Gene Set Gene Set Qualifier Gene Name Alternative Names Recommended Name UniProt ID NCBI Gene ID EC Species Name Taxonomy ID Pathway Information Source Evidence Type PubMed ID Notes Notes/SubPathway BP Gold Standard ACVRL1 P37023 94 Human 9606 GO:BP 14684682 ACVRL1 mutations were found in persons with hereditary haemorrhagic telangiectasia related arterial pulmonary hypertension and in two persons with primary pulmonary hypertension and no HHT BP Gold Standard NOS1 P29475 4842 Human 9606 GO:BP 18048451 18391107 Brachial artery infusion of NOS1-specific inhibitor S-methyl-L-thiocitrulline caused dose-dependent reduction in basal flow and inhibited the forearm vasodilator response to mental stress (18391107). NOS-1 inhibitor 7-nitroindazole administered by intradermal microdialysis on vasodilation induced by whole-body heat stress attenuated cutatneous vascular conductance but had no effect when vasodilation was induced by local skin warming (18048451). AAE Gold Standard PLA2R1 Q13018 22925 Human 9606 Mike L. Keyword search E 7721806 UniProtKB keyword search: arachidonic acid. Soluble and membrane-bound human sPLA2 receptors both bind sPLA2 with high affinities (PMID 7721806) AAE Gold Standard POR P16435 5447 1.6.2.4 Human 9606 Literature E 19448135 11695850 14725854 9799565 Suggested by Chandra from evidence in literature cytochrome P450 BP Likely ACE P12821 1636 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 1668266 23619363 21628354 22932704 Cloned human testis ACE was active with angiotensin I (1668266). Mice with ACE expression absent in kidney (ACE restricted to myelomonocytic cells or liver) blunts hypertension induced by Ang II infusion or nitric oxide sythesis inhibition; reanal responses to high serum Ang II observed in WT mice were effectively prevented in mice lacking kidney ACE (23619363). In a Lebanese population of 270 subjects a possible association of two alleles with hypertension was found (21628354). In 427 essential hypertension patients from the Non-Invasive Atherosclerotic Evaluation in Hypertension study cohort, subjects with the D allele of the ACE I/D polymorphism showed significantly lower diastolic BP (22932704). Blood pressure/Vascular tone BP Likely ADM P35318 133 Human 9606 GO:BP 11410113 In 11410113 arteries were obtained from subgluteal biopsies of patients with coronary heart failure or disease. 200 pmol/l reduced the vasoconstrictor effects of ET-1 on the arteries obtained from biopsies in patients with CHF. BP Likely AGT P01019 183 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 23324949 23108647 22799745 A/A genotype at rs5049 was a risk factor for hypertension in Melanesian Solomon Islanders (23324949). In a study of 180 hypertensive and 188 normotensive subjects the single-nucleotide polymorphism variant g.15241A>G was associated with risk for developing essential hypertension (22799745). Adipocyte-AGT deficient mice maintained the diet-induced obesity phenotype, but did not display the obesity-induced increase in systolic BP or plasma Ang II concentrations (23108647). Blood pressure/Vascular tone BP Likely AGTR1 P30556 185 Human 9606 GO:BP 15117835 Ang II type 1 receptor antagonist irbesartan prevented vasoconstriction by Ang II in vitro in coronary microarteries from heart valve donors (15117835). BP Likely AGTR2 P50052 186 Human 9606 GO:BP 15117835 17159079 Ang II type 2 receptor antagonist PD123319 caused in increase in vasoconstriction by Ang II ex vivo in coronary microarteries from heart valve donors (15117835). Ang II-induced dilation was blunted by PD123319 in presence of valsartan ex vivo in small arteries from subcutaneous tissue from hypertensive diabetic patients after 1 year treatment with valsartan (17159079). BP Likely ANPEP P15144 290 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 1978675 15687497 19330903 17242304 ANPEP from rabbit renal membranes hydrolyzes angiotensin III to yield angiotensin IV (1978675). Human ANPEP was identified and shown to cleave angiotensin III to generate angiotensin IV (15687497). A SNP in ANPEP was associated with 7mmHg increase in systolic BP in nonsmokers in a genome-wide linkage analysis in Mexican-Americans (19330903). Anpep