Human Gene Module / Chromosome 7 / YWHAG

YWHAGtyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma

Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
1 / 6
Rare Variants / Common Variants
9 / 0
Aliases
YWHAG, 14-3-3GAMMA,  EIEE56,  PPP1R170
Associated Syndromes
Williams-Beuren syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
7q11.23
Associated Disorders
-
Relevance to Autism

A de novo missense variant in the YWHAG gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. Heterozygous variants in YWHAG are also responsible for a form of early infantile epileptic encephalopathy (EIEE56; OMIM 617665); in addition to early-onset seizures, intellectual disability and behavioral abnormalities including autism spectrum disorder have been observed in affected individuals (Guella et al., 2017; Kanani et al., 2020). YWHAG is located within the 7q11.23 chromosomal region associated with Williams-Beuren syndrome; Fusco et al., 2014 suggested that, based on genotype-phenotype correlation of deletions within this region, YWHAG haploinsufficiency may cause the severe neurological and neuropsychological deficits including epilepsy and autistic behavior observed in individuals with this syndrome.

Molecular Function

This gene product belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. Both ablation and overexpression of YWHAG have been demonstrated to result in neuronal migration delay in the developing cerebral cortex (Wachi et al., 2016; Cornell et al., 2016).

Reports related to YWHAG (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits. Fusco C , et al. (2013) No -
2 Primary Synaptic, transcriptional and chromatin genes disrupted in autism. De Rubeis S , et al. (2014) Yes -
3 Support Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex. Wachi T , et al. (2015) No -
4 Support Overexpression of the 14-3-3gamma protein in embryonic mice results in neuronal migration delay in the developing cerebral cortex. Cornell B , et al. (2016) No -
5 Support De Novo Mutations in YWHAG Cause Early-Onset Epilepsy. Guella I , et al. (2017) No -
6 Recent recommendation Expanding the genotype-phenotype correlation of de novo heterozygous missense variants in YWHAG as a cause of developmental and epileptic encephalo... Kanani F , et al. (2020) No -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.44A>C p.Glu15Ala missense_variant De novo NA - 28777935 Guella I , et al. (2017)
c.169C>G p.Arg57Gly missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.169C>T p.Arg57Cys missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.394C>T p.Arg132Cys missense_variant De novo NA - 28777935 Guella I , et al. (2017)
c.394C>T p.Arg132Cys missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.398A>C p.Tyr133Ser missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.529C>A p.Leu177Ile missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.532A>G p.Asn178Asp missense_variant De novo NA - 31926053 Kanani F , et al. (2020)
c.148A>C p.Lys50Gln missense_variant De novo NA - 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

CNVs associated with YWHAG(1 CNVs)
7q11.23 63 Deletion-Duplication 91  /  394
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