BBS2

Chr 16AR

Bardet-Biedl syndrome 2

Also known as: BBS, RP74

NCBI Gene: 583 ENSG00000125124 UniProt: Q9BXC9 OMIM: 615981

The protein encoded by this gene is a component of the BBSome complex, which functions as a coat complex that sorts specific membrane proteins to primary cilia and is required for ciliogenesis and ciliary membrane extension. Mutations cause Bardet-Biedl syndrome, an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation, and cognitive disability, as well as retinitis pigmentosa. The gene shows minimal constraint against loss-of-function variants (pLI near zero, LOEUF >1), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 2MIM #615981

Retinitis pigmentosa 74MIM #616562

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · BBS2-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

1.07

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BBS2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.07LOEUF

pLI 0.000

Z-score 1.22

OE 0.79 (0.59–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.87Z-score

OE missense 0.88 (0.80–0.96)

351 obs / 400.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.59–1.07)

0≤0.351.4

Missense OE?0.88 (0.80–0.96)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 31 / 39.3Missense obs/exp: 351 / 400.0Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in BBS2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

882 rare PASS variants

Rare truncating (LoF)

1 in 460

167 rare PASS variants

Rare synonymous (reference)

1 in 87

334 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BBS2. 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 91	1 in 460
South Asian	~43k	1 in 71	1 in 680
Remaining (unassigned)	~30k	1 in 60	1 in 450
European (Finnish)	~27k	1 in 300	1 in 420
Admixed American	~22k	1 in 82	1 in 1,200
African / African American	~21k	1 in 54	1 in 730
East Asian	~20k	1 in 51	1 in 260
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 69	≈ 1 in 1,400

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.