Human Gene Module / Chromosome 17 / PHF12

PHF12PHD finger protein 12

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
22 / 0
EAGLE Score
9.5
Moderate Learn More
Aliases
PHF12, PF1
Associated Syndromes
-
Chromosome Band
17q11.2
Associated Disorders
ID
Genetic Category
Rare Single Gene Mutation
Relevance to Autism

Two de novo protein-truncating variants in the PHF12 gene were identified in ASD probands from the Autism Sequencing Consortium, while an additional protein-truncating variant in this gene was observed in case samples from the Danish iPSYCH study (Satterstrom et al., 2020). TADA analysis of de novo variants from the Simons Simplex Collection and the Autism Sequencing Consortium and protein-truncating variants from iPSYCH in Satterstrom et al., 2020 identified PHF12 as a candidate gene with a false discovery rate (FDR) between 0.01 and 0.05 (0.01 < FDR 0.05). Two de novo variants in the PHF12 gene (one frameshift, one missense) had previously been identified in ASD probands from the Autism Genetics Resource Exchange by whole-genome sequencing in Yuen et al., 2017.

Molecular Function

Acts as a transcriptional repressor. Involved in recruitment of functional SIN3A complexes to DNA. Represses transcription at least in part through the activity of an associated histone deacetylase (HDAC). May also repress transcription in a SIN3A-independent manner through recruitment of functional TLE5 complexes to DNA.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PHF12 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
2 Primary Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
3 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes ID
4 Support - Zhou X et al. (2022) Yes -
5 Support - Erica Rosina et al. (2024) No -
Rare Variants   (22)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2541+5G>A - splice_site_variant De novo - - 35982159 Zhou X et al. (2022)
c.1011G>A p.Val337%3D stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.1261G>A p.Glu421Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1091dup p.Asn365Ter frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.1163dup p.Phe389ValfsTer23 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.2309dup p.Ser772GlnfsTer51 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1162C>T p.Gln388Ter stop_gained De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.3031A>T XP_005258071.1:p.Lys1011Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.674_675del p.Phe225SerfsTer5 frameshift_variant De novo - - 33004838 Wang T et al. (2020)
c.1091dup p.Asn365Ter frameshift_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1748G>A p.Arg583Gln missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.301C>T p.Arg101Trp missense_variant De novo - Simplex 38041506 Erica Rosina et al. (2024)
c.1455_1458del p.Lys485AsnfsTer21 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1172G>A XP_005258071.1:p.Arg391His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1270C>T XP_005258071.1:p.Arg424Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2524G>A XP_005258071.1:p.Gly842Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2584G>A XP_005258071.1:p.Gly862Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2672_2673insGT p.Ser891ArgfsTer22 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2365C>T XP_005258071.1:p.Arg789Trp missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.622G>A XP_005258071.1:p.Asp208Asn missense_variant Familial Paternal - 33004838 Wang T et al. (2020)
c.1687dup p.Arg563ProfsTer7 frameshift_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1142G>A XP_005258071.1:p.Arg381Gln missense_variant Unknown Not maternal - 33004838 Wang T et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 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
icon
1

Increased from to 1

Krishnan Probability Score

Score 0.49785798357344

Ranking 2327/25841 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 0.99995967521355

Ranking 567/18225 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 0.94287778536582

Ranking 15473/18665 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 0.55120501852339

Ranking 240/20870 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
CNVs associated with PHF12(1 CNVs)
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17q11.2 29 Deletion-Duplication 44  /  116
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