HNRNPU
heterogeneous nuclear ribonucleoprotein U, the group of Heterogeneous nuclear ribonucleoproteins
Basic information
Region (hg38): 1:244840637-244864560
Previous symbols: [ "HNRPU", "HNRNPU-AS1", "C1orf199", "NCRNA00201" ]
Links
Phenotypes
GenCC
Source:
- developmental and epileptic encephalopathy, 54 (Moderate), mode of inheritance: AD
- complex neurodevelopmental disorder (Definitive), mode of inheritance: AD
- developmental and epileptic encephalopathy, 54 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Developmental and epileptic encephalopathy 54 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 23708187; 23934111; 25356899; 27652284 |
ClinVar
This is a list of variants' phenotypes submitted to
- Developmental and epileptic encephalopathy, 54 (648 variants)
- not provided (164 variants)
- Inborn genetic diseases (84 variants)
- heterogeneous nuclear ribonucleoprotein G, human (19 variants)
- not specified (7 variants)
- Epileptic encephalopathy (4 variants)
- Intellectual disability (3 variants)
- Seizure;Intellectual disability (2 variants)
- See cases (2 variants)
- HNRNPU-Related Disorder (2 variants)
- HNRNPU-related condition (2 variants)
- Seizure (2 variants)
- Intellectual disability;Seizure (1 variants)
- Neurodevelopmental delay (1 variants)
- Autism spectrum disorder (1 variants)
- Intellectual disability and seizures (1 variants)
- Developmental and epileptic encephalopathy, 1 (1 variants)
- HNRNPU-related developmental and epileptic encephalopathy (1 variants)
- Myoclonic absence seizure (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPU gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 170 | 175 | ||||
| missense | 221 | 62 | 14 | 304 | ||
| nonsense | 18 | 27 | ||||
| start loss | 1 | |||||
| frameshift | 48 | 14 | 67 | |||
| inframe indel | 16 | 25 | ||||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| splice region ? | 1 | 1 | 14 | 28 | 6 | 50 |
| non coding ? | 91 | 33 | 127 | |||
| Total | 71 | 37 | 249 | 332 | 50 |
Highest pathogenic variant AF is 0.00000661
Variants in HNRNPU
This is a list of pathogenic ClinVar variants found in the HNRNPU region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-244841783-G-C | Benign (Jun 14, 2018) | |||
| 1-244841820-G-A | Likely benign (Apr 16, 2019) | |||
| 1-244841924-GTTC-G | Likely benign (Jan 23, 2023) | |||
| 1-244841927-C-T | Likely benign (Jul 13, 2023) | |||
| 1-244841933-T-C | Likely benign (Sep 16, 2022) | |||
| 1-244841939-TC-T | Uncertain significance (Apr 28, 2022) | |||
| 1-244841958-A-G | Likely benign (Oct 17, 2022) | |||
| 1-244841959-G-A | Uncertain significance (Feb 06, 2022) | |||
| 1-244841961-A-G | Likely benign (Jun 20, 2022) | |||
| 1-244841962-T-C | Uncertain significance (Aug 12, 2022) | |||
| 1-244841988-C-T | not specified | Benign (Jan 22, 2024) | ||
| 1-244841989-G-A | Uncertain significance (Aug 01, 2022) | |||
| 1-244841992-C-T | Mitochondrial complex 4 deficiency, nuclear type 11 • Mitochondrial disease | Conflicting classifications of pathogenicity (Apr 27, 2023) | ||
| 1-244841993-G-A | Conflicting classifications of pathogenicity (Jan 18, 2024) | |||
| 1-244841994-G-A | Likely benign (Aug 01, 2022) | |||
| 1-244841999-C-T | Mitochondrial complex 4 deficiency, nuclear type 11 | Pathogenic (Feb 04, 2022) | ||
| 1-244842006-G-T | Uncertain significance (Mar 23, 2022) | |||
| 1-244842008-A-G | Uncertain significance (May 27, 2022) | |||
| 1-244842010-G-A | Uncertain significance (Sep 16, 2018) | |||
| 1-244842016-T-C | Mitochondrial complex 4 deficiency, nuclear type 11 | Likely benign (Jan 17, 2022) | ||
| 1-244842028-G-T | Uncertain significance (Apr 24, 2023) | |||
| 1-244842036-C-T | Likely benign (Aug 17, 2023) | |||
| 1-244842055-A-C | Mitochondrial complex 4 deficiency, nuclear type 11 | Pathogenic (Jan 01, 2014) | ||
| 1-244842059-G-A | Likely pathogenic (Mar 30, 2016) | |||
| 1-244842061-G-C | Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial complex 4 deficiency, nuclear type 11 | Pathogenic/Likely pathogenic (Jan 26, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HNRNPU | protein_coding | protein_coding | ENST00000283179 | 14 | 13377 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000157 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.37 | 253 | 456 | 0.555 | 0.0000225 | 5414 |
| Missense in Polyphen | 12 | 39.76 | 0.30181 | 400 | ||
| Synonymous | -2.83 | 214 | 167 | 1.28 | 0.00000832 | 1527 |
| Loss of Function | 5.84 | 1 | 41.7 | 0.0240 | 0.00000219 | 504 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.000198 | 0.000198 |
| East Asian | 0.0000547 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000879 | 0.00000879 |
| Middle Eastern | 0.0000547 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: DNA- and RNA-binding protein involved in several cellular processes such as nuclear chromatin organization, telomere-length regulation, transcription, mRNA alternative splicing and stability, Xist-mediated transcriptional silencing and mitotic cell progression (PubMed:10490622, PubMed:18082603, PubMed:19029303, PubMed:22325991, PubMed:25986610, PubMed:28622508). Plays a role in the regulation of interphase large-scale gene-rich chromatin organization through chromatin- associated RNAs (caRNAs) in a transcription-dependent manner, and thereby maintains genomic stability (PubMed:1324173, PubMed:8174554, PubMed:28622508). Required for the localization of the long non-coding Xist RNA on the inactive chromosome X (Xi) and the subsequent initiation and maintenance of X-linked transcriptional gene silencing during X-inactivation (By similarity). Plays a role as a RNA polymerase II (Pol II) holoenzyme transcription regulator (PubMed:8174554, PubMed:9353307, PubMed:10490622, PubMed:15711563, PubMed:19617346, PubMed:23811339). Promotes transcription initiation by direct association with the core-TFIIH basal transcription factor complex for the assembly of a functional pre-initiation complex with Pol II in a actin-dependent manner (PubMed:10490622, PubMed:15711563). Blocks Pol II transcription elongation activity by inhibiting the C-terminal domain (CTD) phosphorylation of Pol II and dissociates from Pol II pre-initiation complex prior to productive transcription elongation (PubMed:10490622). Positively regulates CBX5-induced transcriptional gene silencing and retention of CBX5 in the nucleus (PubMed:19617346). Negatively regulates glucocorticoid-mediated transcriptional activation (PubMed:9353307). Key regulator of transcription initiation and elongation in embryonic stem cells upon leukemia inhibitory factor (LIF) signaling (By similarity). Involved in the long non-coding RNA H19-mediated Pol II transcriptional repression (PubMed:23811339). Participates in the circadian regulation of the core clock component ARNTL/BMAL1 transcription (By similarity). Plays a role in the regulation of telomere length (PubMed:18082603). Plays a role as a global pre-mRNA alternative splicing modulator by regulating U2 small nuclear ribonucleoprotein (snRNP) biogenesis (PubMed:22325991). Plays a role in mRNA stability (PubMed:17174306, PubMed:17289661, PubMed:19029303). Component of the CRD-mediated complex that promotes MYC mRNA stabilization (PubMed:19029303). Enhances the expression of specific genes, such as tumor necrosis factor TNFA, by regulating mRNA stability, possibly through binding to the 3'- untranslated region (UTR) (PubMed:17174306). Plays a role in mitotic cell cycle regulation (PubMed:21242313, PubMed:25986610). Involved in the formation of stable mitotic spindle microtubules (MTs) attachment to kinetochore, spindle organization and chromosome congression (PubMed:21242313). Phosphorylation at Ser- 59 by PLK1 is required for chromosome alignement and segregation and progression through mitosis (PubMed:25986610). Contributes also to the targeting of AURKA to mitotic spindle MTs (PubMed:21242313). Binds to double- and single-stranded DNA and RNA, poly(A), poly(C) and poly(G) oligoribonucleotides (PubMed:1628625, PubMed:8068679, PubMed:8174554, PubMed:9204873, PubMed:9405365). Binds to chromatin-associated RNAs (caRNAs) (PubMed:28622508). Associates with chromatin to scaffold/matrix attachment region (S/MAR) elements in a chromatin-associated RNAs (caRNAs)-dependent manner (PubMed:7509195, PubMed:1324173, PubMed:9204873, PubMed:9405365, PubMed:10671544, PubMed:11003645, PubMed:11909954, PubMed:28622508). Binds to the Xist RNA (PubMed:26244333). Binds the long non-coding H19 RNA (PubMed:23811339). Binds to SMN1/2 pre-mRNAs at G/U-rich regions (PubMed:22325991). Binds to small nuclear RNAs (snRNAs) (PubMed:22325991). Binds to the 3'-UTR of TNFA mRNA (PubMed:17174306). Binds (via RNA-binding RGG-box region) to the long non-coding Xist RNA; this binding is direct and bridges the Xist RNA and the inactive chromosome X (Xi) (By similarity). Also negatively regulates embryonic stem cell differentiation upon LIF signaling (By similarity). Required for embryonic development (By similarity). Binds to brown fat long non-coding RNA 1 (Blnc1); facilitates the recruitment of Blnc1 by ZBTB7B required to drive brown and beige fat development and thermogenesis (By similarity). {ECO:0000250|UniProtKB:Q8VEK3, ECO:0000269|PubMed:10490622, ECO:0000269|PubMed:10671544, ECO:0000269|PubMed:11003645, ECO:0000269|PubMed:11909954, ECO:0000269|PubMed:1324173, ECO:0000269|PubMed:15711563, ECO:0000269|PubMed:1628625, ECO:0000269|PubMed:17174306, ECO:0000269|PubMed:17289661, ECO:0000269|PubMed:18082603, ECO:0000269|PubMed:19029303, ECO:0000269|PubMed:19617346, ECO:0000269|PubMed:21242313, ECO:0000269|PubMed:22325991, ECO:0000269|PubMed:23811339, ECO:0000269|PubMed:25986610, ECO:0000269|PubMed:26244333, ECO:0000269|PubMed:28622508, ECO:0000269|PubMed:7509195, ECO:0000269|PubMed:8068679, ECO:0000269|PubMed:8174554, ECO:0000269|PubMed:9204873, ECO:0000269|PubMed:9353307, ECO:0000269|PubMed:9405365}.;
- Disease
- DISEASE: Epileptic encephalopathy, early infantile, 54 (EIEE54) [MIM:617391]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. {ECO:0000269|PubMed:23708187, ECO:0000269|PubMed:25356899}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.388
Intolerance Scores
- loftool
- 0.192
- rvis_EVS
- -0.6
- rvis_percentile_EVS
- 17.75
Haploinsufficiency Scores
- pHI
- 0.514
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.722
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.541
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hnrnpu
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; growth/size/body region phenotype; cellular phenotype; muscle phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;regulation of alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;osteoblast differentiation;chromatin organization;RNA processing;cell cycle;regulation of mitotic cell cycle;dosage compensation by inactivation of X chromosome;RNA metabolic process;negative regulation of telomere maintenance via telomerase;circadian regulation of gene expression;negative regulation of kinase activity;negative regulation of transcription elongation from RNA polymerase II promoter;positive regulation of transcription by RNA polymerase II;mRNA stabilization;cell division;maintenance of protein location in nucleus;cardiac muscle cell development;CRD-mediated mRNA stabilization;cellular response to glucocorticoid stimulus;positive regulation of brown fat cell differentiation;dendritic transport of messenger ribonucleoprotein complex;regulation of mitotic spindle assembly;regulation of chromatin organization;positive regulation of attachment of mitotic spindle microtubules to kinetochore;protein localization to spindle microtubule;RNA localization to chromatin;cellular response to leukemia inhibitory factor;adaptive thermogenesis;positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity;positive regulation of stem cell proliferation;negative regulation of stem cell differentiation
- Cellular component
- nuclear chromosome;kinetochore;condensed chromosome kinetochore;spindle pole;nucleus;nucleoplasm;telomerase holoenzyme complex;centrosome;cell surface;membrane;nuclear matrix;nuclear speck;midbody;dendrite cytoplasm;protein-containing complex;cytoplasmic ribonucleoprotein granule;CRD-mediated mRNA stability complex;catalytic step 2 spliceosome;mitotic spindle;RNA polymerase II transcription factor complex;inactive sex chromosome;mitotic spindle midzone;mitotic spindle microtubule;ribonucleoprotein complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II complex binding;TFIIH-class transcription factor complex binding;DNA binding;chromatin binding;double-stranded DNA binding;single-stranded DNA binding;transcription corepressor activity;RNA binding;double-stranded RNA binding;single-stranded RNA binding;mRNA 3'-UTR binding;actin binding;protein binding;ATP binding;poly(A) binding;snRNA binding;poly(C) RNA binding;chromatin DNA binding;poly(G) binding;pre-mRNA binding;identical protein binding;ribonucleoprotein complex binding;protein-containing complex binding;telomerase RNA binding;RNA polymerase II C-terminal domain binding;sequence-specific double-stranded DNA binding;promoter-specific chromatin binding