Human Gene Module / Chromosome 1 / MTF1

MTF1metal-regulatory transcription factor 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 6
Rare Variants / Common Variants
3 / 1
Aliases
MTF1, MTF-1
Associated Syndromes
-
Chromosome Band
1p34.3
Associated Disorders
ASD, EPS
Relevance to Autism

Genetic association has been found between the MTF1 gene and autism in an AGRE cohort (Serajee et al., 2004).

Molecular Function

The encoded protein is Zn binding transcription factor that mediates regulation of metallothionein genes.

SFARI Genomic Platforms
Reports related to MTF1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Nucleo-cytoplasmic trafficking of metal-regulatory transcription factor 1 is regulated by diverse stress signals Saydam N , et al. (2001) No -
2 Primary Polymorphisms in xenobiotic metabolism genes and autism Serajee FJ , et al. (2004) Yes -
3 Recent Recommendation Metallothioneins and zinc dysregulation contribute to neurodevelopmental damage in a model of perinatal viral infection Williams BL , et al. (2006) No -
4 Support Diagnostic exome sequencing in persons with severe intellectual disability de Ligt J , et al. (2012) No Epilepsy, ASD
5 Support - Rodin RE et al. (2021) Yes -
6 Support - Zhou X et al. (2022) Yes -
Rare Variants   (3)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.189C>T p.Asp63%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.230G>T p.Gly77Val missense_variant De novo - - 33432195 Rodin RE et al. (2021)
c.333del p.Thr112HisfsTer26 frameshift_variant De novo - - 23033978 de Ligt J , et al. (2012)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.779+42G>C C to G intron_variant - - - 15446388 Serajee FJ , et al. (2004)
SFARI Gene score
2

Strong Candidate

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

Score Delta: Score remained at 2

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
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2

Decreased from 3 to 2

Description

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

10/1/2019
4
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3

Decreased from 4 to 3

New Scoring Scheme
Description

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
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4

Increased from No data to 4

Description

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

A single, unreplicated association of common variants was reported by Serajee et al., 2004 (PMID: 15446388).

Krishnan Probability Score

Score 0.44835628481058

Ranking 11602/25841 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 0.99139471705041

Ranking 1747/18225 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 0.93637295403314

Ranking 13175/18665 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).
Larsen Cumulative Evidence Score

Score 10

Ranking 188/461 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.
Zhang D Score

Score 0.38294661034707

Ranking 1652/20870 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.
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