RPS4Y2

Summary

RPS4Y2 (ribosomal protein S4 Y-linked 2, HGNC:18501) is a protein-coding gene on chromosome Yq11.223, encoding Small ribosomal subunit protein eS4, Y isoform 2 (Q8TD47).

The protein encoded by this gene is a ribosomal protein that is highly similar to RPS4Y1. This gene is located in the male-specific region of the Y chromosome.

Source: NCBI Gene 140032 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001039567

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18501
Approved symbol	RPS4Y2
Name	ribosomal protein S4 Y-linked 2
Location	Yq11.223
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000280969
Ensembl biotype	protein_coding
OMIM	400030
Entrez	140032

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000629237

RefSeq mRNA: 1 — MANE Select: NM_001039567 NM_001039567

CCDS: CCDS44028

Canonical transcript exons

ENST00000629237 — 7 exons

Exon	Start	End
ENSE00003760466	20761284	20761381
ENSE00003766131	20756778	20756855
ENSE00003769571	20780931	20781032
ENSE00003771585	20759868	20760048
ENSE00003772521	20779509	20779666
ENSE00003772865	20768805	20768976
ENSE00003773208	20756108	20756166

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 83.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0476 / max 59.7660, expressed in 2 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201203	0.0334	2
201202	0.0142	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.20	gold quality
right testis	UBERON:0004534	51.98	gold quality
testis	UBERON:0000473	51.25	gold quality
left testis	UBERON:0004533	49.57	gold quality
prostate gland	UBERON:0002367	48.86	gold quality
bone marrow cell	CL:0002092	43.90	gold quality
ganglionic eminence	UBERON:0004023	41.80	gold quality
bone marrow	UBERON:0002371	41.73	silver quality
ventricular zone	UBERON:0003053	40.82	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
mucosa of transverse colon	UBERON:0004991	37.20	silver quality
blood	UBERON:0000178	36.52	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.11	gold quality
rectum	UBERON:0001052	35.60	silver quality
skeletal muscle tissue	UBERON:0001134	35.03	gold quality
spleen	UBERON:0002106	34.36	silver quality
tonsil	UBERON:0002372	34.23	gold quality
right lung	UBERON:0002167	33.61	gold quality
muscle tissue	UBERON:0002385	32.27	gold quality
primary visual cortex	UBERON:0002436	31.36	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
small intestine	UBERON:0002108	30.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	30.50	gold quality
vermiform appendix	UBERON:0001154	29.96	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
hypothalamus	UBERON:0001898	29.49	silver quality
placenta	UBERON:0001987	28.48	gold quality
duodenum	UBERON:0002114	28.14	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.41

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• One of the Y-linked copies of the ribosomal protein S4 is expressed during spermatogenesis and germ cell development and the C-terminus of the protein has some degree of functional specialisation of this protein in spermatogenesis. (PMID:20459660)
• LncPRYP4-3 serves as a novel diagnostic biomarker for dissecting subtypes of metabolic associated fatty liver disease by targeting RPS4Y2. (PMID:32494880)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rps4x	ENSDARG00000014690
drosophila_melanogaster	RpS4	FBGN0011284
caenorhabditis_elegans		WBGENE00004473

Paralogs (2): RPS4Y1 (ENSG00000129824), RPS4X (ENSG00000198034)

Protein

Protein identifiers

Small ribosomal subunit protein eS4, Y isoform 2 — Q8TD47 (reviewed: Q8TD47)

Alternative names: 40S ribosomal protein S4, Y isoform 2

All UniProt accessions (1): Q8TD47

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the eukaryotic ribosomal protein eS4 family.

RefSeq proteins (1): NP_001034656* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000876	Ribosomal_eS4	Family
IPR005824	KOW	Domain
IPR013843	Ribosomal_eS4_N	Domain
IPR013845	Ribosomal_eS4_central_region	Domain
IPR014722	Rib_uL2_dom2	Homologous_superfamily
IPR018199	Ribosomal_eS4_N_CS	Conserved_site
IPR032277	Ribosomal_eS4_C	Domain
IPR036986	S4_RNA-bd_sf	Homologous_superfamily
IPR038237	Ribosomal_eS4_central_sf	Homologous_superfamily
IPR041982	Ribosomal_eS4_KOW	Domain

Pfam: PF00467, PF00900, PF08071, PF16121

UniProt features (2 total): chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD47-F1	95.62	0.98

