CAB39

Chr 2

calcium binding protein 39

Also known as: CGI-66, MO25

The protein is a component of a complex that binds and activates the STK11/LKB1 kinase, stabilizing interactions within this serine/threonine protein kinase complex involved in intracellular signaling and protein phosphorylation regulation. Mutations cause autosomal recessive intellectual disability with seizures and language delay, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.63), suggesting some intolerance to complete protein loss.

Summary from RefSeq, UniProt
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0
Active trials
9
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.63
LOEUF
DN
Mechanism· predicted
Clinical SummaryCAB39
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.068
Z-score 2.64
OE 0.30 (0.160.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
2.38Z-score
OE missense 0.49 (0.410.59)
86 obs / 174.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.30 (0.160.63)
00.351.4
Missense OE0.49 (0.410.59)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 5 / 16.6Missense obs/exp: 86 / 174.6Syn Z: 1.17
DN
0.6649th %ile
GOF
0.5955th %ile
LOF
0.3066th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CAB39 · 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.

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Clinical Literature
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