CAMTA2

Chr 17

calmodulin binding transcription activator 2

NCBI Gene: 23125 ENSG00000108509 UniProt: O94983 OMIM: 611508

CAMTA2 encodes a calmodulin-binding transcription activator that regulates gene expression, particularly genes involved in cardiac growth, and may function as a tumor suppressor. Mutations cause autosomal dominant developmental delay, intellectual disability, and congenital heart defects with highly variable expressivity. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic when they occur.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the calmodulin-binding transcription activator protein family. Members of this family share a common domain structure that consists of a transcription activation domain, a DNA-binding domain, and a calmodulin-binding domain. The encoded protein may be a transcriptional coactivator of genes involved in cardiac growth. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— CAMTA2

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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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ClinVar Variants

187 VUS of 237 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.999

Z-score 6.30

OE 0.15 (0.09–0.26)

Highly constrained

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

Missense Constraint?

1.55Z-score

OE missense 0.84 (0.79–0.90)

627 obs / 746.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.15 (0.09–0.26)

0≤0.351.4

Missense OE?0.84 (0.79–0.90)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 10 / 64.6Missense obs/exp: 627 / 746.5Syn Z: 0.38

This gene — mechanism propensity

0.3693th %ile

GOF

0.4381th %ile

LOF

0.73top 10%

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

LOFprediction above median · LOEUF 0.26

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

ClinVar Variant Classifications

237 submitted variants in ClinVar

ClinVar

Classification Summary

VUS187

Likely Benign9

Benign4

Conflicting1

187

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	185	1	0	187
Likely Benign	0	4	0	5	9
Benign	0	1	1	2	4
Conflicting	—				1
Total	1	190	2	7	201

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap CAMTA2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →