Human Gene Module / Chromosome X / HNRNPH2

HNRNPH2heterogeneous nuclear ribonucleoprotein H2 (H')

Score
4
Minimal Evidence Criteria 4.1
Autism Reports / Total Reports
2 / 5
Rare Variants / Common Variants
8 / 0
Aliases
HNRNPH2, FTP3,  HNRPH',  HNRPH2,  hnRNPH'
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
Xq22.1
Associated Disorders
ADHD, ASD, EPS, SCZ
Relevance to Autism

A rare, non-synonymous SNP in the HNRNPH2 gene was first identified in an individual with autism in Piton et al., 2011. Six unrelated females with a common neurodevelopmental phenotype involving developmental delay/intellectual disability were found to have de novo predicted deleterious missense variants in the HNRNPH2 gene; three of these six female patients were diagnosed with ASD (Bain et al., 2016).

Molecular Function

Reports related to HNRNPH2 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Recent Recommendation A UV-responsive internal ribosome entry site enhances serine hydroxymethyltransferase 1 expression for DNA damage repair. Fox JT , et al. (2009) No -
2 Primary Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Piton A , et al. (2010) Yes SCZ
3 Recent recommendation Variants in HNRNPH2 on the X Chromosome Are Associated with a Neurodevelopmental Disorder in Females. Bain JM , et al. (2016) No ASD (3/6 cases), epilepsy/seizures (3/6 cases), AD
4 Support Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder. Takata A , et al. (2018) Yes -
5 Highly Cited Heterogeneous nuclear ribonucleoproteins H, H', and F are members of a ubiquitously expressed subfamily of related but distinct proteins encoded by... Honor B , et al. (1995) No -
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
G to C p.Met396Ile missense_variant Familial Maternal - 20479760 Piton A , et al. (2010)
c.616C>T p.Arg206Trp missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.616C>T p.Arg206Trp missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.617G>A p.Arg206Gln missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.626C>T p.Pro209Leu missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.616C>T p.Arg206Trp missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.616C>T p.Arg206Trp missense_variant De novo - - 27545675 Bain JM , et al. (2016)
c.422T>A p.Met141Lys missense_variant De novo - Simplex 29346770 Takata A , et al. (2018)
Common Variants  

No common variants reported.

SFARI Gene score
4

Minimal Evidence

A rare, non-synonymous SNP in the HNRNPH2 gene was first identified in an individual with autism in Piton et al., 2011. Six unrelated females with a common neurodevelopmental phenotype involving developmental delay/intellectual disability were found to have de novo predicted deleterious missense variants in the HNRNPH2 gene; three of these six female patients were diagnosed with ASD (Bain et al., 2016).

Score Delta: Score remained at 4

4

Minimal Evidence

See all Category 4 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.

1/1/2018
4
icon
4

Score remained at 4

Description

A rare, non-synonymous SNP in the HNRNPH2 gene was first identified in an individual with autism in Piton et al., 2011. Six unrelated females with a common neurodevelopmental phenotype involving developmental delay/intellectual disability were found to have de novo predicted deleterious missense variants in the HNRNPH2 gene; three of these six female patients were diagnosed with ASD (Bain et al., 2016).

10/1/2016
5
icon
4

Decreased from 5 to 4

Description

A rare, non-synonymous SNP in the HNRNPH2 gene was first identified in an individual with autism in Piton et al., 2011. Six unrelated females with a common neurodevelopmental phenotype involving developmental delay/intellectual disability were found to have de novo predicted deleterious missense variants in the HNRNPH2 gene; three of these six female patients were diagnosed with ASD (Bain et al., 2016).

7/1/2014
No data
icon
5

Increased from No data to 5

Description

A rare, non-synonymous SNP in the HNRNPH2 gene was identified in an individual with autism (Piton et al., 2011).

4/1/2014
No data
icon
5

Increased from No data to 5

Description

A rare, non-synonymous SNP in the HNRNPH2 gene was identified in an individual with autism (Piton et al., 2011).

Krishnan Probability Score

Score 0.49504368952014

Ranking 3246/25841 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 0.86828424043336

Ranking 3478/18225 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 0.9236170662671

Ranking 9815/18665 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).
Larsen Cumulative Evidence Score

Score 0

Ranking 448/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.45822334137896

Ranking 848/20870 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.
CNVs associated with HNRNPH2(1 CNVs)
Xq22.1 5 Duplication 9  /  16
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