Human Gene Module / Chromosome 6 / HIVEP2

HIVEP2HIVEP zinc finger 2

SFARI Gene Score
1S
High Confidence, Syndromic Criteria 1.1, Syndromic
Autism Reports / Total Reports
3 / 14
Rare Variants / Common Variants
24 / 0
Aliases
HIVEP2, HIV-EP2,  MBP-2,  MIBP1,  MRD43,  SHN2,  ZAS2,  ZNF40B
Associated Syndromes
-
Chromosome Band
6q24.2
Associated Disorders
DD/NDD, 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.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HIVEP2 (14 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 behavioral phenotypes related to schizophrenia 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 intellectual disability 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 -
9 Support - Miyamoto S et al. (2021) No DD
10 Support - Chuan Z et al. (2022) No DD
11 Support - Chen Y et al. (2021) No -
12 Support - Zhou X et al. (2022) Yes -
13 Support - Sheth F et al. (2023) Yes DD, ID
14 Support - Axel Schmidt et al. (2024) Yes -
Rare Variants   (24)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.3082C>T p.Arg1028Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.6007C>T p.Gln2003Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
c.643C>T p.Arg215Trp missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.3742C>T p.Gln1248Ter stop_gained De novo - - 31406623 Jain A and Atwal PS (2019)
c.2857G>T p.Glu953Ter stop_gained De novo - - 27003583 Steinfeld H , et al. (2016)
c.3067C>T p.His1023Tyr missense_variant Unknown - - 35571021 Chuan Z et al. (2022)
c.6475G>T p.Gly2159Ter stop_gained De novo - - 27003583 Steinfeld H , et al. (2016)
c.5935C>T p.Arg1979Ter stop_gained De novo - - 31207095 Goldsmith H , et al. (2019)
c.3556C>T p.Gln1186Ter stop_gained De novo - - 26153216 Srivastava S , et al. (2015)
c.6667C>T p.Arg2223Ter stop_gained De novo - Simplex 31602191 Park J , et al. (2019)
c.2827C>T p.Arg943Ter stop_gained De novo - Simplex 33958710 Miyamoto S et al. (2021)
c.1189G>T p.Asp397Tyr missense_variant De novo - - 27003583 Steinfeld H , et al. (2016)
c.1502A>C p.Glu501Ala missense_variant Unknown - - 39039281 Axel Schmidt et al. (2024)
c.4928C>T p.Thr1643Ile missense_variant De novo - Simplex 35873028 Chen Y et al. (2021)
c.1707G>C p.Arg569Ser missense_variant Unknown - Simplex 37543562 Sheth F et al. (2023)
c.6609_6616del p.Glu2204Ter frameshift_variant De novo - - 31602191 Park J , et al. (2019)
c.2827C>T p.Arg943Ter stop_gained De novo - Simplex 26153216 Srivastava S , et al. (2015)
c.3434del p.Pro1145ArgfsTer2 frameshift_variant De novo - - 27003583 Steinfeld H , et al. (2016)
c.5614dup p.Glu1872GlyfsTer16 frameshift_variant De novo - - 27003583 Steinfeld H , et al. (2016)
c.6625dup p.Tyr2209LeufsTer53 frameshift_variant De novo - - 27003583 Steinfeld H , et al. (2016)
c.1816G>A p.Val606Met missense_variant Familial Paternal Simplex 37543562 Sheth F et al. (2023)
c.3988C>G p.Pro1330Ala missense_variant Familial Maternal Simplex 37543562 Sheth F et al. (2023)
c.2956_2957del p.Glu986ArgfsTer4 frameshift_variant De novo - - 31207095 Goldsmith H , et al. (2019)
c.5737del p.Asp1913MetfsTer15 frameshift_variant De novo - Simplex 26153216 Srivastava S , et al. (2015)
Common Variants  

No common variants reported.

SFARI Gene score
1S

High Confidence, Syndromic

Score Delta: Score remained at 1S

criteria met
See SFARI Gene'scoring criteria
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.

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."

4/1/2021
1
icon
1

Score remained at 1

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
[Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies2021]
10/1/2019
icon
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.
Original Source
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
Original Source
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).
Original Source
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.
Original Source
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