Early onset hypertension

disease
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Summary

Early onset hypertension (MONDO:0005430) is a disease with 4 cohort genes (1 GWAS associations across 2 studies).

At a glance

  • Cohort genes: 4
  • GWAS associations: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameearly onset hypertension
Mondo IDMONDO:0005430
EFOEFO:0004772
Is cancer (heuristic)no

Data availability: 1 GWAS association (2 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disordervascular disorderarterial disorderhypertensive disorderearly onset hypertension

Related subtypes (11): essential hypertension, secondary hypertension, pulmonary hypertension, chemotherapy-induced hypertension, intracranial hypertension, malignant hypertension, ocular hypertension, kallikrein hypertension, hypertension, pregnancy-induced, resistant hypertension, hypertensive urgency

Genetics & variants

GWAS landscape

1 GWAS associations across 2 studies. Top hits map to 0 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs93089453e-10LINC01320; LINC01320; LINC01320; LINC01320?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST002332Chiang KM20144000A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese.
GCST000390Yang HC20091750Genome-wide association study of young-onset hypertension in the Han Chinese population of Taiwan.

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/intergenic1

MAF distribution

BucketVariants
common (>=0.05)1
low_freq (0.01-0.05)0
rare (<0.01)0
unknown0

Functional consequences

ConsequenceCount
intron_variant; intron_variant; intron_variant; intron_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs93089452;2;2;234059785A>C,G,T0.05intron_variant; intron_variant; intron_variant; intron_variantLINC01320; LINC01320; LINC01320; LINC013203e-10Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

4 cohort genes, 2 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only4

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
RASGRP3HGNC:14545ENSG00000152689Q8IV61Ras guanyl-releasing protein 3gwas
FAM98AHGNC:24520ENSG00000119812Q8NCA5Protein FAM98Agwas
MYADMLHGNC:31019ENSG00000239649myeloid associated differentiation marker like (pseudogene)gwas
SLC25A5P2HGNC:35470ENSG00000235064solute carrier family 25 member 5 pseudogene 2gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
RASGRP3Ras guanyl-releasing protein 3Guanine nucleotide exchange factor (GEF) for Ras and Rap1.
FAM98AProtein FAM98APositively stimulates PRMT1-induced protein arginine methylation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 4 · Druggable fraction: 0.0

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
Other/Unknown41.8×0.097

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
RASGRP3Other/UnknownnoRas-like_Gua-exchang_fac_N, RASGEF_cat_dom, EF_hand_dom
FAM98AOther/UnknownnoFAM98
MYADMLOther/Unknownno
SLC25A5P2Other/Unknownno

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)1
moderate (6-20)1
broad (>20)2
unknown0

Top tissues across cohort

TissueCohort genes
C1 segment of cervical spinal cord1
corpus callosum1
inferior vagus X ganglion1
male germ cell1
sperm1
tibia1
left testis1
right testis1
testis1
cortical plate1
ganglionic eminence1
stromal cell of endometrium1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
RASGRP3255ubiquitousmarkercorpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
FAM98A297ubiquitousmarkertibia, male germ cell, sperm
MYADML6tissue_specificmarkerleft testis, testis, right testis
SLC25A5P25markerganglionic eminence, cortical plate, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
FAM98A1,486
RASGRP31,414
MYADML0
SLC25A5P20

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 2

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
RASGRP3Q8IV6170.51
FAM98AQ8NCA568.95

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 4 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
Activation of RAS in B cells12284.0×9e-04RASGRP3
RAF/MAP kinase cascade161.1×0.016RASGRP3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
tRNA splicing, via endonucleolytic cleavage and ligation1702.2×0.006FAM98A
positive regulation of ruffle assembly1495.6×0.006FAM98A
protein methylation1468.1×0.006FAM98A
lysosome localization1263.3×0.009FAM98A
Ras protein signal transduction1102.8×0.016RASGRP3
small GTPase-mediated signal transduction191.6×0.016RASGRP3
MAPK cascade176.6×0.017RASGRP3
positive regulation of gene expression119.4×0.057FAM98A
positive regulation of cell population proliferation116.8×0.059FAM98A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 4 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

SymbolMoleculesMax phase
RASGRP312
FAM98A00
MYADML00
SLC25A5P200

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
PHORBOL MYRISTATE ACETATE2RASGRP3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

SymbolAssaysType breakdown
RASGRP320Binding:20

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
PHORBOL MYRISTATE ACETATE2RASGRP3

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved1RASGRP3
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug3FAM98A, MYADML, SLC25A5P2

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
FAM98A0
MYADML0
SLC25A5P20

Clinical trials & evidence

Clinical trials

Clinical trials: 0.