BLVRB

Summary

BLVRB (biliverdin reductase B, HGNC:1063) is a protein-coding gene on chromosome 19q13.2, encoding Flavin reductase (NADPH) (P30043). Enzyme that can both act as a NAD(P)H-dependent reductase and a S-nitroso-CoA-dependent nitrosyltransferase.

Enables biliverdin reductase [NAD(P)+] activity; peptidyl-cysteine S-nitrosylase activity; and riboflavin reductase (NADPH) activity. Involved in heme catabolic process; megakaryocyte differentiation; and negative regulation of insulin receptor signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Is active in cytoplasm.

Source: NCBI Gene 645 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 65 total
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1063
Approved symbol	BLVRB
Name	biliverdin reductase B
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	SDR43U1
Ensembl gene	ENSG00000090013
Ensembl biotype	protein_coding
OMIM	600941
Entrez	645

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000263368, ENST00000595483, ENST00000597870, ENST00000601346, ENST00000643519, ENST00000643596, ENST00000858749, ENST00000858750, ENST00000858751, ENST00000858752, ENST00000926837, ENST00000926838

RefSeq mRNA: 1 — MANE Select: NM_000713 NM_000713

CCDS: CCDS33029

Canonical transcript exons

ENST00000263368 — 5 exons

Exon	Start	End
ENSE00000706810	40458155	40458244
ENSE00001504330	40458381	40458545
ENSE00003020423	40465610	40465745
ENSE00003618517	40451364	40451492
ENSE00003892745	40447768	40448046

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 92.5728 / max 4602.9345, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180993	58.5725	1814
180994	33.9116	1816
180995	0.0886	32

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	98.94	gold quality
lower esophagus mucosa	UBERON:0035834	98.77	gold quality
monocyte	CL:0000576	98.37	gold quality
right lobe of liver	UBERON:0001114	98.36	gold quality
body of stomach	UBERON:0001161	98.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.18	gold quality
apex of heart	UBERON:0002098	98.07	gold quality
esophagus mucosa	UBERON:0002469	98.06	gold quality
mononuclear cell	CL:0000842	98.05	gold quality
bone marrow	UBERON:0002371	98.01	gold quality
leukocyte	CL:0000738	97.93	gold quality
spleen	UBERON:0002106	97.83	gold quality
gastrocnemius	UBERON:0001388	97.77	gold quality
blood	UBERON:0000178	97.68	gold quality
mucosa of stomach	UBERON:0001199	97.66	gold quality
esophagus	UBERON:0001043	97.55	gold quality
muscle of leg	UBERON:0001383	97.54	gold quality
granulocyte	CL:0000094	97.37	gold quality
omental fat pad	UBERON:0010414	97.37	gold quality
peritoneum	UBERON:0002358	97.33	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.26	gold quality
right lung	UBERON:0002167	97.25	gold quality
mucosa of transverse colon	UBERON:0004991	97.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.13	gold quality
lower esophagus	UBERON:0013473	97.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.04	gold quality
right atrium auricular region	UBERON:0006631	97.01	gold quality
left coronary artery	UBERON:0001626	96.98	gold quality
liver	UBERON:0002107	96.95	gold quality
upper lobe of left lung	UBERON:0008952	96.95	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	4186.50
E-MTAB-7407	yes	3355.03
E-GEOD-130473	yes	3288.31
E-MTAB-10042	yes	3039.23
E-CURD-122	yes	2255.97
E-HCAD-4	yes	2232.96
E-CURD-112	yes	2219.38
E-MTAB-10432	yes	1734.32
E-MTAB-8884	yes	1504.49
E-CURD-79	yes	1438.67
E-MTAB-8205	yes	1335.02
E-MTAB-6701	yes	1221.96
E-HCAD-6	yes	811.43
E-CURD-6	yes	767.08
E-CURD-114	yes	64.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

6 targeting BLVRB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-6772-3P	97.04	65.89	784
HSA-MIR-4268	94.45	64.09	819

Literature-anchored findings (GeneRIF, showing 8)

