RPL39L

Summary

RPL39L (ribosomal protein L39 like, HGNC:17094) is a protein-coding gene on chromosome 3q27.3, encoding Ribosomal protein eL39-like 2 (Q96EH5). Male germ cell-specific component of the ribosome, which is required for the formation of sperm and male fertility.

This gene encodes a protein sharing high sequence similarity with ribosomal protein L39. Although the name of this gene has been referred to as ‘ribosomal protein L39’ in the public databases, its official name is ‘ribosomal protein L39-like’. 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.

Source: NCBI Gene 116832 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 7 total
• MANE Select transcript: NM_052969

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17094
Approved symbol	RPL39L
Name	ribosomal protein L39 like
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163923
Ensembl biotype	protein_coding
OMIM	607547
Entrez	116832

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 16 protein_coding

ENST00000296277, ENST00000433055, ENST00000455270, ENST00000897301, ENST00000897302, ENST00000925622, ENST00000925623, ENST00000925624, ENST00000925625, ENST00000925626, ENST00000925627, ENST00000925628, ENST00000925629, ENST00000925630, ENST00000925631, ENST00000925632

RefSeq mRNA: 1 — MANE Select: NM_052969 NM_052969

CCDS: CCDS3286

Canonical transcript exons

ENST00000296277 — 3 exons

Exon	Start	End
ENSE00001079662	187139213	187139496
ENSE00001512066	187127999	187128062
ENSE00001768362	187120948	187121328

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.5395 / max 319.8193, expressed in 1647 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45991	12.1893	1601
45990	5.2906	1265
45988	0.8052	366
45989	0.2544	131

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.88	gold quality
right testis	UBERON:0004534	98.85	gold quality
testis	UBERON:0000473	97.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.25	gold quality
ventricular zone	UBERON:0003053	89.22	gold quality
ganglionic eminence	UBERON:0004023	89.20	gold quality
ascending aorta	UBERON:0001496	88.20	gold quality
thoracic aorta	UBERON:0001515	88.10	gold quality
descending thoracic aorta	UBERON:0002345	87.65	gold quality
adult organism	UBERON:0007023	86.76	gold quality
aorta	UBERON:0000947	86.30	gold quality
left coronary artery	UBERON:0001626	85.48	gold quality
popliteal artery	UBERON:0002250	85.19	gold quality
tibial artery	UBERON:0007610	85.19	gold quality
right coronary artery	UBERON:0001625	85.11	gold quality
coronary artery	UBERON:0001621	84.23	gold quality
cortical plate	UBERON:0005343	84.19	gold quality
stromal cell of endometrium	CL:0002255	83.64	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.91	gold quality
left uterine tube	UBERON:0001303	81.90	gold quality
right atrium auricular region	UBERON:0006631	81.16	gold quality
skin of abdomen	UBERON:0001416	80.97	gold quality
embryo	UBERON:0000922	80.86	gold quality
ectocervix	UBERON:0012249	80.70	gold quality
endocervix	UBERON:0000458	80.66	gold quality
skin of leg	UBERON:0001511	80.48	gold quality
sperm	CL:0000019	80.31	gold quality
cardiac atrium	UBERON:0002081	79.87	gold quality
male germ cell	CL:0000015	79.79	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	199.06
E-GEOD-134144	yes	31.34
E-HCAD-13	yes	21.13
E-MTAB-9388	yes	10.99
E-ANND-3	yes	4.76
E-MTAB-6524	no	193.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

4 targeting RPL39L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-144-5P	97.66	69.90	531

Literature-anchored findings (GeneRIF, showing 4)

• locus, structure and expression of the gene and its relevance to the biological activities of the ribosome (PMID:12359333)
• Results show the RP paralog Rpl39l is highly expressed in Embryonic Stem Cells and its expression strongly correlates with hepatocellular carcinoma tumor (HCC) samples with high tumor grading and alpha-fetoprotein level giving it diagnostic potential. (PMID:24452241)
• The ribosomal protein L39-L gene may have effects on the drug resistance mechanism of lung cancer A549 cells. (PMID:24815453)
• High RPL39L expression is associated with drug-resistant lacrimal gland adenoid cystic carcinoma. (PMID:24998577)

Cross-species orthologs

0 orthologs

Paralogs (1): RPL39 (ENSG00000198918)

Protein

Protein identifiers

Ribosomal protein eL39-like 2 — Q96EH5 (reviewed: Q96EH5)

Alternative names: 60S ribosomal protein L39-2, 60S ribosomal protein L39-like, Large ribosomal subunit protein eL39-like

All UniProt accessions (1): Q96EH5

UniProt curated annotations — full annotation on UniProt →

Function. Male germ cell-specific component of the ribosome, which is required for the formation of sperm and male fertility. Replaces the RPL39 paralog in the ribosome of male germ cells. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The male germ cell-specific ribosome displays a ribosomal polypeptide exit tunnel of distinct size and charge states compared with the classical ribosome. It is responsible for regulating the biosynthesis and folding of a subset of male germ-cell-specific proteins that are essential for the formation of sperm.

