Human Gene Module / Chromosome 6 / HIVEP2

HIVEP2HIVEP zinc finger 2

Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
0 / 8
Rare Variants / Common Variants
14 / 0
Aliases
HIVEP2, HIV-EP2,  MBP-2,  MIBP1,  MRD43,  SHN2,  ZAS2,  ZNF40B
Associated Syndromes
-
Genetic Category
Syndromic, Functional
Chromosome Band
6q24.2
Associated Disorders
ASD
Relevance to Autism

Mutations in the HIVEP2 gene are associated with a form of autosomal dominant intellectual disability (MRD43; OMIM 616977); affected individuals frequently display behavioral abnormalities, and autism or autistic features have been observed in a subset of individuals with this disorder (Srivastava et al., 2016; Steinfeld et al., 2016; Goldsmith et al., 2019; Jain and Atwal 2019; Park et al., 2019). Hivep2-deficient mice have been shown to display schizophrenia-like behavioral abnormalities (Takao et al., 2013; Choi et al., 2015; Nakao et al., 2017).

Molecular Function

This gene encodes a member of a family of closely related, large, zinc finger-containing transcription factors. The encoded protein regulates transcription by binding to regulatory regions of various cellular and viral genes that maybe involved in growth, development and metastasis. The protein contains the ZAS domain comprised of two widely separated regions of zinc finger motifs, a stretch of highly acidic amino acids and a serine/threonine-rich sequence.

Reports related to HIVEP2 (8 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Deficiency of schnurri-2, an MHC enhancer binding protein, induces mild chronic inflammation in the brain and confers molecular, neuronal, and beha... Takao K , et al. (2013) No -
2 Support Loss-of-function variants in HIVEP2 are a cause of intellectual disability. Srivastava S , et al. (2015) No -
3 Support Combined behavioral studies and in vivo imaging of inflammatory response and expression of mGlu5 receptors in schnurri-2 knockout mice. Choi JK , et al. (2015) No -
4 Primary Mutations in HIVEP2 are associated with developmental delay, intellectual disability, and dysmorphic features. Steinfeld H , et al. (2016) No ASD
5 Support Immature morphological properties in subcellular-scale structures in the dentate gyrus of Schnurri-2 knockout mice: a model for schizophrenia and i... Nakao A , et al. (2017) No -
6 Support Expanding the phenotype of intellectual disability caused by HIVEP2 variants. Goldsmith H , et al. (2019) No Autistic features, stereotypy
7 Support Novel HIVEP2 Variant p.Q1248* is Associated with Developmental Delay: A Case Report. Jain A and Atwal PS (2019) No -
8 Support Novel HIVEP2 Variants in Patients with Intellectual Disability. Park J , et al. (2019) No -
Rare Variants   (14)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3742C>T p.Gln1248Ter stop_gained De novo NA - 31406623 Jain A and Atwal PS (2019)
c.2857G>T p.Glu953Ter stop_gained De novo NA - 27003583 Steinfeld H , et al. (2016)
c.6475G>T p.Gly2159Ter stop_gained De novo NA - 27003583 Steinfeld H , et al. (2016)
c.5935C>T p.Arg1979Ter stop_gained De novo NA - 31207095 Goldsmith H , et al. (2019)
c.3556C>T p.Gln1186Ter stop_gained De novo NA - 26153216 Srivastava S , et al. (2015)
c.6667C>T p.Arg2223Ter stop_gained De novo NA Simplex 31602191 Park J , et al. (2019)
c.1189G>T p.Asp397Tyr missense_variant De novo NA - 27003583 Steinfeld H , et al. (2016)
c.6609_6616del p.Glu2204Ter frameshift_variant De novo NA - 31602191 Park J , et al. (2019)
c.2827C>T p.Arg943Ter stop_gained De novo NA Simplex 26153216 Srivastava S , et al. (2015)
c.3434del p.Pro1145ArgfsTer2 frameshift_variant De novo NA - 27003583 Steinfeld H , et al. (2016)
c.5614dup p.Glu1872GlyfsTer16 frameshift_variant De novo NA - 27003583 Steinfeld H , et al. (2016)
c.6625dup p.Tyr2209LeufsTer53 frameshift_variant De novo NA - 27003583 Steinfeld H , et al. (2016)
c.2956_2957del p.Glu986ArgfsTer4 frameshift_variant De novo NA - 31207095 Goldsmith H , et al. (2019)
c.5737del p.Asp1913MetfsTer15 frameshift_variant De novo NA Simplex 26153216 Srivastava S , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Mutations in the HIVEP2 gene are associated with a form of autosomal dominant intellectual disability (MRD43; OMIM 616977); affected individuals frequently display behavioral abnormalities, and autism or autistic features have been observed in a subset of individuals with this disorder (Srivastava et al., 2016; Steinfeld et al., 2016; Goldsmith et al., 2019; Jain and Atwal 2019; Park et al., 2019). Hivep2-deficient mice have been shown to display schizophrenia-like behavioral abnormalities (Takao et al., 2013; Choi et al., 2015; Nakao et al., 2017).

Score Delta: Score remained at S

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.

10/1/2019
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1

Increased from to 1

New Scoring Scheme
Description

Mutations in the HIVEP2 gene are associated with a form of autosomal dominant intellectual disability (MRD43; OMIM 616977); affected individuals frequently display behavioral abnormalities, and autism or autistic features have been observed in a subset of individuals with this disorder (Srivastava et al., 2016; Steinfeld et al., 2016; Goldsmith et al., 2019; Jain and Atwal 2019; Park et al., 2019). Hivep2-deficient mice have been shown to display schizophrenia-like behavioral abnormalities (Takao et al., 2013; Choi et al., 2015; Nakao et al., 2017).

Reports Added
[New Scoring Scheme]
Krishnan Probability Score

Score 0.57982738888849

Ranking 588/25841 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.
ExAC Score

Score 0.99999966425227

Ranking 244/18225 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
Sanders TADA Score

Score 0.94929879918756

Ranking 18034/18665 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).
Zhang D Score

Score 0.59522276079534

Ranking 94/20870 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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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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