RPL12

Chr 9

ribosomal protein L12

Also known as: L12, uL11

NCBI Gene: 6136ENSG00000197958UniProt: P30050OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.79
Clinical Summary— RPL12
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 19 VUS of 70 total submissions
Explore recent and relevant literature in Research Assistant →

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 OE0.35 (0.17–0.79)
0≤0.351.4
Missense OE0.63 (0.51–0.78)
0≤0.61.4
Synonymous OE1.24
0≤1.21.6
LoF obs/exp: 4 / 11.5Missense obs/exp: 56 / 89.3Syn Z: -1.06
DN
0.7035th %ile
GOF
0.3491th %ile
LOF
0.4234th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

70 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic1
VUS19
Likely Benign1
34
Pathogenic
1
Likely Pathogenic
19
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
1
0
1
VUS
0
17
2
0
19
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total01738055

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL12 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients