HNRNPA1
protein-codingheterogeneous nuclear ribonucleoprotein A1, the group of Heterogeneous nuclear ribonucleoproteins|RNA binding motif containing|Spliceosomal A complex
Gene summary
This gene encodes a member of a family of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs), which are RNA-binding proteins that associate with pre-mRNAs in the nucleus and influence pre-mRNA processing, as well as other aspects of mRNA metabolism and transport. The protein encoded by this gene is one of the most abundant core proteins of hnRNP complexes and plays a key role in the regulation of alternative splicing. Mutations in this gene have been observed in individuals with amyotrophic lateral sclerosis 20. Multiple alternatively spliced transcript variants have been found. There are numerous pseudogenes of this gene distributed throughout the genome. [provided by RefSeq, Feb 2016]
- HNRPA1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014179
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014181
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0004976
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0000507
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014181
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014179
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014181
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0014179
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal; Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HNRNPA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031157.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 23 | 23 | ||||
| missense | 3 | 16 | 42 | 8 | 69 | |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 4 | 16 | 51 | 31 | 0 | 102 |
Highest pathogenic variant AF is 0.000013137842
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_112420.1 | 10 | MANE Select | |
| Ensembl | ENSP00000341826.7 | 10 | MANE Select | |
| RefSeq | NP_002127.1 | 9 | Standard | |
| Ensembl | ENSP00000333504.8 | 9 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Spliceosome - Homo sapiens (human)
- mRNA Processing
- FGFR2 alternative splicing
- Signaling by FGFR2
- Signal Transduction
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
Molecular Function
- single-stranded DNA binding
- RNA binding
- single-stranded RNA binding
- mRNA binding
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- spliceosomal complex
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340913
- Coding exons
- 10
- Length
- 6896
- Individuals with no LoFs
- 124728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 124729
- p
- 0.00000401
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.82 | 94 | 209 | 0.450 | 0.0000102 | 2439 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00026 | 0.000065 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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.;
Intolerance Scores
- LoFtool
- 0.220
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |