NPPB

Summary

NPPB (natriuretic peptide B, HGNC:7940) is a protein-coding gene on chromosome 1p36.22, encoding Natriuretic peptides B (P16860). Cardiac hormone that plays a key role in mediating cardio-renal homeostasis.

This gene is a member of the natriuretic peptide family and encodes a secreted protein which functions as a cardiac hormone. The protein undergoes two cleavage events, one within the cell and a second after secretion into the blood. The protein’s biological actions include natriuresis, diuresis, vasorelaxation, inhibition of renin and aldosterone secretion, and a key role in cardiovascular homeostasis. A high concentration of this protein in the bloodstream is indicative of heart failure. The presence of myocardial injury is a significant predictor of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients, and there is evidence of increased levels of natriuretic peptide B in hospitalized non-survivor COVID-19 patients. The protein also acts as an antimicrobial peptide with antibacterial and antifungal activity. Mutations in this gene have been associated with postmenopausal osteoporosis.

Source: NCBI Gene 4879 — RefSeq curated summary.

At a glance

• GWAS associations: 51
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_002521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7940
Approved symbol	NPPB
Name	natriuretic peptide B
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120937
Ensembl biotype	protein_coding
OMIM	600295
Entrez	4879

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000376468, ENST00000945854, ENST00000945855, ENST00000945856

RefSeq mRNA: 1 — MANE Select: NM_002521 NM_002521

CCDS: CCDS140

Canonical transcript exons

ENST00000376468 — 3 exons

Exon	Start	End
ENSE00000818947	11858214	11858469
ENSE00001826581	11857464	11857671
ENSE00001871416	11858702	11858945

Expression profiles

Bgee: expression breadth ubiquitous, 146 present calls, max score 99.04.

FANTOM5 (CAGE): breadth broad, TPM avg 9.2663 / max 2175.3784, expressed in 376 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10343	8.9687	367
10344	0.2908	89
10345	0.0069	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	99.04	gold quality
cardiac atrium	UBERON:0002081	98.94	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.29	gold quality
apex of heart	UBERON:0002098	95.42	gold quality
myocardium	UBERON:0002349	92.51	gold quality
heart left ventricle	UBERON:0002084	89.29	gold quality
cardiac ventricle	UBERON:0002082	88.84	gold quality
heart	UBERON:0000948	88.11	gold quality
heart right ventricle	UBERON:0002080	81.53	gold quality
vena cava	UBERON:0004087	77.94	gold quality
nucleus accumbens	UBERON:0001882	76.17	gold quality
left ventricle myocardium	UBERON:0006566	75.21	gold quality
endometrium epithelium	UBERON:0004811	69.53	gold quality
putamen	UBERON:0001874	68.25	gold quality
caudate nucleus	UBERON:0001873	65.52	gold quality
cerebellar vermis	UBERON:0004720	62.46	gold quality
Brodmann (1909) area 10	UBERON:0013541	62.37	gold quality
gastrocnemius	UBERON:0001388	60.55	gold quality
buccal mucosa cell	CL:0002336	60.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.31	gold quality
tendon of biceps brachii	UBERON:0008188	60.29	gold quality
biceps brachii	UBERON:0001507	60.14	gold quality
decidua	UBERON:0002450	59.18	gold quality
deltoid	UBERON:0001476	58.75	gold quality
islet of Langerhans	UBERON:0000006	58.48	gold quality
popliteal artery	UBERON:0002250	58.46	gold quality
tibial artery	UBERON:0007610	58.41	gold quality
cartilage tissue	UBERON:0002418	57.86	gold quality
gluteal muscle	UBERON:0002000	57.83	gold quality
superficial temporal artery	UBERON:0001614	57.69	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	956.34
E-MTAB-7249	yes	2.68
E-MTAB-6142	no	1432.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, EDN1, EPAS1, GATA4, GATA5, GTF3A, HAND2, HESX1, HIF1A, HOPX, IRF6, JUN, MITF, NFKB1, NFKB, NKX2-5, NR3C2, RELA, REST, SHOX2, SHOX, SMAD4, TEF, TXK, XBP1, YY1, ZFP90

miRNA regulators (miRDB)

11 targeting NPPB, 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-3163	100.00	77.23	8605
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-590-5P	99.25	70.76	930

Literature-anchored findings (GeneRIF, showing 40)

• Brain-type natriuretic peptide (hBNP-32) is an antimicrobial peptide active against Gram-positive and Gram-negative bacteria and yeast. (PMID:11410403)
• Molecular forms of human brain natriuretic peptide in plasma. (PMID:11750283)
• Clinical significance of blood measurement in the detection of heart disease in untreated outpatients (PMID:11999635)
• Plasma levels in normotensive Type 2 diabetic patients without cardiac disease and macroalbuminuria. (PMID:12015190)
• human bone marrow endothelial cells are a new source of BNP (PMID:12084525)
• A promoter variation of this protein has an association with low bone-mineral density and rapid postmenopausal bone loss. (PMID:12601551)
• Renal function correlates weakly with BNP and influences the optimal cut point for BNP, particularly in those with an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. (PMID:12612980)
• Low BNP levels do not guarantee an uncomplicated hospital course in patients with acute pulmonary embolism, using a cut-off level of 90 pg/mL. A lower cut-off level of <50 pg/mL identifies 95% of patients with a benign clinical course (PMID:12742987)
• Plasma N-BNP (or BNP) and left ventricular ejection fraction are complementary independent predictors of major adverse events on follow-up after myocardial infarction (PMID:12771003)
• BNP can reliably screen diabetic patients for the presence or absence of left ventricular dysfunction. (PMID:12832317)
• data suggest that amniotic fluid concentrations of human brain natriuretic peptide and endothelin-1 were highest in the twins with polyhydramnios and lowest in oligohydramnios, suggesting their importance in the regulation of amniotic fluid volume (PMID:12861161)
• Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with left ventricular mass as well as with deceleration time. (PMID:12890912)
• a critical role for the metalloproteinase-dependent cleavage event in signaling the strain response (PMID:14645255)
• BNP has a direct effect on cardiac fibroblasts to inhibit fibrotic responses via extracellular signal-related kinase signaling, suggesting that BNP functions as an antifibrotic factor in the heart to prevent cardiac remodeling in pathological conditions. (PMID:14726474)
• natriuretic peptide precursor B prohormone might be a more discerning marker of early cardiac dysfunction than natriuretic peptide precursor B (PMID:14967157)
• In hypertrophic cardiomyopathy, plasma BNP may reflect intraventricular pressure gradient and left ventricular diastolic dysfunction. Plasma ANP reflects left ventricular diastolic dysfunction. (PMID:15118286)
• data suggest that the secretion of Nt-proBNP is increased in type 2 diabetic patients with no overt heart disease, suggesting that type 2 diabetes is associated with a higher prevalence of asymptomatic left ventricular dysfunction than hitherto thought (PMID:15277419)
• BNP testing plays an important role in the screening and diagnosis of left ventricular dysfunction in diabetes (PMID:15525883)
• NT-proBNP, cTnT, or cTnI do not have roles in acute ischemic stroke when other risk factors are considered (PMID:15604421)
• Elevated cirulating levels of this protein is a new independent predictor of the excess overall and cardiovascular mortality in diabetic nephropathy patients without symptoms of heart failure. (PMID:15616804)
• High plasma BNP is a major risk marker for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. (PMID:15619076)
• hemodynamic implications of BNP in acute ischemic patients (PMID:15644628)
• Elevation in this stress peptide is partly explained by ventriculo-vascular uncoupling in heart transplantation, independent of alterations in blood pressure. (PMID:15686715)
• In humans brain natriuretic peptide is mainly secreted by the cardiac ventricles. (PMID:15689309)
• Predictor of morbidity and mortality in patients with heart failure and also in acute coronary syndrome (PMID:15732251)
• an indicator of chronic renal failure in type 2 diabetes. (PMID:15735222)
• Plasma levels in anthracycline-treated breast cancer patients with drug-induced cardiotoxicity. (PMID:15875778)
• discussion of molecular regulation of the brain natriuretic peptide gene [review] (PMID:15911064)
• the heart releases BNP into the systemic circulation early after subarachnoid hemorrhage (PMID:15947264)
• the kidneys extract BNP and NT-proBNP to a similar extent in healthy young men (PMID:16037399)
• Blood levels are promising markers for the diagnosis, prognosis and follow up of heart failure. (PMID:16061439)
• Plasma concentrations of BNP were higher in children with congenital heart defects with left ventricular volume overload compared with right ventricular volume overload or pressure overload. (PMID:16117728)
• Maternal diabetes and suboptimal metabolic control may affect the fetal heart and predominantly stimulate proBNP secretion in conjunction with perinatal stress (PMID:16179421)
• Increase of BNP is correlated with the extent of myocardial ischemia, age, renal insufficiency, and ventricular dysfunction. (PMID:16185779)
• No support for the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via natriuretic peptide clearance receptor. (PMID:16203929)
• BNP levels parallel changes in pulmonary hemodynamics and functional parameters in pulmonary hypertension. (PMID:16236896)
• Right ventricular dysfunction detected by echocardiography and plasma NT-proBNP determination in asymptomatic or minimally symptomatic tetralogy of Fallot patients. (PMID:16236924)
• Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death. (PMID:16236931)
• Plasma BNP levels were related to cardiac reflex parasympathetic dysfunction in type 2 diabetic patients. (PMID:16298451)
• The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. (PMID:16338248)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	nppb	ENSDARG00000052958
mus_musculus	Nppb	ENSMUSG00000029019
rattus_norvegicus	Nppb	ENSRNOG00000008141

