Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype

Mol Psychiatry. 2003 Nov;8(11):933-6. doi: 10.1038/


Two common serotonin transporter (SERT) untranslated region gene variants have been intensively studied, but remain inconclusively linked to depression and other neuropsychiatric disorders. We now report an uncommon coding region SERT mutation, Ile425Val, in two unrelated families with OCD and other serotonin-related disorders. Six of the seven family members with this mutation had OCD (n=5) or obsessive-compulsive personality disorder (n=1) and some also met diagnostic criteria for multiple other disorders (Asperger's syndrome, social phobia, anorexia nervosa, tic disorder and alcohol and other substance abuse/dependence). The four most clinically affected individuals--the two probands and their two slbs--had the I425V SERT gene gain-of-function mutation and were also homozygous for 5'-UTR SERT gene variant with greater transcriptional efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anorexia Nervosa / genetics*
  • Asperger Syndrome / genetics
  • Autistic Disorder / genetics*
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Obsessive-Compulsive Disorder / genetics*
  • Pedigree
  • Phenotype
  • Phobic Disorders / genetics
  • Polymorphism, Single-Stranded Conformational
  • Protein Structure, Tertiary
  • Serotonin Plasma Membrane Transport Proteins


  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins