CIBAR1

Chr 8AR

CBY1 interacting BAR domain containing 1

Also known as: BARMR1, FAM92A, FAM92A1, PAPA9

The CIBAR1 protein regulates mitochondrial ultrastructure by maintaining cristae organization and plays a crucial role in ciliogenesis and limb development through its phospholipid binding activity and ability to induce membrane curvature. Mutations cause postaxial polydactyly type A9 with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variants, suggesting tolerance to complete protein loss.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

?Polydactyly, postaxial, type A9MIM #618219
AR
0
Active trials
3
Pubs (1 yr)
44
P/LP submissions
0%
P/LP missense
1.10
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryCIBAR1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
41 unique Pathogenic / Likely Pathogenic· 36 VUS of 88 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.21
OE 0.71 (0.471.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.97Z-score
OE missense 0.77 (0.660.91)
113 obs / 145.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.71 (0.471.10)
00.351.4
Missense OE0.77 (0.660.91)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 14 / 19.8Missense obs/exp: 113 / 145.9Syn Z: 0.48
DN
0.75top 25%
GOF
0.7127th %ile
LOF
0.2774th %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

88 submitted variants in ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic2
VUS36
Likely Benign4
Benign1
39
Pathogenic
2
Likely Pathogenic
36
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
39
0
39
Likely Pathogenic
1
0
1
0
2
VUS
0
34
2
0
36
Likely Benign
0
2
1
1
4
Benign
0
1
0
0
1
Total13743182

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

View in ClinVar →

Protein Context — Lollipop Plot

CIBAR1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