Paralogs (1): NPPA (ENSG00000175206)

Protein

Protein identifiers

Natriuretic peptides B — P16860 (reviewed: P16860)

Alternative names: Brain natriuretic factor prohormone, Gamma-brain natriuretic peptide, Iso-ANP

All UniProt accessions (1): P16860

UniProt curated annotations — full annotation on UniProt →

Function. Cardiac hormone that plays a key role in mediating cardio-renal homeostasis. May also function as a paracrine antifibrotic factor in the heart. Acts by specifically binding and stimulating NPR1 to produce cGMP, which in turn activates effector proteins that drive various biological responses. Involved in regulating the extracellular fluid volume and maintaining the fluid-electrolyte balance through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion. Binds the clearance receptor NPR3. May affect cardio-renal homeostasis. Able to promote the production of cGMP although its potency is very low compared to brain natriuretic peptide 32. May have a role in cardio-renal homeostasis. Able to promote the production of cGMP.

Subcellular location. Secreted Secreted Secreted Secreted.

Tissue specificity. Detected in the cardiac atria (at protein level). Detected in the kidney distal tubular cells (at protein level). Expressed in bone growth plate, specifically detected in the late proliferative, prehypertrophic and hypertrophic chondrocytes, but not in the resting and early proliferating cells (at protein level).

Post-translational modifications. The precursor molecule is proteolytically cleaved by the endoproteases FURIN or CORIN at Arg-102 to produce brain natriuretic peptide 32 and NT-proBNP. This likely occurs after it has been secreted into the blood, either during circulation or in the target cells. CORIN also cleaves the precursor molecule at additional residues including Arg-99 and possibly Lys-105. In patients with heart failure, processing and degradation of natriuretic peptides B occurs but is delayed, possibly due to a decrease in enzyme level or activity of CORIN and DPP4. Undergoes further proteolytic cleavage by various proteases such as DPP4, MME and possibly FAP, to give rise to a variety of shorter peptides. Cleaved at Pro-104 by the prolyl endopeptidase FAP (seprase) activity (in vitro). Degraded by IDE. During IDE degradation, the resulting products initially increase the activation of NPR1 and can also stimulate NPR2 to produce cGMP before the fragments are completely degraded and inactivated by IDE (in vitro). O-glycosylated on at least seven residues. In cardiomyocytes, glycosylation at Thr-97 is essential for the stability and processing of the extracellular natriuretic peptides B. Glycosylation, especially at Thr-97, may also be important for brain natriuretic peptide 32 stability and/or extracellular distribution. Glycosylation at Thr-97 appears to inhibit FURIN- or CORIN-mediated proteolytic processing, at least in HEK293 cells.

