYB561](/details-gene/1534) participates in the `[electron transport chain](/details-go/GO0022900)` ([GO:0022900](https://www.ebi.ac.uk/QuickGO/term/GO:0022900)) and possesses oxidoreductase activity ([GO:0016491](https://www.ebi.ac.uk/QuickGO/term/GO:0016491)). Its ability to bind metal ions ([GO:0046872](https://www.ebi.ac.uk/QuickGO/term/GO:0046872)) is integral to its electron-carrying capacity. This is also linked to its proposed role in intracellular iron ion homeostasis ([GO:0006879](https://www.ebi.ac.uk/QuickGO/term/GO:0006879)). * **Vesicular Function:** The gene product is a known component of the `[chromaffin granule membrane](/details-go/GO0042584)` ([GO:0042584](https://www.ebi.ac.uk/QuickGO/term/GO:0042584)) and `[lysosomal membrane](/details-go/GO0005765)` ([GO:0005765](https://www.ebi.ac.uk/QuickGO/term/GO:0005765)). In chromaffin granules of the adrenal medulla, it provides the reducing equivalents (via ascorbate recycling) necessary for the synthesis of catecholamine hormones like norepinephrine and epinephrine. This precise function explains the severe phenotype of orthostatic hypotension observed in patients with mutations ([Link](https://doi.org/10.1161/circresaha.117.311949)). ## Research Directions The well-defined molecular function and specific expression pattern of [CYB561](/details-gene/1534) suggest several avenues for future investigation, particularly concerning its role in physiology and disease beyond its known link to orthostatic hypotension. **Testable Hypotheses:** 1. **Hypothesis 1:** Given its exceptional expression in respiratory ciliated epithelium, [CYB561](/details-gene/1534) is a critical component of the lung's antioxidant defense system. Its functional impairment may render the respiratory mucosa more susceptible to damage from inhaled pollutants (e.g., ozone, cigarette smoke) and pathogens, potentially contributing to the pathology of chronic respiratory diseases like COPD or asthma. 2. **Hypothesis 2:** Based on its role in catecholamine synthesis, deficiency of [CYB561](/details-gene/1534) may lead to broader dysautonomia beyond orthostatic hypotension, potentially affecting gut motility, thermoregulation, or other processes controlled by the sympathetic nervous system, consistent with its expression in secretory cells of the gut and other tissues. **Proposed Experiment:** To test the first hypothesis regarding its role in respiratory defense, an *in vitro* experiment could be designed. Primary human bronchial epithelial cells would be cultured at an air-liquid interface (ALI) to induce differentiation into a mucociliary epithelium. `[CYB561](/details-gene/1534)` expression would then be knocked down using siRNA. These cultures, along with scrambled siRNA controls, would be exposed to a controlled dose of an oxidative stressor, such as ozone or cigarette smoke extract. The impact would be assessed by measuring intracellular reactive oxygen species (ROS) levels, quantifying DNA damage markers (e.g., 8-oxo-dG), analyzing ciliary beat frequency via high-speed microscopy, and measuring the secretion of pro-inflammatory cytokines like IL-6 and IL-8 by ELISA. A significant increase in oxidative damage and impairment of ciliary function in the knockdown group would validate the protective role of [CYB561](/details-gene/1534) in the airway. **Therapeutic Potential:** The known clinical association of [CYB561](/details-gene/1534) with a loss-of-function disorder suggests that therapeutic strategies should focus on **activation or functional restoration** rather than inhibition. For patients with the inherited orthostatic hypotension syndrome, potential avenues could include the development of small-molecule chaperones to correct protein misfolding or, in the long term, gene therapy to restore functional protein expression in affected neuroendocrine cells. Systemic inhibition of [CYB561](/details-gene/1534) would likely be detrimental due to its important protective role in essential barrier tissues like the respiratory and gastrointestinal tracts.

Genular Protein ID: 3732004602

Symbol: CY561_HUMAN

Name: Cytochrome b-561

UniProtKB Accession Codes:

P49447 B2RE96 B7Z775 D3DU11 Q5BJG9 Q9BU05 Q9BWR9

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 19 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 16 Ensembl 6 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 5 Rhea 2 SMART 1 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7559396

Title: Genomic structure and expression of the human gene encoding cytochrome b561, an integral protein of the chromaffin granule membrane.

PubMed ID: 7559396

DOI: 10.1074/jbc.270.39.22714

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7980462

Title: Human cytochrome b561: a revised hypothesis for conformation in membranes which reconciles sequence and functional information.

PubMed ID: 7980462

DOI: 10.1042/bj3030915

PubMed ID: 29343526

Title: Mutations in CYB561 causing a novel orthostatic hypotension syndrome.

PubMed ID: 29343526

DOI: 10.1161/circresaha.117.311949

Sequence Information:

  • Length: 251
  • Mass: 27559
  • Checksum: 8EE53AE4D2569B77
  • Sequence:
    • MEGGAAAATP TALPYYVAFS QLLGLTLVAM TGAWLGLYRG GIAWESDLQF NAHPLCMVIG 
LIFLQGNALL VYRVFRNEAK RTTKVLHGLL HIFALVIALV GLVAVFDYHR KKGYADLYSL 
HSWCGILVFV LYFVQWLVGF SFFLFPGASF SLRSRYRPQH IFFGATIFLL SVGTALLGLK 
EALLFNLGGK YSAFEPEGVL ANVLGLLLAC FGGAVLYILT RADWKRPSQA EEQALSMDFK 
TLTEGDSPGS Q

Genular Protein ID: 1385346022

Symbol: B3KTA1_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KTA1

Database IDs:

ARBA 15 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChEBI 3 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 1 InterPro 2 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 1 Rhea 2 SAM 1 SMART 1 SMR 1

Citations:

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 194
  • Mass: 20528
  • Checksum: 7EEE9BC93ABB4C0E
  • Sequence:
    • MEGGAAAATP TALPYYVAFS QLLGLTLVAM TGAWLGLYRG GIAWESDLQF NAHPLCMVIG 
LIFLQGNALL VYRVFRNEAK RTTKVLHGLL HIFALVIALV GEFPDAAFPA TCLPLQAWWR 
CSTTTGRRAT LTCTAYTAGA GSLSLSCTLC SGWWASASSC SPELHSPCGA ATAHSTSSLV 
LPSSSFPWAP PCWA

Genular Protein ID: 2750768337

Symbol: J3QRH5_HUMAN

Name: N/A

UniProtKB Accession Codes:

J3QRH5

Database IDs:

ARBA 15 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChEBI 3 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneTree 1 HGNC 1 InterPro 2 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 1 RefSeq 1 Rhea 2 SAM 1 SMART 1 SMR 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 258
  • Mass: 28267
  • Checksum: A2BB84DC230DC9CA
  • Sequence:
    • MSSVCLSMEG GAAAATPTAL PYYVAFSQLL GLTLVAMTGA WLGLYRGGIA WESDLQFNAH 
PLCMVIGLIF LQGNALLVYR VFRNEAKRTT KVLHGLLHIF ALVIALVGLV AVFDYHRKKG 
YADLYSLHSW CGILVFVLYF VQWLVGFSFF LFPGASFSLR SRYRPQHIFF GATIFLLSVG 
TALLGLKEAL LFNLGGKYSA FEPEGVLANV LGLLLACFGG AVLYILTRAD WKRPSQAEEQ 
ALSMDFKTLT EGDSPGSQ