What you carry at this position in your DNA and what research says about it.
Mental Health Risk: 6/10 evidence, 51 publications.
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Sample genotype (not yours): G/G
Typical Mental Health Susceptibility
Two copies of the common G allele are associated with baseline susceptibility to psychiatric conditions. This genotype does not carry the calcium channel risk variant.
What this genotype means: Baseline risk for psychiatric conditions; Typical brain connectivity patterns; Standard cognitive performance.
Sample genotype (not yours): A/A
Increased Mental Health Susceptibility
Two copies of the A allele are associated with an elevated risk of bipolar disorder, schizophrenia, and depression. This genotype can influence calcium signaling and brain connectivity.
What this genotype means: Elevated risk for bipolar disorder and schizophrenia; Altered prefrontal-amygdala brain connectivity; Potential impact on delayed memory and executive function.
Sample genotype (not yours): G/A
Slightly Increased Mental Health Susceptibility
Carrying one copy of the A allele is linked to a minor increase in susceptibility to several psychiatric conditions. This variant may subtly influence calcium channel signaling in the brain.
What this genotype means: Modestly elevated risk for bipolar disorder; Slightly increased susceptibility to schizophrenia; Subtle variations in emotional brain processing.
Gene function and biological role
Gene Function: The CACNA1C gene encodes the alpha-1C subunit of the L-type voltage-gated calcium channel, which is crucial for regulating calcium entry into excitable cells [1]. These channels play a fundamental role in neurotransmitter release, gene expression, and synaptic plasticity within the brain [2]. Proper calcium signaling is essential for maintaining stable neuronal excitability and supporting complex cognitive processes [3]. Variations in this gene can alter channel function and have been widely implicated in susceptibility to several major psychiatric conditions [4].
Variant Impact: The rs1006737 variant is an intronic single nucleotide polymorphism located within the CACNA1C gene [5]. Although it does not directly alter the amino acid sequence of the calcium channel protein, it is thought to act as a regulatory variant that influences gene expression levels [6]. The presence of the risk-associated A allele has been linked to altered messenger RNA expression of CACNA1C in the prefrontal cortex [1]. This expression change can modify calcium signaling dynamics, affecting functional brain connectivity and emotional processing networks [7].
Key Insight: The risk allele at this locus is shared across multiple distinct psychiatric diagnoses, suggesting a common biological pathway involving calcium channel signaling. Additionally, this variant influences how the brain processes emotional stimuli, such as fearful faces, by altering connectivity between the prefrontal cortex and the amygdala.
Location: CACNA1C. Chromosome 12 · 12p13.33 · 2.2 Mb
Estimated prevalence by population
Global 42.6%; European 44.2%; African 27.2%; East Asian 90.0%; South Asian 56.6%; Americas 51.0%; Ashkenazi 49.5%; Finnish 46.4%; Middle Eastern 57.5%; Amish 47.0%.
Estimated GG genotype frequency.
Global 44.0%; European 44.6%; African 49.9%; East Asian 9.8%; South Asian 37.2%; Americas 40.8%; Ashkenazi 41.7%; Finnish 43.4%; Middle Eastern 36.6%; Amish 43.1%.
Estimated GA genotype frequency.
Global 13.4%; European 11.2%; African 22.9%; East Asian 0.3%; South Asian 6.1%; Americas 8.2%; Ashkenazi 8.8%; Finnish 10.1%; Middle Eastern 5.8%; Amish 9.9%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Neurology & Mental Health
Mood Disorders
Bipolar Disorder. Evidence: 6/10. Source: PMID 18711365. Typical Risk.
Depression. Evidence: 5/10. Source: PMID 19621016. Typical Risk.
Psychotic Disorders
Schizophrenia. Evidence: 6/10. Source: PMID 20098439. Typical Risk.
Cognitive Performance
Cognitive Function. Evidence: 4/10. Source: PMID 22012475. Typical.
Neurodevelopmental Traits
Autism Susceptibility. Evidence: 5/10. Source: PMID 23453885. Typical Risk.
Showing effects for A/A genotype
Bipolar Disorder. Evidence: 6/10. Source: PMID 18711365. Increased Risk.
Depression. Evidence: 5/10. Source: PMID 19621016. Increased Risk.
Schizophrenia. Evidence: 6/10. Source: PMID 20098439. Increased Risk.
Cognitive Function. Evidence: 4/10. Source: PMID 22012475. Reduced Performance.
Autism Susceptibility. Evidence: 5/10. Source: PMID 23453885. Increased Risk.
Showing effects for G/A genotype
Bipolar Disorder. Evidence: 6/10. Source: PMID 18711365. Slightly Increased.
Depression. Evidence: 5/10. Source: PMID 19621016. Slightly Increased.
Schizophrenia. Evidence: 6/10. Source: PMID 20098439. Slightly Increased.
Cognitive Function. Evidence: 4/10. Source: PMID 22012475. Slightly Reduced.
Autism Susceptibility. Evidence: 5/10. Source: PMID 23453885. Slightly Increased.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele represents the baseline genetic profile for this locus. Large-scale genome-wide association studies show no elevated risk for bipolar disorder or schizophrenia associated with this genotype [1]. Brain imaging research indicates typical functional connectivity between the prefrontal cortex and the amygdala during emotional processing tasks [2]. Cognitive assessments, including tests of spatial working memory and verbal fluency, show standard performance levels [3]. Because calcium channel subunit expression remains at typical levels, there is no genetic predisposition to altered calcium signaling from this variant [4]. Overall, this genotype represents the standard reference profile in the general population.
Baseline risk for psychiatric conditions; Typical brain connectivity patterns; Standard cognitive performance.
Sample genotype: AA (Homozygous)
Carrying two copies of the A risk allele is associated with an increased susceptibility to several psychiatric conditions, including bipolar disorder, schizophrenia, and major depressive disorder [1]. This genotype is linked to higher expression of the CACNA1C gene in the prefrontal cortex, which can alter calcium channel dynamics [2]. Neuroimaging studies show that individuals with this genotype exhibit altered connectivity between the prefrontal cortex and the amygdala during emotional tasks [3]. Furthermore, some clinical studies have observed poorer cognitive performance, particularly in areas like delayed memory and executive function, among individuals carrying this genotype [4]. Despite these associations, the absolute increase in risk contributed by this single genetic variant is small, and it is not a standalone diagnostic tool [5]. Maintaining a healthy lifestyle and managing stress can help support overall mental well-being.
Elevated risk for bipolar disorder and schizophrenia; Altered prefrontal-amygdala brain connectivity; Potential impact on delayed memory and executive function.
Sample genotype: GA (Heterozygous)
Possessing one copy of the A allele is associated with a modest increase in the risk of developing bipolar disorder and schizophrenia [1]. This genetic variation is thought to subtly alter the expression of the CACNA1C gene, which encodes a key calcium channel subunit [2]. Research suggests that carriers of the A allele may experience minor differences in brain connectivity, particularly during emotional processing [3]. Studies have also noted subtle impacts on cognitive measures, such as spatial working memory and executive function, compared to non-carriers [4]. The overall effect size of this single variant is very small, meaning it is only one of many genetic and environmental factors that contribute to mental health outcomes [5]. It does not act as a direct diagnostic marker.
Modestly elevated risk for bipolar disorder; Slightly increased susceptibility to schizophrenia; Subtle variations in emotional brain processing.
Variants with shared genetic architecture
rs4765905 · CACNA1C Gene · Chr 12 · Schizophrenia Risk
rs1042779 · ITIH1 Gene · Chr 3 · Bipolar Disorder Risk
rs2535629 · ITIH3 Gene · Chr 3 · Mental Health Risk
Evidence for cis-acting regulation of ANK3 and CACNA1C gene expression.
Content updated August 2026.
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