BPNT1

Summary

BPNT1 (3’(2’), 5’-bisphosphate nucleotidase 1, HGNC:1096) is a protein-coding gene on chromosome 1q41, encoding 3’(2’),5’-bisphosphate nucleotidase 1 (O95861). Phosphatase that converts 3’(2’)-phosphoadenosine 5’-phosphate (PAP) to AMP and inositol 1,4-bisphosphate (Ins(1,4)P2) to inositol 4-phosphate.

BPNT1, also called bisphosphate 3-prime-nucleotidase, or BPntase, is a member of a magnesium-dependent phosphomonoesterase family. Lithium, a major drug used to treat manic depression, acts as an uncompetitive inhibitor of BPntase. The predicted human protein is 92% identical to mouse BPntase. BPntase’s physiologic role in nucleotide metabolism may be regulated by inositol signaling pathways. The inhibition of human BPntase may account for lithium-induced nephrotoxicity.

Source: NCBI Gene 10380 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 55 total — 8 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006085

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1096
Approved symbol	BPNT1
Name	3’(2’), 5’-bisphosphate nucleotidase 1
Location	1q41
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162813
Ensembl biotype	protein_coding
OMIM	604053
Entrez	10380

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000322067, ENST00000354807, ENST00000414869, ENST00000463953, ENST00000469520, ENST00000480959, ENST00000482136, ENST00000498237, ENST00000498791, ENST00000544404, ENST00000548668, ENST00000851065, ENST00000851066, ENST00000861595, ENST00000861596, ENST00000916793

RefSeq mRNA: 4 — MANE Select: NM_006085 NM_001286149, NM_001286150, NM_001286151, NM_006085

CCDS: CCDS41469, CCDS65787, CCDS65788

Canonical transcript exons

ENST00000322067 — 9 exons

Exon	Start	End
ENSE00003478321	220072850	220072957
ENSE00003541331	220069384	220069432
ENSE00003594095	220073967	220074071
ENSE00003622769	220067302	220067393
ENSE00003846091	220089686	220089788
ENSE00003889560	220062757	220062954
ENSE00003893455	220057482	220058992
ENSE00003894047	220059686	220059791
ENSE00003895335	220079727	220079854

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 93.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.8339 / max 288.0773, expressed in 1802 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17546	21.8339	1802

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	93.72	gold quality
mucosa of transverse colon	UBERON:0004991	93.64	gold quality
rectum	UBERON:0001052	92.65	gold quality
epithelial cell of pancreas	CL:0000083	91.79	gold quality
ileal mucosa	UBERON:0000331	91.69	gold quality
duodenum	UBERON:0002114	90.47	gold quality
adrenal tissue	UBERON:0018303	90.21	gold quality
gall bladder	UBERON:0002110	89.26	gold quality
smooth muscle tissue	UBERON:0001135	88.17	gold quality
right adrenal gland	UBERON:0001233	87.97	gold quality
lymph node	UBERON:0000029	87.95	gold quality
stromal cell of endometrium	CL:0002255	87.89	gold quality
right adrenal gland cortex	UBERON:0035827	87.69	gold quality
vermiform appendix	UBERON:0001154	87.62	gold quality
jejunal mucosa	UBERON:0000399	87.36	gold quality
left adrenal gland	UBERON:0001234	87.07	gold quality
transverse colon	UBERON:0001157	87.05	gold quality
kidney epithelium	UBERON:0004819	87.03	silver quality
adrenal gland	UBERON:0002369	86.79	gold quality
left adrenal gland cortex	UBERON:0035825	86.64	gold quality
small intestine	UBERON:0002108	86.39	gold quality
ganglionic eminence	UBERON:0004023	86.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.04	gold quality
pancreatic ductal cell	CL:0002079	85.92	gold quality
adrenal cortex	UBERON:0001235	85.85	gold quality
ventricular zone	UBERON:0003053	85.75	gold quality
intestine	UBERON:0000160	84.76	gold quality
tonsil	UBERON:0002372	84.69	gold quality
prefrontal cortex	UBERON:0000451	84.67	gold quality
calcaneal tendon	UBERON:0003701	84.60	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.84
E-GEOD-124858	no	56.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting BPNT1, 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-4533	100.00	69.48	2758
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-6731-3P	98.61	67.86	749

Literature-anchored findings (GeneRIF, showing 1)

• CircRNA HLCS regulates lens epithelial cell apoptosis via miR-338-3p/BPNT1 axis. (PMID:38493427)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	bpnt1	ENSDARG00000043684
mus_musculus	Bpnt1	ENSMUSG00000026617
rattus_norvegicus	Bpnt1	ENSRNOG00000002378
drosophila_melanogaster	CG7789	FBGN0039698
caenorhabditis_elegans		WBGENE00044063

Paralogs (4): BPNT2 (ENSG00000104331), IMPA1 (ENSG00000133731), IMPA2 (ENSG00000141401), INPP1 (ENSG00000151689)

Protein

Protein identifiers

3’(2’),5’-bisphosphate nucleotidase 1 — O95861 (reviewed: O95861)

Alternative names: 3’-phosphoadenosine 5’-phosphate phosphatase, Bisphosphate 3’-nucleotidase 1, HsPIP, Inositol-polyphosphate 1-phosphatase

All UniProt accessions (7): A6NF51, O95861, F8VRY7, F8VVW8, F8VZG4, F8W1J0, V9HWF9

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatase that converts 3’(2’)-phosphoadenosine 5’-phosphate (PAP) to AMP and inositol 1,4-bisphosphate (Ins(1,4)P2) to inositol 4-phosphate. Is also able to hydrolyze adenosine 3’-phosphate 5’-phosphosulfate (PAPS) to adenosine 5’-phosphosulfate (APS). Probably prevents the toxic accumulation of PAP, a compound which inhibits a variety of proteins, including PAPS-utilizing enzymes such as sulfotransferases, and RNA processing enzymes. Could also play a role in inositol recycling and phosphoinositide metabolism. Is not active on 3’-AMP, inositol-1-phosphate and inositol-1,4,5-triphosphate.

Tissue specificity. Highly expressed in kidney, liver, pancreas and heart. Detected at lower levels in brain, placenta, lung and skeletal muscle.

Activity regulation. Is very sensitive to inhibition by Li(+) (IC(50)=0.3 mM for hydrolysis of PAP; IC(50)=0.6 mM for hydrolysis of inositol-1,4-bis-phosphate). Is not affected by high Na(+) concentrations.

Cofactor. Binds 3 Mg(2+) ions per subunit.

Miscellaneous. Since this enzyme is sensitive to subtherapeutic concentrations of lithium, it is a potential target of lithium therapy, which could explain some of the side effects of this therapy.

Similarity. Belongs to the inositol monophosphatase superfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
O95861-1	1	yes
O95861-2	2
O95861-3	3
O95861-4	4

RefSeq proteins (4): NP_001273078, NP_001273079, NP_001273080, NP_006076* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000760	Inositol_monophosphatase-like	Family
IPR020550	Inositol_monophosphatase_CS	Conserved_site
IPR020583	Inositol_monoP_metal-BS	Binding_site
IPR050725	CysQ/Inositol_MonoPase	Family

Pfam: PF00459

Enzyme classification (BRENDA):

• EC 3.1.3.7 — 3’(2’),5’-bisphosphate nucleotidase (BRENDA: 21 organisms, 69 substrates, 23 inhibitors, 48 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

24 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ADENOSINE 3’,5’-BISPHOSPHATE	0.0005–6	19
ADENOSINE 3’-PHOSPHATE 5’-PHOSPHOSULFATE	0.1–0.61	3
INOSITOL 1,4-BISPHOSPHATE	0.077–0.113	3
ADENOSINE 2’,5’-BISPHOSPHATE	0.007–0.14	2
D-FRUCTOSE 1,6-BISPHOSPHATE	0.566–1.17	2
2’-DEOXYADENOSINE 3’,5’-BISPHOSPHATE	0.0102	1
2’-DEOXYCYTIDINE 3’,5’-BISPHOSPHATE	0.026	1
2’-DEOXYGUANOSINE 3’,5’-BISPHOSPHATE	0.0052	1
2’-DEOXYTHYMIDINE 3’,5’-BISPHOSPHATE	0.022	1
2’-DEOXYURIDINE 3’,5’-BISPHOSPHATE	0.029	1
3’-PHOSPHOADENOSINE 5’-PHOSPHATE	0.0003	1
5’-ADP	41.5	1
5’-PHOSPHOADENYLYL-(3’->5’)-ADENOSINE	0.0016	1
D-MYO-INOSITOL MONOPHOSPHATE	7.11	1
GUANOSINE 2’,5’-BISPHOSPHATE	0.2	1

Catalyzed reactions (Rhea), 5 shown:

• adenosine 3’,5’-bisphosphate + H2O = AMP + phosphate (RHEA:10040)
• 1D-myo-inositol 1,4-bisphosphate + H2O = 1D-myo-inositol 4-phosphate + phosphate (RHEA:15553)
• 1D-myo-inositol 1,3,4-trisphosphate + H2O = 1D-myo-inositol 3,4-bisphosphate + phosphate (RHEA:70319)
• 3’-phosphoadenylyl sulfate + H2O = adenosine 5’-phosphosulfate + phosphate (RHEA:77639)
• adenosine 2’,5’-bisphosphate + H2O = AMP + phosphate (RHEA:77643)

UniProt features (53 total): strand 14, helix 13, binding site 11, modified residue 4, splice variant 3, active site 2, sequence conflict 2, turn 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2WEF	X-RAY DIFFRACTION	1.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95861-F1	96.60	0.95

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): 51 (proton acceptor); 122 (proton acceptor)

Ligand- & substrate-binding residues (11): 195; 198; 220; 224; 247; 74; 74; 117; 117; 119; 120

Post-translational modifications (4): 2, 122, 240, 244

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-156584	Cytosolic sulfonation of small molecules
R-HSA-1430728	Metabolism
R-HSA-156580	Phase II - Conjugation of compounds
R-HSA-211859	Biological oxidations

MSigDB gene sets: 171 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, CTATGCA_MIR153, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN

GO Biological Process (4): nucleobase-containing compound metabolic process (GO:0006139), nervous system development (GO:0007399), phosphatidylinositol phosphate biosynthetic process (GO:0046854), 3’-phosphoadenosine 5’-phosphosulfate metabolic process (GO:0050427)

GO Molecular Function (4): inositol-1,4-bisphosphate 1-phosphatase activity (GO:0004441), 3’(2’),5’-bisphosphate nucleotidase activity (GO:0008441), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (3): mitochondrion (GO:0005739), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Phase II - Conjugation of compounds	1
Biological oxidations	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
primary metabolic process	1
system development	1
glycerophospholipid biosynthetic process	1
sulfur compound metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside bisphosphate metabolic process	1
oxoacid metabolic process	1
inositol bisphosphate phosphatase activity	1
nucleotidase activity	1
cation binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1047 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPNT1	ACBD3	Q9H3P7	851
BPNT1	EPRS1	P07814	689
BPNT1	PSEN2	P49810	655
BPNT1	DISP1	Q96F81	636
BPNT1	PAPSS2	O95340	549
BPNT1	MEF2A	Q02078	497
BPNT1	FCF1	Q9Y324	488
BPNT1	PAPSS1	O43252	484
BPNT1	SULT1B1	O43704	473
BPNT1	TPST2	O60704	463
BPNT1	SDCBP	O00560	449
BPNT1	SUOX	P51687	440
BPNT1	HSF4	Q9ULV5	428
BPNT1	LBR	Q14739	420
BPNT1	DESI1	Q6ICB0	419

IntAct

24 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
APOL2	BPNT1	psi-mi:“MI:0914”(association)	0.530
MTMR1	GMNN	psi-mi:“MI:0914”(association)	0.530
CCP110	BPNT1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
IQCB1	PCP4L1	psi-mi:“MI:0914”(association)	0.350
	SDCBP	psi-mi:“MI:0914”(association)	0.350
BPNT1	LYN	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
ITM2C	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
SNRNP27	BPNT1	psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
TRAF6	BPNT1	psi-mi:“MI:0915”(physical association)	0.000
IKBKE	BPNT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (138): BPNT1 (Co-fractionation), BPNT1 (Co-fractionation), FAHD1 (Co-fractionation), GDPGP1 (Co-fractionation), MEMO1 (Co-fractionation), SDR39U1 (Affinity Capture-MS), CHDH (Affinity Capture-MS), FDXR (Affinity Capture-MS), VARS2 (Affinity Capture-MS), GTPBP10 (Affinity Capture-MS), FEM1B (Affinity Capture-MS), MTG1 (Affinity Capture-MS), POLG (Affinity Capture-MS), ACSF2 (Affinity Capture-MS), GFM2 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A5PK39, B8BJ39, B8BM17, B9N1F9, B9SQI7, E0CSI1, O60733, O80526, O89000, O95861, P11172, P29144, P35433, P97570, P97819, Q06203, Q28DS0, Q2KJD7, Q2QNG7, Q2QXR8, Q2QZ86, Q2RAK2, Q3ZCK3, Q42546, Q5FWT7, Q5HZ68, Q5IH13, Q5IH14, Q5R4C4, Q5R514, Q5R9W8, Q5ZJJ8, Q64514, Q64560, Q6NYG8, Q6PBF6, Q7SXM0, Q7ZXG7, Q8BGR9

Diamond homologs: C4M633, O95861, Q3ZCK3, Q9Z0S1, Q9Z1N4, D4AD37, F1RT67, F6Y5S8, P10497, Q28CL4, Q29JH0, Q2KJ53, Q2YDR3, Q6NTW5, Q80V26, Q869K3, Q9NX62, Q9VYF2, P21327

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	1
Uncertain significance	32
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
153790	GRCh38/hg38 1q32.1-42.12(chr1:204764914-225408698)x3	Pathogenic
161040	GRCh38/hg38 1q41(chr1:215206760-222004068)x1	Pathogenic
224870	Single allele	Pathogenic
2426428	NC_000001.10:g.(?220088791)(220445679_?)del	Pathogenic
2685821	GRCh37/hg19 1q41(chr1:214853277-222111742)x1	Pathogenic
34890	GRCh38/hg38 1q41(chr1:215206760-222004068)x1	Pathogenic
4070985	NM_006085.6(BPNT1):c.793A>C (p.Ile265Leu)	Pathogenic
58129	GRCh38/hg38 1q41(chr1:215447347-221971832)x3	Pathogenic
438260	Single allele	Likely pathogenic

SpliceAI

3394 predictions. Top by Δscore:

Variant	Effect	Δscore
1:220058988:CTTGC:C	acceptor_gain	1.0000
1:220059681:CTAA:C	donor_loss	1.0000
1:220059682:TAA:T	donor_loss	1.0000
1:220059688:C:A	donor_gain	1.0000
1:220059788:TAAT:T	acceptor_gain	1.0000
1:220059789:AATC:A	acceptor_loss	1.0000
1:220059790:ATC:A	acceptor_loss	1.0000
1:220059791:TCTG:T	acceptor_loss	1.0000
1:220059792:C:CC	acceptor_gain	1.0000
1:220059792:CT:C	acceptor_loss	1.0000
1:220067298:ATAC:A	donor_loss	1.0000
1:220067300:AC:A	donor_loss	1.0000
1:220067301:CCTC:C	donor_loss	1.0000
1:220067391:GAC:G	acceptor_gain	1.0000
1:220067394:C:CC	acceptor_gain	1.0000
1:220072848:A:AC	donor_gain	1.0000
1:220072849:C:CC	donor_gain	1.0000
1:220072851:T:TA	donor_gain	1.0000
1:220072854:T:TA	donor_gain	1.0000
1:220072857:T:TA	donor_gain	1.0000
1:220072873:A:AC	donor_gain	1.0000
1:220072874:C:CC	donor_gain	1.0000
1:220073961:GCTTA:G	donor_loss	1.0000
1:220073962:CTTA:C	donor_loss	1.0000
1:220073963:TTACC:T	donor_loss	1.0000
1:220073964:TA:T	donor_loss	1.0000
1:220073965:A:AT	donor_loss	1.0000
1:220073966:CCT:C	donor_gain	1.0000
1:220074067:CAGGT:C	acceptor_gain	1.0000
1:220074068:AGGT:A	acceptor_gain	1.0000

AlphaMissense

1992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:220059724:T:G	D247A	1.000
1:220059726:C:A	W246C	1.000
1:220059726:C:G	W246C	1.000
1:220059728:A:G	W246R	1.000
1:220059728:A:T	W246R	1.000
1:220069423:A:G	W115R	1.000
1:220069423:A:T	W115R	1.000
1:220059717:A:C	C249W	0.999
1:220059723:A:C	D247E	0.999
1:220059723:A:T	D247E	0.999
1:220059724:T:A	D247V	0.999
1:220059724:T:C	D247G	0.999
1:220059725:C:G	D247H	0.999
1:220067363:C:T	G138E	0.999
1:220067369:A:G	L136P	0.999
1:220069406:A:C	D120E	0.999
1:220069406:A:T	D120E	0.999
1:220069407:T:A	D120V	0.999
1:220069408:C:G	D120H	0.999
1:220069415:A:C	D117E	0.999
1:220069415:A:T	D117E	0.999
1:220069416:T:C	D117G	0.999
1:220069419:A:T	V116D	0.999
1:220069425:A:T	V114D	0.999
1:220073971:T:A	E74V	0.999
1:220074037:C:G	R52P	0.999
1:220059718:C:T	C249Y	0.998
1:220059719:A:G	C249R	0.998
1:220059727:C:A	W246L	0.998
1:220059750:A:C	F238L	0.998

dbSNP variants (sampled 300 via entrez): RS1000014211 (1:220072629 A>G), RS1000041751 (1:220072392 C>A), RS1000176619 (1:220087419 G>A,C,T), RS1000192372 (1:220078984 A>G), RS1000385622 (1:220065131 T>C), RS1000559509 (1:220077648 G>A,C), RS1000570396 (1:220083109 C>A,T), RS1000576208 (1:220077402 ATTAT>A), RS1000624101 (1:220082866 C>A,T), RS1000627851 (1:220078811 T>A,G), RS1000781692 (1:220088610 C>G,T), RS1000816258 (1:220063558 C>T), RS1000842762 (1:220090423 G>A), RS1000931479 (1:220057385 C>A), RS1000963971 (1:220057606 G>A,C)

Disease associations

OMIM: gene MIM:604053 | disease phenotypes: MIM:614816, MIM:143890, MIM:276900

GenCC curated gene-disease

Mondo (3): Loeys-Dietz syndrome 4 (MONDO:0013897), hypercholesterolemia, familial, 1 (MONDO:0007750), Usher syndrome (MONDO:0019501)

Orphanet (2): Homozygous familial hypercholesterolemia (Orphanet:391665), Usher syndrome (Orphanet:886)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_83	Waist-to-hip ratio adjusted for BMI	1.000000e-19
GCST005957_15	Waist-to-hip ratio adjusted for BMI (age <50)	5.000000e-14
GCST005958_1	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-23
GCST005962_1	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	4.000000e-33

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066986 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.05	Kd	8.843	nM	CHEMBL5653589
8.05	ED50	8.843	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2147953: Binding affinity to human BPNT1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0088	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
Valproic Acid	increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
beta-lapachone	decreases expression, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
beta-Naphthoflavone	increases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650995	Binding	Binding affinity to human BPNT1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1KM	HyCyte HeLa KO-hBPNT1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab
NCT01505062	PHASE1/PHASE2	TERMINATED	Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
NCT04355689	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00004345	Not specified	TERMINATED	Study of Dietary N-3 Fatty Acids in Patients With Retinitis Pigmentosa and Usher Syndrome
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT01954953	Not specified	UNKNOWN	Clinical and Genetic Examination of Usher Syndrome Patients’ Cohort in Europe
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03319524	Not specified	COMPLETED	Clinical and Genetic Testing of Patients With Usher Syndrome
NCT03901391	Not specified	COMPLETED	Prospective Open Clinical and Genetic Study of Patients With Retinitis Pigmentosa