PIM3

Chr 22

Pim-3 proto-oncogene, serine/threonine kinase

Also known as: pim-3

NCBI Gene: 415116 ENSG00000198355 UniProt: Q86V86 OMIM: 610580

The PIM3 gene encodes a serine/threonine protein kinase that regulates cell survival, protein synthesis, and energy metabolism through phosphorylation of multiple targets including BAD and regulation of MYC transcriptional activity. PIM3 is highly constrained against loss-of-function variants in the general population, but pathogenic variants causing Mendelian disease have not been clearly established in clinical databases. The gene's role in preventing apoptosis and promoting cell survival suggests potential for developmental or neurological phenotypes if disease-causing variants are identified.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and PIM subfamily. This gene is overexpressed in hematological and epithelial tumors and is associated with MYC coexpression. It plays a role in the regulation of signal transduction cascades, contributing to both cell proliferation and survival, and provides a selective advantage in tumorigenesis. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

LOEUF 0.24

Clinical Summary— PIM3

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

39 VUS of 49 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.24LOEUF

pLI 0.982

Z-score 3.24

OE 0.00 (0.00–0.24)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.92Z-score

OE missense 0.81 (0.71–0.93)

151 obs / 186.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.24)

0≤0.351.4

Missense OE?0.81 (0.71–0.93)

0≤0.61.4

Synonymous OE?1.62

0≤1.21.6

LoF obs/exp: 0 / 12.2Missense obs/exp: 151 / 186.4Syn Z: -4.54

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

VUS39

Likely Benign1

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	39	0	39
Likely Benign	1	0	1
Benign	3	1	4
Total	43	1	44

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

View in ClinVar →

139 pathogenic / likely-pathogenic (of 149) ClinVar copy-number / structural variants overlap PIM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →