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…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.24

LOEUF· LoF intol.

—

Mechanism

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

Background carrier burden — how many people carry a rare variant somewhere in PIM3?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

521 rare PASS variants

Rare truncating (LoF)

1 in 4,900

52 rare PASS variants

Rare synonymous (reference)

1 in 150

355 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIM3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 180	1 in 8,900
South Asian	~43k	1 in 280	1 in 4,000
Remaining (unassigned)	~30k	1 in 110	1 in 2,700
European (Finnish)	~26k	1 in 280	1 in 4,700
Admixed American	~22k	1 in 140	1 in 3,700
African / African American	~21k	1 in 180	1 in 240
East Asian	~20k	1 in 240	≈ 1 in 12,000
Ashkenazi Jewish	~13k	1 in 640	none seen
Middle Eastern	~2,884	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 3 of 6 coding exons well covered in gnomAD exomes; exons 1, 2, 3 marginal. Genomes: all 6.? see exons ↓