Human Gene Module / Chromosome 3 / PHF7

PHF7PHD finger protein 7

SFARI Gene Score
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
15 / 0
PHF7, HSPC045,  HSPC226,  NYD-SP6
Associated Syndromes
Chromosome Band
Associated Disorders
Relevance to Autism

A de novo likely gene-disruptive (LGD) variant in PHF7 was identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). Single-molecular molecular inversion probe (smMIP) sequencing of 3,363 probands from cohorts with a primary diagnosis of ASD in Wang et al., 2020 identified 5 ASD-associated LGD variants and one ASD-associated missense variant with a CADD score 30 in the PHF7 gene.

Molecular Function

Spermatogenesis is a complex process regulated by extracellular and intracellular factors as well as cellular interactions among interstitial cells of the testis, Sertoli cells, and germ cells. This gene is expressed in the testis in Sertoli cells but not germ cells. The protein encoded by this gene contains plant homeodomain (PHD) finger domains, also known as leukemia associated protein (LAP) domains, believed to be involved in transcriptional regulation. The protein, which localizes to the nucleus of transfected cells, has been implicated in the transcriptional regulation of spermatogenesis.

SFARI Genomic Platforms
Reports related to PHF7 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
3 Primary Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes DD, ID
4 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (15)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.112C>T p.Arg38Ter stop_gained Unknown - - 33004838 Wang T et al. (2020)
c.803-1G>C - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.920-1G>C - splice_site_variant Unknown - - 33004838 Wang T et al. (2020)
c.1040C>T p.Pro347Leu missense_variant De novo - - 28135719 et al. (2017)
c.275G>A p.Arg92Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.686C>T p.Ala229Val missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.829G>A p.Gly277Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.41+1G>A - splice_site_variant Unknown Not maternal - 33004838 Wang T et al. (2020)
c.587dup p.Ser197IlefsTer12 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.1137dup p.Ser380IlefsTer8 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.111_120del p.Arg38GlyfsTer6 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.939_940del p.Asp315HisfsTer11 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.388del p.Leu130PhefsTer89 frameshift_variant De novo - - 25363768 Iossifov I et al. (2014)
c.356dup p.His120ProfsTer23 frameshift_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.112C>T p.Arg38Ter stop_gained Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
Common Variants  

No common variants reported.

SFARI Gene score

Strong Candidate

Score Delta: Score remained at 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.


Increased from to 2

Krishnan Probability Score

Score 0.49114975384063

Ranking 5756/25841 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: A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at
ExAC Score

Score 0.064913882316604

Ranking 8290/18225 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 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: aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.33754027421519

Ranking 211/18665 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
Zhang D Score

Score -0.52955341150098

Ranking 19480/20870 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.
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