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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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BPNT1
3'(2'), 5'-bisphosphate nucleotidase 1
Chromosome 1 · 1q41
NCBI Gene: 10380Ensembl: ENSG00000162813.19HGNC: HGNC:1096UniProt: B7Z9J7
39PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrion3'(2'),5'-bisphosphate nucleotidase activitycytosolnucleobase-containing compound metabolic processcataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndromepolyneuropathyneurodegenerative diseaseLeigh syndrome
✦AI Summary

BPNT1 (3'(2'), 5'-bisphosphate nucleotidase 1) is a phosphatase enzyme that catalyzes the hydrolysis of 3'(2')-phosphoadenosine 5'-phosphate (PAP) to AMP, preventing toxic PAP accumulation that inhibits sulfotransferases and RNA processing enzymes 1. The enzyme also hydrolyzes inositol 1,4-bisphosphate and plays roles in inositol recycling and phosphoinositide metabolism 2. BPNT1 localizes to the cytosol and is part of a conserved family of lithium-sensitive phosphatases 3. Mechanistically, BPNT1 functions in sulfur assimilation regulation and nucleotide metabolism homeostasis 4. Recent evidence reveals BPNT1 involvement in mammalian rapid tRNA decay (mRTD) pathways for quality control under heat stress, via intracellular pAp level control 5. Clinically, BPNT1 deficiency causes severe liver pathologies including hypoproteinemia, hepatocellular damage, edema, and impaired translation 1. Loss of BPNT1 also produces iron-deficiency anemia and anasarca, though these phenotypes can be rescued through dietary methionine restriction or HIF-2α overexpression 4. Conversely, BPNT1 overexpression promotes triple-negative breast cancer progression and docetaxel resistance through STUB1-mediated LIMA1 degradation 6. BPNT1 downregulation protects lens epithelial cells from UV-induced apoptosis, with therapeutic implications for age-related cataract 78.

Sources cited
1
BPNT1 converts PAP to AMP and inositol 1,4-bisphosphate to inositol 4-phosphate; substrate specificity data
PMID: 10675562
2
BPNT1 deficiency causes severe liver pathology, hepatocellular damage, hypoproteinemia, and impaired translation due to PAP accumulation
PMID: 23479625
3
BPNT1 is a lithium-sensitive phosphatase in the signaling phosphatase family; role in PAP metabolism and lithium pharmacology
PMID: 15583009
4
BPNT1 loss causes iron-deficiency anemia and anasarca; reversible through methionine restriction or HIF-2α overexpression
PMID: 32019729
5
BPNT1 controls intracellular pAp levels in mammalian rapid tRNA decay pathway for quality control under heat stress
PMID: 40595590
6
BPNT1 overexpression promotes triple-negative breast cancer progression and docetaxel resistance via STUB1-mediated LIMA1 degradation
PMID: 41540000
7
BPNT1 expression is downregulated in age-related cataract tissues; BPNT1 upregulation protects lens cells from UV-induced apoptosis
PMID: 34652259
8
BPNT1 downregulation via miR-338-3p reduces UV-induced apoptosis in lens epithelial cells
PMID: 38493427
Disease Associationsⓘ20
cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndromeOpen Targets
0.46Moderate
polyneuropathyOpen Targets
0.31Weak
neurodegenerative diseaseOpen Targets
0.29Weak
Leigh syndromeOpen Targets
0.27Weak
genetic disorderOpen Targets
0.19Weak
smoking initiationOpen Targets
0.13Weak
Developmental cataractOpen Targets
0.11Weak
early-onset non-syndromic cataractOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.07Suggestive
congenital disorder of glycosylation type IIOpen Targets
0.05Suggestive
progressive familial intrahepatic cholestasisOpen Targets
0.04Suggestive
mathematical abilityOpen Targets
0.04Suggestive
Congenital bile acid synthesis defect type 1Open Targets
0.04Suggestive
isolated hyperferritinemiaOpen Targets
0.04Suggestive
congenital analbuminemiaOpen Targets
0.04Suggestive
TMEM199-CDGOpen Targets
0.04Suggestive
familial apolipoprotein C-II deficiencyOpen Targets
0.04Suggestive
Hyperlipoproteinemia type 1Open Targets
0.04Suggestive
mitochondrial myopathy with reversible cytochrome C oxidase deficiencyOpen Targets
0.04Suggestive
MPI-congenital disorder of glycosylationOpen Targets
0.04Suggestive
Pathogenic Variants1
NM_006085.6(BPNT1):c.793A>C (p.Ile265Leu)Pathogenic
Hypercholesterolemia, familial, 1
☆☆☆☆2022→ Residue 265
View on ClinVar ↗
Related Genes
PAPSS2Protein interaction93%PAPSS1Protein interaction93%BPNT2Protein interaction93%ACBD3Protein interaction85%ISYNA1Protein interaction76%GDAShared pathway33%
Tissue Expression6 tissues
Brain
100%
Heart
98%
Liver
71%
Ovary
55%
Lung
44%
Bone Marrow
20%
Gene Interaction Network
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BPNT1PAPSS2PAPSS1BPNT2ACBD3ISYNA1GDA
PROTEIN STRUCTURE
Preparing viewer…
PDB2WEF · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.13LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.77 [0.54–1.13]
RankingsWhere BPNT1 stands among ~20K protein-coding genes
  • #10,280of 20,598
    Most Researched39
  • #5,176of 5,498
    Most Pathogenic Variants1
  • #11,619of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedBPNT1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Mammalian tRNA acetylation determines translation efficiency and tRNA quality control.
PMID: 40595590
Nat Commun · 2025
1.00
2
Bisphosphate nucleotidase 1 promotes progression and docetaxel resistance in triple-negative breast cancer via STUB1-mediated destabilization of LIMA1.
PMID: 41540000
Cell Death Dis · 2026
0.90
3
Modulation of sulfur assimilation metabolic toxicity overcomes anemia and hemochromatosis in mice.
PMID: 32019729
Adv Biol Regul · 2020
0.80
4
Circular RNA erythrocyte membrane protein band 4.1 assuages ultraviolet irradiation-induced apoptosis of lens epithelial cells by stimulating 5'-bisphosphate nucleotidase 1 in a miR-24-3p-dependent manner.
PMID: 34652259
Bioengineered · 2021
0.70
5
Alteration of lithium pharmacology through manipulation of phosphoadenosine phosphate metabolism.
PMID: 15583009
J Biol Chem · 2005
0.60