gene lies within QTLs for blood pressure identified in Dahl salt-sensitive (SS/Jr)-Lewis and Dahl SS/Jr-salt-resistant (SR/Jr) crosses and a SNP is present in the SR but not SS rat (17242304). Blood pressure/Vascular tone BP Likely BMPR2 Q13873 659 Human 9606 GO:BP 18364108 In Chinese pedigree with familial pulmonary arterial hypertension an A-to-T transition at position 1157 segregated within the family and was not found in a panel of 200 chromosomes from normal subjects; no mutation was found in BMPR2 in 10 patients with idiopathic pulmonary arterial hypertension (18364108). BP Likely CALCA P06881 796 Human 9606 GO:BP 10642343 3266556 Systolic BP and mean arterial pressure was significantly higher in male and female CALCA knockout mice (10642343). CALCA evoked dose-dependent falls in perfusion pressure (with noradrenaline as vasocontrictor) in human isolated mesenteric vasculature and human mesenteric arterial rings (3266556). BP Likely CORIN Q9Y5Q5 10699 Human 9606 GO:BP 22437503 16216958 Restoring CORIN expression in heart rescues the hypertension phenotype in KO mice [but not in pregnant mice]; K317E and S472G mutations markedly reduced corin activity in processing pro-ANP in HEK293 cells (from citation, ANP is important in regulating BP- I did not follow this up) (22437503). Genotype-phenotype genetic association study using several population samples (Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Chicago Genetics of Hypertension Study) linked increased risk of prevalent hypertension to SNPs (16216958).. BP Likely CYP11B1 P15538 1584 Human 9606 GO:BP 2022736 Eleven patients with 11beta-hydroxylase deficiency had a single mutation in exon 8 of this gene; 8/11 patients were hypertensive but the authors cite a previous study that showed poor correlation between hypertension and blood levels of 11-deoxycorticosterone (2022736). 6 families were studied and there were individuals heterozygous for the mutation or without the mutation, but no phenotype is given for those family members. BP Likely CYP11B2 P19099 1585 Human 9606 GO:BP 14614232 17334644 In a study that measured resting BP in 2238 healthy Japanese individuals and genotyped several candiate genes, resting BP (systolic and diastolic) in men was significantly higher with the CT or TT genotype and the prevalence of hypertension differed significantly (17334644). Two Japanese patients with corticosterone methyl oxidase type II deficiency had the mutation (435Gly->Ser) in CYP11B2 which reduces the mutant enzyme's 18-hydroxylase activity to form 18-hydroxycorticosterone (14614232). BP Likely ECE1 P42892 1889 Human 9606 GO:BP 7805846 Human ECE1 was cloned and isolated. The enzyme was shown to convert Big ET-1 to ET-1 (7805846). [FC: I assigned Likely because of the evidence linking ET-1 with vasoconstriction] BP Likely EDN1 P05305 1906 Human 9606 GO:BP 2649896 8982507 9422810 11410113 Big ET-1 and ET-1 induced vasoconstriction in arteries obtained from subgluteal biopsies of patients with coronary heart failure and disease(11410113). ET-1 was shown to be a potent constrictor of umbilical vein (9422810, 8982507) and artery (8982507). Human synthetic ET-1 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). BP Likely EDN2 P20800 1907 Human 9606 GO:BP 2649896 8982507 9422810 This was shown to be a potent constrictor of umbilical vein (9422810, 8982507) and artery (8982507). Human synthetic ET-2 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). BP Likely EDN3 P14138 1908 Human 9606 GO:BP 2649896 8982507 Human synthetic ET-3 induced vasocontriction in vitro in porcine coronary artery and depressor/pressor response in vivo in male Wistar rats (2649896). ET-3 was inactive on umbilical vein but contracts umbilical artery (8982507). BP Likely EDNRA P25101 1909 Human 9606 GO:BP 8982507 BQ123 ETA receptor antagonist completely inhibited the ET-1 induced contraction in umbilical artery without affecting response in umbilical vein (8982507). BP Likely EDNRB P24530 1910 Human 9606 GO:BP 8982507 BQ788 antagonizes efficiently the effect of ET-3, which is quite selective for the ETB receptor (8982507). BP Likely ENG P17813 2022 Human 9606 GO:BP 18974388 Transgenic mice overexpressing S-endoglin in endothelial cells showed hypertension, decreased hypertensive response to NO inhibition, decreased vasodilatory response to TGF-beta(1) administration, and decreased endothelial nitric oxide syntahse expression in lungs and kidneys; S-endoglin was found in endothelium and some endothelial cells of human coronary arteries, human veins and lungs; S-endoglin interacts with ALK5 (18974388). BP Likely PPARG P37231 5468 Human 9606 GO:BP 10622252 Two family members (a mother and son) were heterozygous for the P467L mutation in PPARgamma and they had early onset severe insulin resistance and elevated blood pressure; family members without the mutation (homozygous) did not display the phenotype (10622252). A third, unrelated individual was heterozygous for a SNP resulting in V290M mutation. Her clinically unaffected mother and sister were wild type at the locus. BP Likely REN P00797 5972 Human 9606 GO:BP 12045255 Article opens, "The renin-angiotensin system (RAS) is critical for the control of blood pressure and salt balance in mammals." 12045255 identifies a renin receptor and that the binding of renin to the receptro induces (a) an increase of the catalytic efficiency of angiotensinogen conversion into Ang I by renin bound to the receptor compared with renin in the soluble phase. Renin receptor mRNA was found in several human tissues. BP Predicted ACE2 Q9BYF1 59272 Human 9606 GO:BP 18258853 18258853 uses mice BP Predicted ADIPOQ Q15848 9370 Human 9606 GO:BP 17327472 17327472 uses mice. Adiponectin injection decreases BP in dose-dependent manner. BP Predicted ATP6AP2 renin receptor O75787 10159 Human 9606 GO:BP REACT_147707.2 12045255 15746149 Silent mutation (c.321C->T, p.D107D) was found in a family with X-linked mental retardation; it can cause exon skipping but the receptor still binds renin and facilitates Ang I generation on the cell surface; the mutation was not found in 900 healthy individuals (15746149). Fetal HMC were transformed and expressed the renin receptor on cell surface; these cells could bind renin; assays demonstrated that membrane-bound renin increased catalytic efficiency of angiotensinogen cleavage; receptor was localized to mesangium in glomeruli and vascular structures of kidney cortex and subendothelium in coronary arteries (12045255). BP Predicted CARTPT Q16568 9607 Human 9606 GO:BP 11711504 Intracerebroventricular injection of CART 55-102 in male Japanese White rabbits elicited dose-related increases in mean arterial pressure and renal sympathetic nerve activity (11711504). BP Predicted CD34 P28906 947 Human 9606 GO:BP 17505307 17505307 is in rats. CD34+ cell therapy significantly caused attenuation of heatstroke induced hypotension. BP Predicted CPS1 P31327 1373 Human 9606 GO:BP 14718356 CPS1 polymorphism significantly influences venous nitric oxide concentration and both NOS-dependent and -independent vasodilation, assessed by forearm blood flow (14718356). BP Predicted ENPEP Q07075 2028 Human 9606 GO:BP 19608358 Recombinant ENPEP enzyme administered to spontaneously hypertensive rats during pregnancy decreased systolic BP (19608358). BP Predicted GCH1 P30793 2643 Human 9606 GO:BP 17717598 An investigation of common genetic variation in GCH1 found that C+243T was associated with diastolic and systolic BP, principally in females (17717598). BP Predicted GCLC P48506 2729 Human 9606 GO:BP 12598062 Association study that found the T allele of a polymorphism (-129C/T) associated with impairment of endothelium-dependent dilation of coronary arteries and was highly frequent in patients with myocaridal infarction (12598062). BP Predicted GCLM P48507 2730 Human 9606 GO:BP 12975258 The minor -588T allele (-588C/T) had an independent association with impaired dilation or enhanced constriction of epicardial coronay arteries in response to acetylcholine (12975258). BP Predicted HTR2B P41595 3357 Human 9606 GO:BP 15625277 R393X mutation transfected into LMTK- cells demonstrated a partial loss of NO coupling, assessed by the dose-response effect of agonists on NOS activity (15625277). BP Predicted LRP5 O75197 4041 Human 9606 GO:BP 18721193 LRP5 SNPs F549F and V1119V were associated with higher systolic blood pressure in a cross-sectional association study of 73 Finnish children with premature adrenarche and 97 age- and gender-matched healthy controls. BP Predicted NOS3 P29474 4846 Human 9606 GO:BP 8999856 HUVEC with eNOS knocked down failed to produce NO in response to ET-1 (8999856). BP Predicted NPPA P01160 4878 Human 9606 GO:BP 6230082 6547996 Human precursor protein CDD-ANF was cloned; in rat preproCDD-ANF mRNA is syntesized in atria but not in the ventricles and markedly decreases on water deprivation (6547996). "alpha-human atrial natriuretic polypeptide" had vasorelaxant activity when injected into rats (6230082). BP Predicted P2RX4 Q99571 5025 Human 9606 GO:BP 11606481 15130891 Cardiac transgenic expression of human P2RX4 in mice exhibited significantly elevated basal cardiac contractility with greater rates of contraction and relaxation, left ventricular developed pressure and cardiac output compared with nontransgenic animals (11606481). P2X4R Tg mice crossed with CSQ mice (phenotype: hypertrophy, heart failure, and premature death) results in a survival benefit for the CSQ/P2X4R mouse (15130891). BP Predicted PCSK5 Q92824 5125 Human 9606 GO:BP 8901832 PCSK5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, and when co-transfected with a human prorenin expression vector in cultured GH4C1 cells, active renin was secreted (8901832). BP Predicted PLCB3 Q01970 5331 Human 9606 GO:BP 18468998 18468998 is in mice. alpha1D adrenergic receptor signals through a GPCR whcih activates phospholipase Cbeta (PLCB3). I this paper the alpha1D adrenergic receptor was knocked out, and those mice displayed a hypotensive phenotype and were resistant to salt-induced hypertension. At best, this evidence is indirect for the involvement of PLCB3 in regulation of BP. BP Predicted AKT1 P31749 207 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted CALM1 P62158 801 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted CAV1 Q03135 857 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted CMA1 P23946 1215 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 Blood pressure/Vascular tone BP Predicted COL1A2 P08123 1278 Human 9606 GO:BP 17334644 Gene polymorphisms and resting BP was investigated in 2238 healthy Japanese individuals. Systolic BP was signifcantly higher in men with the SS genotype than in men of other genotypes (no difference in women). The prevalence of hypertension did not differ among genotypes for men. FC: I'm not sure why this paper is listed for COL1A2 because it does not look like there is evidence linking the gene to the regulation of BP. However, other genes are linked to BP (QPCT and CYP11B2). BP Predicted CPA3 P15088 1359 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 2708524 2443571 CPA3 was purified from human mast cells and could hydrolyze angiotensin I (2708524, 2443571). Blood pressure/Vascular tone BP Predicted CTSG P08311 1511 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 Blood pressure/Vascular tone BP Predicted CTSZ Q9UBR2 1522 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 Blood pressure/Vascular tone BP Predicted DHFR P00374 1719 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted DNM2 P50570 1785 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted GCHFR P30047 2644 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted HSP90AA1 P07900 3320 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted LYPLA1 O75608 10434 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted MME P08473 4311 Human 9606 Metabolism of angiotensinogen to angiotensins REACT_147707.2 Blood pressure/Vascular tone BP Predicted NOSIP Q9Y314 51070 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted NOSTRIN Q8IVI9 115677 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted PRKG2 Q13237 5593 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted PTS Q03393 5805 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted SPR P35270 6697 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted WASL O00401 8976 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone BP Predicted ZDHHC21 Q8IVQ6 340481 Human 9606 eNOS activation and regulation REACT_147707.2 Blood pressure/Vascular tone