BBS2-related ciliopathy

disease

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Summary

BBS2-related ciliopathy (MONDO:1040048) is a disease caused by BBS2 (GenCC Strong), with 1 cohort gene.

At a glance

Causal gene: BBS2 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	BBS2-related ciliopathy
Mondo ID	MONDO:1040048
GARD	0027250
Is cancer (heuristic)	no

Also known as: BBS2-related ciliopathy

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › BBS2-related ciliopathy

Subtypes (2): Bardet-Biedl syndrome 2, retinitis pigmentosa 74

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

6 retrieved; paginated sample, class counts are floors:

4 pathogenic/likely pathogenic, 1 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066989	NM_031885.5(BBS2):c.1397+1G>A	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4569	NM_031885.5(BBS2):c.224T>G (p.Val75Gly)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
499851	NM_031885.5(BBS2):c.535-2A>G	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
648475	NM_031885.5(BBS2):c.950A>G (p.Tyr317Cys)	BBS2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
555474	NM_031885.5(BBS2):c.2060-1G>T	BBS2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1399619	NM_031885.5(BBS2):c.1601G>A (p.Cys534Tyr)	BBS2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
BBS2	Strong	Autosomal recessive	BBS2-related ciliopathy	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BBS2	Orphanet:110	Bardet-Biedl syndrome
BBS2	Orphanet:791	Retinitis pigmentosa

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
BBS2	HGNC:967	ENSG00000125124	Q9BXC9	BBSome complex member BBS2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS2	BBSome complex member BBS2	The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BBS2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, Bardet-Biedl_syndrome_2_prot, BBS2_GAE_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
adrenal tissue	1
peripheral nervous system	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS2	262	ubiquitous	marker	adrenal tissue, right adrenal gland cortex, peripheral nervous system

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS2	1,824

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BBS2	Q9BXC9	89.49

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
BBSome-mediated cargo-targeting to cilium	1	496.5×	0.008	BBS2
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	BBS2
Cilium Assembly	1	108.8×	0.012	BBS2
Organelle biogenesis and maintenance	1	66.0×	0.015	BBS2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of appetite by leptin-mediated signaling pathway	1	4213.0×	0.004	BBS2
artery smooth muscle contraction	1	1872.4×	0.004	BBS2
regulation of cilium beat frequency involved in ciliary motility	1	1872.4×	0.004	BBS2
striatum development	1	1123.5×	0.004	BBS2
negative regulation of multicellular organism growth	1	1123.5×	0.004	BBS2
melanosome transport	1	766.0×	0.004	BBS2
brain morphogenesis	1	732.7×	0.004	BBS2
Golgi to plasma membrane protein transport	1	526.6×	0.004	BBS2
positive regulation of multicellular organism growth	1	495.6×	0.004	BBS2
sperm axoneme assembly	1	468.1×	0.004	BBS2
adult behavior	1	468.1×	0.004	BBS2
vasodilation	1	366.4×	0.005	BBS2
photoreceptor cell maintenance	1	358.6×	0.005	BBS2
non-motile cilium assembly	1	290.6×	0.006	BBS2
cartilage development	1	251.5×	0.006	BBS2
hippocampus development	1	230.8×	0.006	BBS2
cerebral cortex development	1	205.5×	0.007	BBS2
fat cell differentiation	1	181.2×	0.007	BBS2
intracellular protein localization	1	104.7×	0.012	BBS2
gene expression	1	79.9×	0.014	BBS2
visual perception	1	79.5×	0.014	BBS2
cilium assembly	1	73.6×	0.014	BBS2
negative regulation of gene expression	1	69.1×	0.014	BBS2

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
BBS2	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	BBS2

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)
BBS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: BBS2