Human Gene Module / Chromosome 17 / KANSL1

KANSL1KAT8 regulatory NSL complex subunit 1

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
6 / 13
Rare Variants / Common Variants
28 / 0
EAGLE Score
1.1
Limited Learn More
Aliases
KANSL1, CENP-36,  KDVS,  KIAA1267,  MSL1v1,  NSL1,  hMSL1v1
Associated Syndromes
Koolen-De Vries syndrome
Chromosome Band
17q21.31
Associated Disorders
ASD
Genetic Category
Rare Single Gene Mutation, Syndromic, Functional
Relevance to Autism

Koolen-De Vries syndrome (OMIM 610443), also known as 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterized by developmental delay, intellectual disability, hypotonia, and characteristic facial dysmorphism that is caused either by a truncating variant in the KANSL1 gene or a 17q21.31 microdeletion encompassing the KANSL1 gene. Koolen et al., 2016 described a novel cohort of 45 individuals with Koolen-De Vries syndrome and observed behavioral problems, including autism or autistic traits, in 57% of cases. A de novo missense variant in the KANSL1 gene was also identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Molecular Function

This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The corresponding protein in Drosophila interacts with K(lysine) acetyltransferase 8, which is also a subunit of both the MLL1 and NSL1 complexes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KANSL1 (13 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Primary The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant Koolen DA , et al. (2015) No ASD or autistic features
3 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
4 Support - Valentino F et al. (2021) No DD, epilepsy/seizures
5 Support - Rosenthal SB et al. (2021) Yes -
6 Support - Pode-Shakked B et al. (2021) No ADHD, epilepsy/seizures
7 Support - Li D et al. (2022) Yes -
8 Support - Li T et al. (2022) No -
9 Support - Woodbury-Smith M et al. (2022) Yes -
10 Support - N.Y.) (07/2) Yes -
11 Support - Shimelis H et al. (2023) No -
12 Support - M Cecilia Poli et al. () No -
13 Support - Zain Awamleh et al. (2024) No -
Rare Variants   (28)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.286T>C p.Leu96%3D synonymous_variant De novo - - 35901164 N.Y.) (07/2)
c.190C>T p.Arg64Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.727C>T p.Gln243Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.868C>T p.Arg290Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.56G>A p.Arg19Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.895C>T p.Arg299Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2692A>T p.Lys898Ter stop_gained De novo - - 38177409 M Cecilia Poli et al. ()
c.1421G>A p.Arg474His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1775G>A p.Arg592Gln missense_variant De novo - - 33004838 Wang T et al. (2020)
c.1855C>T p.Arg619Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1871G>A p.Arg624His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2861G>A p.Arg954Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3031C>T p.Arg1011Ter stop_gained Unknown - - 36475376 Shimelis H et al. (2023)
c.3056G>A p.Arg1019His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3185G>A p.Arg1062His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.3301C>T p.Arg1101Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.238dup p.Ala80GlyfsTer7 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1639_1646del p.Gly547Ter frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.247_250dup p.Cys84SerfsTer4 frameshift_variant Unknown - - 34968013 Li D et al. (2022)
c.3221G>A p.Arg1074Gln missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.3019C>T p.Arg1007Trp missense_variant Familial Paternal - 33004838 Wang T et al. (2020)
c.3291dup p.Thr1098HisfsTer20 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.729A>C p.Gln243His missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.985_986del p.Leu329GlufsTer22 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1138T>C p.Leu380%3D synonymous_variant De novo - - 35205252 Woodbury-Smith M et al. (2022)
c.1420C>T p.Arg474Cys missense_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
c.985_986del p.Leu329GlufsTer22 frameshift_variant De novo - - 34356170 Valentino F et al. (2021)
c.502_503insGTTCTGATCAT p.Ser168CysfsTer38 frameshift_variant De novo - Simplex 34580403 Pode-Shakked B et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

S

Syndromic

See all Category S Genes

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."

10/1/2019
icon
1

Increased from to 1

New Scoring Scheme
Description

Koolen-De Vries syndrome (OMIM 610443), also known as 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterized by developmental delay, intellectual disability, hypotonia, and characteristic facial dysmorphism that is caused either by a truncating variant in the KANSL1 gene or a 17q21.31 microdeletion encompassing the KANSL1 gene. Koolen et al., 2016 described a novel cohort of 45 individuals with Koolen-De Vries syndrome and observed behavioral problems, including autism or autistic traits, in 57% of cases. A de novo missense variant in the KANSL1 gene was also identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.49463655612574

Ranking 3533/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.999733505943

Ranking 817/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.94326258665127

Ranking 15620/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Sanders TADA Score

Score 0.94445466157328

Ranking 16082/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.43411215621075

Ranking 1079/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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