POGZ

Gene Facts

• HGNC Symbol: POGZ (HGNC:18801)
• HGNC Name: pogo transposable element derived with ZNF domain
• Gene type: protein-coding gene
• Locus type: gene with protein product
• Previous symbols: No previous names found
• Alias symbols: KIAA0461, ZNF635, ZNF280E
• %HI: 29.96
• pLI: 1
• LOEUF: 0.2
• Cytoband: 1q21.3
• Genomic Coordinates:

  GRCh37/hg19:	chr1:151375200-151431970
  GRCh38/hg38:	chr1:151402724-151459494

• MANE Select Transcript: NM_015100.4 ENST00000271715.7
• Function: Plays a role in mitotic cell cycle progression and is involved in kinetochore assembly and mitotic sister chromatid cohesion. Probably through its association with CBX5 plays a role in mitotic chromosome segregation by regulating aurora kinase B/AURKB activation and AURKB and CBX5 dissociation from chromosome arms (PubMed:20562864). Promotes the repair of DNA double-strand breaks through the homologous recombination pathway (PubMed:26721387). {ECO:0000269|PubMed:20562864, ECO:0000269|PubMed:2672... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

• Dosage ID: ISCA-34084
• ClinGen Curation ID: CCID:007690
• Curation Status: Complete
• Issue Type: Dosage Curation - Gene
• Haploinsufficiency: Sufficient Evidence for Haploinsufficiency (3)
• Triplosensitivity: No Evidence for Triplosensitivity (0)
• Last Evaluated: 12/27/2017

Haploinsufficiency (HI) Score Details

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

HI Disease

• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

HI Evidence

• PUBMED: 27148570
  In Ye Y et al 2015, they had 7 patients with developmental delay and microcephaly, and de novo loss-of function mutations in POGZ were detected by whole-exome sequencing in 6 of the patients. Four of the patients had frameshift mutation, one patient had nonsense mutation, and another one had a heterozygous deletion of exons 4-19. All of these variants were predicted to cause loss of function.
• PUBMED: 26942287
  In Stessman et al 2016, they collected clinical and molecular data of 25 individuals with disruptive mutations in POGZ by diagnostic whole-exome, whole-genome, or targeted sequencing of 5,223 patients with neurodevelopmental disorders (intellectual disability and autism spectrum disorders primarily). All of the variants were de novo, either frameshift or nonsense mutations. They concluded that the dosage of POGZ, specifically in neurons, is essential for normal learning in a habituation paradigm.
• PUBMED: 26739615
  White et al 2016. They identified de novo heterozygous truncating variants in POGZ in 5 unrelated individuals. Careful review of the phenotypes revealed shared features that included developmental delay, ID, hypotonia, behavioral abnormalities and similar facial characteristics. Variable features included short stature, microcephaly, strabismus and hearing loss. They suggested that loss of function variants in POGZ lead to an identifiable syndrome of neurodevelopmental disorders with specific phenotypic traits.

• HI Evidence Comments: Heterozygous mutation in POGZ can cause White-Sutton syndrome (OMIM 616364). WHSUS is a neurodevelopmental disorder characterized by delayed psychomotor development shows in infancy, and a characteristic constellation of dysmorphic facial features. A big number of patients also have autism. In Allelic Variants 614787.0001, there is patient with White-Sutton syndrome, was identified with a heterozygous de novo 1 bp deletion in the POGZ gene, resulting in frameshift and premature termination (Leu1119CysfsTer). 614787.0002. In a girl with White-Sutton syndrome, they identified a heterozygous de novo A-to-T transversion at chromosome coordinate g.151,378,800 (chr1.151,378,800A-T, GRCh37) in the exon 19 of POGZ gene, resulting in a Leu904-to-ter substitution, predicted to result in a loss of function.

Triplosensitivity (TS) Score Details

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