BBS1

Chr 11ARDigenic recessive

Bardet-Biedl syndrome 1

Also known as: BBS2L2

NCBI Gene: 582 ENSG00000174483 UniProt: Q8NFJ9 OMIM: 209901

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 OMIM 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 OMIM ResearchGenerating clinical summary…

LOFmechanismAR/Digenic recessiveLOEUF 0.984 OMIM phenotypes

Clinical Summary— BBS1

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Gene-Disease Validity (ClinGen)

BBS1-related ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

261 unique Pathogenic / Likely Pathogenic· 383 VUS of 1245 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — BBS1

Authoritative clinical overview · Recommended first read

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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

ClinVar Variant Classifications

1245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic118

Likely Pathogenic143

VUS383

Likely Benign511

Benign29

Conflicting51

118

Pathogenic

143

Likely Pathogenic

383

VUS

511

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	79	5	34	0	118
Likely Pathogenic	117	18	6	2	143
VUS	3	313	53	14	383
Likely Benign	1	2	247	261	511
Benign	0	1	26	2	29
Conflicting	—				51
Total	200	339	366	279	1,235

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap BBS1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →