CAMTA1

Chr 1AD

calmodulin binding transcription activator 1

Also known as: CANPMR, CECBA

NCBI Gene: 23261 ENSG00000171735 OMIM: 611501

The CAMTA1 protein is a transcription factor containing DNA-binding domains, ankyrin repeats, and calmodulin-binding motifs that functions in the nucleus. Loss-of-function mutations cause autosomal dominant cerebellar dysfunction with variable cognitive and behavioral abnormalities. The gene is highly intolerant to loss-of-function variants, supporting haploinsufficiency as the mechanism of disease.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene contains a CG1 DNA-binding domain, a transcription factor immunoglobulin domain, ankyrin repeats, and calmodulin-binding IQ motifs. The encoded protein is thought to be a transcription factor and may be a tumor suppressor. However, a translocation event is sometimes observed between this gene and the WWTR1 gene, with the resulting WWTR1-CAMTA1 oncoprotein leading to epithelioid hemangioendothelioma, a malignant vascular cancer. [provided by RefSeq, Mar 2017]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.171 OMIM phenotype

Clinical Summary— CAMTA1

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Gene-Disease Validity (ClinGen)

cerebellar dysfunction with variable cognitive and behavioral abnormalities · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 7.37

OE 0.09 (0.05–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.26Z-score

OE missense 0.71 (0.67–0.76)

725 obs / 1017.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.09 (0.05–0.17)

0≤0.351.4

Missense OE?0.71 (0.67–0.76)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 7 / 76.6Missense obs/exp: 725 / 1017.9Syn Z: 0.71

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCAMTA1-related cerebellar dysfunction with variable cognitive and behavioural abnormalitiesLOFAD

This gene — mechanism propensity

0.2997th %ile

GOF

0.3094th %ile

LOF

0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.17 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFHere, we show that global or nervous system deletion of CAMTA1 in mice causes severe ataxia with Purkinje cell degeneration and cerebellar atrophy, partially resembling the consequences of haploinsufficiency of the human CAMTA1 locus.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References