Human Gene Module / Chromosome 2 / TPO

TPOThyroid peroxidase

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
2 / 2
Rare Variants / Common Variants
2 / 2
Aliases
TPO, MSA,  TDH2A,  TPX
Associated Syndromes
-
Chromosome Band
2p25.3
Associated Disorders
-
Relevance to Autism

Family-based tests of association computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository revealed that several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, a significant association in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 x 10-06, OR = 1.46 (1.24- 1.72)) was observed (Ramos et al., 2012).

Molecular Function

This gene encodes a membrane-bound glycoprotein. The encoded protein acts as an enzyme and plays a central role in thyroid gland function. The protein functions in the iodination of tyrosine residues in thyroglobulin and phenoxy-ester formation between pairs of iodinated tyrosines to generate the thyroid hormones, thyroxine and triiodothyronine.

External Links
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Human
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SFARI Genomic Platforms
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Reports related to TPO (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Immune function genes CD99L2, JARID2 and TPO show association with autism spectrum disorder Ramos PS , et al. (2012) Yes -
2 Support - Ruohao Wu et al. (2024) Yes -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.295C>T p.Gln99Ter stop_gained Familial Maternal Simplex 38764027 Ruohao Wu et al. (2024)
c.1226T>C p.Leu409Pro missense_variant Familial Paternal Simplex 38764027 Ruohao Wu et al. (2024)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.180-2007G>A;c.216-2007G>A minor allele, G intron_variant - - - 22681640 Ramos PS , et al. (2012)
c.349+609T>G;c.385+609T>G minor allele, A intron_variant - - - 22681640 Ramos PS , et al. (2012)
SFARI Gene score
2

Strong Candidate

Family-based tests of association computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository revealed that several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, a significant association in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 x 10-06, OR = 1.46 (1.24- 1.72) was observed (Ramos et al., 2012).

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

Family-based tests of association computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository revealed that several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, a significant association in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 x 10-06, OR = 1.46 (1.24- 1.72) was observed (Ramos et al., 2012).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Family-based tests of association computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository revealed that several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, a significant association in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 x 10-06, OR = 1.46 (1.24- 1.72) was observed (Ramos et al., 2012).

Reports Added
[New Scoring Scheme]
10/1/2017
icon
4

Increased from to 4

Description

Family-based tests of association computed on the 22,904 single nucleotide polymorphisms (SNPs) from the 2,012 immune-related genes on 1,510 trios available at the Autism Genetic Resource Exchange (AGRE) repository revealed that several SNPs in immune-related genes remained statistically significantly associated with ASD after adjusting for multiple comparisons. Specifically, a significant association in the thyroid peroxidase gene (TPO) (rs1514687, P = 5.72 x 10-06, OR = 1.46 (1.24- 1.72) was observed (Ramos et al., 2012).

Krishnan Probability Score

Score 0.49415718650131

Ranking 3804/25841 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 1.3559687560264E-7

Ranking 15618/18225 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 0.94675444952688

Ranking 16998/18665 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 326/461 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 -0.13819173526326

Ranking 13778/20870 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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