PRMT5
protein arginine methyltransferase 5, the group of 7BS protein arginine methyltranferases
Basic information
Region (hg38): 14:22920525-22929408
Previous symbols: [ "HRMT1L5", "SKB1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
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 PRMT5 gene is commonly pathogenic or not.
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 | 3 | |||||
| missense | 23 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 2 | 2 | ||||
| non coding | 0 | |||||
| Total | 0 | 0 | 23 | 2 | 3 |
Variants in PRMT5
This is a list of pathogenic ClinVar variants found in the PRMT5 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 14-22920927-G-A | not specified | Uncertain significance (Dec 02, 2024) | ||
| 14-22920990-T-G | not specified | Uncertain significance (Dec 19, 2022) | ||
| 14-22920995-G-A | not specified | Uncertain significance (Dec 20, 2022) | ||
| 14-22922448-G-A | not specified | Uncertain significance (Dec 11, 2024) | ||
| 14-22922485-C-A | not specified | Uncertain significance (Mar 06, 2023) | ||
| 14-22922554-T-C | Likely benign (Dec 01, 2023) | |||
| 14-22922736-A-C | Likely benign (Nov 01, 2023) | |||
| 14-22923061-C-T | not specified | Uncertain significance (Jul 26, 2022) | ||
| 14-22923092-T-C | not specified | Uncertain significance (Sep 11, 2024) | ||
| 14-22924086-C-T | not specified | Uncertain significance (Mar 03, 2025) | ||
| 14-22924315-C-T | not specified | Uncertain significance (Oct 28, 2024) | ||
| 14-22924316-G-A | not specified | Uncertain significance (Jan 09, 2025) | ||
| 14-22924339-C-T | not specified | Uncertain significance (Dec 21, 2022) | ||
| 14-22924494-T-G | not specified | Uncertain significance (Feb 12, 2025) | ||
| 14-22924507-G-A | not specified | Uncertain significance (Dec 09, 2024) | ||
| 14-22924514-G-C | not specified | Uncertain significance (May 16, 2024) | ||
| 14-22924534-T-C | not specified | Uncertain significance (Oct 22, 2024) | ||
| 14-22924714-T-C | Likely benign (Nov 01, 2023) | |||
| 14-22926251-C-T | not specified | Uncertain significance (Dec 02, 2022) | ||
| 14-22926270-A-G | not specified | Uncertain significance (Aug 19, 2023) | ||
| 14-22926296-G-A | not specified | Uncertain significance (Dec 25, 2024) | ||
| 14-22926511-G-A | not specified | Uncertain significance (Dec 14, 2023) | ||
| 14-22926727-T-C | not specified | Uncertain significance (Oct 01, 2024) | ||
| 14-22926736-C-G | not specified | Likely benign (Sep 07, 2022) | ||
| 14-22927537-G-A | not specified | Uncertain significance (Apr 18, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PRMT5 | protein_coding | protein_coding | ENST00000324366 | 17 | 9075 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000559 | 125740 | 0 | 6 | 125746 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.03 | 210 | 375 | 0.560 | 0.0000208 | 4180 |
| Missense in Polyphen | 61 | 138.32 | 0.44101 | 1628 | ||
| Synonymous | 0.915 | 123 | 137 | 0.900 | 0.00000707 | 1241 |
| Loss of Function | 5.58 | 1 | 38.3 | 0.0261 | 0.00000196 | 415 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.0000998 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.000163 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine- activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development. Methylates histone H3 'Arg-8', which may repress transcription. Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain- containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21917714, PubMed:21258366). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM- 1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951). Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653). Acts as a transcriptional corepressor in CRY1- mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity). Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918). Symmetrically methylates NCL (PubMed:21081503). {ECO:0000250|UniProtKB:Q8CIG8, ECO:0000269|PubMed:10531356, ECO:0000269|PubMed:11152681, ECO:0000269|PubMed:11747828, ECO:0000269|PubMed:12411503, ECO:0000269|PubMed:12718890, ECO:0000269|PubMed:15737618, ECO:0000269|PubMed:17709427, ECO:0000269|PubMed:20159986, ECO:0000269|PubMed:20421892, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21081503, ECO:0000269|PubMed:21258366, ECO:0000269|PubMed:21917714, ECO:0000269|PubMed:22269951, ECO:0000269|PubMed:25092918, ECO:0000269|PubMed:25284789, ECO:0000269|PubMed:26700805}.;
- Pathway
- RNA transport - Homo sapiens (human);Gene expression (Transcription);Generic Transcription Pathway;snRNP Assembly;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Metabolism of RNA;Metabolism of non-coding RNA;Chromatin organization;Regulation of TP53 Activity through Methylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling events mediated by HDAC Class I;E2F transcription factor network;p53 pathway
(Consensus)
Recessive Scores
- pRec
- 0.315
Intolerance Scores
- loftool
- 0.159
- rvis_EVS
- -0.56
- rvis_percentile_EVS
- 19.54
Haploinsufficiency Scores
- pHI
- 0.561
- hipred
- Y
- hipred_score
- 0.840
- ghis
- 0.644
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Prmt5
- Phenotype
- growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- prmt5
- Affected structure
- slow muscle cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- spliceosomal snRNP assembly;DNA-templated transcription, termination;regulation of mitotic nuclear division;cell population proliferation;peptidyl-arginine methylation;peptidyl-arginine methylation, to symmetrical-dimethyl arginine;circadian regulation of gene expression;histone arginine methylation;peptidyl-arginine N-methylation;endothelial cell activation;histone H4-R3 methylation;regulation of DNA methylation;negative regulation of cell differentiation;positive regulation of oligodendrocyte differentiation;regulation of ERK1 and ERK2 cascade;Golgi ribbon formation;liver regeneration;regulation of signal transduction by p53 class mediator;negative regulation of nucleic acid-templated transcription;positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
- Cellular component
- nucleus;nucleoplasm;cytoplasm;Golgi apparatus;cytosol;methylosome;histone methyltransferase complex
- Molecular function
- transcription corepressor activity;protein binding;methyltransferase activity;methyl-CpG binding;histone-arginine N-methyltransferase activity;protein-arginine N-methyltransferase activity;protein-arginine omega-N symmetric methyltransferase activity;identical protein binding;ribonucleoprotein complex binding;histone methyltransferase activity (H4-R3 specific);protein heterodimerization activity;E-box binding