SLC6A4 – Autism Spectrum Disorder

SLC6A4 encodes the serotonin transporter (SERT) and has been investigated as a candidate in autism spectrum disorder (ASD) based on serotonin’s role in neurodevelopment. Association studies including both case–control and family‐based transmission/disequilibrium tests have yielded largely negative results for common and rare SLC6A4 variants in ASD. No pathogenic coding alleles have segregated in families and large screens have not shown enrichment of rare exonic changes in cases compared to controls.

Genetic evidence is limited: in a high‐throughput screen of ~350 unrelated ASD cases and ~420 controls, rare SLC6A4 coding variants, including c.1815A>C (p.Lys605Asn), occurred at similar frequencies in both groups ([PMID:19360675]). Functional data demonstrate that the 5-HTT‐linked promoter region polymorphism (5-HTTLPR) short allele reduces SLC6A4 transcription and platelet serotonin uptake ([PMID:10050973]), but this variant does not confer elevated ASD risk. Overall, the current evidence supports a limited clinical validity for SLC6A4 in ASD. Additional studies integrating deeper phenotyping and larger cohorts would be required to clarify any small‐effect contributions. Key Take-home: SLC6A4 variants alter transporter function but lack robust association with ASD susceptibility.

References

• Autism research : official journal of the International Society for Autism Research • 2008 • A large-scale screen for coding variants in SERT/SLC6A4 in autism spectrum disorders. PMID:19360675
• American journal of medical genetics • 1999 • Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. PMID:10050973

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