HNRNPA1
heterogeneous nuclear ribonucleoprotein A1, the group of Heterogeneous nuclear ribonucleoproteins|RNA binding motif containing|Spliceosomal A complex
Basic information
Region (hg38): 12:54280193-54287088
Previous symbols: [ "HNRPA1" ]
Links
Phenotypes
GenCC
Source:
- inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis type 20 (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
- inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Supportive), mode of inheritance: AD
- amyotrophic lateral sclerosis type 20 (Strong), mode of inheritance: AD
- inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong), mode of inheritance: AD
- inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amyotrophic lateral sclerosis 20; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3; Myopathy, distal, 3 | AD | 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 | Musculoskeletal; Neurologic | 20116073; 23455423; 34722876 |
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPA1 gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.
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 | 9 | |||||
| missense | 26 | 30 | ||||
| nonsense | 1 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 3 | 30 | 10 | 0 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| HNRNPA1 | protein_coding | protein_coding | ENST00000340913 | 10 | 6896 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.000888 | 124728 | 0 | 1 | 124729 | 0.00000401 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.82 | 94 | 209 | 0.450 | 0.0000102 | 2439 |
| Missense in Polyphen | 6 | 42.627 | 0.14076 | 619 | ||
| Synonymous | -1.19 | 87 | 74.0 | 1.18 | 0.00000373 | 700 |
| Loss of Function | 4.18 | 0 | 20.3 | 0.00 | 0.00000105 | 248 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000258 | 0.0000646 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection (PubMed:17371836). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:28431233}.;
- Disease
- DISEASE: Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (IBMPFD3) [MIM:615424]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. {ECO:0000269|PubMed:23455423}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amyotrophic lateral sclerosis 20 (ALS20) [MIM:615426]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:23455423, ECO:0000269|PubMed:27694260}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Spliceosome - Homo sapiens (human);mRNA Processing;FGFR2 alternative splicing;Signaling by FGFR2;Signal Transduction;Signaling by FGFR;Metabolism of RNA;mRNA Splicing - Major Pathway;EGFR1;Coregulation of Androgen receptor activity;IL6;Signaling by Receptor Tyrosine Kinases;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Intolerance Scores
- loftool
- 0.220
- rvis_EVS
- -0.19
- rvis_percentile_EVS
- 39.68
Haploinsufficiency Scores
- pHI
- 0.806
- hipred
- Y
- hipred_score
- 0.712
- ghis
- 0.655
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Hnrnpa1
- Phenotype
- growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; 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); 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); digestive/alimentary phenotype; renal/urinary system phenotype;
Gene ontology
- Biological process
- regulation of alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;RNA export from nucleus;fibroblast growth factor receptor signaling pathway;viral process;RNA metabolic process;negative regulation of telomere maintenance via telomerase;positive regulation of telomere maintenance via telomerase;cellular response to glucose starvation;mRNA transport;nuclear export;import into nucleus;cellular response to sodium arsenite
- Cellular component
- nucleus;nucleoplasm;spliceosomal complex;cytoplasm;membrane;extracellular exosome;catalytic step 2 spliceosome;ribonucleoprotein complex
- Molecular function
- single-stranded DNA binding;RNA binding;single-stranded RNA binding;mRNA binding;protein binding;protein domain specific binding;miRNA binding;pre-mRNA binding;telomeric repeat-containing RNA binding;G-rich strand telomeric DNA binding