Human Gene Module / Chromosome 1 / HIVEP3

HIVEP3human immunodeficiency virus type I enhancer binding protein 3

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
8 / 1
Aliases
HIVEP3, KBP-1,  KBP1,  KRC,  SHN3,  Schnurri-3,  ZAS3,  ZNF40C
Associated Syndromes
-
Chromosome Band
1p34.2
Associated Disorders
-
Relevance to Autism

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Molecular Function

This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HIVEP3 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Recent Recommendation Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases Stessman HA , et al. (2017) Yes -
3 Positive Association Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017) Yes -
4 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
5 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Support - Cirnigliaro M et al. (2023) Yes -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2771C>A p.Ser924Tyr missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.6128G>A p.Arg2043Lys missense_variant De novo - Simplex 28714951 Lim ET , et al. (2017)
c.3157A>T p.Arg1053Trp missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.4087T>C p.Ser1363Pro missense_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.5482G>A p.Asp1828Asn missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.1753dup p.Arg585ProfsTer20 frameshift_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.6142C>T p.Arg2048Ter stop_gained Familial Paternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.6601C>T p.Gln2201Ter stop_gained De novo - Multiplex (monozygotic twins) 28191889 Stessman HA , et al. (2017)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-721+84175G>A;c.-801+84175G>A - intron_variant - - - 28540026 Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium (2017)
SFARI Gene score
2

Strong Candidate

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

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.

10/1/2019
3
icon
2

Decreased from 3 to 2

New Scoring Scheme
Description

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Reports Added
[New Scoring Scheme]
7/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
1/1/2019
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
7/1/2017
3
icon
3

Decreased from 3 to 3

Description

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Reports Added
[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
1/1/2017
icon
3

Increased from to 3

Description

A de novo loss-of-function (LoF) variant in the HIVEP3 gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in two probands (suspected twins) from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017.

Krishnan Probability Score

Score 0.45141574809937

Ranking 10661/25841 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 0.030810601663664

Ranking 9012/18225 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 0.6726588190024

Ranking 1002/18665 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 0.59537944425295

Ranking 93/20870 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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