Chemotherapy-induced hypertension

Summary

Chemotherapy-induced hypertension (MONDO:0005585) is a disease with 2 cohort genes (3 GWAS associations across 1 studies).

At a glance

• Cohort genes: 2
• GWAS associations: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	chemotherapy-induced hypertension
Mondo ID	MONDO:0005585
Is cancer (heuristic)	no

Data availability: 3 GWAS associations (1 study).

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › hypertensive disorder › chemotherapy-induced hypertension

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

Genetics & variants

GWAS landscape

3 GWAS associations across 1 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
rs6453204	6e-08	SV2C	?	3.3
rs1943466	1e-06	GRAMD1B	?	1.82
rs130318	4e-06	PARVB	?	1.72

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002567	Schneider BP	2014	255	0	Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100.

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	3

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	3

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6453204	5	76143375	A>G,T	0.05	intron_variant	SV2C	6e-08	Tier 4: intronic/intergenic
rs1943466	11	123393934	C>A	0.05	intron_variant	GRAMD1B	1e-06	Tier 4: intronic/intergenic
rs130318	22	44080184	T>A,C	0.05	intron_variant	PARVB	4e-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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PARVB	HGNC:14653	ENSG00000188677	Q9HBI1	Beta-parvin	gwas
SV2C	HGNC:30670	ENSG00000122012	Q496J9	Synaptic vesicle glycoprotein 2C	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PARVB	Beta-parvin	Adapter protein that plays a role in integrin signaling via ILK and in activation of the GTPases CDC42 and RAC1 by guanine exchange factors, such as ARHGEF6.
SV2C	Synaptic vesicle glycoprotein 2C	Plays a role in the control of regulated secretion in neural and endocrine cells, enhancing selectively low-frequency neurotransmission.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Transporter	1	38.9×	0.051
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PARVB	Other/Unknown	no		CH_dom, Parvin, CH_dom_sf
SV2C	Transporter	yes		MFS_sugar_transport-like, Sugar_transporter_CS, MFS

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1
dorsal root ganglion	1
substantia nigra pars compacta	1
substantia nigra pars reticulata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PARVB	235	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, muscle of leg
SV2C	160	broad	marker	substantia nigra pars reticulata, substantia nigra pars compacta, dorsal root ganglion

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SV2C	1,184
PARVB	726

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SV2C	Q496J9	6
PARVB	Q9HBI1	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Toxicity of botulinum toxin type A (botA)	1	1427.5×	0.003	SV2C
Toxicity of botulinum toxin type D (botD)	1	1142.0×	0.003	SV2C
Toxicity of botulinum toxin type F (botF)	1	1142.0×	0.003	SV2C
Neurotoxicity of clostridium toxins	1	713.8×	0.003	SV2C
Regulation of cytoskeletal remodeling and cell spreading by IPP complex components	1	713.8×	0.003	PARVB
Uptake and actions of bacterial toxins	1	407.9×	0.004	SV2C
Cell-extracellular matrix interactions	1	335.9×	0.004	PARVB
Bacterial Infection Pathways	1	167.9×	0.007	SV2C
Infectious disease	1	12.4×	0.088	SV2C
Disease	1	6.5×	0.147	SV2C

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 term	Cohort genes	Fold	FDR	Sample cohort genes
establishment or maintenance of cell polarity regulating cell shape	1	2106.5×	0.004	PARVB
cell projection assembly	1	468.1×	0.008	PARVB
regulation of synaptic vesicle exocytosis	1	227.7×	0.008	SV2C
lamellipodium assembly	1	221.7×	0.008	PARVB
neurotransmitter transport	1	210.7×	0.008	SV2C
substrate adhesion-dependent cell spreading	1	172.0×	0.008	PARVB
actin cytoskeleton organization	1	39.6×	0.026	PARVB
chemical synaptic transmission	1	38.6×	0.026	SV2C

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PARVB	0	0
SV2C	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	SV2C
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PARVB

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PARVB	0	—
SV2C	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.