RPL3L

Chr 16AR

ribosomal protein L3 like

Also known as: CMD2D

NCBI Gene: 6123ENSG00000140986UniProt: Q92901

This gene encodes a protein that shares sequence similarity with ribosomal protein L3. The protein belongs to the L3P family of ribosomal proteins. Unlike the ubiquitous expression of ribosomal protein genes, this gene has a tissue-specific pattern of expression, with the highest levels of expression in skeletal muscle and heart. It is not currently known whether the encoded protein is a functional ribosomal protein or whether it has evolved a function that is independent of the ribosome. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2DMIM #619371
AR
190
ClinVar variants
46
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RPL3L
🧬
Gene-Disease Validity (ClinGen)
cardiomyopathy, dilated, 2D · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
46 Pathogenic / Likely Pathogenic· 131 VUS of 190 total submissions

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.
1.61LOEUF
pLI 0.000
Z-score -0.53
OE 1.13 (0.81–1.61)
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.
-0.69Z-score
OE missense 1.12 (1.02–1.23)
301 obs / 269.3 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 (0.81–1.61)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.12 (1.02–1.23)
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.1.31
0≤1.21.6
LoF obs/exp: 22 / 19.5Missense obs/exp: 301 / 269.3Syn Z: -2.58

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic2
VUS131
Likely Benign10
Benign1
Conflicting2
44
Pathogenic
2
Likely Pathogenic
131
VUS
10
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
5
39
0
44
Likely Pathogenic
0
1
1
0
2
VUS
2
107
22
0
131
Likely Benign
0
5
1
4
10
Benign
0
1
0
0
1
Conflicting
—2
Total2119634190

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

View in ClinVar →

Protein Context — Lollipop Plot

RPL3L · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cardiomyopathy, dilated, 2D

MIM #619371

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel compound heterozygous variants in the RPL3L gene causing dilated cardiomyopathy type-2D: a case report and literature review.
Yang Q et al.·BMC Med Genomics
2023Review
Pathogenetic mechanisms of muscle-specific ribosomes in dilated cardiomyopathy.
Murphy MR et al.·Nat Cardiovasc Res
2026Case report
Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy.
Al-Hassnan ZN et al.·Circ Genom Precis Med
2020
Novel Compound Heterozygous Missense Variants in RPL3L Gene Associated With Neonatal Dilated Cardiomyopathy.
Zhang X et al.·Am J Med Genet A
2026Case report
Bi-allelic missense disease-causing variants in RPL3L associate neonatal dilated cardiomyopathy with muscle-specific ribosome biogenesis.
Ganapathi M et al.·Hum Genet
2020
Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.
Cao J et al.·Alzheimers Dement
2025
Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.
Weng LC et al.·Circ Genom Precis Med
2020Meta-analysis
Genotypic and phenotypic characterization of critical pediatric cardiomyopathy: A 20-patient cohort study.
Xu Y et al.·Clin Chim Acta
2026Cohort
A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes.
Ren Y et al.·Front Public Health
2022Cohort
Whole exome sequencing reveals pathogenic variants in MYO3A, MYO15A and COL9A3 and differential frequencies in ancestral alleles in hearing impairment genes among individuals from Cameroon.
Wonkam A et al.·Hum Mol Genet
2021
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