Human Gene Module / Chromosome 17 / KRT26

KRT26keratin 26

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
26 / 0
Aliases
KRT26, CK26,  K25,  K25IRS2,  K26,  KRT25B
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
17q21.2
Associated Disorders
-
Relevance to Autism

Rare inherited loss-of-function and damaging missense variants in the KRT26 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in a cohort of Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified KRT26 as an ASD candidate gene with a PTADA of 0.005182.

Molecular Function

The protein encoded by this gene is a member of the keratin superfamily.

Reports related to KRT26 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Excess of rare, inherited truncating mutations in autism. Krumm N , et al. (2015) Yes -
2 Recent Recommendation Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders. Li J , et al. (2017) Yes -
Rare Variants   (26)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1060G>T p.Glu354Ter stop_gained Familial - - 28831199 Li J , et al. (2017)
c.277C>T p.Arg93Cys missense_variant Familial - - 28831199 Li J , et al. (2017)
G>T p.Ser37Ter stop_gained Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
A>T p.? splice_site_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
A>T p.? splice_site_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.110C>A p.Ser37Ter stop_gained Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
C>G p.Glu316Gln missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
C>G p.Glu316Gln missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1187+2T>A - splice_site_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.1187+2T>A - splice_site_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1078C>T p.Arg360Ter stop_gained Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1164C>A p.Cys388Ter stop_gained Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
CTTTA>TTTTC p.? splice_site_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.277C>T p.Arg93Cys missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.488A>T p.Asp163Val missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.946G>C p.Glu316Gln missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.946G>C p.Glu316Gln missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.949C>T p.Leu317Phe missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1024C>T p.Leu342Phe missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1352C>T p.Ser451Phe missense_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.1352C>T p.Ser451Phe missense_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.2T>C p.Met1? initiator_codon_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.286del p.Ser96ProfsTer9 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
c.286del p.Ser96ProfsTer9 frameshift_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.1066del p.Leu356CysfsTer21 frameshift_variant Familial Paternal Simplex 25961944 Krumm N , et al. (2015)
c.274_287del p.Asp92LeufsTer27 frameshift_variant Familial Maternal Simplex 25961944 Krumm N , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Rare inherited loss-of-function and damaging missense variants in the KRT26 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in a cohort of Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified KRT26 as an ASD candidate gene with a PTADA of 0.005182.

Score Delta: Score remained at 4

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.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Rare inherited loss-of-function and damaging missense variants in the KRT26 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in a cohort of Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified KRT26 as an ASD candidate gene with a PTADA of 0.005182.

Reports Added
[New Scoring Scheme]
7/1/2017
icon
4

Increased from to 4

Description

Rare inherited loss-of-function and damaging missense variants in the KRT26 gene were identified in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in a cohort of Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified KRT26 as an ASD candidate gene with a PTADA of 0.005182.

Krishnan Probability Score

Score 0.4474068962732

Ranking 12478/25841 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.
ExAC Score

Score 7.2281173313109E-10

Ranking 16640/18225 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
Sanders TADA Score

Score 0.92839890290527

Ranking 10905/18665 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).
Zhang D Score

Score -0.081499763439597

Ranking 11628/20870 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.
Submit New Gene

Report an Error

SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
Close