BBS12-related ciliopathy

Summary

BBS12-related ciliopathy (MONDO:1040045) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	BBS12-related ciliopathy
Mondo ID	MONDO:1040045
GARD	0027247
Is cancer (heuristic)	no

Also known as: BBS12-related ciliopathy

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › ciliopathy › BBS12-related ciliopathy

Related subtypes (35): Alstrom syndrome, Marden-Walker syndrome, nephronophthisis 1, Bardet-Biedl syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Jeune syndrome, Joubert syndrome, Meckel syndrome, retinal ciliopathy, oculocerebrodental syndrome, CEP290-related ciliopathy, IFT140-related recessive ciliopathy, BBS9-related ciliopathy, BBS10-related ciliopathy, CEP164-related ciliopathy, CFAP418-related ciliopathy, WDPCP-related ciliopathy, SDCCAG8-related ciliopathy, KIF7-related ciliopathy, Alsahan-Harris syndrome, OFD1-related ciliopathy, BBS7-related ciliopathy, BBS1-related ciliopathy, BBS4-related ciliopathy, LZTFL1-related ciliopathy, BBS5-related ciliopathy, BBS2-related ciliopathy, TTC8-related ciliopathy, MKKS-related ciliopathy, ARL6-related ciliopathy, MKS1-related ciliopathy, TUBB4B-related ciliopathy, INTU-related skeletal ciliopathy, ciliopathy-IFT74

Subtypes (1): Bardet-Biedl syndrome 12

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 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
347503	NM_152618.3(BBS12):c.1499T>C (p.Val500Ala)	BBS12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
434490	NM_152618.3(BBS12):c.1859A>G (p.Gln620Arg)	BBS12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3780958	NM_152618.3(BBS12):c.763C>T (p.His255Tyr)	BBS12	Uncertain significance	criteria provided, single submitter
501682	NM_152618.3(BBS12):c.1135A>G (p.Lys379Glu)	BBS12	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
BBS12	Orphanet:110	Bardet-Biedl syndrome

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
BBS12	HGNC:26648	ENSG00000181004	Q6ZW61	Chaperonin-containing T-complex member BBS12	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BBS12	Chaperonin-containing T-complex member BBS12	Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis.

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)
BBS12	Other/Unknown	no		Cpn60/GroEL/TCP-1, GroEL-like_apical_dom_sf, TCP-1-like_intermed_sf

Expression context

Cohort genes with no expression data: 0.

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
bronchial epithelial cell	1
primordial germ cell in gonad	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BBS12	204	ubiquitous	yes	primordial germ cell in gonad, sperm, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BBS12	653

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
BBS12	Q6ZW61	73.92

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	BBS12
Cargo trafficking to the periciliary membrane	1	248.3×	0.008	BBS12
Cilium Assembly	1	108.8×	0.012	BBS12
Organelle biogenesis and maintenance	1	66.0×	0.015	BBS12

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 stem cell differentiation	1	842.6×	0.004	BBS12
chaperone-mediated protein complex assembly	1	702.2×	0.004	BBS12
eating behavior	1	601.9×	0.004	BBS12
intraciliary transport	1	561.7×	0.004	BBS12
photoreceptor cell maintenance	1	358.6×	0.004	BBS12
negative regulation of fat cell differentiation	1	312.1×	0.004	BBS12
stem cell differentiation	1	300.9×	0.004	BBS12
fat cell differentiation	1	181.2×	0.006	BBS12

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
BBS12	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	BBS12

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)
BBS12	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.