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Atlas / Disease / Primary aldosteronism

Primary aldosteronism

disease
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Also known as Conn syndromeConn's syndromeprimary hyperaldosteronism

Summary

Primary aldosteronism (MONDO:0001422) is a disease with 1 cohort gene (30 GWAS associations across 8 studies) and 121 clinical trials. Top therapeutic interventions include spironolactone, finerenone, and captopril.

At a glance

  • Cohort genes: 1
  • GWAS associations: 30
  • ClinVar variants: 2
  • Clinical trials: 121

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameprimary aldosteronism
Mondo IDMONDO:0001422
DOIDDOID:12028
ICD-10-CME26.0, E26.01
ICD-11197924221
NCITC34510
SNOMED CT190507007
UMLSC1384514
MedGen278002
Is cancer (heuristic)no

Also known as: Conn syndrome · Conn’s syndrome · primary aldosteronism · primary hyperaldosteronism

Data availability: 2 ClinVar variants · 30 GWAS associations (8 studies).

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › adrenal gland disorder › adrenal cortex disorder › adrenal gland hyperfunction › hyperaldosteronism › primary aldosteronism

Subtypes (4): primary unilateral adrenal hyperplasia, aldosterone-producing adrenal cortex adenoma, ectopic aldosterone-producing tumor, familial hyperaldosteronism

Genetics & variants

GWAS landscape

30 GWAS associations across 8 studies. Top hits map to 13 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs15355325e-19B3GLCT - RXFP2T1.92
rs20259082e-14B3GLCT - RXFP2A1.71
rs2842779e-12CASZ1C1.47
rs21373209e-12LSP1A1.44
rs37906045e-11WNT2BA1.5
rs59055875e-10NDP - RBM39P1C1.35
rs10050021e-09NDP-AS1, NDPA1.41
rs49803792e-09LSP1T1.36
rs354862e-09TBX3-AS1 - UBA52P7G1.39
rs66795316e-09LINC02794C
rs354427521e-08B3GLCT - RXFP2CA1.42
rs20238433e-08HOTTIPT1.41
rs93548264e-08ADGRB3C1.53
rs1457251899e-08GMLT1.34
rs171456361e-07RPS11P7 - LINC03053G3.8
rs46392183e-07BRD8T1.48
rs5690164e-07SRSF1P1 - KLHL1T
rs109930005e-07LINC01508C1.46
rs68504156e-07CCKARA16.57
rs1504416526e-07SC4MOP - H2APG2.95
rs24457547e-07GLDN - DMXL2G2.01
rs58830641e-06HOTTIPA1.43
rs13977989864e-06EML6AG2.39
rs49803867e-06LSP1A1.46

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90129615Le Floch E20225620Identification of risk loci for primary aldosteronism in genome-wide association studies.
GCST90129620Le Floch E20225620Identification of risk loci for primary aldosteronism in genome-wide association studies.
GCST90271575Naito T202339233,802Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Study.
GCST90271576Naito T202339233,802Genetic Risk of Primary Aldosteronism and Its Contribution to Hypertension: A Cross-Ancestry Meta-Analysis of Genome-Wide Association Study.
GCST90129616Le Floch E20223390Identification of risk loci for primary aldosteronism in genome-wide association studies.
GCST90129621Le Floch E20223390Identification of risk loci for primary aldosteronism in genome-wide association studies.
GCST90129617Le Floch E20222330Identification of risk loci for primary aldosteronism in genome-wide association studies.
GCST90129622Le Floch E20222330Identification of risk loci for primary aldosteronism in genome-wide association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic24

