CAMTA1

Chr 1AD

calmodulin binding transcription activator 1

Also known as: CANPMR, CECBA

NCBI Gene: 23261 ENSG00000171735 UniProt: Q9Y6Y1 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…

Primary Disease Associations & Inheritance

Cerebellar dysfunction with variable cognitive and behavioral abnormalitiesMIM #614756

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · cerebellar dysfunction with variable cognitive and behavioral abnormalities · AD · ClinGen 2023

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in CAMTA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 35

1,812 rare PASS variants

Rare truncating (LoF)

1 in 1,600

77 rare PASS variants

Rare synonymous (reference)

1 in 34

910 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CAMTA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 43	1 in 1,800
South Asian	~43k	1 in 29	1 in 1,400
Remaining (unassigned)	~30k	1 in 32	1 in 1,600
European (Finnish)	~27k	1 in 100	1 in 3,700
Admixed American	~22k	1 in 34	1 in 1,600
African / African American	~21k	1 in 33	1 in 1,100
East Asian	~20k	1 in 38	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 140	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 33	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.