BBS1

Chr 11

Bardet-Biedl syndrome 1

Also known as: BBS2L2

NCBI Gene: 582 ENSG00000174483 UniProt: Q8NFJ9

The encoded protein is required for assembly and ciliary localization of the BBSome complex, which functions as a coat complex that sorts specific membrane proteins to primary cilia and controls ciliary trafficking essential for the sonic hedgehog pathway. Mutations cause Bardet-Biedl syndrome 1, a multisystem ciliopathy affecting the eyes, limbs, heart, and reproductive system. Inheritance is autosomal recessive.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

Mutations in this gene have been observed in patients with the major form (type 1) of Bardet-Biedl syndrome. The encoded protein may play a role in eye, limb, cardiac and reproductive system development. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBardet-Biedl syndrome 1

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · BBS1-related ciliopathy · AR · ClinGen 2023

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

0.98

LOEUF

LOF

Mechanism· G2P

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GeneReview available — BBS1

Authoritative clinical overview · Recommended first read

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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?

0.98LOEUF

pLI 0.000

Z-score 1.64

OE 0.69 (0.50–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.16Z-score

OE missense 0.98 (0.89–1.07)

335 obs / 343.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.50–0.98)

0≤0.351.4

Missense OE?0.98 (0.89–1.07)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 23 / 33.2Missense obs/exp: 335 / 343.1Syn Z: -0.03

Background carrier burden — how many people carry a rare variant somewhere in BBS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 85

785 rare PASS variants

Rare truncating (LoF)

1 in 1,400

141 rare PASS variants

Rare synonymous (reference)

1 in 160

288 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BBS1. 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 110	1 in 1,800
South Asian	~43k	1 in 58	1 in 1,000
Remaining (unassigned)	~30k	1 in 67	1 in 1,300
European (Finnish)	~27k	1 in 190	≈ 1 in 6,700
Admixed American	~22k	1 in 55	1 in 830
African / African American	~21k	1 in 50	1 in 1,100
East Asian	~20k	1 in 45	1 in 1,500
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 52	≈ 1 in 960

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.