Mutations in SPATA5 Are Associated with Microcephaly, Intellectual Disability, Seizures, and Hearing Loss

Am J Hum Genet. 2015 Sep 3;97(3):457-64. doi: 10.1016/j.ajhg.2015.07.014. Epub 2015 Aug 20.


Using whole-exome sequencing, we have identified in ten families 14 individuals with microcephaly, developmental delay, intellectual disability, hypotonia, spasticity, seizures, sensorineural hearing loss, cortical visual impairment, and rare autosomal-recessive predicted pathogenic variants in spermatogenesis-associated protein 5 (SPATA5). SPATA5 encodes a ubiquitously expressed member of the ATPase associated with diverse activities (AAA) protein family and is involved in mitochondrial morphogenesis during early spermatogenesis. It might also play a role in post-translational modification during cell differentiation in neuronal development. Mutations in SPATA5 might affect brain development and function, resulting in microcephaly, developmental delay, and intellectual disability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Amino Acid Sequence
  • Base Sequence
  • Exome / genetics
  • Female
  • Gene Frequency
  • Genes, Recessive
  • Hearing Loss / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Microcephaly / genetics*
  • Molecular Sequence Data
  • Mutation / genetics
  • Seizures / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA


  • Homeodomain Proteins
  • SPATA5 protein, human
  • ATPases Associated with Diverse Cellular Activities