HNRNPL
protein-codingheterogeneous nuclear ribonucleoprotein L, the group of RNA binding motif containing|Heterogeneous nuclear ribonucleoproteins
Gene summary
Heterogeneous nuclear RNAs (hnRNAs) which include mRNA precursors and mature mRNAs are associated with specific proteins to form heterogenous ribonucleoprotein (hnRNP) complexes. Heterogeneous nuclear ribonucleoprotein L is among the proteins that are stably associated with hnRNP complexes and along with other hnRNP proteins is likely to play a major role in the formation, packaging, processing, and function of mRNA. Heterogeneous nuclear ribonucleoprotein L is present in the nucleoplasm as part of the HNRP complex. HNRP proteins have also been identified outside of the nucleoplasm. Exchange of hnRNP for mRNA-binding proteins accompanies transport of mRNA from the nucleus to the cytoplasm. Since HNRP proteins have been shown to shuttle between the nucleus and the cytoplasm, it is possible that they also have cytoplasmic functions. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- HNRPL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to HNRNPL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001533.3. 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 | 1 | 3 | 4 | |||
| missense | 58 | 58 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 68 | 1 | 3 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001524.2 | 13 | MANE Select | |
| Ensembl | ENSP00000221419.4 | 13 | MANE Select | |
| RefSeq | NP_001005335.1 | 11 | Standard | |
| RefSeq | NP_001372580.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mRNA Processing
- Metabolism of RNA
- mRNA Splicing - Major Pathway
- mRNA Splicing
- Processing of Capped Intron-Containing Pre-mRNA
Biological Process
- regulation of alternative mRNA splicing, via spliceosome
- mRNA splicing, via spliceosome
- RNA processing
- circadian rhythm
- RNA metabolic process
Molecular Function
- RNA binding
- mRNA 3'-UTR binding
- protein binding
- transcription regulatory region DNA binding
- pre-mRNA intronic binding
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- membrane
- ribonucleoprotein granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000221419
- Coding exons
- 13
- Length
- 15960
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.54 | 144 | 323 | 0.446 | 0.0000184 | 3809 |
| Missense (PolyPhen) | 25 | 96.315 | 0.25957 | 1179 | ||
| Synonymous | -4.72 | 197 | 129 | 1.53 | 0.00000822 | 1137 |
| Loss of Function | 4.34 | 2 | 25.8 | 0.0776 | 0.00000118 | 322 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| 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: Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts (PubMed:2687284). Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter (PubMed:11809897). {ECO:0000269|PubMed:11809897, ECO:0000269|PubMed:22570490, ECO:0000269|PubMed:25623890, ECO:0000269|PubMed:26051023, ECO:0000269|PubMed:2687284}.;
Intolerance Scores
- RVIS EVS
- -0.63
- RVIS percentile EVS
- 17.03
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |