Human Gene Module / Chromosome 7 / POT1

POT1Protection of telomeres 1 homolog (S. pombe)

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 3
Rare Variants / Common Variants
4 / 0
Aliases
POT1, HPOT1
Associated Syndromes
-
Chromosome Band
7q31.33
Associated Disorders
-
Relevance to Autism

A novel recurrent duplication involving of an exomic region of the POT1 gene was identified in two unrelated ASD cases in Prasad et al., 2012; however, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete in one of two families (i.e. not all affected siblings were positive for the CNV).

Molecular Function

Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to POT1 (3 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary A discovery resource of rare copy number variations in individuals with autism spectrum disorder Prasad A , et al. (2013) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (4)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.866A>G p.Lys289Arg missense_variant De novo - - 35982159 Zhou X et al. (2022)
- - copy_number_gain Familial Paternal Simplex 23275889 Prasad A , et al. (2013)
- - copy_number_gain Familial Maternal Multiplex 23275889 Prasad A , et al. (2013)
c.771-1G>A - splice_site_variant Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A novel recurrent duplication involving of an exomic region of the POT1 gene was identified in two unrelated ASD cases in Prasad et al., 2012; however, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete in one of two families (i.e. not all affected siblings were positive for the CNV).

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

A novel recurrent duplication involving of an exomic region of the POT1 gene was identified in two unrelated ASD cases in Prasad et al., 2012; however, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete in one of two families (i.e. not all affected siblings were positive for the CNV).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A novel recurrent duplication involving of an exomic region of the POT1 gene was identified in two unrelated ASD cases in Prasad et al., 2012; however, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete in one of two families (i.e. not all affected siblings were positive for the CNV).

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

Increased from to 4

Description

A novel recurrent duplication involving of an exomic region of the POT1 gene was identified in two unrelated ASD cases in Prasad et al., 2012; however, no comparison with controls was reported, and segregation of the CNV with ASD was incomplete in one of two families (i.e. not all affected siblings were positive for the CNV).

Krishnan Probability Score

Score 0.41183878214643

Ranking 22291/25841 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 0.52272721670327

Ranking 5346/18225 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 0.94197960203546

Ranking 15134/18665 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 -0.1837198616433

Ranking 15052/20870 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