Hypertensive nephropathy

Summary

Hypertensive nephropathy (MONDO:0024633) is a disease with 3 cohort genes (5 GWAS associations across 9 studies) and 7 clinical trials.

At a glance

• Cohort genes: 3
• GWAS associations: 5
• Clinical trials: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertensive nephropathy
Mondo ID	MONDO:0024633
MeSH	C563161
OMIM	608026
NCIT	C4757
SNOMED CT	38481006
UMLS	C0848548
MedGen	167258
Is cancer (heuristic)	no

Also known as: HNP1 · hypertensive nephropathy · hypertensive renal disease

Data availability: 5 GWAS associations (9 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › hypertensive nephropathy

Related subtypes (56): renal hypertension, kidney failure, nephritis, impaired renal function disease, nephrocalcinosis, atheroembolism of kidney, renal artery disease, nephrosis, cystic kidney disease, anuria, stricture or kinking of ureter, proteinuria, renal infectious disease, diabetes insipidus, orthostatic proteinuria, kidney hypertrophy, chronic kidney disease, hydronephrosis, renal tubular transport disease, kidney cortex necrosis, kidney papillary necrosis, perinephritis, renal aminoaciduria, autosomal dominant progressive nephropathy with hypertension, nephrolithiasis, X-linked diffuse leiomyomatosis-Alport syndrome, tubulointerstitial nephritis and uveitis syndrome, distal renal tubular acidosis, oligomeganephronia, duplication of urethra, renal tubular dysgenesis, exstrophy-epispadias complex, fetal lower urinary tract obstruction, IgG4-related kidney disease, congenital primary megaureter, renal nutcracker syndrome, renal hypoplasia, renal dysplasia, congenital megacalycosis, glomerular disorder, congenital renal artery stenosis, kidney neoplasm, renal tubule disorder, pyonephrosis, Arnold stickler bourne syndrome, C1q nephropathy, atypical Fanconi syndrome-neonatal hyperinsulinism syndrome, idiopathic non-lupus full-house nephropathy, lachiewicz sibley syndrome, crush syndrome, obstructive nephropathy, inherited kidney disorder, acute tubulointerstitial nephritis, kidney cortex disease, non-syndromic supernumerary kidneys, neonatal renal venous thrombosis

Subtypes (2): malignant hypertensive renal disease, benign hypertensive renal disease

Genetics & variants

GWAS landscape

5 GWAS associations across 9 studies. Top hits map to 3 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1402625	4e-07	LSAMP	?
rs142696488	6e-07	PCDH10 - PABPC4L	C	2.78
rs3783702	7e-07	FKBP3	A	1.77
rs146679300	2e-06	CRIPT	A	2.54
rs2485016	2e-06	LINC00421 - PARP4P2	C	2.11

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90652132	Liu TY	2025	2,212	175,194	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90473525	UK Biobank Whole-Genome Sequencing Consortium	2025	1,928	456,512	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90079964	Backman JD	2021	1,660	386,252	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083950	Backman JD	2021	1,660	386,252	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90079963	Backman JD	2021	1,504	386,426	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083949	Backman JD	2021	1,504	386,426	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90103402	Fitzgerald T	2022	618	170,139	CNest: A novel copy number association discovery method uncovers 862 new associations from 200,629 whole-exome sequence datasets in the UK Biobank.
GCST011909	Kim HR	2021	310	2,294	A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men.
GCST90726895	Kim HI	2026	145	43,881	Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	3
intron_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1402625	3	117077095	C>A,T	0.05	intergenic_variant	LSAMP	4e-07	Tier 4: intronic/intergenic
rs142696488	4	134037496	G>A,C	0.029	intron_variant	PCDH10 - PABPC4L	6e-07	Tier 4: intronic/intergenic
rs3783702	14	45129551	G>A	0.125	intron_variant	FKBP3	7e-07	Tier 4: intronic/intergenic
rs146679300	2	46661369	G>A	0.032	intergenic_variant	CRIPT	2e-06	Tier 4: intronic/intergenic
rs2485016	13	19347240	A>C,G	0.056	intergenic_variant	LINC00421 - PARP4P2	2e-06	Tier 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

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PABPC4L	HGNC:31955	ENSG00000254535	P0CB38	Polyadenylate-binding protein 4-like	gwas
FKBP3	HGNC:3719	ENSG00000100442	Q00688	Peptidyl-prolyl cis-trans isomerase FKBP3	gwas
LINC00421	HGNC:42755	ENSG00000236834		long intergenic non-protein coding RNA 421	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PABPC4L	Polyadenylate-binding protein 4-like	May bind RNA.
FKBP3	Peptidyl-prolyl cis-trans isomerase FKBP3	FK506- and rapamycin-binding proteins (FKBPs) constitute a family of receptors for the two immunosuppressants which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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.

Family	Genes	Fold	FDR
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PABPC4L	Other/Unknown	no		RRM_dom, RRM_euk-type, PABP_1234
FKBP3	Enzyme (other)	yes	5.2.1.8	PPIase_FKBP_dom, FKBP3_BTHB, FKBP3
LINC00421	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
caput epididymis	1
male germ line stem cell (sensu Vertebrata) in testis	1
placenta	1
biceps brachii	1
skeletal muscle tissue of biceps brachii	1
vastus lateralis	1
parotid gland	1
right testis	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PABPC4L	154	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, caput epididymis, placenta
FKBP3	288	ubiquitous	marker	skeletal muscle tissue of biceps brachii, biceps brachii, vastus lateralis
LINC00421	38		yes	right testis, parotid gland, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKBP3	3,497
PABPC4L	1,625
LINC00421	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FKBP3	Q00688	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PABPC4L	P0CB38	91.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 3 evidence-associated genes (0 with Reactome annotation).

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 term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of gene expression	1	38.7×	0.026	PABPC4L

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PABPC4L	0	0
FKBP3	0	0
LINC00421	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FKBP3	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FKBP3	5.2.1.8	peptidylprolyl isomerase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	FKBP3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	PABPC4L, LINC00421

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PABPC4L	0	—
FKBP3	4	—
LINC00421	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 7.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE4	1
PHASE2/PHASE3	1
PHASE2	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07187713	PHASE4	RECRUITING	ACE Reno, Pico Cell Matrix and Its Effect on eGFR in Chronic Kidney Diseases
NCT00582777	PHASE2/PHASE3	COMPLETED	African American Study of Kidney Disease and Hypertension ABPM Pilot Study
NCT07240987	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Stem Cells for Chronic Kidney Diseases
NCT06948292	PHASE2	COMPLETED	Role of QRX-3 in Chronic Kidney Disease Patients in Outpatients Clinics
NCT02477163	Not specified	COMPLETED	Ayurvedic Management of Chronic Kidney Disease
NCT04495231	Not specified	COMPLETED	Sympathetic Activity and Cardiometabolic Complications
NCT04633993	Not specified	COMPLETED	Effectiveness of Implementation of a Patient-centered Self-management Program in Patients With Hypertensive Nephropathy