Subunit / interactions. Component of a male germ cell-specific 60S large ribosomal subunit (LSU), which contains RPL10L and RPL39L, instead of RPL10 and RPL39 paralogs. The composition of the rest of the complex is similar to classical ribosomes.

Subcellular location. Cytoplasm.

Tissue specificity. Testis specific.

Similarity. Belongs to the eukaryotic ribosomal protein eL39 family.

RefSeq proteins (1): NP_443201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000077	Ribosomal_eL39	Family
IPR020083	Ribosomal_eL39_CS	Conserved_site
IPR023626	Ribosomal_eL39_dom_sf	Homologous_superfamily

Pfam: PF00832

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EH5-F1	93.99	0.93

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-156827	L13a-mediated translational silencing of Ceruloplasmin expression
R-HSA-156902	Peptide chain elongation
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-192823	Viral mRNA Translation
R-HSA-2408557	Selenocysteine synthesis
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72706	GTP hydrolysis and joining of the 60S ribosomal subunit
R-HSA-72764	Eukaryotic Translation Termination
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-9633012	Response of EIF2AK4 (GCN2) to amino acid deficiency
R-HSA-975956	Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-9954709	Ribosome Quality Control (RQC) complex extracts and degrades nascent peptide
R-HSA-9954714	PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA
R-HSA-9954716	ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA

MSigDB gene sets: 148 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, TSENG_IRS1_TARGETS_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_TRANSLATION, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, MODULE_99, FISCHER_DREAM_TARGETS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, WANG_PROSTATE_CANCER_ANDROGEN_INDEPENDENT, REACTOME_METABOLISM_OF_RNA, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, NUYTTEN_EZH2_TARGETS_DN, GOCC_CYTOSOLIC_LARGE_RIBOSOMAL_SUBUNIT, LIN_APC_TARGETS

GO Biological Process (2): translation (GO:0006412), spermatogenesis (GO:0007283)

GO Molecular Function (2): structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (4): cytosolic large ribosomal subunit (GO:0022625), cytoplasm (GO:0005737), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Ribosome-associated quality control	3
Translation	2
Cap-dependent Translation Initiation	2
Nonsense-Mediated Decay (NMD)	2
Eukaryotic Translation Initiation	1
Eukaryotic Translation Elongation	1
Influenza Viral RNA Transcription and Replication	1
Selenoamino acid metabolism	1
rRNA processing in the nucleus and cytosol	1
Signaling by ROBO receptors	1
Cellular response to starvation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
structural molecule activity	1
ribosome	1
binding	1
large ribosomal subunit	1
cytosolic ribosome	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2965 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPL39L	RPL10L	Q96L21	752
RPL39L	RPL36AL	Q969Q0	675
RPL39L	RPS4Y2	Q8TD47	648
RPL39L	RPL3L	Q92901	628
RPL39L	RPL36A	P09896	627
RPL39L	RPS4X	P12631	599
RPL39L	RPL22L1	Q6P5R6	565
RPL39L	RPL27A	P46776	533
RPL39L	RPL38	P23411	514
RPL39L	RPL22	P35268	506
RPL39L	RPL15	P39030	472
RPL39L	RPL29	P47914	471
RPL39L	RPS4Y1	P22090	470
RPL39L	RPL23A	P29316	469
RPL39L	RPL28	P46779	461

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RPL39L	CCNDBP1	psi-mi:“MI:0915”(physical association)	0.670
SRPK2	RPL39L	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
	EBAG9	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): RPL39L (Two-hybrid), RPL39L (Proximity Label-MS), RPL39L (Cross-Linking-MS (XL-MS)), RPL39L (Biochemical Activity)

