PABPN1
poly(A) binding protein nuclear 1, the group of RNA binding motif containing
Basic information
Region (hg38): 14:23321457-23326163
Previous symbols: [ "OPMD", "PABP2" ]
Links
Phenotypes
GenCC
Source:
- oculopharyngeal muscular dystrophy (Definitive), mode of inheritance: AD
- oculopharyngeal muscular dystrophy (Strong), mode of inheritance: AD
- oculopharyngeal muscular dystrophy (Supportive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Oculopharyngeal muscular dystrophy 1 | AD/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 | Musculoskeletal | 13997067; 13963574; 9462747; 11712939; 15725589; 15694141; 16648376; 20301305; 21647273; 21742497; 21956377; 22817818 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (28 variants)
- Oculopharyngeal_muscular_dystrophy_1 (25 variants)
- Inborn_genetic_diseases (24 variants)
- not_specified (6 variants)
- Oculopharyngeal_muscular_dystrophy (5 variants)
- PABPN1-related_disorder (3 variants)
- BCL2L2-PABPN1-related_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PABPN1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004643.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | |||||
| missense | 39 | 41 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 42 | 6 | 1 |
Highest pathogenic variant AF is 0.00047820935
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PABPN1 | protein_coding | protein_coding | ENST00000216727 | 7 | 4897 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.392 | 0.606 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 89 | 152 | 0.587 | 0.00000935 | 1926 |
| Missense in Polyphen | 14 | 48.164 | 0.29067 | 511 | ||
| Synonymous | -1.85 | 74 | 56.4 | 1.31 | 0.00000294 | 650 |
| Loss of Function | 2.67 | 3 | 13.6 | 0.220 | 8.64e-7 | 164 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000264 | 0.0000264 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product (By similarity). Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length (By similarity). Increases the affinity of poly(A) polymerase for RNA (By similarity). Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense- mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes (PubMed:11371506). Binds to poly(A) and to poly(G) with high affinity (By similarity). May protect the poly(A) tail from degradation (By similarity). Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). {ECO:0000250|UniProtKB:Q28165, ECO:0000269|PubMed:11371506, ECO:0000269|PubMed:27871484}.;
- Disease
- DISEASE: Oculopharyngeal muscular dystrophy (OPMD) [MIM:164300]: A form of late-onset slowly progressive myopathy characterized by eyelid ptosis, dysphagia and, sometimes by other cranial and limb- muscle involvement. {ECO:0000269|PubMed:12673802}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Influenza A - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);mRNA Processing;Disease;Gene expression (Transcription);polyadenylation of mrna;NS1 Mediated Effects on Host Pathways;Host Interactions with Influenza Factors;Influenza Infection;RNA Polymerase II Transcription;Metabolism of RNA;Processing of Intronless Pre-mRNAs;Processing of Capped Intronless Pre-mRNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;Infectious disease;mRNA Splicing - Major Pathway;Inhibition of Host mRNA Processing and RNA Silencing;mRNA Splicing;mRNA 3,-end processing;Processing of Capped Intron-Containing Pre-mRNA
(Consensus)
Recessive Scores
- pRec
- 0.272
Haploinsufficiency Scores
- pHI
- 0.0519
- hipred
- Y
- hipred_score
- 0.626
- ghis
- 0.403
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.915
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pabpn1
- Phenotype
- muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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);
Gene ontology
- Biological process
- MAPK cascade;mRNA splicing, via spliceosome;termination of RNA polymerase II transcription;RNA processing;muscle contraction;poly(A)+ mRNA export from nucleus;mRNA 3'-end processing;modification by virus of host mRNA processing;cellular response to lipopolysaccharide;positive regulation of polynucleotide adenylyltransferase activity
- Cellular component
- nucleus;nucleoplasm;cytoplasm;nuclear speck;nuclear inclusion body;ribonucleoprotein complex
- Molecular function
- RNA binding;protein binding;RNA polymerase binding