SON

Gene Facts

• HGNC Symbol: SON (HGNC:11183)
• HGNC Name: SON DNA and RNA binding protein
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: C21orf50
• Alias symbols: DBP-5, NREBP, KIAA1019, BASS1, FLJ21099, FLJ33914
• %HI: 3.75
• pLI: 1
• LOEUF: 0.05
• Cytoband: 21q22.11
• Genomic Coordinates:

  GRCh37/hg19:	chr21:34915344-34949787
  GRCh38/hg38:	chr21:33543038-33577481

• MANE Select Transcript: NM_138927.4 ENST00000356577.10
• Function: RNA-binding protein that acts as a mRNA splicing cofactor by promoting efficient splicing of transcripts that possess weak splice sites. Specifically promotes splicing of many cell-cycle and DNA-repair transcripts that possess weak splice sites, such as TUBG1, KATNB1, TUBGCP2, AURKB, PCNT, AKT1, RAD23A, and FANCG. Probably acts by facilitating the interaction between Serine/arginine-rich proteins such as SRSF2 and the RNA polymerase II. Also binds to DNA; binds to the consensus DNA sequence: 5'-... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-18088
• ClinGen Curation ID: CCID:007916
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 04/24/2019

Haploinsufficiency (HI) Score Details

• HI Score: 3
• HI Evidence Strength: Sufficient Evidence for Haploinsufficiency

HI Disease

• ZTTK (ZHU-TOKITA-TAKENOUCHI-KIM SYNDROME) syndrome

HI Evidence

• PUBMED: 25590979
  Zhu et al. (2015). This group analyzed 119 trios by WES. Heterzygous de novo frameshift mutation (4-bp deletion) was identified in a 5-year-old girl with with intellectual disability, seizures, dysmorphic features, white matter abnormalities, intestinal atresia, and VSD.
• PUBMED: 27256762
  Takenouchi et al (2016) this study describe a 13 year old male with the same de novo frameshift mutation (as seen in Zhu 2015 study) within exon 3 that is predicted to result in haploinsufficiency. This patient had intellectual disability, congenital heart disease, distinctive facial features, long slender extremities, and hyperextensible joints.
• PUBMED: 27545680
  Kim et al (2016) describe 20 individuals with loss of function mutations in SON. Common phenotypic features include "ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations". Trios study by WES reveals that 17/20 had frameshift indels (including the patient (patient 3) reported by Zhu et al. (2015)), 1/20 had nonsense mutation, 1/20 had in-frame deletion, and 1/20 had whole gene deletion including 5 other genes: GART, SON, DONSON, CRYZL1, ITSN1 and ATP5O. So 17 cases can be considered as additional de novo LOF variants identified in this study.

• HI Evidence Comments: PMID: 27545676 Tokita et al (2016) performed WES on over 6,000 subjects and identified de novo truncating mutations in SON in 6 individuals with Intellectual Disability, Congenital Malformations, and Failure to Thrive. In total, there are over 20 individuals with ZTTK syndrome carrying a de novo LOF variant of SON gene. ZTTK (ZHU-TOKITA-TAKENOUCHI-KIM SYNDROME) syndrome is the name given to individuals with SON gene mutation or deletion. The syndrome is characterized by "delayed psychomotor development and intellectual disability. Affected individuals have characteristic dysmorphic facial features, hypotonia, poor feeding, poor overall growth, and eye or visual abnormalities. Most patients also have musculoskeletal abnormalities, and some have congenital defects of the heart and urogenital system. Brain imaging usually shows developmental abnormalities such as gyral changes, cortical and/or cerebellar atrophy, and thin corpus callosum".

Triplosensitivity (TS) Score Details

• TS Score: 0
• TS Evidence Strength: No Evidence for Triplosensitivity