Epidermodysplasia verruciformis, susceptibility to, 4

disease

On this page

Also known as EV4

Summary

Epidermodysplasia verruciformis, susceptibility to, 4 (MONDO:0032666) is a disease caused by RHOH (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: RHOH (GenCC Strong)
Cohort genes: 1
ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	epidermodysplasia verruciformis, susceptibility to, 4
Mondo ID	MONDO:0032666
OMIM	618307
DOID	DOID:0061094
NCIT	C176608
UMLS	C4749042
MedGen	1648396
Is cancer (heuristic)	no

Also known as: EV4

Data availability: 4 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › epidermodysplasia verruciformis, susceptibility to › epidermodysplasia verruciformis, susceptibility to, 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 no classifications from unflagged records, 1 benign/likely benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3384151	NM_004310.5(RHOH):c.245G>A (p.Cys82Tyr)	RHOH	no classifications from unflagged records	no classifications from unflagged records
4846922	NM_004310.5(RHOH):c.478C>T (p.Gln160Ter)	RHOH	Uncertain significance	criteria provided, single submitter
617610	NM_004310.5(RHOH):c.114C>G (p.Tyr38Ter)	RHOH	no classifications from unflagged records	no classifications from unflagged records
477858	NM_004310.5(RHOH):c.144T>C (p.Asp48=)	RHOH	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RHOH	Strong	Autosomal recessive	epidermodysplasia verruciformis, susceptibility to, 4	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RHOH	Orphanet:324294	T-cell immunodeficiency with epidermodysplasia verruciformis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RHOH	HGNC:686	ENSG00000168421	Q15669	Rho-related GTP-binding protein RhoH	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RHOH	Rho-related GTP-binding protein RhoH	Negative regulator of hematopoietic progenitor cell proliferation, survival and migration.

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.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RHOH	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTPase_Rho, Small_GTP-bd

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)

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

Top tissues across cohort

Tissue	Cohort genes
bone marrow cell	1
lymph node	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RHOH	174	broad	marker	bone marrow cell, lymph node, vermiform appendix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RHOH	4,044

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RHOH	Q15669	92.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHOH GTPase cycle	1	308.6×	0.003	RHOH

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mast cell activation	1	2407.4×	0.003	RHOH
positive regulation of T cell differentiation	1	455.5×	0.007	RHOH
T cell differentiation	1	383.0×	0.007	RHOH
small GTPase-mediated signal transduction	1	183.2×	0.009	RHOH
negative regulation of canonical NF-kappaB signal transduction	1	172.0×	0.009	RHOH
actin filament organization	1	118.7×	0.011	RHOH
regulation of DNA-templated transcription	1	31.6×	0.036	RHOH
signal transduction	1	16.1×	0.062	RHOH

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RHOH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RHOH	3.6.5.2	small monomeric GTPase

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

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

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RHOH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RHOH