MAF distribution

BucketVariants
common (>=0.05)20
low_freq (0.01-0.05)2
rare (<0.01)1
unknown1

Functional consequences

ConsequenceCount
intron_variant17
intergenic_variant6
non_coding_transcript_exon_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs15355321331540261T>A,C,G0.05intergenic_variantB3GLCT - RXFP25e-19Tier 4: intronic/intergenic
rs20259081331652262G>A,C,T0.05intergenic_variantB3GLCT - RXFP22e-14Tier 4: intronic/intergenic
rs284277110730740C>A,T0.05intron_variantCASZ19e-12Tier 4: intronic/intergenic
rs2137320111863112G>A,C0.05intron_variantLSP19e-12Tier 4: intronic/intergenic
rs37906041112504257C>A,G0.05intron_variantWNT2B5e-11Tier 4: intronic/intergenic
rs5905587X43974750T>C,G0.05intergenic_variantNDP - RBM39P15e-10Tier 4: intronic/intergenic
rs1005002X43967818G>A0.05intron_variantNDP-AS1, NDP1e-09Tier 4: intronic/intergenic
rs4980379111867384C>A,T0.05intron_variantLSP12e-09Tier 4: intronic/intergenic
rs3548612115088757G>A,C,T0.05intron_variantTBX3-AS1 - UBA52P72e-09Tier 4: intronic/intergenic
rs6679531148058508T>C0.05intron_variantLINC027946e-09Tier 4: intronic/intergenic
rs354427521331605366CA>C,CAA0.05intergenic_variantB3GLCT - RXFP21e-08Tier 4: intronic/intergenic
rs2023843727203602C>T0.05intron_variantHOTTIP3e-08Tier 4: intronic/intergenic
rs9354826669190944C>A,G,T0.45intron_variantADGRB34e-08Tier 4: intronic/intergenic
rs1457251898142901261intergenic_variantGML9e-08Tier 4: intronic/intergenic
rs17145636X39992235A>G0.021intron_variantRPS11P7 - LINC030531e-07Tier 4: intronic/intergenic
rs46392185138162784C>A,G,T0.49intron_variantBRD83e-07Tier 4: intronic/intergenic
rs5690161369527955T>C0.05intron_variantSRSF1P1 - KLHL14e-07Tier 4: intronic/intergenic
rs10993000990319403T>A,C0.36intron_variantLINC015085e-07Tier 4: intronic/intergenic
rs6850415426489534G>A0.006intron_variantCCKAR6e-07Tier 4: intronic/intergenic
rs150441652X37982786A>G0.032intron_variantSC4MOP - H2AP6e-07Tier 4: intronic/intergenic
rs24457541551413789A>G0.086intergenic_variantGLDN - DMXL27e-07Tier 4: intronic/intergenic
rs5883064727202260ACT>A0.42non_coding_transcript_exon_variantHOTTIP1e-06Tier 4: intronic/intergenic
rs1397798986254762228A>AG0.05intron_variantEML64e-06Tier 4: intronic/intergenic
rs4980386111874478C>A,T0.05intron_variantLSP17e-06Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic

ClinVarVariant (HGVS)GeneClassificationReview
189779NM_021098.3(CACNA1H):c.4645A>G (p.Met1549Val)CACNA1HPathogeniccriteria provided, single submitter
4279088NM_021098.3(CACNA1H):c.1838A>T (p.Tyr613Phe)CACNA1HLikely pathogenicno assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
CACNA1HOrphanet:642671Familial hyperaldosteronism type IV
CACNA1HOrphanet:64280Childhood absence epilepsy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
CACNA1HHGNC:1395ENSG00000196557O95180Voltage-dependent T-type calcium channel subunit alpha-1Hclinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
CACNA1HVoltage-dependent T-type calcium channel subunit alpha-1HVoltage-sensitive calcium channel that gives rise to T-type calcium currents.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

FamilyGenesFoldFDR
Ion channel1111.5×0.009

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
CACNA1HIon channelyesVDCC_T_a1, Ion_trans_dom, Volt_channel_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
lower esophagus1
lower esophagus muscularis layer1
muscle layer of sigmoid colon1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
CACNA1H166broadmarkerlower esophagus muscularis layer, muscle layer of sigmoid colon, lower esophagus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
CACNA1H1,564

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
CACNA1HO951805

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes1671.8×0.008CACNA1H
NCAM signaling for neurite out-growth1271.9×0.008CACNA1H
Smooth Muscle Contraction1265.6×0.008CACNA1H
Cellular responses to mechanical stimuli1259.6×0.008CACNA1H
NCAM1 interactions1248.3×0.008CACNA1H
Muscle contraction177.2×0.022CACNA1H
Axon guidance145.1×0.029CACNA1H
Nervous system development142.9×0.029CACNA1H
Cellular responses to stimuli131.5×0.035CACNA1H
Developmental Biology114.5×0.069CACNA1H

