Human Gene Module / Chromosome 11 / TECTA

TECTAtectorin alpha

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
12 / 0
Aliases
TECTA, DFNA12,  DFNA8,  DFNB21
Associated Syndromes
-
Chromosome Band
11q23.3
Associated Disorders
-
Relevance to Autism

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Molecular Function

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TECTA (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
2 Support Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations Toma C , et al. (2013) Yes -
3 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
4 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
5 Recent Recommendation Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
6 Support Both rare and common genetic variants contribute to autism in the Faroe Islands Leblond CS , et al. (2019) Yes -
7 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3521G>A p.Arg1174Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.4894G>A p.Asp1632Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1533C>T p.Asp511%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1870G>A p.Ala624Thr missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.907G>A p.Glu303Lys missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.5818G>A p.Ala1940Thr missense_variant De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.4552C>T p.Gln1518Ter stop_gained Familial Maternal Multiplex 23999528 Toma C , et al. (2013)
c.4085G>A p.Trp1362Ter stop_gained Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.6162+1G>A - splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.4085G>A p.Trp1362Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.2061C>A p.Asn687Lys missense_variant Familial Both parents Simplex 30675382 Leblond CS , et al. (2019)
c.6275_6276insGAGG p.Gly2093ArgfsTer4 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Reports Added
[Both rare and common genetic variants contribute to autism in the Faroe Islands.2019]
7/1/2017
icon
4

Increased from to 4

Description

Two de novo missense variants and one de novo frameshift variant in the TECTA gene were detected in ASD probands from the Simons Simplex Collection (Sanders et al., 2012; Iossifov et al., 2014) and the Autism Sequencing Consortium (De Rubeis et al., 2014); one of the missense variants was later determined to be a postzygotic mosaic mutation (PZM) in Lim et al., 2017. A second non-synonymous PZM in this gene was identified in an ASD proband in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 14/84,448 expected; hypergeometric P-value of 3.9E-03). A maternally-transmitted nonsense variant in TECTA was detected in both affected siblings in a multiplex ASD family in Toma et al., 2014.

Krishnan Probability Score

Score 0.4966946648738

Ranking 2539/25841 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 1.0649856511351E-12

Ranking 17347/18225 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 0.93015884746684

Ranking 11355/18665 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 -0.089133509265959

Ranking 11929/20870 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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