Human Gene Module / Chromosome 2 / TM4SF20

TM4SF20Transmembrane 4 L six family member 20

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
10 / 0
Aliases
TM4SF20, UNQ518/PRO994,  PRO994,  TCCE518
Associated Syndromes
-
Chromosome Band
2q36.3
Associated Disorders
ASD, EPS
Relevance to Autism

A complex 4 kb deletion in 2q36.3 that removes an exon from the TM4SF20 gene was identified in 15 unrelated families (predominantly from Southeast Asia) that segregated with early childhood communication disorders, ranging from early language delay to autism spectrum disorder, and white matter hyperintensities (WMH) (Wiszniewski et al., 2013).

Molecular Function

This gene encodes a multi-pass membrane protein that belongs to the L6 tetraspanin family.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to TM4SF20 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary TM4SF20 ancestral deletion and susceptibility to a pediatric disorder of early language delay and cerebral white matter hyperintensities Wiszniewski W , et al. (2013) No ASD, epilepsy
2 Support - Krgovic D et al. (2022) Yes ADHD
3 Support - Zhou X et al. (2022) Yes -
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss Unknown - Unknown 23810381 Wiszniewski W , et al. (2013)
c.532G>A p.Asp178Asn missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_loss Familial Maternal Simplex 23810381 Wiszniewski W , et al. (2013)
- - copy_number_loss Familial Paternal Simplex 23810381 Wiszniewski W , et al. (2013)
- - copy_number_loss Familial Maternal Multiplex 23810381 Wiszniewski W , et al. (2013)
- - copy_number_loss Familial Paternal Multiplex 23810381 Wiszniewski W , et al. (2013)
c.184-2A>T - splice_site_variant Unknown Not maternal - 35813072 Krgovic D et al. (2022)
- - copy_number_loss Familial Paternal Extended multiplex 23810381 Wiszniewski W , et al. (2013)
- - copy_number_loss Familial Maternal Multi-generational 23810381 Wiszniewski W , et al. (2013)
c.152G>A p.Trp51Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

A complex 4 kb deletion in 2q36.3 that removes an exon from the TM4SF20 gene was identified in 15 unrelated families (predominantly from Southeast Asia) that segregated with early childhood communication disorders, ranging from early language delay to autism spectrum disorder, and white matter hyperintensities (WMH) (Wiszniewski et al., 2013).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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
S
icon
S

Score remained at S

New Scoring Scheme
Description

A complex 4 kb deletion in 2q36.3 that removes an exon from the TM4SF20 gene was identified in 15 unrelated families (predominantly from Southeast Asia) that segregated with early childhood communication disorders, ranging from early language delay to autism spectrum disorder, and white matter hyperintensities (WMH) (Wiszniewski et al., 2013).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.48093267654099

Ranking 7999/25841 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 2.1881439282987E-6

Ranking 14778/18225 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 0.92898971604305

Ranking 11053/18665 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
Larsen Cumulative Evidence Score

Score 4

Ranking 324/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.087613880509588

Ranking 6381/20870 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
Submit New Gene

Report an Error