Human Gene Module / Chromosome 17 / PER1

PER1period homolog 1 (Drosophila)

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
4 / 7
Rare Variants / Common Variants
7 / 2
Aliases
PER1, PER,  hPER,  RIGUI,  MGC88021
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
17p13.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the PER1 gene and autism in an AGRE cohort (Nicholas et al., 2007). In addition, rare mutations in the PER1 gene have been identified in individuals with ASD (Neale et al., 2012).

Molecular Function

This gene is a member of the Period family of genes and is expressed in a circad ian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in t he mammalian brain.

Reports related to PER1 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Per1 and Per2 gene expression in the rat suprachiasmatic nucleus: circadian profile and the compartment-specific response to light. Yan L , et al. (1999) No -
2 Primary Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Nicholas B , et al. (2007) Yes -
3 Recent Recommendation Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Liu AC , et al. (2007) No -
4 Recent Recommendation Laminin receptor 1: a novel protein interacting with human circadian clock protein, hPer1. Wang Y , et al. (2007) No -
5 Support Patterns and rates of exonic de novo mutations in autism spectrum disorders. Neale BM , et al. (2012) Yes -
6 Support Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders. Li J , et al. (2017) Yes -
7 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. Ruzzo EK , et al. (2019) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2458C>T p.Arg820Ter stop_gained Familial - Simplex 28831199 Li J , et al. (2017)
c.232G>T p.Gly78Cys missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.454G>C p.Glu152Gln missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.1114G>A p.Asp372Asn missense_variant Familial - Simplex 28831199 Li J , et al. (2017)
c.2506C>T p.Arg836Ter stop_gained De novo NA Multiplex 31398340 Ruzzo EK , et al. (2019)
c.3802A>G p.Met1268Val missense_variant De novo NA Simplex 22495311 Neale BM , et al. (2012)
c.2602del p.Trp868GlyfsTer48 frameshift_variant Familial - Simplex 28831199 Li J , et al. (2017)
Common Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1498-38C>G C/G intron_variant - - - 17264841 Nicholas B , et al. (2007)
- C to A downstream_gene_variant - - - 17264841 Nicholas B , et al. (2007)
SFARI Gene score
3

Suggestive Evidence

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

Score Delta: Decreased from 4 to 3

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

Reports Added
[New Scoring Scheme]
7/1/2019
4
icon
4

Decreased from 4 to 4

Description

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

10/1/2017
4
icon
4

Decreased from 4 to 4

Description

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

7/1/2014
No data
icon
4

Increased from No data to 4

Description

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

There is a single small study of 90 probands with high-functioning autism and 20 additional cases. Two SNPS in PER1 showed significant association. The study has not been replicated.

Krishnan Probability Score

Score 0.49162170199649

Ranking 5335/25841 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 0.87574896158966

Ranking 3421/18225 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 0.94808887533699

Ranking 17541/18665 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 3

Ranking 353/461 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 0.50795627263562

Ranking 467/20870 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.
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
DQX1 ATP-dependent RNA helicase DQX1 Human Protein Binding 165545 Q8TE96-2
FAM65B family with sequence similarity 65, member B Human Protein Binding 9750 Q9Y4F9
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We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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