Human Gene Module / Chromosome 3 / QRICH1

QRICH1glutamine rich 1

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 14
Rare Variants / Common Variants
57 / 0
Aliases
-
Associated Syndromes
Ververi-Brady syndrome, DD, Ververi-Brady syndrome
Chromosome Band
3p21.31
Associated Disorders
DD/NDD, ID, ASD
Relevance to Autism

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD.

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 QRICH1 (14 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 Prevalence and architecture of de novo mutations in developmental disorders et al. (2017) No -
3 Recent Recommendation Phenotypic spectrum associated with de novo mutations in QRICH1 gene Ververi A , et al. (2017) No ASD
4 Support De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis Wang S , et al. (2018) No -
5 Support - Lui JC et al. (2019) No ID
6 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
7 Support - Cope H et al. (2020) No ID
8 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
9 Support QRICH1 variants in Ververi-Brady syndrome-delineation of the genotypic and phenotypic spectrum Föhrenbach M et al. (2020) No DD, ID, impaired social interactions
10 Support - Baruch Y et al. (2021) No ADHD
11 Recent Recommendation - Kumble S et al. (2021) No ASD, ADHD, epilepsy/seizures
12 Support - Zhou X et al. (2022) Yes -
13 Support - Wang D et al. (2023) No -
14 Recent Recommendation - Kuokuo Li et al. (2024) Yes -
Rare Variants   (57)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.46C>T p.Arg16Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.139C>T p.Gln47Ter stop_gained De novo - Simplex 28135719 et al. (2017)
c.1531C>T p.Arg511Ter stop_gained De novo - - 30281152 Lui JC et al. (2019)
c.1378C>T p.Gln460Ter stop_gained De novo - - 32730690 Cope H et al. (2020)
c.541C>T p.Gln181Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.823C>T p.Gln275Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.1787-2A>G - splice_site_variant De novo - - 34859529 Kumble S et al. (2021)
c.1896-2A>G - splice_site_variant De novo - - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained De novo - Simplex 28135719 et al. (2017)
c.1258C>T p.Gln420Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained Unknown - - 34859529 Kumble S et al. (2021)
c.2216G>A p.Trp739Ter stop_gained De novo - - 34859529 Kumble S et al. (2021)
c.704G>A p.Arg235Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1607G>A p.Arg536Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2038G>T p.Gly680Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2267G>A p.Arg756Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2071C>T p.Gln691Ter stop_gained De novo - - 31452935 Feliciano P et al. (2019)
c.756G>T p.Met252Ile missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.851C>T p.Pro284Leu missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained Unknown - - 25363760 De Rubeis S , et al. (2014)
c.1731C>T p.Phe577%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.1606C>T p.Arg536Ter stop_gained De novo - Simplex 30281152 Lui JC et al. (2019)
c.2047+1G>A - splice_site_variant De novo - Unknown 30257206 Wang S , et al. (2018)
c.1180C>G p.His394Asp missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1304A>G p.Gln435Arg missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1579G>A p.Gly527Arg missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1649A>G p.Tyr550Cys missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1720T>G p.Tyr574Asp missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1807G>T p.Val603Leu missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.1884C>G p.Phe628Leu missense_variant De novo - - 34859529 Kumble S et al. (2021)
c.310-2A>C - splice_site_variant Familial Paternal - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained De novo - Simplex 28692176 Ververi A , et al. (2017)
c.1604C>T p.Ala535Val missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
c.2204A>G p.Asn735Ser missense_variant Unknown - - 25363760 De Rubeis S , et al. (2014)
c.1671G>A p.Lys557%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1953dup p.Arg652AlafsTer9 frameshift_variant De novo - Simplex 28135719 et al. (2017)
c.136del p.Gln46SerfsTer200 frameshift_variant De novo - - 34859529 Kumble S et al. (2021)
c.985del p.His329ThrfsTer39 frameshift_variant De novo - - 34859529 Kumble S et al. (2021)
c.1292dup p.Pro432ThrfsTer23 frameshift_variant De novo - - 34859529 Kumble S et al. (2021)
c.1626del p.Tyr543MetfsTer23 frameshift_variant De novo - - 34859529 Kumble S et al. (2021)
c.1954C>T p.Arg652Ter stop_gained De novo - Simplex 33009816 Föhrenbach M et al. (2020)
c.768_769del p.Ser257LeufsTer46 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.137del p.Gln46ArgfsTer200 frameshift_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1788dup p.Tyr597LeufsTer9 frameshift_variant De novo - Simplex 37331002 Wang D et al. (2023)
c.1147_1150del p.Leu383PhefsTer6 frameshift_variant De novo - - 34859529 Kumble S et al. (2021)
c.1263G>C p.Gln421His missense_variant Familial Maternal - 25363760 De Rubeis S , et al. (2014)
c.1263G>C p.Gln421His missense_variant Familial Paternal - 25363760 De Rubeis S , et al. (2014)
c.2207G>A p.Ser736Asn missense_variant De novo - Simplex 33009816 Föhrenbach M et al. (2020)
c.246del p.Ser83ValfsTer163 frameshift_variant De novo - Simplex 33738978 Baruch Y et al. (2021)
c.914dup p.Gly306ArgfsTer48 frameshift_variant Familial Maternal - 34859529 Kumble S et al. (2021)
c.961del p.Asp321ThrfsTer47 frameshift_variant Familial Paternal - 34859529 Kumble S et al. (2021)
c.1953dup p.Arg652AlafsTer9 frameshift_variant De novo - Simplex 28692176 Ververi A , et al. (2017)
c.1655del p.Phe552SerfsTer14 frameshift_variant Familial Paternal - 34859529 Kumble S et al. (2021)
c.832_833del p.Ser278LeufsTer25 frameshift_variant De novo - Simplex 33009816 Föhrenbach M et al. (2020)
c.138_139delinsTT p.Gln46_Gln47delinsHisTer stop_gained De novo - Multiplex 28692176 Ververi A , et al. (2017)
c.1812_1813del p.Glu605GlyfsTer25 frameshift_variant De novo - Multiplex 33009816 Föhrenbach M et al. (2020)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD. A second de novo likely gene-disruptive variant in the QRICH1 gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019; in the same report; a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified QRICH1 as an ASD candidate gene with a q-value 0.1.

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.

10/1/2020
2
icon
2

Score remained at 2

Description

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD. A second de novo likely gene-disruptive variant in the QRICH1 gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019; in the same report; a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified QRICH1 as an ASD candidate gene with a q-value 0.1.

Reports Added
[Prevalence and architecture of de novo mutations in developmental disorders2017] [Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020] [QRICH1 variants in Ververi-Brady syndrome-delineation of the genotypic and phenotypic spectrum2020]
10/1/2019
4
icon
2

Decreased from 4 to 2

New Scoring Scheme
Description

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD. A second de novo likely gene-disruptive variant in the QRICH1 gene was identified in an ASD proband from the SPARK cohort in Feliciano et al., 2019; in the same report; a meta-analysis of de novo variants in 4773 published ASD trios and 465 SPARK trios using TADA identified QRICH1 as an ASD candidate gene with a q-value 0.1.

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
10/1/2018
4
icon
4

Decreased from 4 to 4

Description

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD.

Reports Added
[De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis.2018]
7/1/2017
icon
4

Increased from to 4

Description

A de novo frameshift variant in the QRICH1 gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014. De novo loss-of-function variants in QRICH1 were subsequently identified in three patients presenting with developmental delay/intellectual disability in Ververi et al., 2017; one of these three patients was also diagnosed with ASD.

Krishnan Probability Score

Score 0.44727578657135

Ranking 13179/25841 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 0.99606974804658

Ranking 1437/18225 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 0.2835523766945

Ranking 167/18665 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 0.31759004135664

Ranking 2476/20870 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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