BBS9

Chr 7AR

Bardet-Biedl syndrome 9

Also known as: B1, C18, D1, PTHB1

NCBI Gene: 27241ENSG00000122507UniProt: Q3SYG4

This gene is downregulated by parathyroid hormone in osteoblastic cells, and therefore is thought to be involved in parathyroid hormone action in bones. The exact function of this gene has not yet been determined. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Bardet-Biedl syndrome 9MIM #615986
AR
521
ClinVar variants
75
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— BBS9
🧬
Gene-Disease Validity (ClinGen)
BBS9-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
75 Pathogenic / Likely Pathogenic· 192 VUS of 521 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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.
0.84LOEUF
pLI 0.000
Z-score 2.51
OE 0.63 (0.48–0.84)
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.
0.40Z-score
OE missense 0.95 (0.87–1.02)
432 obs / 456.3 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.0.63 (0.48–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.87–1.02)
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.1.05
0≤1.21.6
LoF obs/exp: 35 / 55.1Missense obs/exp: 432 / 456.3Syn Z: -0.47

ClinVar Variant Classifications

521 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic35
VUS192
Likely Benign236
Benign6
Conflicting12
40
Pathogenic
35
Likely Pathogenic
192
VUS
236
Likely Benign
6
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
28
0
40
Likely Pathogenic
14
3
18
0
35
VUS
5
162
23
2
192
Likely Benign
0
4
118
114
236
Benign
0
0
6
0
6
Conflicting
—12
Total31169193116521

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

View in ClinVar →

Protein Context — Lollipop Plot

BBS9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

BBS9-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

1 OMIM entry

OMIM

Bardet-Biedl syndrome 9

MIM #615986

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — BBS9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel BBS1 deletion and BBS9 nonsense pathogenic variant in Bardet-Biedl syndrome.
Li JM et al.·Ophthalmic Genet
2025
Nonsyndromic craniosynostosis: novel coding variants.
Sewda A et al.·Pediatr Res
2019
Comprehensive clinical and genetic characterization of Bardet-Biedl Syndrome: insights from the largest Turkish cohort.
Demir Ş et al.·Eur J Pediatr
2025Cohort
Meta-analysis of genotype-phenotype associations in Bardet-Biedl syndrome uncovers differences among causative genes.
Niederlova V et al.·Hum Mutat
2019Meta-analysis
Clinical and genetic aspects of Bardet-Biedl syndrome in adults in Norway.
Rustad CF et al.·Orphanet J Rare Dis
2025
Circ_BBS9 as an early diagnostic biomarker for lung adenocarcinoma: direct interaction with IFIT3 in the modulation of tumor immune microenvironment.
Peng D et al.·Front Immunol
2024
Novel biallelic variant in BBS9 causative of Bardet-Biedl syndrome: expanding the spectrum of disease-causing genetic alterations.
Suárez-González J et al.·BMC Med Genomics
2021Case report
Knockdown of Bardet-Biedl syndrome gene BBS9/PTHB1 leads to cilia defects.
Veleri S et al.·PLoS One
2012
Novel homozygous protein-truncating mutation of BBS9 identified in a Chinese consanguineous family with Bardet-Biedl syndrome.
Tang HY et al.·Mol Genet Genomic Med
2021Case report
Cytogenomic aberrations in isolated multicystic dysplastic kidney in children.
Chen TJ et al.·Pediatr Res
2022
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
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