Bardet-Biedl syndrome 12

Summary

Bardet-Biedl syndrome 12 (MONDO:0014440) is a disease caused by BBS12 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: BBS12 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 378

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bardet-Biedl syndrome 12
Mondo ID	MONDO:0014440
MeSH	C565921
OMIM	615989
DOID	DOID:0110134
UMLS	C1859570
MedGen	347910
GARD	0010211
Is cancer (heuristic)	no

Also known as: Bardet-Biedl syndrome 12 · Bardet-Biedl syndrome caused by mutation in BBS12 · Bardet-Biedl syndrome type 12 · BBS12 · BBS12 Bardet-Biedl syndrome

Data availability: 378 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Bardet-Biedl syndrome › Bardet-Biedl syndrome 12

Related subtypes (21): Bardet-Biedl syndrome 1, Bardet-Biedl syndrome 3, Bardet-Biedl syndrome 6, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome 4, Bardet-Biedl syndrome 5, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome 8, Bardet-Biedl syndrome 9, Bardet-Biedl syndrome 10, Bardet-Biedl syndrome 11, Bardet-Biedl syndrome 13, Bardet-Biedl syndrome 14, Bardet-Biedl syndrome 15, Bardet-Biedl syndrome 16, Bardet-Biedl syndrome 17, Bardet-Biedl syndrome 18, Bardet-Biedl syndrome 19, Bardet-Biedl syndrome 22, Bardet-Biedl syndrome 20, bardet-biedl syndrome 21

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

378 retrieved; paginated sample, class counts are floors:

182 uncertain significance, 55 pathogenic/likely pathogenic, 53 likely pathogenic, 28 conflicting classifications of pathogenicity, 25 likely benign, 17 benign, 12 pathogenic, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069707	NM_152618.3(BBS12):c.445C>T (p.Gln149Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069739	NM_152618.3(BBS12):c.694dup (p.Ile232fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069940	NM_152618.3(BBS12):c.2053C>T (p.Gln685Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070029	NM_152618.3(BBS12):c.590_591del (p.Ser196_Tyr197insTer)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071069	NM_152618.3(BBS12):c.1663_1667del (p.Glu555fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071214	NM_152618.3(BBS12):c.398del (p.Pro133fs)	BBS12	Pathogenic	criteria provided, multiple submitters, no conflicts
1073016	NM_152618.3(BBS12):c.869_873del (p.Val290fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073319	NM_152618.3(BBS12):c.1813_1814del (p.Asn605fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075926	NM_152618.3(BBS12):c.172G>T (p.Glu58Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1147	NM_152618.3(BBS12):c.1063C>T (p.Arg355Ter)	BBS12	Pathogenic	criteria provided, multiple submitters, no conflicts
1149	NM_152618.3(BBS12):c.1483_1484del (p.Glu495fs)	BBS12	Pathogenic	no assertion criteria provided
1151	NM_152618.3(BBS12):c.1115_1116del (p.Gly371_Phe372insTer)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180724	NM_152618.3(BBS12):c.2019del (p.Trp673fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1324316	NM_152618.3(BBS12):c.683del (p.Gln228fs)	BBS12	Pathogenic	criteria provided, single submitter
1422450	NM_152618.3(BBS12):c.780_781del (p.His260fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1448812	NM_152618.3(BBS12):c.911_912del (p.Cys304fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457852	NM_152618.3(BBS12):c.1455del (p.Asn485fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458879	NM_152618.3(BBS12):c.1733C>A (p.Ser578Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1460214	NM_152618.3(BBS12):c.189del (p.Ser64fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1934917	NM_152618.3(BBS12):c.1007del (p.Thr336fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2021677	NM_152618.3(BBS12):c.1673del (p.Leu558fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2061333	NM_152618.3(BBS12):c.1719del (p.Ser574fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2069346	NM_152618.3(BBS12):c.1799C>G (p.Ser600Ter)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2181208	NM_152618.3(BBS12):c.1993GTT[1] (p.Val666del)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2435112	NM_152618.3(BBS12):c.695_731del (p.Ile232fs)	BBS12	Pathogenic	criteria provided, multiple submitters, no conflicts
2498304	NM_152618.3(BBS12):c.1480dup (p.Thr494fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2679993	NM_152618.3(BBS12):c.1672_1673del (p.Leu558fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2734653	NM_152618.3(BBS12):c.1616del (p.Gly539fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2820216	NM_152618.3(BBS12):c.1149del (p.Asp383fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2861657	NM_152618.3(BBS12):c.1626del (p.Glu543fs)	BBS12	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
BBS12	Definitive	Autosomal recessive	Bardet-Biedl syndrome 12	7

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	gencc,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.