Induction. Up-regulated by SHOX in osteogenic cells.

Miscellaneous. Plasma levels of natriuretic peptides B, brain natriuretic peptide 32 and NT-proBNP are widely used for screening and diagnosis of heart failure (HF), as these markers are typically higher in patients with severe HF.

Similarity. Belongs to the natriuretic peptide family.

RefSeq proteins (1): NP_002512* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000663	Natr_peptide	Family
IPR002408	Natriuretic_peptide_brain	Family
IPR030480	Natr_peptide_CS	Conserved_site
IPR050787	Natriuretic_peptide	Family

Pfam: PF00212

UniProt features (41 total): peptide 18, glycosylation site 8, site 4, mutagenesis site 4, sequence variant 3, signal peptide 1, chain 1, disulfide bond 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1YK1	X-RAY DIFFRACTION	2.9
3N56	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P16860-F1	60.42	0.07

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 (4): 99–100 (cleavage; by corin); 102–103 (cleavage; by furin or corin); 104–105 (cleavage; by fap); 105–106 (cleavage; by corin)

Disulfide bonds (1): 112–128

Glycosylation sites (8): 41, 62, 63, 70, 74, 79, 84, 97

Mutagenesis-validated functional residues (4):

Position	Phenotype
97	prevents o-glycosylation at this residue. decreased extracellular levels of nppb due to decreased stability after secret
99	loss of furin-mediated proteolytic processing in hek293 cells, however processing in hl1 cells, likely mediated by corin
102	loss of furin-mediated proteolytic processing in hek293 cells, however processing in hl1 cells, likely mediated by corin
105	no effect on proteolytic processing in hek293 or hl1 cells. loss of corin-mediated processing in hl1 cells; when associa

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 168 (showing top): GOBP_EXCRETION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_522, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_CGMP_BIOSYNTHETIC_PROCESS, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_GROWTH, GOBP_REGULATION_OF_SYSTEMIC_ARTERIAL_BLOOD_PRESSURE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CYCLIC_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS

GO Biological Process (18): negative regulation of systemic arterial blood pressure (GO:0003085), cardiac conduction system development (GO:0003161), cGMP biosynthetic process (GO:0006182), protein folding (GO:0006457), cell surface receptor signaling pathway (GO:0007166), receptor guanylyl cyclase signaling pathway (GO:0007168), neuropeptide signaling pathway (GO:0007218), body fluid secretion (GO:0007589), regulation of blood pressure (GO:0008217), negative regulation of angiogenesis (GO:0016525), obsolete cGMP-mediated signaling (GO:0019934), negative regulation of cell growth (GO:0030308), positive regulation of urine volume (GO:0035810), positive regulation of renal sodium excretion (GO:0035815), vasodilation (GO:0042311), regulation of vascular permeability (GO:0043114), blood vessel diameter maintenance (GO:0097746), system process (GO:0003008)

GO Molecular Function (6): signaling receptor binding (GO:0005102), hormone activity (GO:0005179), diuretic hormone activity (GO:0008613), hormone receptor binding (GO:0051427), protein binding (GO:0005515), guanylate cyclase activator activity (GO:0030250)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood circulation	3
regulation of biological quality	2
vascular process in circulatory system	2
cellular anatomical structure	2
regulation of systemic arterial blood pressure	1
negative regulation of blood pressure	1
cardiac muscle tissue development	1
purine ribonucleotide biosynthetic process	1
cyclic nucleotide biosynthetic process	1
cGMP metabolic process	1
cellular process	1
protein maturation	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor signaling pathway	1
secretion	1
regulation of body fluid levels	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
regulation of urine volume	1
renal sodium excretion	1
regulation of renal sodium excretion	1
positive regulation of secretion	1
positive regulation of multicellular organismal process	1
blood vessel diameter maintenance	1
regulation of tube diameter	1
multicellular organismal process	1
protein binding	1
receptor ligand activity	1
hormone activity	1
signaling receptor binding	1
binding	1
guanylate cyclase activity	1
cyclase activator activity	1
guanylate cyclase regulator activity	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NPPB	NPR1	P16066	996
NPPB	NPR3	P17342	986
NPPB	NPPA	P01160	969
NPPB	NPR2	P20594	946
NPPB	NPPC	P23582	903
NPPB	TNNI3	P19429	874
NPPB	CRP	P02741	871
NPPB	ACE	P12821	810
NPPB	REN	P00797	765
NPPB	TNNT2	P45379	763
NPPB	MYH6	P13533	762
NPPB	MYH7	P12883	756
NPPB	AGT	P01019	712
NPPB	MED13	Q9UHV7	700
NPPB	MMEL1	Q495T6	697

IntAct

32 interactions, top by confidence:

A	B	Type	Score
NPPB	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NOTCH2NLA	NPPB	psi-mi:“MI:0915”(physical association)	0.670
	NPPB	psi-mi:“MI:0915”(physical association)	0.560
NPPB	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	NPPB	psi-mi:“MI:0915”(physical association)	0.560
KRT40	NPPB	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	NPPB	psi-mi:“MI:0915”(physical association)	0.560
NPPB	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
NPPB		psi-mi:“MI:0915”(physical association)	0.560
NPPB	KRT40	psi-mi:“MI:0915”(physical association)	0.560
NPPB	GEMIN4	psi-mi:“MI:0915”(physical association)	0.560
NPPB	SERTAD3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	NPPB	psi-mi:“MI:0915”(physical association)	0.560
NPPB	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
DPP4	NPPB	psi-mi:“MI:0194”(cleavage reaction)	0.440
EWSR1	NPPB	psi-mi:“MI:0915”(physical association)	0.370
NPPB	TCAF2	psi-mi:“MI:0914”(association)	0.350
NPPB	ACOT7	psi-mi:“MI:0914”(association)	0.350
NPPB	GEMIN4	psi-mi:“MI:0915”(physical association)	0.000
NPPB	SERTAD3	psi-mi:“MI:0915”(physical association)	0.000
NPPB	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): PSMA3 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), NPPB (Two-hybrid), SERTAD3 (Two-hybrid), GEMIN4 (Two-hybrid), CYSRT1 (Two-hybrid), NPPB (Reconstituted Complex), NPPB (Reconstituted Complex), NPPB (Reconstituted Complex), FAM115C (Affinity Capture-MS), FAM101B (Affinity Capture-MS), FARS2 (Affinity Capture-MS)

ESM2 similar proteins: B0VXV8, B8K1V9, D1MZV3, D5J9S0, D9IX97, O46540, O77559, P01021, P01142, P01143, P01160, P05125, P06296, P07499, P0C7P5, P0C7P6, P12272, P13085, P16860, P18104, P22858, P23582, P27596, P52211, P55206, P55207, P56283, P56469, P61312, P68515, P79799, P83228, P84715, P97297, Q09GK2, Q27J49, Q2PE51, Q2XXL8, Q61839, Q62949

Diamond homologs: B0VXV8, B3EWY2, B3EWY3, D1MZV3, O46540, O46541, P01160, P01161, P05125, P07499, P07500, P07501, P07634, P09196, P0CV87, P0DMD6, P13204, P13205, P16859, P16860, P18104, P18144, P18908, P18909, P23582, P24259, P27104, P27596, P40753, P55206, P55207, P56283, P82972, P83230, P83231, P83962, P83964, P83965, Q2XXL8, Q3SAF5

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
SHOX	“up-regulates quantity by expression”	NPPB	“transcriptional regulation”
XBP1	“up-regulates quantity by expression”	NPPB	“transcriptional regulation”
NFKB1	unknown	NPPB	“transcriptional regulation”
NKX2-5	unknown	NPPB	“transcriptional regulation”
RELA	unknown	NPPB	“transcriptional regulation”
TEF	unknown	NPPB	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

271 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11858209:CTTA:C	donor_loss	1.0000
1:11858210:TTAC:T	donor_loss	1.0000
1:11858211:TAC:T	donor_loss	1.0000
1:11858212:A:AC	donor_gain	1.0000
1:11858212:ACCTT:A	donor_loss	1.0000
1:11858213:C:CC	donor_gain	1.0000
1:11857667:CAGCA:C	acceptor_gain	0.9900
1:11857670:CA:C	acceptor_gain	0.9900
1:11857672:C:CC	acceptor_gain	0.9900
1:11858208:GCTTA:G	donor_loss	0.9900
1:11858212:AC:A	donor_gain	0.9900
1:11858213:CC:C	donor_gain	0.9900
1:11858213:CCT:C	donor_gain	0.9900
1:11858696:TCTCA:T	donor_loss	0.9900
1:11858697:CTCAC:C	donor_loss	0.9900
1:11858698:TCA:T	donor_loss	0.9900
1:11858699:CACC:C	donor_loss	0.9900
1:11858700:A:C	donor_loss	0.9900
1:11858701:C:CA	donor_loss	0.9900
1:11858703:TGTA:T	donor_gain	0.9900
1:11857669:GCA:G	acceptor_gain	0.9800
1:11857670:CAC:C	acceptor_gain	0.9800
1:11858213:CCTT:C	donor_gain	0.9800
1:11858213:CCTTT:C	donor_gain	0.9800
1:11857668:AGCA:A	acceptor_gain	0.9700
1:11857676:C:CT	acceptor_gain	0.9700
1:11857673:T:A	acceptor_loss	0.9600
1:11858470:C:CC	acceptor_gain	0.9600
1:11858475:A:AC	acceptor_gain	0.9600
1:11858701:CCTG:C	donor_gain	0.9600

AlphaMissense

846 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11858263:A:C	F113L	0.987
1:11858263:A:T	F113L	0.987
1:11858265:A:G	F113L	0.987
1:11858264:A:C	F113C	0.971
1:11858219:C:G	C128S	0.958
1:11858220:A:T	C128S	0.958
1:11858267:C:G	C112S	0.952
1:11858268:A:T	C112S	0.952
1:11858268:A:G	C112R	0.947
1:11858243:A:G	I120T	0.939
1:11858249:T:A	D118V	0.931
1:11858246:C:G	R119P	0.928
1:11858219:C:T	C128Y	0.911
1:11858220:A:G	C128R	0.911
1:11858265:A:T	F113I	0.906
1:11858266:G:C	C112W	0.905
1:11858267:C:T	C112Y	0.902
1:11858265:A:C	F113V	0.893
1:11858267:C:A	C112F	0.893
1:11858243:A:C	I120S	0.891
1:11858249:T:G	D118A	0.890
1:11858261:C:A	G114V	0.885
1:11858261:C:T	G114E	0.884
1:11858219:C:A	C128F	0.880
1:11858250:C:G	D118H	0.876
1:11858264:A:G	F113S	0.872
1:11858230:A:C	S124R	0.871
1:11858230:A:T	S124R	0.871
1:11858232:T:G	S124R	0.871
1:11858268:A:C	C112G	0.869

dbSNP variants (sampled 300 via entrez): RS1000181116 (1:11859531 C>G,T), RS1000285064 (1:11857893 C>T), RS1000622449 (1:11858870 T>A,G), RS1000694639 (1:11859120 T>C), RS1000720725 (1:11859974 C>A), RS1000826385 (1:11859324 T>A,G), RS1001358853 (1:11859300 G>A,T), RS1001577003 (1:11857816 A>C), RS1001805899 (1:11857205 G>A), RS1001841946 (1:11858587 T>C), RS1001935289 (1:11857945 TAAAC>T), RS1003370919 (1:11857022 T>C), RS1003952553 (1:11858519 C>T), RS1006263489 (1:11857194 C>G,T), RS1006294789 (1:11857369 C>A,G,T)

Disease associations

OMIM: gene MIM:600295 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

51 associations (top):

Study	Trait	p-value
GCST000395_2	Systolic blood pressure	2.000000e-13
GCST001236_11	Blood pressure	2.000000e-16
GCST002736_1	B-type natriuretic peptide levels	1.000000e-09
GCST003298_1	NT-proBNP levels in acute coronary syndrome	1.000000e-15
GCST004776_9	Systolic blood pressure	1.000000e-16
GCST004777_45	Diastolic blood pressure	3.000000e-18
GCST004923_1	Tuberculosis	1.000000e-11
GCST005205_1	N-terminal pro B-type natriuretic peptide levels	9.000000e-68
GCST005205_2	N-terminal pro B-type natriuretic peptide levels	8.000000e-48
GCST005206_1	B-type natriuretic peptide levels	4.000000e-52
GCST005208_1	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio	5.000000e-103
GCST006021_17	Systolic blood pressure	8.000000e-17
GCST006166_114	Diastolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-23
GCST006167_19	Mean arterial pressure x alcohol consumption interaction (2df test)	6.000000e-10
GCST006168_40	Pulse pressure x alcohol consumption interaction (2df test)	1.000000e-17
GCST006168_9	Pulse pressure x alcohol consumption interaction (2df test)	2.000000e-20
GCST006187_2	Diastolic blood pressure (cigarette smoking interaction)	9.000000e-40
GCST006187_3	Diastolic blood pressure (cigarette smoking interaction)	2.000000e-29
GCST006188_17	Systolic blood pressure (cigarette smoking interaction)	5.000000e-43
GCST006188_18	Systolic blood pressure (cigarette smoking interaction)	9.000000e-35
GCST006190_20	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-18
GCST006190_21	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-19
GCST006190_27	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-21
GCST006190_28	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-18
GCST006190_41	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	6.000000e-13
GCST006190_67	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-11
GCST006192_14	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-14
GCST006192_16	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-29
GCST006192_17	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-21
GCST006192_2	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-32

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0006920	BNP measurement
EFO:0005278	cardiovascular disease biomarker measurement
EFO:0006336	diastolic blood pressure
EFO:0004745	NT-proBNP measurement
EFO:0008469	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0006527	smoking status measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
Doxorubicin	increases expression	5
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	4
Carvedilol	affects cotreatment, affects expression, decreases expression	4
methylmercuric chloride	increases expression, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
Cyclophosphamide	increases expression	3
bisphenol F	increases expression, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
dinophysistoxin 1	decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
bisphenol S	decreases expression, increases expression	2
Valsartan	increases expression, decreases expression, decreases reaction	2
Fulvestrant	affects cotreatment, increases methylation, decreases reaction, increases expression	2
Telmisartan	affects expression, decreases expression	2
Aldosterone	affects abundance, decreases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Copper	increases expression, affects binding, decreases expression	2
Cytarabine	increases expression	2
Norepinephrine	affects abundance, decreases abundance	2
Oxygen	increases expression, increases secretion, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Spironolactone	decreases expression, affects cotreatment, affects expression	2
Tretinoin	increases expression	2
MYK-461	decreases reaction, increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	increases expression	1
5-hydroxy-6,8,11,14-eicosatetraenoic acid	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1YV	Abcam HeLa NPPB KO	Cancer cell line	Female

Clinical trials (associated diseases)

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