• quantum mechanics/molecular mechanics potential energy surfaces show that the lowest energy pathway proceeds with a positively charged pyrrole intermediate via two transition states (PMID:18241201)
• Data suggest that isoenzymes BVRA and BVRB play different roles in energy metabolism and in pathogenesis of abdominal obesity and hypertriglyceridemia. [REVIEW] (PMID:25726384)
• miR-127-5p suppressed NF-kappaB activity by directly targeting BLVRB in hepatocellular carcinoma cells. (PMID:26708147)
• These data define the first physiologically relevant function of BLVRB and implicate its activity and/or heme-regulated BV tetrapyrrole(s) in a unique redox-regulated bioenergetic pathway. (PMID:27207795)
• These results provide promising chemical scaffolds for the development of enhanced BLVRB inhibitors and identify chemical probes to better dissect the role of biliverdins, alternative substrates, and BLVRB function in physiologically relevant cellular contexts. (PMID:29487133)
• Early stages of lineage fate potential require glutamine anaplerotic functions and an intact Pentose phosphate pathway, which are, in part, regulated by BLVRB activity. In principle, BLVRB inhibition represents an alternative strategy for modulating cellular glutamine utilization with consequences for cancer and hematopoietic metabolism. (PMID:29500232)
• Structure, dynamics and function of the evolutionarily changing biliverdin reductase B family. (PMID:32246827)
• Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis. (PMID:37371462)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	blvrb	ENSDARG00000096829
mus_musculus	Blvrb	ENSMUSG00000040466
rattus_norvegicus	Blvrb	ENSRNOG00000024410
rattus_norvegicus		ENSRNOG00000064875
drosophila_melanogaster	CG9471	FBGN0037749

Protein

Protein identifiers

Flavin reductase (NADPH) — P30043 (reviewed: P30043)

Alternative names: Biliverdin reductase B, Biliverdin-IX beta-reductase, Green heme-binding protein, NADPH-dependent diaphorase, NADPH-flavin reductase, S-nitroso-CoA-assisted nitrosyltransferase

All UniProt accessions (6): P30043, A0A2R8Y7Y9, A0A2R8YEP4, M0QZL1, M0R192, V9HWI1

UniProt curated annotations — full annotation on UniProt →

Function. Enzyme that can both act as a NAD(P)H-dependent reductase and a S-nitroso-CoA-dependent nitrosyltransferase. Promotes fetal heme degradation during development. Also expressed in adult tissues, where it acts as a regulator of hematopoiesis, intermediary metabolism (glutaminolysis, glycolysis, TCA cycle and pentose phosphate pathway) and insulin signaling. Has a broad specificity oxidoreductase activity by catalyzing the NAD(P)H-dependent reduction of a variety of flavins, such as riboflavin, FAD or FMN, biliverdins, methemoglobin and PQQ (pyrroloquinoline quinone). Contributes to fetal heme catabolism by catalyzing reduction of biliverdin IXbeta into bilirubin IXbeta in the liver. Biliverdin IXbeta, which constitutes the major heme catabolite in the fetus is not present in adult. Does not reduce bilirubin IXalpha. Can also reduce the complexed Fe(3+) iron to Fe(2+) in the presence of FMN and NADPH. Acts as a protein nitrosyltransferase by catalyzing nitrosylation of cysteine residues of target proteins, such as HMOX2, INSR and IRS1. S-nitroso-CoA-dependent nitrosyltransferase activity is mediated via a ‘ping-pong’ mechanism: BLVRB first associates with both S-nitroso-CoA and protein substrate, nitric oxide group is then transferred from S-nitroso-CoA to Cys-109 and Cys-188 residues of BLVRB and from S-nitroso-BLVRB to the protein substrate. Inhibits insulin signaling by mediating nitrosylation of INSR and IRS1, leading to their inhibition.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Tissue specificity. Predominantly expressed in liver and erythrocytes. At lower levels in heart, lung, adrenal gland and cerebrum. Expressed in adult red blood cells.

Activity regulation. Mesobiliverdin acts as a competitive inhibitor for flavin reduction, indicating that flavin and tetrapyrrole substrates compete for the same site. Inhibited by a wide range of xanthene-based drugs, such as phloxine B, erythrosin B, tamibarotene, sulfasalazine, olsalazine, febuxostat, ataluren (PTC124) and deferasirox.

Similarity. Belongs to the BLVRB family.

