RPS6KB2

Chr 11

ribosomal protein S6 kinase B2

Also known as: KLS, P70-beta, P70-beta-1, P70-beta-2, S6K-beta2, S6K2, S6KB, S6KI(2)

NCBI Gene: 6199 ENSG00000175634 UniProt: Q9UBS0 OMIM: 608939

This gene encodes a serine/threonine kinase that phosphorylates ribosomal protein S6 and eukaryotic translation initiation factor 4B, promoting protein synthesis and cell proliferation downstream of mTOR signaling. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows very low constraint against loss-of-function variants in the population.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.54

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.20Z-score

OE missense 1.03 (0.94–1.13)

316 obs / 305.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.84–1.54)

0≤0.351.4

Missense OE?1.03 (0.94–1.13)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 29 / 25.6Missense obs/exp: 316 / 305.9Syn Z: -1.67

Background carrier burden — how many people carry a rare variant somewhere in RPS6KB2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 68

753 rare PASS variants

Rare truncating (LoF)

1 in 450

159 rare PASS variants

Rare synonymous (reference)

1 in 180

313 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPS6KB2. 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 94	1 in 420
South Asian	~43k	1 in 61	1 in 460
Remaining (unassigned)	~30k	1 in 61	1 in 540
European (Finnish)	~27k	1 in 250	1 in 1,700
Admixed American	~22k	1 in 54	1 in 510
African / African American	~21k	1 in 56	1 in 980
East Asian	~20k	1 in 54	1 in 320
Ashkenazi Jewish	~13k	1 in 1,300	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 52	1 in 320

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): All 15 coding exons well covered in gnomAD exomes and genomes.? see exons ↓