Human Gene Module / Chromosome 15 / RFX7

RFX7regulatory factor X7

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
3 / 4
Rare Variants / Common Variants
21 / 0
Aliases
RFX7, RFXDC2
Associated Syndromes
-
Chromosome Band
15q21.3
Associated Disorders
ADHD, ASD
Relevance to Autism

A de novo frameshift variant and two de novo missense variants in the RFX7 gene have been identified in ASD probands from the Autism Sequencing Consortium and the Simons Simplex Collection (De Rubeis et al., 2014; Iossifov et al. 2014). Genetic and phenotypic characterization of individuals with potentially deleterious variants in three brain-expressed members of the RFX family (RFX3, RFX4, or RFX7) in Harris et al., 2021 identified 14 unrelated individuals with variants in the RFX7 gene; global developmental delay/intellectual disability and dysmorphic features were frequently observed in this cohort, and five individuals also presented with autism spectrum disorder.

Molecular Function

RFX7 is a member of the regulatory factor X (RFX) family of transcription factors.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to RFX7 (4 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 Recent recommendation - Harris HK et al. (2021) No ASD, ADHD
4 Support - Zhou X et al. (2022) Yes -
Rare Variants   (21)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3511G>A p.Val1171Ile missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.834T>G p.Pro278%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.3438T>C p.Pro1146%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.2225C>G p.Ser742Ter stop_gained De novo - Simplex 33658631 Harris HK et al. (2021)
c.2233G>T p.Glu745Ter stop_gained De novo - Simplex 33658631 Harris HK et al. (2021)
c.2284G>T p.Gly762Ter stop_gained De novo - Simplex 33658631 Harris HK et al. (2021)
c.2718C>A p.Tyr906Ter stop_gained De novo - Simplex 33658631 Harris HK et al. (2021)
c.2718C>G p.Tyr906Ter stop_gained De novo - Simplex 33658631 Harris HK et al. (2021)
c.2844C>G p.Pro948%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.3083C>T p.Pro1028Leu missense_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.3085A>G p.Ile1029Val missense_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.4358A>G p.His1453Arg missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.2596C>T p.Pro866Ser missense_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2707dup p.Thr903AsnfsTer9 frameshift_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.1822dup p.Thr608AsnfsTer12 frameshift_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.3080del p.Thr1027IlefsTer3 frameshift_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.3032del p.Ser1011IlefsTer19 frameshift_variant De novo - Simplex 33658631 Harris HK et al. (2021)
c.1836dup p.Ala613SerfsTer7 frameshift_variant De novo - Simplex 25363760 De Rubeis S , et al. (2014)
c.2859_2864del p.Pro964_Thr965del inframe_deletion De novo - Simplex 33658631 Harris HK et al. (2021)
c.1399_1400del p.Met467GlufsTer19 frameshift_variant Unknown - Multiplex 33658631 Harris HK et al. (2021)
c.2170_2171insTGTT p.Trp724LeufsTer13 frameshift_variant De novo - Simplex 33658631 Harris HK et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

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.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

4/1/2022
icon
3S

Increased from to 3S

Krishnan Probability Score

Score 0.44732271340882

Ranking 12737/25841 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 0.99968094633594

Ranking 851/18225 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 0.25470504268797

Ranking 146/18665 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 0.44528312877679

Ranking 968/20870 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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