BBS1

Chr 11ARDigenic recessive

Bardet-Biedl syndrome 1

Also known as: BBS2L2

NCBI Gene: 582ENSG00000174483UniProt: Q8NFJ9

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]

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 1MIM #209900
ARDigenic recessive
{Bardet-Biedl syndrome 1, modifier of}MIM #209900
ARDigenic recessive
{Bardet-Biedl syndrome 1, modifier of}MIM #209900
ARDigenic recessive
Bardet-Biedl syndrome 1MIM #209900
ARDigenic recessive
590
ClinVar variants
163
Pathogenic / LP
0.00
pLI score
2
Active trials
Clinical Summary— BBS1
🧬
Gene-Disease Validity (ClinGen)
BBS1-related ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
163 Pathogenic / Likely Pathogenic· 168 VUS of 590 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.98LOEUF
pLI 0.000
Z-score 1.64
OE 0.69 (0.50–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.16Z-score
OE missense 0.98 (0.89–1.07)
335 obs / 343.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.50–0.98)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 23 / 33.2Missense obs/exp: 335 / 343.1Syn Z: -0.03

ClinVar Variant Classifications

590 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic77
Likely Pathogenic86
VUS168
Likely Benign228
Benign8
Conflicting23
77
Pathogenic
86
Likely Pathogenic
168
VUS
228
Likely Benign
8
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
4
37
0
77
Likely Pathogenic
62
10
12
2
86
VUS
2
127
30
9
168
Likely Benign
1
0
139
88
228
Benign
0
0
8
0
8
Conflicting
—23
Total10114122699590

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BBS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BBS1-related Bardet-Biedl syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM
BBS1 GENE; BBS1
MIM #209901 · *

Bardet-Biedl syndrome 1

MIM #209900

Molecular basis of disorder known

Autosomal recessiveDigenic recessive

{Bardet-Biedl syndrome 1, modifier of}

MIM #209900

Molecular basis of disorder known

Autosomal recessiveDigenic recessive

{Bardet-Biedl syndrome 1, modifier of}

MIM #209900

Molecular basis of disorder known

Autosomal recessiveDigenic recessive

Bardet-Biedl syndrome 1

MIM #209900

Molecular basis of disorder known

Autosomal recessiveDigenic recessive
📖
GeneReview available — BBS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Spectrum of Genetic Variants in the Most Common Genes Causing Inherited Retinal Disease in a Large Molecularly Characterized United Kingdom Cohort.
Lin S et al.·Ophthalmol Retina
2024Cohort
[Bardet-Biedl syndrome].
Rooryck C et al.·Ann Endocrinol (Paris)
2008Review
Phenotypic and Genetic Spectrum in 309 Consecutive Pediatric Patients with Inherited Retinal Disease.
Priglinger CS et al.·Int J Mol Sci
2024Cohort
FGFR2 residence in primary cilia is necessary for epithelial cell signaling.
Nita A et al.·J Cell Biol
2025
BBS1 branchpoint variant is associated with non-syndromic retinitis pigmentosa.
Fadaie Z et al.·J Med Genet
2022
Lethal neonatal respiratory failure due to biallelic variants in BBS1 and monoallelic variant in TTC21B.
Viehl L et al.·Pediatr Nephrol
2023
Novel BBS1 deletion and BBS9 nonsense pathogenic variant in Bardet-Biedl syndrome.
Li JM et al.·Ophthalmic Genet
2025
Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort.
Demir Ş et al.·Eur J Pediatr
2025Cohort
Ectopic expression of BBS1 rescues male infertility, but not retinal degeneration, in a BBS1 mouse model.
Cring MR et al.·Gene Ther
2022Functional
Clinical and genetic aspects of Bardet-Biedl syndrome in adults in Norway.
Rustad CF et al.·Orphanet J Rare Dis
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Bardet-Biedl Syndrome 1Retinal Degeneration

First-in-Human, Dose Escalation Trial of AXV-101 in BBS1-Related Retinal Degeneration

NOT YET RECRUITING
NCT07269665Phase EARLY_PHASE1Axovia TherapeuticsStarted 2026-02-23
AXV-101
Morbid ObesityBariatric SurgeryTelerehabilitation

Exercise to Fight Obesity

RECRUITING
NCT06934681Phase NAInstituto de Investigacion Sanitaria La FeStarted 2025-05-19
Usual Care GroupControlled exercise with telerehabilitation

External Resources

Links to major genomics databases and tools