PUM1
pumilio RNA binding family member 1, the group of Small nucleolar RNA protein coding host genes|Pumilio homology domain containing
Basic information
Region (hg38): 1:30931506-31065991
Links
Phenotypes
GenCC
Source:
- spinocerebellar ataxia 47 (Limited), mode of inheritance: AD
- spinocerebellar ataxia 47 (Moderate), mode of inheritance: AD
- neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Spinocerebellar ataxia 47; Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism | 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 | Craniofacial; Genitourinary; Musculoskeletal; Neurologic | 29474920; 30903679; 31859446; 35386260 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (164 variants)
- Inborn_genetic_diseases (68 variants)
- Spinocerebellar_ataxia_47 (33 variants)
- PUM1-related_disorder (26 variants)
- PUM1-associated_developmental_disability-ataxia-seizure_syndrome (9 variants)
- not_specified (7 variants)
- Intellectual_disability (2 variants)
- Neurodevelopmental_disorder (1 variants)
- Global_developmental_delay (1 variants)
- Neurodevelopmental_delay (1 variants)
- See_cases (1 variants)
- Hereditary_breast_ovarian_cancer_syndrome (1 variants)
- Late-onset_spinocerebellar_ataxia (1 variants)
- Spastic_ataxia (1 variants)
- Seizure (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001020658.2. 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 | 18 | 23 | ||||
| missense | 199 | 14 | 220 | |||
| nonsense | 10 | |||||
| start loss | 0 | |||||
| frameshift | 7 | |||||
| splice donor/acceptor (+/-2bp) | 3 | |||||
| Total | 9 | 14 | 205 | 32 | 3 |
Highest pathogenic variant AF is 0.00000209778
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PUM1 | protein_coding | protein_coding | ENST00000426105 | 21 | 134486 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 4.47e-8 | 125743 | 0 | 5 | 125748 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 4.42 | 361 | 687 | 0.525 | 0.0000389 | 7728 |
| Missense in Polyphen | 69 | 212.92 | 0.32406 | 2412 | ||
| Synonymous | 0.424 | 257 | 266 | 0.967 | 0.0000164 | 2401 |
| Loss of Function | 6.82 | 3 | 60.0 | 0.0500 | 0.00000325 | 645 |
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 | 0.0000463 | 0.0000462 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:21572425, PubMed:18328718, PubMed:21653694, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA- binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding for regulators of p53/TP53. Involved in embryonic stem cell renewal by facilitating the exit from the ground state: acts by targeting mRNAs coding for naive pluripotency transcription factors and accelerates their down-regulation at the onset of differentiation (By similarity). Binds specifically to miRNA MIR199A precursor, with PUM2, regulates miRNA MIR199A expression at a postranscriptional level (PubMed:28431233). {ECO:0000250|UniProtKB:Q80U78, ECO:0000269|PubMed:18328718, ECO:0000269|PubMed:18776931, ECO:0000269|PubMed:20818387, ECO:0000269|PubMed:20860814, ECO:0000269|PubMed:21397187, ECO:0000269|PubMed:21572425, ECO:0000269|PubMed:21653694, ECO:0000269|PubMed:22345517, ECO:0000269|PubMed:22955276, ECO:0000269|PubMed:25340845, ECO:0000269|PubMed:25768905, ECO:0000269|PubMed:26724866, ECO:0000269|PubMed:28431233, ECO:0000269|PubMed:29474920}.;
- Disease
- DISEASE: Spinocerebellar ataxia 47 (SCA47) [MIM:617931]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA47 is an autosomal dominant disease with a highly variable phenotype and incomplete penetrance. Clinical features include developmental disability, ataxia, and seizures. {ECO:0000269|PubMed:29474920}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking
(Consensus)
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- loftool
- 0.229
- rvis_EVS
- -1.02
- rvis_percentile_EVS
- 8.1
Haploinsufficiency Scores
- pHI
- 0.362
- hipred
- Y
- hipred_score
- 0.662
- ghis
- 0.621
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- 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
- Pum1
- Phenotype
- cellular phenotype; endocrine/exocrine gland 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); reproductive system phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- spermatogenesis;adult locomotory behavior;posttranscriptional regulation of gene expression;posttranscriptional gene silencing;production of miRNAs involved in gene silencing by miRNA;regulation of mRNA stability;stem cell differentiation;regulation of cell cycle;regulation of chromosome segregation;regulation of gene silencing by miRNA;mRNA destabilization;positive regulation of RIG-I signaling pathway;positive regulation of gene silencing by miRNA
- Cellular component
- P-body;nucleus;nucleoplasm;cytosol;cytoplasmic stress granule;nuclear speck
- Molecular function
- RNA binding;mRNA 3'-UTR binding;protein binding;miRNA binding