Human Gene Module / Chromosome 20 / TM9SF4

TM9SF4transmembrane 9 superfamily member 4

SFARI Gene Score
High Confidence Criteria 1.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
1 / 0
Limited Learn More
TM9SF4, dJ836N17.2
Associated Syndromes
Chromosome Band
Associated Disorders
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

A de novo missense variant that was predicted to be damaging (defined as MPC 2) was identified in the TM9SF4 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014), while four protein-truncating variants in this gene were observed in case samples from the Danish iPSYCH study (Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified TM9SF4 as a candidate gene with a false discovery rate (FDR) between 0.01 and 0.05 (0.01 < FDR 0.05).

Molecular Function

Associates with proteins harboring glycine-rich transmembrane domains and ensures their efficient localization to the cell surface.

SFARI Genomic Platforms
Reports related to TM9SF4 (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Recent recommendation Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1136T>A p.Met379Lys missense_variant De novo NA Simplex 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score

High Confidence

Score Delta: Score remained at 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.


Increased from to 1

Krishnan Probability Score

Score 0.41235142036082

Ranking 22129/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.99997077241139

Ranking 538/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.93671457882888

Ranking 13286/18665 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
Zhang D Score

Score -0.30557254736385

Ranking 17288/20870 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