BBS5

Chr 2AR

Bardet-Biedl syndrome 5

NCBI Gene: 129880 ENSG00000163093 UniProt: Q8N3I7 OMIM: 615983

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 OMIM 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 OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.892 OMIM phenotypes

Clinical Summary— BBS5

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Gene-Disease Validity (ClinGen)

BBS5-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

80 unique Pathogenic / Likely Pathogenic· 167 VUS of 476 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 — BBS5

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?

0.89LOEUF

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

ClinVar Variant Classifications

476 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43

Likely Pathogenic37

VUS167

Likely Benign184

Benign27

Conflicting10

Pathogenic

Likely Pathogenic

167

VUS

184

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	25	6	12	0	43
Likely Pathogenic	27	7	3	0	37
VUS	4	136	24	3	167
Likely Benign	1	1	100	82	184
Benign	0	0	23	4	27
Conflicting	—				10
Total	57	150	162	89	468

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 19) ClinVar copy-number / structural variants overlap BBS5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →