CACNA1C rs1006737: Calcium Signaling and Mental Health

Brain cells rely on precisely controlled electrical and chemical signals. Calcium channels help connect these signals to activity inside the cell—and CACNA1C provides instructions for an important part of that machinery.

The CACNA1C rs1006737 variant became a prominent subject in psychiatric genetics after studies linked its A allele with bipolar disorder. Researchers subsequently investigated its relationship with schizophrenia, recurrent depression, brain activity, and calcium-channel function [R, R].

Genotypes in this article use forward-strand A/G notation.

Here is what scientists have found and how to understand your result.

You can explore your available result through the free CACNA1C GeneExplorer entry.

What Does the CACNA1C Gene Do?

The CACNA1C gene encodes the main pore-forming component of CaV1.2, a type of voltage-gated calcium channel. These channels sit in cell membranes. When the electrical conditions change, they open and allow calcium ions to enter. Inside the cell, calcium acts as a signal that can influence electrical activity, communication, and the regulation of other genes.

CaV1.2 channels are important in both the brain and the heart. In the brain, they participate in processes related to memory, fear responses, and neuronal signaling. In the heart, they help coordinate the calcium movements involved in each heartbeat [R].

This gives CACNA1C a different role from genes involved in making or breaking down neurotransmitters. It helps shape how cells respond electrically and translate incoming signals into internal activity.

What Is the rs1006737 Variant?

Rs1006737 is a common, noncoding variant within an intron of CACNA1C. It does not directly replace an amino acid in the channel protein.

Instead, researchers have investigated whether the DNA region marked by rs1006737 influences how the gene is regulated. The marker sits within a group of linked variants, so an association with rs1006737 does not establish that this particular DNA letter causes every observed effect [R]. The A allele is the allele associated with higher psychiatric susceptibility in several of the studies discussed below.

CACNA1C rs1006737 and Bipolar Disorder

A 2008 genome-wide association analysis examined 4,387 people with bipolar disorder and 6,209 controls. It supported an association between rs1006737 and bipolar disorder, helping identify calcium-channel biology as an important direction for psychiatric research [R].

The reported association was approximately 1.18 times the odds per A allele. In other words, each A allele was associated with about 18% higher odds in that analysis—not an 18% probability of developing bipolar disorder [R].

Larger research subsequently strengthened the evidence for the gene region. A 2011 analysis involving 11,974 bipolar-disorder cases and 51,792 controls confirmed a genome-wide significant association at CACNA1C and highlighted a broader involvement of calcium-channel genes [R].

The important discovery was biological as well as statistical: differences in the machinery controlling calcium entry into cells could contribute to psychiatric susceptibility.

Links With Depression and Schizophrenia

Researchers also asked whether the association extended beyond bipolar disorder.

A UK study examined 1,196 people with recurrent major depression, 479 with schizophrenia, and 15,316 comparison participants. It reported associations between the A allele and both conditions, with allelic odds ratios of approximately 1.15 [R].

Depression, bipolar disorder, and schizophrenia are not interchangeable. However parts of their underlying biology can overlap, even when their clinical features differ.

What Do GG, AG, and AA Results Show?

Your genotype identifies which two alleles are recorded at rs1006737:

• GG: No copies of the A allele associated with higher susceptibility in the studies above.

• AG: One A allele. Under the additive models commonly used in association research, this contributes one copy of the reported association.

• AA: Two A alleles. This generally corresponds to a larger statistical contribution than AG within the same model.

These are common genetic differences. AA is not a diagnosis, and GG does not rule out a mental-health condition.

What Might the Variant Change in Brain Cells?

One particularly interesting study moved beyond comparing diagnoses and examined human-derived neurons in the laboratory.

Researchers generated neurons from more than 20 individuals with different rs1006737 genotypes. Neurons from people with the AA genotype showed:

• higher CACNA1C messenger RNA expression;

• greater L-type calcium-channel current density.

These results provided a possible functional connection between the associated genetic region and calcium signaling in neurons [R].

CACNA1C, Emotional Processing, and Working Memory

Brain-imaging research has explored another part of the story.

A 2010 study reported genotype-related differences in hippocampal activation during emotional processing and prefrontal activation during a working-memory task. These findings connected the associated genetic region with brain circuits relevant to memory and emotion [R]. An activation difference is not automatically an advantage or disadvantage. Greater activation can reflect differences in how a circuit recruits resources during a particular task.

One Marker Within a Much Larger Genetic Picture

Psychiatric genetics has expanded considerably since the early CACNA1C studies.

A 2025 study analyzed 158,036 bipolar-disorder cases and approximately 2.8 million controls, identifying 298 associated genomic regions. This illustrates how many parts of the genome contribute to susceptibility [R].

Rs1006737 is therefore best understood as one informative marker within a much larger network. Its research value comes from helping connect genetic associations with biological mechanisms.

Frequently Asked Questions

Is rs1006737 a calcium-deficiency variant?

No. The studies discussed here concern calcium-channel signaling and psychiatric associations. They do not establish that your genotype measures blood calcium or determines whether you need calcium supplements.

Is this the same as a rare CACNA1C-related disorder?

No. Common rs1006737 variation should be distinguished from rare pathogenic CACNA1C variants associated with conditions such as Timothy syndrome. Those variants can have very different effects on channel function. [R]

Can I find rs1006737 in my raw DNA file?

Coverage depends on your testing provider and chip version. If the marker is present and readable, GeneExplorer can display the recorded genotype. A missing marker does not establish whether you carry G or A.

Explore CACNA1C in GeneExplorer

CACNA1C offers a compelling connection between genetics, calcium channels, and mental-health research.

If you already have a consumer DNA file, explore CACNA1C rs1006737 in GeneExplorer to see your available result and its research context. You can also analyze your DNA for free to get started.

For related brain biology, read about COMT and dopamine metabolism, DRD2 and dopamine receptors, or BDNF and neuroplasticity.