PBRM1-related BAFopathy

Summary

PBRM1-related BAFopathy (MONDO:0700122) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	PBRM1-related BAFopathy
Mondo ID	MONDO:0700122
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › BAFopathy › PBRM1-related BAFopathy

Related subtypes (14): Coffin-Siris syndrome 1, Baraitser-Winter syndrome 1, intellectual disability-sparse hair-brachydactyly syndrome, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, Coffin-Siris syndrome 5, Dias-Logan syndrome, Coffin-Siris syndrome 8, intellectual developmental disorder with severe speech and ambulation defects, Coffin-Siris syndrome 6, intellectual developmental disorder with speech delay, dysmorphic facies, and t-cell abnormalities, ACTL6A-related BAFopathy, SMARCC1-associated developmental dysgenesis syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177320	NM_001405607.1(PBRM1):c.1587-3C>G	PBRM1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PBRM1	Orphanet:404511	Clear cell papillary renal cell carcinoma

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
PBRM1	HGNC:30064	ENSG00000163939	Q86U86	Protein polybromo-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PBRM1	Protein polybromo-1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

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)
PBRM1	Other/Unknown	no		BAH_dom, Bromodomain, HMG_box_dom

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
amniotic fluid	1
cortical plate	1
ganglionic eminence	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PBRM1	289	ubiquitous	marker	cortical plate, ganglionic eminence, amniotic fluid

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PBRM1	3,540

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PBRM1	Q86U86	30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Formation of the polybromo-BAF (pBAF) complex	1	634.4×	0.005	PBRM1
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	300.5×	0.005	PBRM1
RMTs methylate histone arginines	1	146.4×	0.007	PBRM1

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
regulation of G0 to G1 transition	1	674.1×	0.005	PBRM1
regulation of nucleotide-excision repair	1	601.9×	0.005	PBRM1
regulation of mitotic metaphase/anaphase transition	1	495.6×	0.005	PBRM1
positive regulation of T cell differentiation	1	455.5×	0.005	PBRM1
transcription elongation by RNA polymerase II	1	443.5×	0.005	PBRM1
positive regulation of myoblast differentiation	1	366.4×	0.005	PBRM1
positive regulation of double-strand break repair	1	343.9×	0.005	PBRM1
regulation of G1/S transition of mitotic cell cycle	1	306.4×	0.005	PBRM1
positive regulation of cell differentiation	1	267.5×	0.005	PBRM1
mitotic cell cycle	1	133.8×	0.010	PBRM1
chromatin remodeling	1	73.0×	0.016	PBRM1
negative regulation of cell population proliferation	1	42.1×	0.026	PBRM1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PBRM1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PBRM1	2	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PBRM1
LUTEOLIN	2	PBRM1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PBRM1	193	Binding:193

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PBRM1	193

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

2 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PBRM1
LUTEOLIN	2	PBRM1

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	1	PBRM1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.