HNRNPUheterogeneous nuclear ribonucleoprotein U
Autism Reports / Total Reports
5 / 17Rare Variants / Common Variants
58 / 0Aliases
HNRNPU, EIEE54-AS1, HNRPU, SAF-A, SAFA, U21.1, hnRNP U, pp120, HNRNPUAssociated Syndromes
-Genetic Category
Rare Single Gene Mutation, Syndromic, FunctionalChromosome Band
1q44Associated Disorders
EP, DD/NDD, ID, EPS, ASDRelevance to Autism
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017).
Molecular Function
This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391).
Reports related to HNRNPU (17 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. | Carvill GL , et al. (2013) | No | ID, epilepsy/seizures |
2 | Support | De novo mutations in epileptic encephalopathies. | Epi4K Consortium , et al. (2013) | No | ID, epilepsy/seizures, ASD |
3 | Support | De novo mutations in moderate or severe intellectual disability. | Hamdan FF , et al. (2014) | No | ID, epilepsy/seizures, autistic features |
4 | Support | Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients. | de Kovel CG , et al. (2016) | No | ID, epilepsy/seizures |
5 | Support | De novo genic mutations among a Chinese autism spectrum disorder cohort. | Wang T , et al. (2016) | Yes | - |
6 | Recent Recommendation | Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability. | Bramswig NC , et al. (2017) | No | - |
7 | Support | Genomic diagnosis for children with intellectual disability and/or developmental delay. | Bowling KM , et al. (2017) | Yes | - |
8 | Primary | Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. | Lim ET , et al. (2017) | Yes | - |
9 | Support | Clinical and molecular characterization of de novo loss of function variants in HNRNPU. | Leduc MS , et al. (2017) | No | ASD |
10 | Support | De novo mutations in HNRNPU result in a neurodevelopmental syndrome. | Yates TM , et al. (2017) | No | Epilepsy/seizures, ASD |
11 | Support | HRPU-2, a Homolog of Mammalian hnRNP U, Regulates Synaptic Transmission by Controlling the Expression of SLO-2 Potassium Channel in Caenorhabditis ... | Liu P , et al. (2017) | No | - |
12 | Support | An episode of acute encephalopathy with biphasic seizures and late reduced diffusion followed by hemiplegia and intractable epilepsy observed in a ... | Shimada S , et al. (2018) | No | Epilepsy/seizures, DD, ID, autistic behavior, ster |
13 | Support | Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability. | Borlot F , et al. (2019) | No | Autistic features |
14 | Support | Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes | Feliciano P et al. (2019) | Yes | - |
15 | Support | Clinical findings of 21 previously unreported probands with HNRNPU-related syndrome and comprehensive literature review | Durkin A et al. (2020) | No | - |
16 | Support | Clinical and genetic characteristics of patients with Doose syndrome | Hinokuma N et al. (2020) | No | - |
17 | Support | Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders | Wang T et al. (2020) | Yes | - |
Rare Variants (58)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | NA | - | 31273778 | Borlot F , et al. (2019) | |
- | - | copy_number_gain | Unknown | - | - | 28393272 | Bramswig NC , et al. (2017) | |
c.1681C>T | p.Gln561Ter | stop_gained | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1714C>T | p.Arg572Ter | stop_gained | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1852C>T | p.Gln618Ter | stop_gained | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.67C>T | p.Arg23Ter | stop_gained | Unknown | - | - | 28554332 | Bowling KM , et al. (2017) | |
c.1060+1G>A | - | splice_site_variant | De novo | NA | - | 28944577 | Yates TM , et al. (2017) | |
c.508C>T | p.Gln170Ter | stop_gained | De novo | NA | - | 31452935 | Feliciano P et al. (2019) | |
c.523C>T | p.Gln175Ter | stop_gained | De novo | NA | - | 28393272 | Bramswig NC , et al. (2017) | |
c.817C>T | p.Gln273Ter | stop_gained | De novo | NA | - | 28393272 | Bramswig NC , et al. (2017) | |
c.1744-2del | - | splice_site_variant | Familial | Maternal | - | 33004838 | Wang T et al. (2020) | |
c.67C>T | p.Arg23Ter | stop_gained | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.692-1G>A | - | splice_site_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.418G>A | p.Glu140Lys | missense_variant | De novo | NA | - | 28944577 | Yates TM , et al. (2017) | |
c.619C>T | p.Gln207Ter | stop_gained | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1686+1G>C | - | splice_site_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2365C>T | p.Arg789Ter | stop_gained | De novo | NA | Multiplex | 33004838 | Wang T et al. (2020) | |
c.1089G>A | p.Trp363Ter | stop_gained | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1450C>T | p.Arg484Ter | stop_gained | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1801C>T | p.Arg601Ter | stop_gained | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.960G>A | p.Trp320Ter | stop_gained | De novo | NA | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1089G>A | p.Trp363Ter | stop_gained | De novo | NA | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.1714C>T | p.Arg572Ter | stop_gained | De novo | NA | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.511C>T | p.Gln171Ter | stop_gained | De novo | NA | Simplex | 25356899 | Hamdan FF , et al. (2014) | |
c.970A>G | p.Arg324Gly | missense_variant | De novo | NA | - | 28393272 | Bramswig NC , et al. (2017) | |
c.1088G>A | p.Trp363Ter | stop_gained | De novo | NA | Multiplex | 32319732 | Durkin A et al. (2020) | |
c.1132T>C | p.Ser378Pro | missense_variant | De novo | NA | - | 28393272 | Bramswig NC , et al. (2017) | |
c.359C>T | p.Pro120Leu | missense_variant | De novo | NA | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.469G>C | p.Gly157Arg | missense_variant | De novo | NA | Simplex | 28714951 | Lim ET , et al. (2017) | |
c.334dup | p.Ala112GlyfsTer33 | frameshift_variant | De novo | NA | - | 33004838 | Wang T et al. (2020) | |
c.1211A>G | p.Asp404Gly | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
c.1507C>T | p.Pro522Ser | missense_variant | Familial | Paternal | - | 27824329 | Wang T , et al. (2016) | |
c.2167+35_*4156del | p.? | copy_number_loss | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.878A>G | p.Tyr293Cys | missense_variant | De novo | NA | Simplex | 32913952 | Hinokuma N et al. (2020) | |
c.2357G>A | p.Trp786Ter | stop_gained | Unknown | Not maternal | - | 23708187 | Carvill GL , et al. (2013) | |
c.1687-4_1692del | - | splice_site_variant | De novo | NA | - | 23934111 | Epi4K Consortium , et al. (2013) | |
c.1050_1051del | p.Thr351LysfsTer4 | frameshift_variant | Unknown | - | - | 33004838 | Wang T et al. (2020) | |
c.837_839del | p.Glu279del | inframe_deletion | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.23del | p.Val8GlufsTer4 | frameshift_variant | De novo | NA | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1755dup | p.Val586CysfsTer7 | frameshift_variant | De novo | NA | - | 27652284 | de Kovel CG , et al. (2016) | |
c.1641del | p.Asp548IlefsTer5 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.76del | p.Ser26LeufsTer35 | frameshift_variant | De novo | NA | Simplex | 29858110 | Shimada S , et al. (2018) | |
c.1681del | p.Gln561SerfsTer45 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1836del | p.Tyr613IlefsTer11 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1571dup | p.Lys525GlufsTer25 | frameshift_variant | De novo | NA | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.1664del | p.Leu555ArgfsTer51 | frameshift_variant | De novo | NA | Simplex | 28944577 | Yates TM , et al. (2017) | |
c.706_707del | p.Glu236ThrfsTer6 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.847_857del | p.Phe283SerfsTer5 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.395_401del | p.Asn132ThrfsTer63 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.454_466del | p.Ala152ThrfsTer41 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.712_715del | p.Lys238AlafsTer100 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.1925_1926del | p.Leu642ProfsTer5 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.2083_2084del | p.Ser695TrpfsTer6 | frameshift_variant | De novo | NA | Simplex | 32319732 | Durkin A et al. (2020) | |
c.651_660del | p.Gly218AlafsTer118 | frameshift_variant | De novo | NA | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.2270_2271del | p.Pro757ArgfsTer7 | frameshift_variant | De novo | NA | Simplex | 28815871 | Leduc MS , et al. (2017) | |
c.706_707del | p.Glu236ThrfsTer6 | frameshift_variant | De novo | NA | Not simplex | 32319732 | Durkin A et al. (2020) | |
c.1756_1757insGT | p.Val586GlyfsTer2 | frameshift_variant | Unknown | Not maternal | - | 33004838 | Wang T et al. (2020) | |
c.1367_1368insGA | p.Phe456LeufsTer8 | frameshift_variant | De novo | NA | Simplex | 28944577 | Yates TM , et al. (2017) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
Score Delta: Score remained at 4S
criteria met
See SFARI Gene'scoring criteriaWe 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.
10/1/2020

Score remained at 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
4/1/2020

Score remained at 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
10/1/2019

Decreased from 4S to 1
New Scoring Scheme
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
7/1/2019

Decreased from 4S to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
7/1/2018

Decreased from 4.4 + S to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017; Yates et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder in Epi4K Consortium; Epilepsy Phenome/Genome Project 2013, Bramswig et al., 2017, Leduc et al., 2017, and Yates et al., 2017.
4/1/2018

Decreased from 4S to 4.4 + S
Description
4S
7/1/2017

Increased from to 4S
Description
Two non-synonymous postzygotic mosaic mutations (PZMs) in the HNRNPU gene were identified in ASD probands in Lim et al., 2017; comparison with a background set of 84,448 privately inherited variants demonstrated that this gene harbored more PZMs than expected based on background rates (2/571 observed vs. 5/84,448 expected; hypergeometric P-value of 4.5E-04). Additional damaging variants in the HNRNPU gene have been identified in ASD probands (Wang et al., 2016; Bowling et al., 2017). Mutations in the HNRNPU gene have also been associated with early infantile epileptic encephalopathy-54 (EIEE54; OMIM 617391) (Carvill et al., 2013; Epi4K Consortium; Epilepsy Phenome/Genome Project 2013; Hamdan et al., 2014; de Kovel et al., 2016; Bramswig et al., 2017; Leduc et al., 2017); a diagnosis of autism or autistic features have been observed in several patients with this disorder.
Krishnan Probability Score
Score 0.57111211166452
Ranking 825/25841 scored genes
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ExAC Score
Score 0.99990332258243
Ranking 673/18225 scored genes
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Sanders TADA Score
Score 0.7919757025084
Ranking 2076/18665 scored genes
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Zhang D Score
Score 0.38266856349508
Ranking 1654/20870 scored genes
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