RefSeq proteins (1): NP_000704* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016040	NAD(P)-bd_dom	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR051606	Polyketide_Oxido-like	Family

Pfam: PF13460

Enzyme classification (BRENDA):

• EC 1.3.1.24 — biliverdin reductase (BRENDA: 18 organisms, 80 substrates, 52 inhibitors, 70 Km, 26 kcat entries)
• EC 1.5.1.30 — flavin reductase (NADPH) (BRENDA: 19 organisms, 71 substrates, 35 inhibitors, 59 Km, 26 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BILIVERDIN	0.001–0.1633	29
NADPH	—	22
FMN	—	20
NADPH	0.001–0.059	19
NADH	0.107–2	14
BILIVERDIN IXALPHA	0.0004–0.023	5
FAD	0.0036–0.236	4
RIBOFLAVIN	0.0013–0.04	4
NADH	0.208–0.65	3
2-THIOFMN	0.007	1
GALACTOFLAVIN	0.04	1
OXIDIZED RIBOFLAVIN	0.053	1
CIBACRON MARINE	—	0

Catalyzed reactions (Rhea), 7 shown:

• reduced riboflavin + NADP(+) = riboflavin + NADPH + 2 H(+) (RHEA:19377)
• FMNH2 + NAD(+) = FMN + NADH + 2 H(+) (RHEA:21620)
• FMNH2 + NADP(+) = FMN + NADPH + 2 H(+) (RHEA:21624)
• S-nitroso-CoA + L-cysteinyl-[protein] = S-nitroso-L-cysteinyl-[protein] + CoA (RHEA:78379)
• L-cysteinyl-[SCAN] + S-nitroso-CoA = S-nitroso-L-cysteinyl-[SCAN] + CoA (RHEA:78383)
• S-nitroso-L-cysteinyl-[SCAN] + L-cysteinyl-[protein] = L-cysteinyl-[SCAN] + S-nitroso-L-cysteinyl-[protein] (RHEA:78387)
• bilirubin IXbeta + NADP(+) = biliverdin IXbeta + NADPH + H(+) (RHEA:78395)

UniProt features (57 total): binding site 18, strand 11, helix 10, mutagenesis site 8, active site 2, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
1HDO	X-RAY DIFFRACTION	1.15
1HE2	X-RAY DIFFRACTION	1.2
5OOH	X-RAY DIFFRACTION	1.2
5OOG	X-RAY DIFFRACTION	1.33
7ERA	X-RAY DIFFRACTION	1.35
6OPL	X-RAY DIFFRACTION	1.37
1HE3	X-RAY DIFFRACTION	1.4
1HE4	X-RAY DIFFRACTION	1.4
7ER8	X-RAY DIFFRACTION	1.45
7ER9	X-RAY DIFFRACTION	1.45
1HE5	X-RAY DIFFRACTION	1.5
7ERB	X-RAY DIFFRACTION	1.5
7ERC	X-RAY DIFFRACTION	1.5
8ELL	X-RAY DIFFRACTION	1.52
9C16	X-RAY DIFFRACTION	1.58
7ER6	X-RAY DIFFRACTION	1.6
7ERE	X-RAY DIFFRACTION	1.6
9C17	X-RAY DIFFRACTION	1.63
7ER7	X-RAY DIFFRACTION	1.7
8K4K	X-RAY DIFFRACTION	1.7
9C18	X-RAY DIFFRACTION	1.9
7ERD	X-RAY DIFFRACTION	2
8ELM	X-RAY DIFFRACTION	2.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30043-F1	97.71	0.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 109 (s-nitroso-cysteine intermediate; for s-nitroso-coa-dependent nitrosyltransferase activity); 188 (s-nitroso-cysteine intermediate; for s-nitroso-coa-dependent nitrosyltransferase activity)

Ligand- & substrate-binding residues (18): 38; 39; 54; 55; 75; 76; 78; 87; 109; 132; 153; 154 …

Post-translational modifications (2): 42, 82

Mutagenesis-validated functional residues (8):

Position	Phenotype
14–16	abolished binding to nad(p)h and s-nitroso-coa, leading to abolished nad(p)h-dependent reductase and a s-nitroso-coa-dep
14	increased affinity for coenzyme a.
78	induces both an increase in active site micro-millisecond motions and an increase in the rate constants of coenzyme-bind
78	decreased affinity for coenzyme a.
109	abolished s-nitroso-coa-dependent nitrosyltransferase activity; when associated with r-188.
111	abolished nad(p)h-dependent reductase activity.
153	reduced affinity for biliverdin.
188	abolished s-nitroso-coa-dependent nitrosyltransferase activity; when associated with r-109.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-189483	Heme degradation
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-1430728	Metabolism
R-HSA-189445	Metabolism of porphyrins
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9711123	Cellular response to chemical stress

MSigDB gene sets: 331 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MODULE_93, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, BOYLAN_MULTIPLE_MYELOMA_PCA1_DN, FARMER_BREAST_CANCER_CLUSTER_7, GNF2_PRDX2, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, KAAB_FAILED_HEART_ATRIUM_DN, XU_GH1_AUTOCRINE_TARGETS_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_METABOLISM_OF_PORPHYRINS, GOBP_ERYTHROCYTE_HOMEOSTASIS

GO Biological Process (4): megakaryocyte differentiation (GO:0030219), heme catabolic process (GO:0042167), negative regulation of insulin receptor signaling pathway (GO:0046627), insulin receptor signaling pathway (GO:0008286)

GO Molecular Function (9): biliverdin reductase [NAD(P)H] activity (GO:0004074), peptidyl-cysteine S-nitrosylase activity (GO:0035605), riboflavin reductase (NADPH) activity (GO:0042602), FMN reductase (NADPH) activity (GO:0052873), FMN reductase (NADH) activity (GO:0052874), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), transferase activity (GO:0016740)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of porphyrins	1
Cellular response to chemical stress	1
Metabolism	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
FMN reductase [NAD(P)H] activity	2
catalytic activity	2
myeloid cell differentiation	1
porphyrin-containing compound catabolic process	1
heme metabolic process	1
pigment catabolic process	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor	1
transferase activity, transferring nitrogenous groups	1
catalytic activity, acting on a protein	1
riboflavin reductase [NAD(P)H] activity	1
molecular_function	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

2362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLVRB	BLVRA	P53004	935
BLVRB	DIAPH3	Q9NSV4	828
BLVRB	IYD	Q6PHW0	820
BLVRB	ALAS2	P22557	731
BLVRB	FECH	P22830	730
BLVRB	GNB5	O14775	715
BLVRB	MYO5A	Q9Y4I1	667
BLVRB	SNCB	Q16143	555
BLVRB	DIAPH2	O60879	531
BLVRB	ALAD	P13716	521
BLVRB	TXN	P10599	514
BLVRB	ISOC1	Q96CN7	475
BLVRB	HMOX1	P09601	461
BLVRB	HMOX2	P30519	452
BLVRB	GATA1	P15976	448

IntAct

42 interactions, top by confidence:

A	B	Type	Score
BLVRB	ANXA10	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
ARL6IP6	YKT6	psi-mi:“MI:0914”(association)	0.530
NENF	BLVRB	psi-mi:“MI:0914”(association)	0.530
RPL31	BLVRB	psi-mi:“MI:0915”(physical association)	0.370
BLVRB	ORM1	psi-mi:“MI:0915”(physical association)	0.370
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GTF2E2	UBA6	psi-mi:“MI:0914”(association)	0.350
FGB	NME2	psi-mi:“MI:0914”(association)	0.350
PFN2	DIAPH1	psi-mi:“MI:0914”(association)	0.350
FCGR2A	PLPBP	psi-mi:“MI:0914”(association)	0.350
STYX	BANF1	psi-mi:“MI:0914”(association)	0.350
SH3GL3	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
rep	XPO1	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BLVRB	NDUFA3	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
GTF2E2	STX7	psi-mi:“MI:0914”(association)	0.350
FAM24B	SHTN1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
FGB	KIF2A	psi-mi:“MI:0914”(association)	0.350
HOXC5	PDLIM1	psi-mi:“MI:0914”(association)	0.350
RPL35A	SMCHD1	psi-mi:“MI:0914”(association)	0.350
GSX1	YKT6	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), UFM1 (Co-fractionation), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS), BLVRB (Affinity Capture-MS)

ESM2 similar proteins: A0PJE2, A4FUZ6, A6QP05, D2WKD9, F1QWW8, O49213, O66148, O75884, O88736, O88851, P13653, P15904, P23591, P30043, P52556, P56658, P56937, Q06136, Q0IH28, Q0VCN1, Q0VFE7, Q13630, Q2KIJ5, Q3T0R4, Q41578, Q42850, Q566S6, Q59987, Q5R6U1, Q5RBE5, Q5RJY4, Q5ZID0, Q62904, Q66KC4, Q67WR2, Q6GV12, Q6IAN0, Q6P5L8, Q6PAY8, Q7XKF3

