Human Gene Module / Chromosome 1 / HNRNPR

HNRNPRheterogeneous nuclear ribonucleoprotein R

SFARI Gene Score
2S
Strong Candidate, Syndromic Criteria 2.1, Syndromic
Autism Reports / Total Reports
3 / 7
Rare Variants / Common Variants
13 / 0
Aliases
HNRNPR, HNRPR,  hnRNP-R
Associated Syndromes
-
Chromosome Band
1p36.12
Associated Disorders
DD/NDD, ADHD, ASD
Relevance to Autism

Duijkers et al., 2019 reported four individuals with de novo variants in the HNRNPR gene that presented with multisystem developmental defects including abnormalities of the brain and skeleton, dysmorphic facies, brachydactyly, seizures, and hypoplastic external genitalia; stereotypic movements were observed in two of these individuals, while autism spectrum disorder (pervasive developmental disorder) in addition to stereotypic movements was reported in a third. Gillentine et al., 2021 reported five previously unpublished individuals with HNRNPR variants; autism spectrum disorder was reported in two of these individuals, while autistic traits was reported in a third. De novo missense variants in HNRNPR have also been identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Satterstrom et al., 2020).

Molecular Function

This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to HNRNPR (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support - Helbig KL et al. (2016) No DD
3 Primary - Duijkers FA et al. (2019) No ASD, ADHD, stereotypy
4 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
5 Recent Recommendation - Gillentine MA et al. (2021) No ASD or autistic features, ADHD
6 Support - Zhou X et al. (2022) Yes -
7 Support - Salehi S et al. (2023) No -
Rare Variants   (13)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1663C>T p.Gln555Ter stop_gained De novo - - 26795593 Helbig KL et al. (2016)
c.195+1G>T - splice_site_variant De novo - - 33874999 Gillentine MA et al. (2021)
c.1763G>A p.Arg588His missense_variant De novo - - 31079900 Duijkers FA et al. (2019)
c.1702C>T p.Arg568Cys missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.1706A>G p.Tyr465Cys missense_variant Unknown - - 33874999 Gillentine MA et al. (2021)
c.1763G>A p.Arg588His missense_variant De novo - - 33874999 Gillentine MA et al. (2021)
c.548C>T p.Pro183Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1354C>T p.Arg452Trp missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1307dup p.Pro437ThrfsTer6 frameshift_variant De novo - - 31079900 Duijkers FA et al. (2019)
c.1350dup p.Gln451ThrfsTer31 frameshift_variant De novo - - 31079900 Duijkers FA et al. (2019)
c.1652dupG p.Pro552SerfsTer34 frameshift_variant De novo - - 31079900 Duijkers FA et al. (2019)
c.1548G>C p.Arg516Ser missense_variant De novo - Simplex 31981491 Satterstrom FK et al. (2020)
c.1324dup p.Arg442LysfsTer40 frameshift_variant Unknown - - 33874999 Gillentine MA et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
2S

Strong Candidate, Syndromic

Score Delta: Score remained at 2S

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.

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."

4/1/2022
icon
2S

Increased from to 2S

Krishnan Probability Score

Score 0.57157699539832

Ranking 769/25841 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 0.99907907430442

Ranking 1051/18225 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 0.73443610406691

Ranking 1411/18665 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 0.22072330914565

Ranking 3918/20870 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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