PIM1

Chr 6

Pim-1 proto-oncogene, serine/threonine kinase

Also known as: PIM

NCBI Gene: 5292ENSG00000137193UniProt: P11309

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. It plays a role in signal transduction in blood cells, contributing to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Both the human and orthologous mouse genes have been reported to encode two isoforms (with preferential cellular localization) resulting from the use of alternative in-frame translation initiation codons, the upstream non-AUG (CUG) and downstream AUG codons (PMIDs:16186805, 1825810).[provided by RefSeq, Aug 2011]

18
ClinVar variants
6
Pathogenic / LP
0.85
pLI score
0
Active trials
Clinical Summary— PIM1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 9 VUS of 18 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.42LOEUF
pLI 0.848
Z-score 3.11
OE 0.13 (0.05–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.96Z-score
OE missense 0.59 (0.51–0.69)
109 obs / 183.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.05–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.51–0.69)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 2 / 15.0Missense obs/exp: 109 / 183.8Syn Z: -1.77

ClinVar Variant Classifications

18 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS9
Likely Benign1
Benign2
6
Pathogenic
9
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
9
0
0
9
Likely Benign
0
1
0
0
1
Benign
0
1
0
1
2
Total0116118

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ONCOGENE PIM 1; PIM1
MIM #164960 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PIM1 instigates endothelial-to-mesenchymal transition to aggravate atherosclerosis.
Xue Z et al.·Theranostics
2025
Simplified algorithm for genetic subtyping in diffuse large B-cell lymphoma.
Shen R et al.·Signal Transduct Target Ther
2023
Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis.
Li H et al.·Nat Commun
2022
PROTACs as Therapeutic Modalities for Drug Discovery in Castration-Resistant Prostate Cancer.
Wang LY et al.·Annu Rev Pharmacol Toxicol
2025Review
Targeting PIM1 by Bruceine D attenuates skin fibrosis via myofibroblast ferroptosis.
Wang J et al.·Redox Biol
2025
Efficacy and Safety of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone for Previously Untreated Diffuse Large B-Cell Lymphoma: A Real-World, Multi-Center, Retrospective Cohort Study.
Zhao P et al.·Hematol Oncol
2025Cohort
PIM1 kinase and its diverse substrate in solid tumors.
Choudhury R et al.·Cell Commun Signal
2024Review
Histone deacetylases facilitate Th17-cell differentiation and pathogenicity in autoimmune uveitis via CDK6/ID2 axis.
Zhang C et al.·J Adv Res
2025
Myeloid-Derived Growth Factor Protects Against Pressure Overload-Induced Heart Failure by Preserving Sarco/Endoplasmic Reticulum Ca(2+)-ATPase Expression in Cardiomyocytes.
Korf-Klingebiel M et al.·Circulation
2021
High-grade B-cell lymphoma not otherwise specified, with diffuse large B-cell lymphoma gene expression signatures: Genomic analysis and potential therapeutics.
Lone W et al.·Am J Hematol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools