CIBAR2

Chr 16

CBY1 interacting BAR domain containing 2

Also known as: FAM92B

NCBI Gene: 339145 ENSG00000153789 UniProt: Q6ZTR7 OMIM: 617274

The protein facilitates ciliogenesis by recruiting and fusing endosomal vesicles at distal appendages during early stages of cilium formation, working in cooperation with CBY1. Mutations cause autosomal recessive Joubert syndrome, a ciliopathy characterized by cerebellar vermis hypoplasia, abnormal breathing patterns, and developmental delay. The gene shows minimal constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in cilium assembly. Predicted to be located in cell projection; centriole; and cytoplasm. Predicted to be active in ciliary basal body and ciliary transition zone. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.43

Clinical Summary— CIBAR2

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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

75 VUS of 86 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.43LOEUF

pLI 0.000

Z-score 0.26

OE 0.93 (0.62–1.43)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.54Z-score

OE missense 1.33 (1.19–1.48)

232 obs / 174.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.93 (0.62–1.43)

0≤0.351.4

Missense OE?1.33 (1.19–1.48)

0≤0.61.4

Synonymous OE?1.29

0≤1.21.6

LoF obs/exp: 15 / 16.1Missense obs/exp: 232 / 174.8Syn Z: -1.94

This gene — mechanism propensity

0.74top 25%

GOF

0.6542th %ile

LOF

0.2969th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS75

Likely Benign5

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	0	75	75
Likely Benign	1	4	5
Benign	0	1	1
Total	1	80	81

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap CIBAR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →