BBS2

Chr 16AR

Bardet-Biedl syndrome 2

Also known as: BBS, RP74

NCBI Gene: 583 ENSG00000125124 UniProt: Q9BXC9 OMIM: 615981

The protein encoded by this gene is a component of the BBSome complex, which functions as a coat complex that sorts specific membrane proteins to primary cilia and is required for ciliogenesis and ciliary membrane extension. Mutations cause Bardet-Biedl syndrome, an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation, and cognitive disability, as well as retinitis pigmentosa. The gene shows minimal constraint against loss-of-function variants (pLI near zero, LOEUF >1), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.073 OMIM phenotypes

Clinical Summary— BBS2

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Gene-Disease Validity (ClinGen)

BBS2-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

278 unique Pathogenic / Likely Pathogenic· 461 VUS of 1366 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — BBS2

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?

1.07LOEUF

pLI 0.000

Z-score 1.22

OE 0.79 (0.59–1.07)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.87Z-score

OE missense 0.88 (0.80–0.96)

351 obs / 400.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.59–1.07)

0≤0.351.4

Missense OE?0.88 (0.80–0.96)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 31 / 39.3Missense obs/exp: 351 / 400.0Syn Z: 0.24

ClinVar Variant Classifications

1366 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90

Likely Pathogenic188

VUS461

Likely Benign515

Benign37

Conflicting50

Pathogenic

188

Likely Pathogenic

461

VUS

515

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	76	4	10	0	90
Likely Pathogenic	162	23	1	2	188
VUS	5	394	49	13	461
Likely Benign	0	5	212	298	515
Benign	0	2	33	2	37
Conflicting	—				50
Total	243	428	305	315	1,341

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap BBS2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →