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BLVRA biliverdin reductase A [ Homo sapiens (human) ]

Gene ID: 644, updated on 2-Nov-2024

Summary

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Official Symbol
BLVRAprovided by HGNC
Official Full Name
biliverdin reductase Aprovided by HGNC
Primary source
HGNC:HGNC:1062
See related
Ensembl:ENSG00000106605 MIM:109750; AllianceGenome:HGNC:1062
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
BVR; BLVR; BVRA; BVRalpha
Summary
The protein encoded by this gene belongs to the biliverdin reductase family, members of which catalyze the conversion of biliverdin to bilirubin in the presence of NADPH or NADH. Mutations in this gene are associated with hyperbiliverdinemia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2011]
Expression
Ubiquitous expression in spleen (RPKM 33.2), lung (RPKM 23.1) and 25 other tissues See more
Orthologs
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Genomic context

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See BLVRA in Genome Data Viewer
Location:
7p13
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (43758122..43807342)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (43915726..43965608)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (43798279..43846941)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:43593671-43594870 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18123 Neighboring gene lncRNA upregulator of antiviral response interferon signaling Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:43616728-43617927 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18124 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25909 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25910 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25911 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_99082 Neighboring gene Sharpr-MPRA regulatory region 11578 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:43686409-43687270 Neighboring gene Sharpr-MPRA regulatory region 11574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:43688133-43688994 Neighboring gene serine/threonine kinase 17a Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25913 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:43691438-43692181 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18125 Neighboring gene NFE2L2 motif-containing MPRA enhancer 272 Neighboring gene cytochrome c oxidase assembly factor 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:43769138-43769866 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:43768408-43769137 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25915 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25916 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:43789145-43789664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:43789665-43790184 Neighboring gene uncharacterized LOC107986727 Neighboring gene CRISPRi-validated cis-regulatory element chr7.1855 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18126 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18127 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25917 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25918 Neighboring gene Sharpr-MPRA regulatory region 4653 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18128 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_99190 Neighboring gene URGCP-MRPS24 readthrough Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18129 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18130 Neighboring gene uncharacterized LOC124901620 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 25921 Neighboring gene mitochondrial ribosomal protein S24

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/β-catenin pathway. Chen X, et al. J Mol Histol, 2024 Apr. PMID 38216836
  2. Predictive role BLVRA mRNA expression in hepatocellular cancer. Kubícková KN, et al. Ann Hepatol, 2016 Nov-Dec 2016. PMID 27740521
  3. Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity. Cimini FA, et al. Biochim Biophys Acta Mol Basis Dis, 2019 Jun 1. PMID 30826467
  4. Targeting biliverdin reductase overcomes multidrug resistance in leukemia HL60 cells. Kim SS, et al. Anticancer Res, 2013 Nov. PMID 24222129
  5. Biliverdin reductase deficiency triggers an endothelial-to-mesenchymal transition in human endothelial cells. Klóska D, et al. Arch Biochem Biophys, 2019 Dec 15. PMID 31704097

See all (99) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/beta-catenin pathway.
    Title: BLVRA exerts its biological effects to induce malignant properties of hepatocellular carcinoma cells via Wnt/β-catenin pathway.
  2. Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.
    Title: Associations between UGT1A1, SLCO1B1, SLCO1B3, BLVRA and HMOX1 polymorphisms and susceptibility to neonatal severe hyperbilirubinemia in Chinese Han population.
  3. Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control.
    Title: Biliverdin reductase-A protein levels are reduced in type 2 diabetes and are associated with poor glycometabolic control.
  4. Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.
    Title: Reduced Biliverdin Reductase-A Expression in Visceral Adipose Tissue is Associated with Adipocyte Dysfunction and NAFLD in Human Obesity.
  5. Associations between G6PD, OATP1B1 and BLVRA variants and susceptibility to neonatal hyperbilirubinaemia in a Chinese Han population.
    Title: Associations between G6PD, OATP1B1 and BLVRA variants and susceptibility to neonatal hyperbilirubinaemia in a Chinese Han population.
  6. TLR4 counteracts BVRA signaling in human leukocytes via differential regulation of AMPK, mTORC1 and mTORC2.
    Title: TLR4 counteracts BVRA signaling in human leukocytes via differential regulation of AMPK, mTORC1 and mTORC2.
  7. Biliverdin reductase deficiency triggers an endothelial-to-mesenchymal transition in human endothelial cells
    Title: Biliverdin reductase deficiency triggers an endothelial-to-mesenchymal transition in human endothelial cells.
  8. Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity.
    Title: Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity.
  9. Data found that BVR-A interacts with BACE1, and its loss would favor the CKI-mediated phosphorylation of BACE1 and the associated increased Abeta production along with the alteration of brain insulin signaling. These results suggest that the impairment of BVR-A is an early molecular event contributing to both the onset of brain insulin resistance and the increased Abeta production observed in Alzheimer disease.
    Title: Biliverdin reductase-A impairment links brain insulin resistance with increased Aβ production in an animal model of aging: Implications for Alzheimer disease.
  10. Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls.
    Title: Genetic Variations in Bilirubin Metabolism Genes and Their Association with Unconjugated Hyperbilirubinemia in Adults.
Submit: New GeneRIF Correction See all GeneRIFs (36)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hyperbiliverdinemia
MedGen: C3279964 OMIM: 614156 GeneReviews: Not available
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables biliberdin reductase (NAD+) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables biliverdin reductase (NADP+) activity IEA
Inferred from Electronic Annotation
more info
  
enables biliverdin reductase [NAD(P)+] activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables biliverdin reductase [NAD(P)+] activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables zinc ion binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in heme catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 

