RPL12

Chr 9

ribosomal protein L12

Also known as: L12, uL11

NCBI Gene: 6136 ENSG00000197958 UniProt: P30050 OMIM: 180475

This gene encodes a ribosomal protein that is a component of the large 60S ribosomal subunit and binds directly to 26S ribosomal RNA, functioning in cellular protein synthesis. Mutations cause autosomal dominant spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type, characterized by skeletal abnormalities including spine and growth plate involvement. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.793), suggesting some constraint on protein function.

OMIM ResearchSummary from RefSeq, UniProt

Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L11P family of ribosomal proteins. It is located in the cytoplasm. The protein binds directly to the 26S rRNA. This gene is co-transcribed with the U65 snoRNA, which is located in its fourth intron. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

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

0.79

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.053

Z-score 2.06

OE 0.35 (0.17–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.25Z-score

OE missense 0.63 (0.51–0.78)

56 obs / 89.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.17–0.79)

0≤0.351.4

Missense OE?0.63 (0.51–0.78)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 4 / 11.5Missense obs/exp: 56 / 89.3Syn Z: -1.06

Background carrier burden — how many people carry a rare variant somewhere in RPL12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 740

148 rare PASS variants

Rare truncating (LoF)

1 in 4,200

32 rare PASS variants

Rare synonymous (reference)

1 in 650

82 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RPL12. 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 800	1 in 3,700
South Asian	~43k	1 in 620	1 in 7,100
Remaining (unassigned)	~30k	1 in 700	1 in 5,000
European (Finnish)	~27k	1 in 420	≈ 1 in 8,800
Admixed American	~22k	1 in 400	≈ 1 in 7,000
African / African American	~21k	1 in 400	1 in 3,100
East Asian	~20k	1 in 560	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 770	none seen
Middle Eastern	~2,884	≈ 1 in 720	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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