Ribosomal protein L3-like (RPL3L) was evaluated for autosomal recessive dilated cardiomyopathy (DCM). RPL3L encodes a 60S ribosomal protein involved in protein translation and is highly expressed in cardiac and skeletal muscle (Van Raay TJ et al; 1996 PMID: 8921388). The first study that associated RPL3L with dilated cardiomyopathy (DCM) was published in 2020. A cohort of 205 DCM cases from Saudi Arabia were screened by WES/WGS and a single case of neonatal DCM was found to be homozygous for RPL3L p.Arg116His (Hassnan et al. 2020; PMID: 32870709). In another study of neonatal DCM, RPL3L variants were detected in three cases: p.Asp308Val - p.Arg343Trp in trans (non-consanguineous family); Thr189Met - p.Asp308Asn in trans (consanguineous family) and p.Gly27Asp - Arg116His in trans (non-consanguineous family) (Ganapathi et al. 2020; PMID: 32514796). Nannapaneni et al. 2022 (PMID: 35323613) reported a case of neonatal DCM carrying p.Ala359GlyfsTer4 - p.Gly27Asp in trans (non-consanguineous family). Two more cases of neonatal DCM in non-consanguineous families carried p.Val231Phe - p.Ala51Thr in trans and p.Gly27Asp - p.Ala359fs*6 respectively (Das et al. 2022; PMID: 36291431 and Yang et al. 2023; PMID: 37308880). Grimes et al. 2023 (PMID: 36733907) generated Rpl3l gene-deleted mice with CRISPR-Cas to examine the role of this gene in the heart but Rpl3lā/ā mice showed no overt changes in cardiac structure or function at baseline or after pressure overload hypertrophy, possibly due to overexpression of another ribosomal gene, RPL3. Another study showed that in Rpl3l gene-deleted mice loss of RPL3L-ribosomes results in reduced cardiac contractility but no dilated cardiomyopathy phenotype was observed even under pressure overload (Shiraishi et al. 2023; PMID: 37080962). RPL3L gene expression in the human and mouse hearts was studied in Bajpai et al. 2023; PIMD: 38254943. Although functional study data linking RPL3L with DCM is limited at this point, the genetic evidence is strong enough to result in an overall classification of Moderate. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on May 30th, 2025 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.