RPS6KB2

Chr 11

ribosomal protein S6 kinase B2

NCBI Gene: 6199ENSG00000175634UniProt: Q9UBS0

Phosphorylates specifically ribosomal protein S6 (PubMed:29750193). Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7 (PubMed:29750193)

107
ClinVar variants
11
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RPS6KB2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 92 VUS of 107 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.54LOEUF
pLI 0.000
Z-score -0.62
OE 1.13 (0.84–1.54)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.20Z-score
OE missense 1.03 (0.94–1.13)
316 obs / 305.9 exp
Tolerant

Tolerant to missense variation

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.1.13 (0.84–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.94–1.13)
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.1.19
0≤1.21.6
LoF obs/exp: 29 / 25.6Missense obs/exp: 316 / 305.9Syn Z: -1.67

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic2
VUS92
Likely Benign3
Benign1
9
Pathogenic
2
Likely Pathogenic
92
VUS
3
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
2
0
2
VUS
0
87
5
0
92
Likely Benign
0
0
2
1
3
Benign
0
0
1
0
1
Total087191107

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

View in ClinVar →

Protein Context — Lollipop Plot

RPS6KB2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Altered gene expression and PTSD symptom dimensions in World Trade Center responders.
Marchese S et al.·Mol Psychiatry
2022Meta-analysis
USF1-induced RPS6KB2 activation influences aggressive phenotype in B-cell non-Hodgkin lymphoma.
Liu Z et al.·Hum Cell
2025
Identification of Drug-Targetable Genes for Eczema and Dermatitis Using Integrated Genomic and Proteomic Approaches.
Yang S et al.·Dermatitis
2025Meta-analysis
Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report.
Ferrari A et al.·Genes (Basel)
2023Case report
Genetic alterations in cell cycle regulation-associated genes may promote primary progression of gastrointestinal stromal tumors.
Li P et al.·Lab Invest
2020
Genetic variants in the mTOR pathway and breast cancer risk in African American women.
Cheng TD et al.·Carcinogenesis
2016
Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition.
Rodríguez-Cortez VC et al.·Nat Commun
2015
NRF1 motif sequence-enriched genes involved in ER/PR -ve HER2 +ve breast cancer signaling pathways.
Ramos J et al.·Breast Cancer Res Treat
2018
Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers.
Sun Z et al.·BMC Med Genomics
2014
Upregulation of long noncoding RNA AP003419.16 predicts high risk of aging‑associated idiopathic pulmonary fibrosis.
Hao X et al.·Mol Med Rep
2017
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