BLVRA

Chr 7ADAR

biliverdin reductase A

Also known as: BLVR, BVR, BVRA, BVRalpha

NCBI Gene: 644ENSG00000106605UniProt: P53004

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]

Primary Disease Associations & Inheritance

HyperbiliverdinemiaMIM #614156
ADAR
109
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BLVRA
🧬
Gene-Disease Validity (ClinGen)
hyperbiliverdinemia · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 51 VUS of 109 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 1.79
OE 0.51 (0.30–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.35Z-score
OE missense 0.92 (0.81–1.06)
147 obs / 159.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.30–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.06)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.79
0≤1.21.6
LoF obs/exp: 8 / 15.7Missense obs/exp: 147 / 159.3Syn Z: 1.34

ClinVar Variant Classifications

109 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic2
VUS51
Likely Benign16
Benign13
Conflicting3
24
Pathogenic
2
Likely Pathogenic
51
VUS
16
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
2
0
2
VUS
0
44
6
1
51
Likely Benign
0
2
7
7
16
Benign
0
5
1
7
13
Conflicting
—3
Total0514015109

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BLVRA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hyperbiliverdinemia

MIM #614156

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China.
Liu X et al.·Sci Rep
2024Cohort
BLVRA promotes glioblastoma progression by regulating fatty acid metabolism.
Li L et al.·Sci Rep
2025
Biliverdin reductase deficiency triggers an endothelial-to-mesenchymal transition in human endothelial cells.
Klóska D et al.·Arch Biochem Biophys
2019
Identification of monocyte-associated biomarkers in systemic lupus erythematosus and their pan-cancer analysis.
Chen H et al.·Lupus
2023
A homozygous nonsense mutation (c.214C->A) in the biliverdin reductase alpha gene (BLVRA) results in accumulation of biliverdin during episodes of cholestasis.
Nytofte NS et al.·J Med Genet
2011Case report
Improvement of prognostic performance in severely injured patients by integrated clinico-transcriptomics: a translational approach.
Rittirsch D et al.·Crit Care
2015Cohort
Modulation and proteomic changes on the heme pathway following treatment with 5-aminolevulinic acid.
Sansaloni-Pastor S et al.·J Photochem Photobiol B
2022
Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.
Yang H et al.·PLoS One
2015Cohort
An Integrated Clinico-transcriptomic Approach Identifies a Central Role of the Heme Degradation Pathway for Septic Complications after Trauma.
Rittirsch D et al.·Ann Surg
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools