rs11651301 (CACNG1): Aripiprazole Movement Side Effects
Key takeaways
- CACNG1, a calcium channel auxiliary subunit gene, was flagged as a candidate for movement-related side effects of the antipsychotic aripiprazole
- The finding is preliminary: CACNG1 did not reach genome-wide significance and was identified as a supporting candidate locus
- The rs11651301 ALT allele is linked to reduced CACNG1 expression in skeletal muscle
- Evidence comes from one study of 384 patients with no reported independent replication for this locus
Key takeaways
- CACNG1, a calcium channel auxiliary subunit gene, was flagged as a candidate for movement-related side effects of the antipsychotic aripiprazole
- The finding is preliminary: CACNG1 did not reach genome-wide significance and was identified as a supporting candidate locus
- The rs11651301 ALT allele is linked to reduced CACNG1 expression in skeletal muscle
- Evidence comes from one study of 384 patients with no reported independent replication for this locus
What the research says A genome-wide association study (GWAS) of 384 schizophrenia patients receiving aripiprazole monotherapy identified CACNG1 (Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 1 - a protein that assists in regulating calcium channel activity) as a candidate locus within a network of ion channel and transporter genes hypothesized to underlie movement-related adverse drug reactions (ADRs), including extrapyramidal effects (involuntary muscle movements and rigidity) and motor restlessness. The primary genome-wide-significant finding from that study was a separate variant, rs4149181 in SLC22A8 (P = 2.28 × 10^-8); the gene was identified as a supporting candidate in the network-level discussion rather than as a primary discovery. Independently, tissue expression data show that the rs11651301 ALT allele is associated with reduced expression of this gene in skeletal muscle GTEx Portal.
Reported associations
- Movement-related adverse drug reactions to aripiprazole: CACNG1 was listed among candidate loci in a 384-patient GWAS of movement-related ADRs (extrapyramidal side effects, motor restlessness, and other abnormal movements) in schizophrenia patients on aripiprazole monotherapy; the locus did not reach the standard genome-wide significance threshold of P < 5 × 10^-8.
- Skeletal muscle gene expression: The rs11651301 ALT allele is associated with reduced CACNG1 expression in skeletal muscle tissue (p = 2.1 × 10^-6) GTEx Portal.
Evidence quality The sole available genetic study is a single-cohort GWAS (discovery cohort, n = 384 analyzed from 431 recruited) with no independently published replication specifically for CACNG1. The locus was raised in the network-level discussion of candidate genes rather than as a primary finding; the study's combined prediction model (AUC 0.84, a measure of predictive accuracy ranging from 0.5 for chance to 1.0 for perfect) covers only the six primary genome-wide loci and does not quantify this gene's individual contribution. Tissue expression data from GTEx v11 (953 donors) show a statistically significant eQTL association (expression quantitative trait locus - a genetic variant that influences how much a gene is expressed) in skeletal muscle (p = 2.1 × 10^-6), but this reflects a gene-expression mechanism rather than a clinical outcome GTEx Portal. Overall, evidence for rs11651301 is preliminary and requires independent replication before firm conclusions can be drawn.
Tissue-specific expression effects
- CACNG1: The ALT allele is associated with reduced expression in skeletal muscle GTEx Portal.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What does the CACNG1 gene do?
CACNG1 encodes a protein called Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 1, which helps regulate how calcium channels function. Expression data from GTEx show that rs11651301 influences the gene's activity in skeletal muscle.
Is rs11651301 linked to aripiprazole side effects?
CACNG1, the gene containing rs11651301, was listed as a candidate locus in a genome-wide study of movement-related side effects in people taking aripiprazole. However, it did not reach genome-wide significance and has not been independently replicated, so the evidence remains preliminary.
What are movement-related adverse drug reactions to aripiprazole?
These include extrapyramidal side effects (such as involuntary muscle movements and rigidity), motor restlessness, and other abnormal movements that some people experience when taking the antipsychotic drug aripiprazole.
Does rs11651301 affect CACNG1 gene expression?
According to GTEx tissue expression data from 953 donors, the ALT allele of rs11651301 is associated with reduced CACNG1 expression in skeletal muscle. This is a mechanism-level finding about gene activity, not a direct clinical outcome.
How strong is the evidence for rs11651301?
The evidence is preliminary. A single study of 384 patients mentioned CACNG1 as a supporting candidate gene within a biological network hypothesis, but it was not a primary genome-wide significant hit, and no independent replication has been reported for this locus.