Brain small vessel disease 5 with osteoporosis

Summary

Brain small vessel disease 5 with osteoporosis (MONDO:0979880) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain small vessel disease 5 with osteoporosis
Mondo ID	MONDO:0979880
OMIM	621331
DOID	DOID:0061235
GARD	0028126
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › familial porencephaly › brain small vessel disease 5 with osteoporosis

Related subtypes (6): brain small vessel disease 1 with or without ocular anomalies, brain small vessel disease 2A, autosomal dominant, brain small vessel disease 3, brain small vessel disease 4, brain small vessel disease 6 with leukoencephalopathy, brain small vessel disease 2B, autosomal recessive

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

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4082148	ARHGEF15, VAL360MET	ARHGEF15	Pathogenic	no assertion criteria provided
4082149	ARHGEF15, ARG21CYS	ARHGEF15	Pathogenic	no assertion criteria provided
4082150	ARHGEF15, GLN683TER	ARHGEF15	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
ARHGEF15	HGNC:15590	ENSG00000198844	O94989	Rho guanine nucleotide exchange factor 15	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ARHGEF15	Rho guanine nucleotide exchange factor 15	Guanine nucleotide exchange factor (GEF) that activates RhoA, playing a role in the regulation of actin cytoskeleton organization.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ARHGEF15	Other/Unknown	no		DH_dom, PH-like_dom_sf, DBL_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)

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

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
omental fat pad	1
peritoneum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ARHGEF15	198	broad	marker	apex of heart, omental fat pad, peritoneum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ARHGEF15	712

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ARHGEF15	O94989	62.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Cell death signalling via NRAGE, NRIF and NADE	1	219.6×	0.020	ARHGEF15
p75 NTR receptor-mediated signalling	1	187.2×	0.020	ARHGEF15
NRAGE signals death through JNK	1	184.2×	0.020	ARHGEF15
Death Receptor Signaling	1	139.3×	0.020	ARHGEF15
G alpha (12/13) signalling events	1	137.6×	0.020	ARHGEF15
RHOA GTPase cycle	1	74.6×	0.026	ARHGEF15
CDC42 GTPase cycle	1	72.3×	0.026	ARHGEF15
RAC1 GTPase cycle	1	61.1×	0.026	ARHGEF15
RHO GTPase cycle	1	60.1×	0.026	ARHGEF15
GPCR downstream signalling	1	43.4×	0.032	ARHGEF15
Signaling by GPCR	1	40.1×	0.032	ARHGEF15
Signaling by Rho GTPases	1	34.2×	0.032	ARHGEF15
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.032	ARHGEF15
Signal Transduction	1	10.2×	0.098	ARHGEF15

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
negative regulation of synapse maturation	1	5617.3×	9e-04	ARHGEF15
retina vasculature morphogenesis in camera-type eye	1	3370.4×	9e-04	ARHGEF15
regulation of postsynapse assembly	1	343.9×	0.005	ARHGEF15
positive regulation of stress fiber assembly	1	312.1×	0.005	ARHGEF15
regulation of actin cytoskeleton organization	1	157.5×	0.007	ARHGEF15
regulation of small GTPase mediated signal transduction	1	144.0×	0.007	ARHGEF15

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
ARHGEF15	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	1	ARHGEF15

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)
ARHGEF15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.