Human Gene Module / Chromosome 8 / PCM1

PCM1pericentriolar material 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
6 / 6
Rare Variants / Common Variants
7 / 0
Aliases
PCM1, PTC4,  RET/PCM-1
Associated Syndromes
-
Chromosome Band
8p22
Associated Disorders
-
Relevance to Autism

A de novo missense variant that was predicted to be damaging was identified in the PCM1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified PCM1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Molecular Function

The protein encoded by this gene is a component of centriolar satellites, which are electron dense granules scattered around centrosomes. Inhibition studies show that this protein is essential for the correct localization of several centrosomal proteins, and for anchoring microtubules to the centrosome.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PCM1 (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Recent Recommendation Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
4 Support - Woodbury-Smith M et al. (2022) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Support - Tuncay IO et al. (2023) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1072-7T>A - splice_region_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2981A>G p.Glu994Gly missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3595A>G p.Ser1199Gly missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.1988T>C p.Met663Thr missense_variant Familial Paternal - 37492102 Tuncay IO et al. (2023)
c.3836C>G p.Thr1279Arg missense_variant Familial Maternal - 37492102 Tuncay IO et al. (2023)
c.1423C>T p.Gln475Ter stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.6006_6007del p.Glu2003AspfsTer6 frameshift_variant Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo missense variant that was predicted to be damaging was identified in the PCM1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified PCM1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

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 de novo missense variant that was predicted to be damaging was identified in the PCM1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified PCM1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

A de novo missense variant that was predicted to be damaging was identified in the PCM1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified PCM1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

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

Increased from to 4

Description

A de novo missense variant that was predicted to be damaging was identified in the PCM1 gene in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014), while transmitted protein-truncating variants (PTVs) in this gene were observed in ASD probands from the Autism Sequencing Consortium and the iHART cohort (De Rubeis et al., 2014; Ruzzo et al., 2019). TADA analysis of de novo and transmitted variants from iHART, the Simons Simplex Collection, the Autism Sequencing Consortium, and the Autism Genome Project in Ruzzo et al., 2019 identified PCM1 as an ASD candidate gene with a false discovery rate (FDR) < 0.1.

Krishnan Probability Score

Score 0.49459408555739

Ranking 3562/25841 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
Sanders TADA Score

Score 0.39760000004125

Ranking 276/18665 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 0.43891569096301

Ranking 1040/20870 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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