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
aldosterone biosynthetic process13370.4×0.003CACNA1H
cortisol biosynthetic process12106.5×0.003CACNA1H
positive regulation of acrosome reaction11532.0×0.003CACNA1H
cellular response to potassium ion11053.2×0.003CACNA1H
obsolete inorganic cation transmembrane transport1936.2×0.003CACNA1H
calcium ion import1802.5×0.003CACNA1H
myoblast fusion1601.9×0.003CACNA1H
calcium ion import across plasma membrane1543.6×0.003CACNA1H
regulation of heart contraction1495.6×0.003CACNA1H
cellular response to hormone stimulus1383.0×0.003CACNA1H
regulation of membrane potential1230.8×0.005CACNA1H
muscle contraction1208.1×0.005CACNA1H
muscle organ development1166.8×0.006CACNA1H

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

SymbolExample approved molecule
CACNA1HPIMOZIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
CACNA1H104

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PIMOZIDE4CACNA1H
MIBEFRADIL4CACNA1H
NIMODIPINE4CACNA1H
TACRINE4CACNA1H
CILNIDIPINE3CACNA1H
SUVECALTAMIDE2CACNA1H
FLUNARIZINE2CACNA1H
APINOCALTAMIDE2CACNA1H
Z1602CACNA1H
ULIXACALTAMIDE1CACNA1H

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

SymbolAssaysType breakdown
CACNA1H124Binding:102, Functional:17, ADMET:4, Toxicity:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

SymbolChEMBL assays
CACNA1H124

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

10 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

CompoundMax phaseCohort target (bioactivity)
PIMOZIDE4CACNA1H
MIBEFRADIL4CACNA1H
NIMODIPINE4CACNA1H
TACRINE4CACNA1H
CILNIDIPINE3CACNA1H
SUVECALTAMIDE2CACNA1H
FLUNARIZINE2CACNA1H
APINOCALTAMIDE2CACNA1H
Z1602CACNA1H
ULIXACALTAMIDE1CACNA1H

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1CACNA1H
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 121.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified96
PHASE49
PHASE29
PHASE33
PHASE1/PHASE22
PHASE2/PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05030545PHASE4RECRUITINGCardiovascular Manifestations of MR Activation in Primary Aldosteronism: Pilot Clinical Study
NCT06457074PHASE4RECRUITINGFinerenone for Patients With Primary Aldosteronism (FAIRY)
NCT06523465PHASE4RECRUITINGStatin Combined with Amlodipine Treats Primary Aldosteronism
NCT01959711PHASE4COMPLETEDRandomized Clinical Trial of Posterior Retroperitoneoscopic Adrenalectomy Versus Lateral Laparoscopic Adrenalectomy
NCT02127840PHASE4UNKNOWNInfluence of Synacthen Infusion on the Results of Adrenal Venous Sampling in Patient With Primary Aldosteronism
NCT05814770PHASE4UNKNOWNComparing the Efficacy and Safety of Finerenone and Spironolactone in the Treatment of Primary Aldosteronism
NCT05924620PHASE4COMPLETEDEfficacy and Safety of Finerenone in Patients With Primary Aldosteronism
NCT06164379PHASE4UNKNOWNEfficacy and Safety of Finerenone vs. Spironolactone in Patients With Primary Aldosteronism
NCT06381323PHASE4COMPLETEDThe Clinical Efficacy and Safety of Finerenone in the Treatment of Primary Aldosteronism
NCT06100367PHASE2/PHASE3ACTIVE_NOT_RECRUITING11C-Metomidate PET/CT for Endocrine Hypertension and Characterisation of Adrenal Tumours
NCT07007793PHASE3RECRUITINGA Study to Assess Efficacy and Safety of Baxdrostat in Participants With Primary Aldosteronism
NCT03398785PHASE3COMPLETEDAdrenal Artery Ablation Treats Primary Aldosteronism
NCT03653845PHASE3UNKNOWNAdrenal Artery Ablation for Primary Aldosteronism
NCT05472493PHASE2RECRUITINGNuclear Imaging for Subtype Diagnosis of Primary Aldosteronism
NCT06478875PHASE2NOT_YET_RECRUITINGEvaluation of [68Ga]Ga-PentixaFor PET Imaging for the Identification of Unilateral Adrenal Secretion of ALdosterON in Patients With Primary Aldosteronism
NCT06616142PHASE1/PHASE2RECRUITINGSubtyping Primary Aldosteronism With Para-chloro-2-[18F]Fluoroethyl-etomidate
NCT06773663PHASE1/PHASE2RECRUITINGApplication of Al18F-NOTA-Pentixafor PET/CT for Primary Aldosteronism
NCT07470983PHASE2RECRUITINGA Phase II Clinical Study on the Efficacy and Safety of HRS-1780 in Participants With Primary Aldosteronism
NCT07550465PHASE2NOT_YET_RECRUITINGStudy of QLS1410 in the Treatment of Primary Aldosteronism.
NCT00732771PHASE2COMPLETEDProof-of-concept for the Aldosterone Synthase Inhibitor LCI699 in Patients With Primary Hyperaldosteronism
NCT03174171PHASE2COMPLETEDOpen-label Study on Treatment of Primary Aldosteronism With Everolimus
NCT04007406PHASE2COMPLETEDDP13 - A Phase II Study in Patients With Primary Aldosteronism
NCT04179019PHASE2COMPLETEDCalcium Channel Blockade in Primary Aldosteronism
NCT04605549PHASE2COMPLETEDA Study of CIN-107 in Adults With Primary Aldosteronism
NCT03990701EARLY_PHASE1COMPLETEDPrimary Aldosteronism and Surgically Curable Forms in Hypertension Patients Using 11C-Metomidate
NCT00669266Not specifiedRECRUITINGAdrenal Tumors - Pathogenesis and Therapy
NCT03224312Not specifiedRECRUITINGChongqing Primary Aldosteronism Study
NCT03474237Not specifiedENROLLING_BY_INVITATIONA Prospective Cohort Study for Patients With Adrenal Diseases
NCT04020783Not specifiedRECRUITINGPrimary Aldosteronism: Prospective Screening Registry in China
NCT04278404Not specifiedRECRUITINGPharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS)
NCT04409431Not specifiedRECRUITINGEffects of Adrenal Artery Ablation and Spironolactone in Patients With Primary Aldosteronism
NCT05368090Not specifiedRECRUITINGEndoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism
NCT05405101Not specifiedRECRUITINGRandomised Trial Comparing Thermal Ablation With Adrenalectomy in the Treatment of Unilateral Asymmetric PA
NCT05446779Not specifiedACTIVE_NOT_RECRUITINGPostmortem Evaluation of Adrenal and Other Endocrine Tumors in Patients With Sudden Death
NCT05501080Not specifiedRECRUITINGThe Effect of SAAE on Ventricular Remodeling in PA Patients
NCT05561361Not specifiedRECRUITINGThe Effect of SAAE on Vascular Endothelial Function in PA Patients
NCT05636995Not specifiedACTIVE_NOT_RECRUITINGHyperAldosteronism in Pregnancy Predicted Impacts (H.A.P.P.I. Trial)
NCT05638269Not specifiedRECRUITINGA Multicentre Study on Features of the Gut Microbiota of Patients With Critical Chronic Diseases in China
NCT05765786Not specifiedRECRUITINGDiagnosing Variable Primary Aldosteronism.
NCT05925569Not specifiedACTIVE_NOT_RECRUITINGElectronic Alert to Improve Testing For Primary Aldosteronism in Patients With Hypertension

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
SPIRONOLACTONE46
FINERENONE45
CAPTOPRIL41
CINNARIZINE41
CORTICOTROPIN41
EPLERENONE41
OSILODROSTAT41
SPINOSAD41
BAXDROSTAT31
BLOOD, WHOLE31
POTASSIUM31
XL55031
ALDOSTERONE21
DEXFADROSTAT21
CHEMBL156222303
CHEMBL3045803
CHEMBL452286901

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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This page pulls from 73 datasets indexed by BioBTree:

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