BBS5

Chr 2

Bardet-Biedl syndrome 5

NCBI Gene: 129880 ENSG00000163093 UniProt: Q8N3I7

The protein is a component of the BBSome complex that functions as a coat complex required for sorting specific membrane proteins to primary cilia and promoting ciliary membrane extension through Rab8-mediated vesicle trafficking. Mutations cause Bardet-Biedl syndrome, a ciliopathy characterized by retinal dystrophy, obesity, polydactyly, renal abnormalities, and learning disabilities. Inheritance is autosomal recessive.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtBardet-Biedl syndrome 5

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · BBS5-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

0.89

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — BBS5

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.89LOEUF

pLI 0.000

Z-score 1.95

OE 0.55 (0.35–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.85Z-score

OE missense 0.82 (0.72–0.94)

148 obs / 180.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.35–0.89)

0≤0.351.4

Missense OE?0.82 (0.72–0.94)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 12 / 21.8Missense obs/exp: 148 / 180.1Syn Z: 1.07

Background carrier burden — how many people carry a rare variant somewhere in BBS5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

385 rare PASS variants

Rare truncating (LoF)

1 in 1,700

92 rare PASS variants

Rare synonymous (reference)

1 in 180

146 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for BBS5. 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 300	1 in 2,100
South Asian	~43k	1 in 180	1 in 1,200
Remaining (unassigned)	~30k	1 in 220	1 in 640
European (Finnish)	~27k	1 in 720	1 in 2,200
Admixed American	~22k	1 in 140	1 in 1,000
African / African American	~21k	1 in 110	1 in 680
East Asian	~20k	1 in 150	1 in 1,600
Ashkenazi Jewish	~13k	1 in 400	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 210	≈ 1 in 720

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): 10 of 12 coding exons well covered in gnomAD exomes; exons 2, 8 marginal. Genomes: all 12.? see exons ↓