PIM1
Pim-1 proto-oncogene, serine/threonine kinase
Basic information
Region (hg38): 6:37170152-37175428
Previous symbols: [ "PIM" ]
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 PIM1 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 | 1 | |||||
| missense | 4 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 1 | |||||
| Total | 0 | 0 | 3 | 1 | 2 |
Variants in PIM1
This is a list of pathogenic ClinVar variants found in the PIM1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-37170529-G-A | Benign (Aug 20, 2018) | |||
| 6-37170607-A-T | not specified | Uncertain significance (Feb 12, 2025) | ||
| 6-37170818-T-A | Neoplasm | - (-) | ||
| 6-37171022-GGGAGAGCTGGTGAGT-G | Neoplasm | - (-) | ||
| 6-37171277-C-G | not specified | Uncertain significance (Aug 01, 2024) | ||
| 6-37171363-A-G | not specified | Likely benign (Aug 20, 2024) | ||
| 6-37173123-C-T | Benign (Jul 18, 2018) | |||
| 6-37173163-G-A | not specified | Uncertain significance (Jan 07, 2025) | ||
| 6-37174072-C-T | not specified | Uncertain significance (Oct 24, 2023) | ||
| 6-37174075-C-A | not specified | Uncertain significance (Oct 10, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PIM1 | protein_coding | protein_coding | ENST00000373509 | 6 | 5224 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.848 | 0.151 | 125744 | 0 | 4 | 125748 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.96 | 109 | 184 | 0.593 | 0.00000911 | 2029 |
| Missense in Polyphen | 27 | 71.275 | 0.37881 | 813 | ||
| Synonymous | -1.77 | 101 | 80.8 | 1.25 | 0.00000424 | 621 |
| Loss of Function | 3.11 | 2 | 15.0 | 0.134 | 7.29e-7 | 155 |
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) | 0.0000268 | 0.0000264 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl- X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post- translational levels. Phosphorylation of CDKN1B,induces 14-3-3- proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis. {ECO:0000269|PubMed:10664448, ECO:0000269|PubMed:12431783, ECO:0000269|PubMed:15528381, ECO:0000269|PubMed:16356754, ECO:0000269|PubMed:1825810, ECO:0000269|PubMed:18593906, ECO:0000269|PubMed:19749799}.;
- Pathway
- AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Ectoderm Differentiation;Imatinib and Chronic Myeloid Leukemia;Interleukin-4 and 13 signaling;IL5-mediated signaling events;C-MYB transcription factor network;GMCSF-mediated signaling events;Validated targets of C-MYC transcriptional activation;Role of Calcineurin-dependent NFAT signaling in lymphocytes;IL3-mediated signaling events
(Consensus)
Recessive Scores
- pRec
- 0.264
Intolerance Scores
- loftool
- rvis_EVS
- 0.28
- rvis_percentile_EVS
- 71.27
Haploinsufficiency Scores
- pHI
- 0.636
- hipred
- Y
- hipred_score
- 0.831
- ghis
- 0.407
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pim1
- Phenotype
- growth/size/body region phenotype; hematopoietic system phenotype; normal phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- pim1
- Affected structure
- optokinetic behavior
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- protein phosphorylation;apoptotic process;cell cycle;multicellular organism development;cell population proliferation;cytokine-mediated signaling pathway;hyaluronan metabolic process;negative regulation of apoptotic process;negative regulation of DNA-binding transcription factor activity;protein autophosphorylation;positive regulation of cardiac muscle cell proliferation;vitamin D receptor signaling pathway;positive regulation of cardioblast proliferation
- Cellular component
- nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;plasma membrane
- Molecular function
- protein serine/threonine kinase activity;protein binding;ATP binding;transcription factor binding;manganese ion binding;ribosomal small subunit binding