RPL3L

Chr 16AR

ribosomal protein L3 like

Also known as: CMD2D

NCBI Gene: 6123 ENSG00000140986 UniProt: Q92901 OMIM: 617416

This protein is a heart- and skeletal muscle-specific ribosomal component that replaces the standard RPL3 paralog in striated muscle cells and regulates muscle function by inhibiting myotube growth. Mutations cause autosomal recessive dilated cardiomyopathy, primarily affecting cardiac muscle with potential involvement of skeletal muscle given the protein's tissue distribution. The gene shows low constraint against loss-of-function variants, consistent with its tissue-restricted expression pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

ARLOEUF 1.611 OMIM phenotype

Clinical Summary— RPL3L

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Gene-Disease Validity (ClinGen)

cardiomyopathy, dilated, 2D · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

7 unique Pathogenic / Likely Pathogenic· 117 VUS of 139 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

-0.69Z-score

OE missense 1.12 (1.02–1.23)

301 obs / 269.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.81–1.61)

0≤0.351.4

Missense OE?1.12 (1.02–1.23)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 22 / 19.5Missense obs/exp: 301 / 269.3Syn Z: -2.58

ClinVar Variant Classifications

139 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic2

VUS117

Likely Benign9

Benign1

Conflicting2

Pathogenic

Likely Pathogenic

117

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	5	0	0	5
Likely Pathogenic	1	1	0	0	2
VUS	5	110	2	0	117
Likely Benign	0	5	0	4	9
Benign	0	1	0	0	1
Conflicting	—				2
Total	6	122	2	4	136

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap RPL3L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →