α1-A680T variant in GUCY1A3 as a candidate conferring protection from pulmonary hypertension among Kyrgyz highlanders.
BACKGROUND
Human variation in susceptibility to hypoxia-induced pulmonary hypertension is well recognized. High-altitude residents who do not develop pulmonary hypertension may host protective gene mutations.


RESULTS
Exome sequencing was conducted on 24 unrelated Kyrgyz highlanders living 2400 to 3800 m above sea level, 12 (10 men; mean age, 54 years) with an elevated mean pulmonary artery pressure (mean±SD, 38.7±2.7 mm Hg) and 12 (11 men; mean age, 52 years) with a normal mean pulmonary artery pressure (19.2±0.6 mm Hg) to identify candidate genes that may influence the pulmonary vascular response to hypoxia. A total of 140 789 exomic variants were identified and 26 116 (18.5%) were classified as novel or rare. Thirty-three novel or rare potential pathogenic variants (frameshift, essential splice-site, and nonsynonymous) were found exclusively in either ≥3 subjects with high-altitude pulmonary hypertension or ≥3 highlanders with a normal mean pulmonary artery pressure. A novel missense mutation in GUCY1A3 in 3 subjects with a normal mean pulmonary artery pressure encodes an α1-A680T soluble guanylate cyclase (sGC) variant. Expression of the α1-A680T sGC variant in reporter cells resulted in higher cyclic guanosine monophosphate production compared with the wild-type enzyme and the purified α1-A680T sGC exhibited enhanced sensitivity to nitric oxide in vitro.


CONCLUSIONS
The α1-A680T sGC variant may contribute to protection against high-altitude pulmonary hypertension and supports sGC as a pharmacological target for reducing pulmonary artery pressure in humans at altitude.
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.). m.wilkins@imperial.ac.uk.
Martin R
MR
Wilkins
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Almaz A
AA
Aldashev
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
John
J
Wharton
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Christopher J
CJ
Rhodes
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Jana
J
Vandrovcova
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Dalia
D
Kasperaviciute
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Shriram G
SG
Bhosle
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Michael
M
Mueller
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Sandra
S
Geschka
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Stuart
S
Rison
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Baktybek
B
Kojonazarov
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Nicholas W
NW
Morrell
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Inga
I
Neidhardt
Nur Basak
NB
Surmeli
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Nur Basek
NB
Surmeli
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Tim J
TJ
Aitman
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Johannes-Peter
JP
Stasch
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Soenke
S
Behrends
From the Department of Medicine, Imperial College London, London, United Kingdom (M.R.W., J.W., C.J.R., S.R.); National Academy of Sciences of Kyrgyz Republic, Bishkek, Kyrgyz Republic (A.A.A.); Physiological Genomics and Medicine Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London, United Kingdom (J.V., T.J.A.); NIHR BRC Clinical Genome Informatics Facility, Imperial College London, London, United Kingdom (D.K., S.G.B., M.M.); Cardiology Research, Bayer Pharma AG, Wuppertal, Germany (S.G., J.-P.S.); Department of Pharmacology, The School of Pharmacy, Martin-Luther-University, Halle, Germany (J.-P.S.); Department of Pulmonary Pharmacotherapy, University of Giessen and Marburg Lung Center, Giessen, Germany (B.K.); Department of Medicine, University of Cambridge, Cambridge, United Kingdom (N.W.M.); Department of Pharmacology, Toxicology, and Clinical Pharmacy, University of Braunschweig-Center of Pharmaceutical Engineering, Braunschweig, Germany (I.N., S.B.); and Department of Chemistry, The Scripps Research Institute, La Jolla, CA (N.B.S., M.A.M.).
Michael A
MA
Marletta
D000483:Alleles; D000532:Altitude Sickness / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase
C000605660:GUCY1A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
cyclic nucleotide; exome; hypoxia; pulmonary hypertension