Human Gene Module / Chromosome 8 / RUNX1T1

RUNX1T1RUNX1 partner transcriptional co-repressor 1

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
8q21.3
Associated Disorders
-
Relevance to Autism

Two de novo loss-of-function (LoF) variants and a de novo missense variant in the RUNX1T1 gene have been identified in ASD probands from the Autism Sequencing Consortium, the SPARK cohort, and the Simons Simplex Collection (Satterstrom et al., 2020; Zhou et al., 2022). Transmission and de novo association (TADA) analysis of whole-exome and whole-genome sequencing data from the Autism Sequencing Consortium, the Simons Simplex Collection, the MSSNG cohort, and the SPARK cohort in Trost et al., 2022 identified RUNX1T1 as an ASD-associated gene with a false discovery rate (FDR) < 0.1. More recently, Aref-Eshghi et al., 2024 provided detailed clinical and molecular information on three individuals exhibiting neurodevelopmental and congenital anomalies with germline de novo variants in the RUNX1T1 gene; common features included craniofacial dysmorphism and neurodevelopmental issues such as developmental delay, learning disability, attention deficit hyperactivity disorder, and autism.

Molecular Function

Transcriptional corepressor which facilitates transcriptional repression via its association with DNA-binding transcription factors and recruitment of other corepressors and histone-modifying enzymes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
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SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RUNX1T1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Recent Recommendation - Trost B et al. (2022) Yes -
4 Recent Recommendation - Erfan Aref-Eshghi et al. () Yes ID, epilepsy/seizures, learning disability
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.727C>T p.Leu243%3D stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.106C>T p.Gln36Ter stop_gained De novo - - 39568205 Erfan Aref-Eshghi et al. ()
c.1342T>A p.Leu448Met missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1234G>A p.Gly412Arg missense_variant De novo - - 39568205 Erfan Aref-Eshghi et al. ()
c.1561C>T p.His521Tyr missense_variant De novo - Simplex 39568205 Erfan Aref-Eshghi et al. ()
c.1229_1230del p.Ala410ValfsTer13 frameshift_variant De novo - - 31981491 Satterstrom FK et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

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.

1/1/2023
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.76533216366828

Ranking 25/25841 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 0.99912168797246

Ranking 1037/18225 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 0.93795622927219

Ranking 13699/18665 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 0.41333575798781

Ranking 1308/20870 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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