Human Gene Module / Chromosome 7 / PHF14

PHF14PHD finger protein 14

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
6 / 7
Rare Variants / Common Variants
21 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
7p21.3
Associated Disorders
-
Relevance to Autism

De novo missense variants in the PHF14 gene have been identified in an ASD proband from the SPARK cohort (Feliciano et al., 2019) and the Autism Sequencing Consortium cohort (Satterstrom et al., 2020), while additional rare de novo non-coding variation in this gene has also been observed in ASD probands (Sanders et al., 2015; Yuen et al., 2017). Zhou et al., 2022 reported that PHF14 forms a complex with MECP2 and TCF20; in the same report, the authors described two individuals with de novo variants in PHF14 who presented with neurodevelopmental phenotypes, including a patient with a de novo PHF14 missense variant that abolished the MECP2-PHF14-TCF20 interaction.

Molecular Function

Predicted to enable histone binding activity. Predicted to be involved in histone H3-K14 acetylation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of mesenchymal cell proliferation involved in lung development; and negative regulation of platelet-derived growth factor receptor-alpha signaling pathway. Predicted to be located in nucleus. Predicted to be part of MOZ/MORF histone acetyltransferase complex.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to PHF14 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci Sanders SJ , et al. (2015) Yes -
2 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
3 Primary Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
4 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
5 Recent Recommendation - Zhou J et al. (2022) No Autistic features
6 Support - Zhou X et al. (2022) Yes -
7 Support - Vijay Gupta et al. (2024) Yes -
Rare Variants   (21)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1573A>T p.Arg525Ter stop_gained De novo - - 35074918 Zhou J et al. (2022)
c.2312+41A>T - intron_variant De novo - - 26402605 Sanders SJ , et al. (2015)
c.964T>G p.Cys322Gly missense_variant De novo - - 35074918 Zhou J et al. (2022)
c.519A>G p.Thr173= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.2388A>G p.Gly796= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1046-428G>A - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.1981-747C>T - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2180+722G>A - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2773-3814T>C - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2773-7350dup - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.-347A>G - 5_prime_UTR_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2655-18575C>G - intron_variant De novo - Simplex 28263302 C Yuen RK et al. (2017)
c.2077-348G>A - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.2181-946A>G - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.901-2727A>G - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.2772+9398T>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.997G>A p.Ala333Thr missense_variant De novo - - 31452935 Feliciano P et al. (2019)
c.2772+16252T>C - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.2772+28080G>T - intron_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.769G>A p.Glu257Lys missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.73A>C p.Ser25Arg missense_variant De novo - Simplex 39769462 Vijay Gupta et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Interaction with MECP2 and TCF20

Score Delta: Score remained at 3

criteria met
See SFARI Gene'scoring criteria
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.

4/1/2022
icon
3

Increased from to 3

Description

Interaction with MECP2 and TCF20

Krishnan Probability Score

Score 0.48808974766494

Ranking 6820/25841 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 0.20653923959948

Ranking 7019/18225 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 0.79023710254872

Ranking 2049/18665 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 0.33891537289728

Ranking 2152/20870 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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