Diamond homologs: P30043, P52556, Q8X7P7, Q923D2, D4GP33, P09147, P09609, P13226, P22715, P26503, P45602, P73212, Q56093, Q9F7D4, Q9KDV3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BLVRB	“down-regulates quantity”	bilirubin(2-)	“chemical modification”
BLVRB	“up-regulates quantity”	biliverdin(2-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

65 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

752 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40448044:CTC:C	acceptor_gain	1.0000
19:40448047:C:A	acceptor_loss	1.0000
19:40448047:C:CC	acceptor_gain	1.0000
19:40451359:CTTAC:C	donor_loss	1.0000
19:40451361:TAC:T	donor_loss	1.0000
19:40451362:A:AC	donor_gain	1.0000
19:40451362:A:C	donor_loss	1.0000
19:40451363:C:CC	donor_gain	1.0000
19:40451488:GAAAG:G	acceptor_gain	1.0000
19:40451489:AAAG:A	acceptor_gain	1.0000
19:40451490:AAG:A	acceptor_gain	1.0000
19:40451491:AG:A	acceptor_gain	1.0000
19:40451492:GC:G	acceptor_loss	1.0000
19:40451493:C:CC	acceptor_gain	1.0000
19:40458379:A:AC	donor_gain	1.0000
19:40458380:C:CT	donor_gain	1.0000
19:40458419:T:TA	donor_gain	1.0000
19:40458544:ACC:A	acceptor_loss	1.0000
19:40448042:GTCTC:G	acceptor_gain	0.9900
19:40448045:TC:T	acceptor_gain	0.9900
19:40448046:CCTA:C	acceptor_gain	0.9900
19:40448049:A:AC	acceptor_gain	0.9900
19:40448054:G:C	acceptor_gain	0.9900
19:40448054:G:GC	acceptor_gain	0.9900
19:40451363:CCT:C	donor_gain	0.9900
19:40451363:CCTA:C	donor_gain	0.9900
19:40451363:CCTAT:C	donor_gain	0.9900
19:40458377:G:C	donor_gain	0.9900
19:40458383:AGGT:A	donor_gain	0.9900
19:40458384:G:C	donor_gain	0.9900

AlphaMissense

1308 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40451488:G:C	F113L	0.995
19:40451488:G:T	F113L	0.995
19:40451490:A:G	F113L	0.995
19:40451435:T:A	D131V	0.994
19:40451436:C:G	D131H	0.994
19:40458162:G:C	C109W	0.994
19:40465660:C:T	G10D	0.994
19:40458221:C:G	G90R	0.993
19:40465642:C:T	G16E	0.992
19:40465622:C:G	A23P	0.990
19:40451435:T:G	D131A	0.989
19:40451436:C:A	D131Y	0.989
19:40458467:C:T	G53E	0.989
19:40465643:C:A	G16W	0.989
19:40458163:C:T	C109Y	0.988
19:40458220:C:T	G90D	0.988
19:40458172:A:T	V106D	0.987
19:40458398:C:A	G76V	0.987
19:40458398:C:T	G76D	0.987
19:40458399:C:G	G76R	0.987
19:40458413:A:T	V71D	0.987
19:40458467:C:A	G53V	0.987
19:40447965:C:T	G182D	0.986
19:40447966:C:G	G182R	0.986
19:40458164:A:G	C109R	0.986
19:40458200:C:G	A97P	0.986
19:40458208:A:T	I94N	0.986
19:40465621:G:T	A23E	0.986
19:40465669:G:T	A7E	0.986
19:40451433:G:C	H132D	0.985

dbSNP variants (sampled 300 via entrez): RS1000258318 (19:40450699 C>T), RS1000400647 (19:40463023 C>G,T), RS1000450109 (19:40459110 A>T), RS1000504001 (19:40463958 G>A), RS1001007305 (19:40464285 G>A), RS1001050949 (19:40451202 T>A), RS1001057494 (19:40458646 C>T), RS1001316195 (19:40463671 T>G), RS1001548216 (19:40464529 C>T), RS1001589352 (19:40447384 A>G), RS1002183726 (19:40464578 T>C), RS1002198620 (19:40452204 G>A,T), RS1002202228 (19:40459190 A>G), RS1002206034 (19:40453865 G>A), RS1002213552 (19:40458684 G>A,T)

