Human Gene Module / Chromosome 8 / KAT6A

KAT6AK(lysine) acetyltransferase 6A

Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
2 / 7
Rare Variants / Common Variants
19 / 0
Aliases
KAT6A, MOZ,  MRD32,  MYST-3,  MYST3,  RUNXBP2,  ZC2HC6A,  ZNF220
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
8p11.21
Associated Disorders
ASD
Relevance to Autism

A de novo frameshift variant in the KAT6A gene has been identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Furthermore, one of the four patients with a de novo KAT6A nonsense variant identified in Arboleda et al., 2015 was diagnosed with ASD.

Molecular Function

This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases and is part of a complex that acetylates lysine-9 residues in histone 3. In addition, it acts as a co-activator for several transcription factors. Variants in this gene are associated with autosomal dominant mental retardation-32 (MRD32; OMIM 616268).

Reports related to KAT6A (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder. Iossifov I , et al. (2014) Yes -
2 Support De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay. Arboleda VA , et al. (2015) No ASD (1 case)
3 Support Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features. Tham E , et al. (2015) No Microcephaly, craniosynostosis, hypotonia, feeding
4 Recent recommendation Low load for disruptive mutations in autism genes and their biased transmission. Iossifov I , et al. (2015) Yes -
5 Support Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder. Millan F , et al. (2016) No ASD (1 case)
6 Support Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. Lelieveld SH , et al. (2016) No -
7 Support Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Trujillano D , et al. (2016) No Delayed speech and language development, motor del
Rare Variants   (19)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
del(4) - frameshift_variant De novo - Simplex 25363768 Iossifov I , et al. (2014)
c.3385C>T p.Arg1129Ter stop_gained De novo - Simplex 25728775 Arboleda VA , et al. (2015)
c.3385C>T p.Arg1129Ter stop_gained De novo - Simplex 25728775 Arboleda VA , et al. (2015)
c.3070C>T p.Arg1024Ter stop_gained De novo - Simplex 25728775 Arboleda VA , et al. (2015)
c.3385C>T p.Arg1129Ter stop_gained De novo - Simplex 25728775 Arboleda VA , et al. (2015)
c.3879dupA p.Glu1294ArgfsTer19 frameshift_variant De novo - Simplex 25728777 Tham E , et al. (2015)
c.3116_3117delCT p.Ser1039Ter frameshift_variant De novo - Multiplex (monozygotic twins) 25728777 Tham E , et al. (2015)
c.4292dupT p.Leu1431PhefsTer8 frameshift_variant De novo - Simplex 25728777 Tham E , et al. (2015)
c.4108G>T p.Glu1370Ter stop_gained De novo - Simplex 25728777 Tham E , et al. (2015)
c.3830_3831insTT p.Arg1278SerfsTer17 frameshift_variant De novo - Simplex 25728777 Tham E , et al. (2015)
- - copy_number_loss De novo - Simplex 25728777 Tham E , et al. (2015)
c.3462delA p.Gly1155AlafsTer21 frameshift_variant De novo - Simplex 27133397 Millan F , et al. (2016)
c.3287delG p.Cys1096PhefsTer27 frameshift_variant De novo - Simplex 27133397 Millan F , et al. (2016)
c.3230delA p.Asn1077MetfsTer46 frameshift_variant De novo - Simplex 27133397 Millan F , et al. (2016)
c.3070C>T p.Arg1024Ter stop_gained De novo - Simplex 27133397 Millan F , et al. (2016)
c.1928A>G p.Asn643Ser missense_variant De novo - Simplex 27133397 Millan F , et al. (2016)
c.3040-1_3040delGA - splice_site_variant De novo - Multiplex 27133397 Millan F , et al. (2016)
c.4665C>G p.Ser1555Arg missense_variant De novo - - 27479843 Lelieveld SH , et al. (2016)
c.3655del p.Leu1219TyrfsTer75 frameshift_variant De novo - Simplex 27848944 Trujillano D , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

A de novo frameshift variant in the KAT6A gene has been identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Variants in this gene are associated with autosomal dominant mental retardation-32 (MRD32; OMIM 616268). One of the four patients with a de novo KAT6A nonsense variant and intellectual disability that was identified in Arboleda et al., 2015 was also diagnosed with ASD. An additional patient with ASD, intellectual disability, and epilepsy was found to have a de novo splice-site variant in KAT6A in Millan et al., 2016; however, this patient also had a sister with ID and autism, and the presence of the KAT6A variant in her was not reported.

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

04-01-2017
3S

Initial score established: 3S

Description

A de novo frameshift variant in the KAT6A gene has been identified in an ASD proband from the Simons Simplex Collection (PMID 25363768). Variants in this gene are associated with autosomal dominant mental retardation-32 (MRD32; OMIM 616268). One of the four patients with a de novo KAT6A nonsense variant and intellectual disability that was identified in Arboleda et al., 2015 was also diagnosed with ASD. An additional patient with ASD, intellectual disability, and epilepsy was found to have a de novo splice-site variant in KAT6A in Millan et al., 2016; however, this patient also had a sister with ID and autism, and the presence of the KAT6A variant in her was not reported.

CNVs associated with KAT6A(1 CNVs)
8p11.21 9 Deletion 18  /  26
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