Function

Pathways and Gene Ontology

Reactome pathways

50 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-72649	Translation initiation complex formation
R-HSA-72689	Formation of a pool of free 40S subunits
R-HSA-72695	Formation of the ternary complex, and subsequently, the 43S complex
R-HSA-72702	Ribosomal scanning and start codon recognition
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-9735869	SARS-CoV-1 modulates host translation machinery
R-HSA-9754678	SARS-CoV-2 modulates host translation machinery
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-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
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-156842	Eukaryotic Translation Elongation
R-HSA-1643685	Disease
R-HSA-168255	Influenza Infection
R-HSA-168273	Influenza Viral RNA Transcription and Replication
R-HSA-2262752	Cellular responses to stress
R-HSA-2408522	Selenoamino acid metabolism
R-HSA-376176	Signaling by ROBO receptors
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 62 (showing top): GOBP_TRANSLATION, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, REACTOME_METABOLISM_OF_RNA, GOCC_RIBOSOME, GOCC_CYTOSOLIC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_SMALL_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOMAL_SUBUNIT, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOCC_CYTOSOLIC_RIBOSOME, GOMF_RRNA_BINDING, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, chrYq11, REACTOME_SELENOAMINO_ACID_METABOLISM, REACTOME_INFECTIOUS_DISEASE, REACTOME_RRNA_PROCESSING

GO Biological Process (1): translation (GO:0006412)

GO Molecular Function (3): RNA binding (GO:0003723), structural constituent of ribosome (GO:0003735), rRNA binding (GO:0019843)

GO Cellular Component (3): cytosolic small ribosomal subunit (GO:0022627), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Cap-dependent Translation Initiation	4
Translation	2
Nonsense-Mediated Decay (NMD)	2
Ribosome-associated quality control	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
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	1
Signaling by ROBO receptors	1
Cellular response to starvation	1
SARS-CoV-1-host interactions	1
SARS-CoV-2-host interactions	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
nucleic acid binding	1
structural molecule activity	1
ribosome	1
RNA binding	1
small ribosomal subunit	1
cytosolic ribosome	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1893 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS4Y2	EIF1AY	O14602	750
RPS4Y2	RPL39L	Q96EH5	648
RPS4Y2	HSFY1	Q96LI6	634
RPS4Y2	KDM5D	Q9BY66	630
RPS4Y2	USP9Y	O00507	607
RPS4Y2	RBMY1A1	P0DJD3	602
RPS4Y2	RPL10L	Q96L21	597
RPS4Y2	PRKY	O43930	585
RPS4Y2	DDX3Y	O15523	584
RPS4Y2	CDY2A	Q9Y6F7	577
RPS4Y2	ZFY	P08048	575
RPS4Y2	BPY2	O14599	571
RPS4Y2	TMSB4Y	O14604	555
RPS4Y2	A6NEC3	A6NEC3	546
RPS4Y2	VCY	O14598	544
RPS4Y2	PRY	O14603	544

IntAct

57 interactions, top by confidence:

A	B	Type	Score
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
LRRC46	TBP	psi-mi:“MI:0914”(association)	0.640
CSNK1E	POTEF	psi-mi:“MI:0914”(association)	0.530
MRPL2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
KRR1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
ZNF428	S100A10	psi-mi:“MI:0914”(association)	0.530
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
rl36a_rl36l_human	IPO5	psi-mi:“MI:0914”(association)	0.350
rl3_rl3l_human	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
RPS4Y1	CCT3	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
RPLP0	ZNF320	psi-mi:“MI:0914”(association)	0.350
RBM4B	ZNF320	psi-mi:“MI:0914”(association)	0.350
RPL4	ZNF320	psi-mi:“MI:0914”(association)	0.350
SURF6	GTPBP10	psi-mi:“MI:0914”(association)	0.350
RPL7A	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ZNF668	GTPBP10	psi-mi:“MI:0914”(association)	0.350
PRKRA	GTPBP10	psi-mi:“MI:0914”(association)	0.350
NEIL1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ZNF346	POTEF	psi-mi:“MI:0914”(association)	0.350
MBNL1	A2ML1	psi-mi:“MI:0914”(association)	0.350
RPS6		psi-mi:“MI:0914”(association)	0.350
RPS8		psi-mi:“MI:0914”(association)	0.350
DAXX		psi-mi:“MI:0914”(association)	0.350
H1-1		psi-mi:“MI:0914”(association)	0.350

BioGRID (83): RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Proximity Label-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS), RPS4Y2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D8PCI6, A4FWA9, A6VGZ7, G1TK17, O22424, O59950, O62738, O62739, P0CX35, P0CX36, P22090, P41042, P46299, P46300, P47836, P47837, P47961, P49204, P49398, P49401, P51405, P62701, P62702, P62703, P62704, P62705, P79103, P79183, P87158, Q0W1X6, Q4GXU6, Q4PMB3, Q56FH2, Q5UAP0, Q642H9, Q6GVM7, Q6PBC4, Q76MY1, Q76N24, Q861U7

Diamond homologs: A0A1D8PCI6, A1RS06, A2BMD1, A3DNB9, A3MWZ7, A4FWA9, A4WLL4, A4YCX8, A5UL76, A6UQ56, A6UWV0, A6VGZ7, A8ACD4, A8MB20, A9A9Q2, B1L778, B1Y9S4, B8D5V8, C3MQ71, C3MVJ0, C3N5T9, C3NEF5, C3NH97, C4KHG8, G1TK17, O05634, O22424, O26123, O28366, O59430, O59950, O62738, O62739, O81363, P0C233, P0CX35, P0CX36, P14023, P22090, P41042