Disease associations

OMIM: gene MIM:600941 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003827_4	Otitis media	2.000000e-07
GCST003828_1	Otitis media (chronic)	3.000000e-08
GCST003829_4	Otitis media (recurrent)	1.000000e-07
GCST90002385_512	High light scatter reticulocyte count	2.000000e-19
GCST90002386_207	High light scatter reticulocyte percentage of red cells	7.000000e-18
GCST90002387_54	Immature fraction of reticulocytes	2.000000e-13
GCST90002405_549	Reticulocyte count	5.000000e-15
GCST90002406_529	Reticulocyte fraction of red cells	9.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5019 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 102,628 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1164729	FEBUXOSTAT	4	3,499
CHEMBL25202	TAMIBAROTENE	4	5,139
CHEMBL256997	ATALUREN	4	1,920
CHEMBL421	SULFASALAZINE	4	73,629
CHEMBL425	OLSALAZINE	4	16,848
CHEMBL550348	DEFERASIROX	4	1,593

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

16 potent at pChembl≥5 of 16 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	Kd	70	nM	OLSALAZINE
7.15	Kd	70.79	nM	OLSALAZINE
6.80	Kd	160	nM	ERYTHROSINE
6.80	Kd	158.5	nM	ERYTHROSINE
6.70	Kd	200	nM	ATALUREN
6.70	Kd	199.5	nM	ATALUREN
6.36	Kd	440	nM	SULFASALAZINE
6.36	Kd	436.5	nM	SULFASALAZINE
5.87	Kd	1360	nM	CHEMBL1205178
5.87	Kd	1349	nM	CHEMBL1205178
5.86	Kd	1380	nM	TAMIBAROTENE
5.79	Kd	1630	nM	FEBUXOSTAT
5.79	Kd	1622	nM	FEBUXOSTAT
5.77	Kd	1710	nM	DEFERASIROX
5.77	Kd	1698	nM	DEFERASIROX

PubChem BioAssay actives

16 with measured affinity, of 40 total; 8 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-[(3-carboxy-4-hydroxyphenyl)diazenyl]-2-hydroxybenzoic acid	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	0.0700	uM
3’,6’-dihydroxy-2’,4’,5’,7’-tetraiodospiro[2-benzofuran-3,9’-xanthene]-1-one	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	0.1585	uM
3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	0.1995	uM
2-hydroxy-5-[[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	0.4365	uM
2,3,4,5-tetrachloro-6-(2,4,5,7-tetrabromo-3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	1.3490	uM
4-[(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]benzoic acid	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	1.3800	uM
Febuxostat	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	1.6218	uM
Deferasirox	1815675: Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as dissociation constant by isothermal titration calorimetry	kd	1.6982	uM

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
sodium arsenite	increases abundance, increases expression	4
Arsenic Trioxide	increases expression	3
Cyclosporine	increases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	increases expression	2
Benzo(a)pyrene	increases expression	2
Cisplatin	affects expression, increases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
afimoxifene	decreases reaction, increases expression	1
ochratoxin A	decreases expression	1
cupric chloride	increases expression	1
ciglitazone	increases expression, affects binding	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
7,3’-dihydroxy-4’-methoxyisoflavone	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
ICG 001	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5038172	Binding	Binding affinity to human N-terminal His6-tagged and thrombin cleavage fused BLVRB expressed in Escherichia coli BL21 (DE3) assessed as change in enthalpy by isothermal titration calorimetry	Repositioning Food and Drug Administration-Approved Drugs for Inhibiting Biliverdin IXβ Reductase B as a Novel Thrombocytopenia Therapeutic Target. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2SU	Abcam HEK293T BLVRB KO	Transformed cell line	Female
CVCL_SF27	HAP1 BLVRB (-) 1	Cancer cell line	Male
CVCL_SF28	HAP1 BLVRB (-) 2	Cancer cell line	Male
CVCL_SF29	HAP1 BLVRB (-) 3	Cancer cell line	Male
CVCL_SF30	HAP1 BLVRB (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.