Human Gene Module / Chromosome 11 / PHRF1

PHRF1PHD and ring finger domains 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
6 / 0
Aliases
PHRF1, PPP1R125,  RNF221
Associated Syndromes
-
Chromosome Band
11p15.5
Associated Disorders
-
Relevance to Autism

Three de novo missense variants in the PHRF1 gene were identified in simplex ASD probands, with no de novo events in this gene observed in 1,786 unaffected siblings from the Simons Simplex Collection (P=0.20) (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015).

Molecular Function

This gene encodes a protein of unknown function.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PHRF1 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Support Excess of rare, inherited truncating mutations in autism Krumm N , et al. (2015) Yes -
4 Recent Recommendation Low load for disruptive mutations in autism genes and their biased transmission Iossifov I , et al. (2015) Yes -
5 Support - Zhou X et al. (2022) Yes -
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.4265-7C>T - splice_region_variant De novo - - 35982159 Zhou X et al. (2022)
c.1361T>C p.Leu454Pro missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2979C>G p.Ser993%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.4690C>G p.Leu1564Val missense_variant De novo - Simplex 25961944 Krumm N , et al. (2015)
c.4108G>A p.Asp1370Asn missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3982G>A p.Asp1328Asn missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Three de novo missense variants in the gene were identified in simplex ASD probands, with no de novo events in this gene observed in 1,786 unaffected siblings from the Simons Simplex Collection (P=0.20) (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

Three de novo missense variants in the gene were identified in simplex ASD probands, with no de novo events in this gene observed in 1,786 unaffected siblings from the Simons Simplex Collection (P=0.20) (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[New Scoring Scheme]
1/1/2016
icon
3

Increased from to 3

Description

Three de novo missense variants in the gene were identified in simplex ASD probands, with no de novo events in this gene observed in 1,786 unaffected siblings from the Simons Simplex Collection (P=0.20) (De Rubeis et al., 2014; Iossifov et al., 2014; Krumm et al., 2015). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017).

Reports Added
[Synaptic, transcriptional and chromatin genes disrupted in autism.2014] [Excess of rare, inherited truncating mutations in autism.2015] [The contribution of de novo coding mutations to autism spectrum disorder2014] [Low load for disruptive mutations in autism genes and their biased transmission.2015]
Krishnan Probability Score

Score 0.44734002765061

Ranking 12644/25841 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 0.94891901120207

Ranking 2698/18225 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
Iossifov Probability Score

Score 0.889

Ranking 157/239 scored genes


[Show Scoring Methodology]
Supplementary dataset S2 in the paper by Iossifov et al. (PNAS 112, E5600-E5607 (2015)) lists 239 genes with a probability of at least 0.8 of being associated with autism risk (column I). This probability metric combines the evidence from de novo likely-gene- disrupting and missense mutations and assesses it against the background mutation rate in unaffected individuals from the University of Washington’s Exome Variant Sequence database (evs.gs.washington.edu/EVS/). The list of probability scores can be found here: www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516376112/- /DCSupplemental/pnas.1516376112.sd02.xlsx
Original Source
Sanders TADA Score

Score 0.93013228397046

Ranking 11348/18665 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 0.4036545868259

Ranking 1418/20870 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