General protein information

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Preferred Names
biliverdin reductase A
Names
BVR A
biliverdin reductase IXalpha
biliverdin-IX alpha-reductase
testis tissue sperm-binding protein Li 61n
NP_000703.2
NP_001240752.1
XP_011513776.1
XP_016868009.1
XP_024302635.1
XP_054214770.1
XP_054214771.1
XP_054214772.1
XP_054214773.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_031876.1 RefSeqGene

    Range
    5008..53670
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000712.4 → NP_000703.2  biliverdin reductase A

    See identical proteins and their annotated locations for NP_000703.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    BM710258, U34877, X93086
    Consensus CDS
    CCDS5472.1
    UniProtKB/Swiss-Prot
    A8K747, O95019, P53004, Q86UX0, Q96QL4, Q9BRW8
    UniProtKB/TrEMBL
    A0A140VJF4
    Related
    ENSP00000265523.4, ENST00000265523.9
    Conserved Domains (2) summary
    pfam01408
    Location:18 → 125
    GFO_IDH_MocA; Oxidoreductase family, NAD-binding Rossmann fold
    pfam09166
    Location:133 → 243
    Biliv-reduc_cat; Biliverdin reductase, catalytic

  2. NM_001253823.2 → NP_001240752.1  biliverdin reductase A

    See identical proteins and their annotated locations for NP_001240752.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an additional 5' non-coding exon compared to variant 1. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AK291862, BM710258, CA418616
    Consensus CDS
    CCDS5472.1
    UniProtKB/Swiss-Prot
    A8K747, O95019, P53004, Q86UX0, Q96QL4, Q9BRW8
    UniProtKB/TrEMBL
    A0A140VJF4
    Related
    ENSP00000385757.1, ENST00000402924.5
    Conserved Domains (2) summary
    pfam01408
    Location:18 → 125
    GFO_IDH_MocA; Oxidoreductase family, NAD-binding Rossmann fold
    pfam09166
    Location:133 → 243
    Biliv-reduc_cat; Biliverdin reductase, catalytic

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    43758122..43807342
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011515474.3 → XP_011513776.1  biliverdin reductase A isoform X1

    See identical proteins and their annotated locations for XP_011513776.1

    UniProtKB/Swiss-Prot
    A8K747, O95019, P53004, Q86UX0, Q96QL4, Q9BRW8
    UniProtKB/TrEMBL
    A0A140VJF4
    Conserved Domains (2) summary
    pfam01408
    Location:18 → 125
    GFO_IDH_MocA; Oxidoreductase family, NAD-binding Rossmann fold
    pfam09166
    Location:133 → 243
    Biliv-reduc_cat; Biliverdin reductase, catalytic

  2. XM_024446867.2 → XP_024302635.1  biliverdin reductase A isoform X1

    UniProtKB/Swiss-Prot
    A8K747, O95019, P53004, Q86UX0, Q96QL4, Q9BRW8
    UniProtKB/TrEMBL
    A0A140VJF4
    Conserved Domains (2) summary
    pfam01408
    Location:18 → 125
    GFO_IDH_MocA; Oxidoreductase family, NAD-binding Rossmann fold
    pfam09166
    Location:133 → 243
    Biliv-reduc_cat; Biliverdin reductase, catalytic

  3. XM_017012520.3 → XP_016868009.1  biliverdin reductase A isoform X1

    UniProtKB/Swiss-Prot
    A8K747, O95019, P53004, Q86UX0, Q96QL4, Q9BRW8
    UniProtKB/TrEMBL
    A0A140VJF4
    Conserved Domains (2) summary
    pfam01408
    Location:18 → 125
    GFO_IDH_MocA; Oxidoreductase family, NAD-binding Rossmann fold
    pfam09166
    Location:133 → 243
    Biliv-reduc_cat; Biliverdin reductase, catalytic

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    43915726..43965608
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054358795.1 → XP_054214770.1  biliverdin reductase A isoform X1

  2. XM_054358796.1 → XP_054214771.1  biliverdin reductase A isoform X1

  3. XM_054358798.1 → XP_054214773.1  biliverdin reductase A isoform X1

  4. XM_054358797.1 → XP_054214772.1  biliverdin reductase A isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P53004.2 GenPept UniProtKB/Swiss-Prot:P53004

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