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RPS4Y2	“form complex”	“40S cytosolic small ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Eukaryotic Translation Initiation	9	50.5×	1e-12
Cap-dependent Translation Initiation	9	50.5×	1e-12
SARS-CoV-1 modulates host translation machinery	9	50.5×	1e-12
Eukaryotic Translation Elongation	9	45.6×	3e-12
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	9	44.5×	3e-12
Influenza Viral RNA Transcription and Replication	10	39.2×	7e-13
Nonsense-Mediated Decay (NMD)	9	38.1×	1e-11
SARS-CoV-2 modulates host translation machinery	9	36.6×	2e-11

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	15	38.6×	8e-18
ribosomal small subunit biogenesis	8	25.3×	1e-07
translation	16	22.8×	1e-15
rRNA processing	6	11.8×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1511 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:20756852:ATTT:A	donor_gain	1.0000
Y:20756853:TTT:T	donor_gain	1.0000
Y:20756854:TT:T	donor_gain	1.0000
Y:20756856:G:GG	donor_gain	1.0000
Y:20756856:GTGA:G	donor_loss	1.0000
Y:20756857:TGAG:T	donor_loss	1.0000
Y:20756858:G:GT	donor_loss	1.0000
Y:20756859:AG:A	donor_loss	1.0000
Y:20768803:A:AG	acceptor_gain	1.0000
Y:20768804:G:GG	acceptor_gain	1.0000
Y:20779503:CTCTA:C	acceptor_loss	1.0000
Y:20779504:TCTAG:T	acceptor_loss	1.0000
Y:20779505:CTA:C	acceptor_loss	1.0000
Y:20779506:TAG:T	acceptor_loss	1.0000
Y:20779507:A:AG	acceptor_gain	1.0000
Y:20779507:AG:A	acceptor_gain	1.0000
Y:20779507:AGGCA:A	acceptor_loss	1.0000
Y:20779508:G:GG	acceptor_gain	1.0000
Y:20779508:G:T	acceptor_loss	1.0000
Y:20779508:GG:G	acceptor_gain	1.0000
Y:20779508:GGC:G	acceptor_gain	1.0000
Y:20779508:GGCA:G	acceptor_gain	1.0000
Y:20779662:GCAAT:G	donor_gain	1.0000
Y:20779667:G:GG	donor_gain	1.0000
Y:20756410:GAA:G	donor_gain	0.9900
Y:20756562:GACTC:G	donor_gain	0.9900
Y:20756772:TTTCA:T	acceptor_loss	0.9900
Y:20756773:TTCAG:T	acceptor_loss	0.9900
Y:20756774:TCA:T	acceptor_loss	0.9900
Y:20756775:CAGGC:C	acceptor_loss	0.9900

AlphaMissense

1733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:20756853:T:C	F27L	0.958
Y:20756855:T:A	F27L	0.958
Y:20756855:T:G	F27L	0.958
Y:20779628:T:C	F218L	0.951
Y:20779630:T:A	F218L	0.951
Y:20779630:T:G	F218L	0.951
Y:20761316:T:C	F99L	0.894
Y:20761318:C:A	F99L	0.894
Y:20761318:C:G	F99L	0.894
Y:20761346:T:C	F109L	0.881
Y:20761348:T:A	F109L	0.881
Y:20761348:T:G	F109L	0.881
Y:20768967:T:C	F175L	0.844
Y:20768969:T:A	F175L	0.844
Y:20768969:T:G	F175L	0.844
Y:20779652:T:C	F226L	0.841
Y:20779654:T:A	F226L	0.841
Y:20779654:T:G	F226L	0.841
Y:20779599:T:A	V208E	0.831
Y:20756804:G:C	K10N	0.817
Y:20756804:G:T	K10N	0.817
Y:20768958:T:C	F172L	0.817
Y:20768960:T:A	F172L	0.817
Y:20768960:T:G	F172L	0.817
Y:20756826:T:A	W18R	0.814
Y:20756826:T:C	W18R	0.814
Y:20768923:T:A	V160E	0.796
Y:20759933:G:C	R49S	0.784
Y:20759933:G:T	R49S	0.784
Y:20768810:G:C	K122N	0.776

dbSNP variants (sampled 300 via entrez): RS1000117736 (Y:20772154 G>C), RS1000170809 (Y:20773684 G>A), RS1000482247 (Y:20763878 G>A), RS1002153232 (Y:20756795 G>A), RS1002516877 (Y:20765914 G>T), RS1004330880 (Y:20758245 G>A), RS1004620593 (Y:20759976 A>T), RS1006358354 (Y:20777606 G>A), RS1006406358 (Y:20778686 C>T), RS1006718065 (Y:20770476 T>C), RS1007140544 (Y:20771779 T>A), RS1008398896 (Y:20763352 G>T), RS1008722721 (Y:20755276 A>G), RS1009147505 (Y:20756647 G>A), RS1009364430 (Y:20760885 T>G)

Disease associations

OMIM: gene MIM:400030 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0001450	Y-linked inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
MRK 003	increases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Vanadates	increases expression	1

Clinical trials (associated diseases)

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