BBS12

Chr 4

Bardet-Biedl syndrome 12

Also known as: C4orf24

NCBI Gene: 166379 ENSG00000181004 UniProt: Q6ZW61

The protein functions as a molecular chaperone within the chaperonin-containing T-complex (TRiC), facilitating protein folding through ATP hydrolysis and playing a role in ciliogenesis and adipocyte differentiation. Mutations cause Bardet-Biedl syndrome type 12, a multisystem ciliopathy affecting the eyes, kidneys, genitourinary system, and causing obesity and polydactyly. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is part of a complex that is involved in membrane trafficking. The encoded protein is a molecular chaperone that aids in protein folding upon ATP hydrolysis. This protein also plays a role in adipocyte differentiation. Defects in this gene are a cause of Bardet-Biedl syndrome type 12. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, May 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBardet-Biedl syndrome 12

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · BBS12-related ciliopathy · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.96

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.000

Z-score 1.70

OE 0.62 (0.41–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.34Z-score

OE missense 0.95 (0.87–1.04)

348 obs / 366.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.41–0.96)

0≤0.351.4

Missense OE?0.95 (0.87–1.04)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 14 / 22.7Missense obs/exp: 348 / 366.1Syn Z: 1.13

Background carrier burden — how many people carry a rare variant somewhere in BBS12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

815 rare PASS variants

Rare truncating (LoF)

1 in 930

128 rare PASS variants

Rare synonymous (reference)

1 in 200

326 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BBS12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 79	1 in 940
South Asian	~43k	1 in 60	1 in 640
Remaining (unassigned)	~30k	1 in 58	1 in 1,900
European (Finnish)	~27k	1 in 350	≈ 1 in 27,000
Admixed American	~22k	1 in 59	1 in 640
African / African American	~21k	1 in 61	1 in 1,600
East Asian	~20k	1 in 67	1 in 880
Ashkenazi Jewish	~13k	1 in 130	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 78	1 in 410

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