ESM2 similar proteins: A0A1D8PDT4, A2STI9, A4G029, A6VIE9, A9A8D5, B0R7X9, C0H3Z0, C5A7H4, C6A264, G1SYU7, O16130, O74175, P04538, P04650, P05767, P11340, P22452, P51424, P51425, P51426, P52814, P54573, P62891, P62892, P62893, Q05293, Q18EU6, Q24154, Q37928, Q3T051, Q59GN2, Q5JGT6, Q5SMI4, Q6BHV8, Q6CW22, Q6F482, Q6KAJ8, Q6M0V9, Q758D8, Q8L8W6

Diamond homologs: A0A1D8PDT4, A2BN55, A2STI9, A3CWZ6, A3DNH3, A4G029, A4YH79, A5UL33, A6URE0, A6UVQ6, A6VIE9, A8MAL5, A9A8D5, B0R7X9, B6YWY4, B8GEU4, B9LUV0, C3MR76, C3MXG5, C3MZB1, C3N7D1, C3NGA3, C4KII9, C5A7H4, C6A264, G1SYU7, O16130, O27650, O28212, P04650, P05767, P0DJ61, P13005, P22452, P48536, P51424, P51425, P51426, P52814, P54056

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPL39L	“form complex”	“60S cytosolic large ribosomal subunit”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

7 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

450 predictions. Top by Δscore:

Variant	Effect	Δscore
3:187127993:TCCTA:T	donor_loss	1.0000
3:187127994:CCTAC:C	donor_loss	1.0000
3:187127995:CTACC:C	donor_loss	1.0000
3:187127996:TACCT:T	donor_loss	1.0000
3:187127997:A:C	donor_loss	1.0000
3:187127998:CCTTT:C	donor_loss	1.0000
3:187121324:CACCA:C	acceptor_gain	0.9900
3:187121326:CCA:C	acceptor_gain	0.9900
3:187121327:CAC:C	acceptor_gain	0.9900
3:187121329:C:CC	acceptor_gain	0.9900
3:187131991:A:AC	donor_gain	0.9900
3:187131992:A:C	donor_gain	0.9900
3:187139211:A:AC	donor_gain	0.9900
3:187139212:C:CC	donor_gain	0.9900
3:187139212:CCGG:C	donor_gain	0.9900
3:187128060:AATCT:A	acceptor_loss	0.9800
3:187128062:TC:T	acceptor_loss	0.9800
3:187128063:C:CA	acceptor_loss	0.9800
3:187128063:C:CC	acceptor_gain	0.9800
3:187128064:T:A	acceptor_loss	0.9800
3:187139207:ACTT:A	donor_loss	0.9800
3:187139208:CTT:C	donor_loss	0.9800
3:187139209:TTA:T	donor_loss	0.9800
3:187139210:T:TG	donor_loss	0.9800
3:187139212:C:CT	donor_loss	0.9800
3:187121287:T:C	acceptor_gain	0.9600
3:187128065:G:C	acceptor_loss	0.9600
3:187121325:ACCA:A	acceptor_gain	0.9500
3:187121326:CCAC:C	acceptor_gain	0.9500
3:187121327:CA:C	acceptor_gain	0.9500

AlphaMissense

334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:187121149:A:G	L51P	0.620
3:187121166:T:A	R45S	0.602
3:187121166:T:G	R45S	0.602
3:187121169:C:A	W44C	0.571
3:187121169:C:G	W44C	0.571
3:187121271:C:A	K10N	0.571
3:187121271:C:G	K10N	0.571

dbSNP variants (sampled 300 via entrez): RS1000238479 (3:187130973 C>A), RS1000587625 (3:187137983 C>A), RS1000662868 (3:187125485 C>T), RS1001181372 (3:187125063 G>A), RS1001213952 (3:187132101 G>A,C), RS1001422055 (3:187137585 G>T), RS1001559448 (3:187124557 A>C,G), RS1001847929 (3:187137313 A>G,T), RS1001878907 (3:187136986 A>C,G), RS1001944081 (3:187139525 T>C), RS1002010228 (3:187131390 A>T), RS1002175571 (3:187129541 G>A), RS1002278343 (3:187122831 A>G), RS1002323377 (3:187135391 C>T), RS1002329016 (3:187122559 T>G)

Disease associations

OMIM: gene MIM:607547 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008152_93	Weight	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	decreases expression	2
Tretinoin	decreases expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
bisphenol A	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
MRK 003	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
picoxystrobin	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Coumestrol	increases expression, affects cotreatment	1
Estradiol	decreases expression	1
Indomethacin	increases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Ursodeoxycholic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.