TSPY3

Summary

TSPY3 (testis specific protein Y-linked 3, HGNC:33876) is a protein-coding gene on chromosome Yp11.2, encoding Testis-specific Y-encoded protein 3 (P0CV98). May be involved in sperm differentiation and proliferation.

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in sex differentiation. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleus.

Source: NCBI Gene 728137 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001077697

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33876
Approved symbol	TSPY3
Name	testis specific protein Y-linked 3
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Aliases	CT78
Ensembl gene	ENSG00000228927
Ensembl biotype	protein_coding
Entrez	728137

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000424594, ENST00000440483, ENST00000457222, ENST00000469322, ENST00000491844

RefSeq mRNA: 9 — MANE Select: NM_001077697 NM_001077697, NM_001422056, NM_001422070, NM_001422072, NM_001422080, NM_001422081, NM_001422087, NM_001422088, NM_001422089

CCDS: CCDS48204

Canonical transcript exons

ENST00000457222 — 6 exons

Exon	Start	End
ENSE00001719444	9399979	9400124
ENSE00001747539	9399766	9399877
ENSE00001774191	9398421	9398952
ENSE00001781353	9400231	9400312
ENSE00001954357	9401007	9401217
ENSE00003692666	9399560	9399637

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 77.81.

Top tissues by expression

106 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	77.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.18	gold quality
testis	UBERON:0000473	68.75	gold quality
right testis	UBERON:0004534	68.69	gold quality
left testis	UBERON:0004533	68.03	gold quality
monocyte	CL:0000576	48.67	gold quality
stromal cell of endometrium	CL:0002255	47.61	gold quality
leukocyte	CL:0000738	46.78	gold quality
duodenum	UBERON:0002114	42.63	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
sural nerve	UBERON:0015488	35.18	gold quality
gall bladder	UBERON:0002110	33.92	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
endocervix	UBERON:0000458	32.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
urinary bladder	UBERON:0001255	30.66	gold quality
lymph node	UBERON:0000029	29.94	gold quality
liver	UBERON:0002107	29.94	gold quality
cortex of kidney	UBERON:0001225	29.53	silver quality
prefrontal cortex	UBERON:0000451	29.45	gold quality
uterine cervix	UBERON:0000002	29.32	gold quality
vermiform appendix	UBERON:0001154	29.16	gold quality
blood	UBERON:0000178	28.94	silver quality
kidney	UBERON:0002113	27.63	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting TSPY3, 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-335-3P	99.93	73.36	4958
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-1537-5P	98.70	68.33	999
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-4640-3P	94.58	63.02	263

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
drosophila_melanogaster	Set	FBGN0014879
drosophila_melanogaster	Nap1	FBGN0015268
drosophila_melanogaster	CG3708	FBGN0040345
drosophila_melanogaster	mil	FBGN0267366
caenorhabditis_elegans		WBGENE00005007
caenorhabditis_elegans		WBGENE00017075

Paralogs (19): SET (ENSG00000119335), TSPY2 (ENSG00000168757), NAP1L5 (ENSG00000177432), TSPYL6 (ENSG00000178021), TSPYL5 (ENSG00000180543), TSPYL2 (ENSG00000184205), NAP1L3 (ENSG00000186310), NAP1L2 (ENSG00000186462), NAP1L1 (ENSG00000187109), TSPYL4 (ENSG00000187189), TSPYL1 (ENSG00000189241), NAP1L4 (ENSG00000205531), TSPY8 (ENSG00000229549), SETSIP (ENSG00000230667), TSPY4 (ENSG00000233803), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Testis-specific Y-encoded protein 3 — P0CV98 (reviewed: P0CV98)

All UniProt accessions (3): P0CV98, A0A1W2PPS3, F2Z2I4

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in sperm differentiation and proliferation.

Subcellular location. Cytoplasm. Nucleus.

Polymorphism. Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. 35 tandemly repeated gene copies on Yp11 originating from one individual have been reported.

Similarity. Belongs to the nucleosome assembly protein (NAP) family.

RefSeq proteins (9): NP_001071165, NP_001408985, NP_001408999, NP_001409001, NP_001409009, NP_001409010, NP_001409016, NP_001409017, NP_001409018 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0CV98-F1	75.85	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MESENCHYME_DEVELOPMENT, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_MESODERM_DEVELOPMENT, GOBP_CHROMATIN_REMODELING, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, GOMF_CHROMATIN_BINDING, GOMF_HISTONE_BINDING, chrYp11, GOBP_GONADAL_MESODERM_DEVELOPMENT, GOBP_NUCLEOSOME_ORGANIZATION, MIR3140_5P

GO Biological Process (4): nucleosome assembly (GO:0006334), spermatogenesis (GO:0007283), gonadal mesoderm development (GO:0007506), cell differentiation (GO:0030154)

GO Molecular Function (2): chromatin binding (GO:0003682), histone binding (GO:0042393)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
cellular anatomical structure	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
male gamete generation	1
mesoderm development	1
gonad development	1
mesenchyme development	1
cellular developmental process	1
binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

3 interactions, top by confidence:

A	B	Type	Score
C8orf33	TSPY2	psi-mi:“MI:0914”(association)	0.350
TSPY3	TSPY8	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): TSPY3 (Two-hybrid), TSPY10 (Two-hybrid), TSPY3 (Two-hybrid), TSPY10 (Two-hybrid), WDR54 (Affinity Capture-MS), TSPY8 (Affinity Capture-MS), XAF1 (Affinity Capture-MS), TSPY10 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: A0A494C1R9, A2ZX50, A6NKD2, B8AEC1, B8B2R4, B8B4K9, B9FU45, F4JEI8, O19110, O59797, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0DME0, P53997, P78920, Q01105, Q01534, Q0P5N2, Q18240, Q5R5G8, Q5VND6, Q63945, Q69JW2, Q69ZB3, Q70Z17, Q70Z18, Q70Z19, Q7TQI8, Q86VY4, Q8N831, Q8VD63, Q94K07, Q9BE64, Q9CA59, Q9EQU5, Q9H0U9, Q9H2G4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:9399636:AG:A	donor_loss	1.0000
Y:9399637:GG:G	donor_loss	1.0000
Y:9399648:G:GT	donor_gain	1.0000
Y:9399755:T:A	acceptor_gain	1.0000
Y:9399760:T:A	acceptor_gain	1.0000
Y:9399762:ACAG:A	acceptor_loss	1.0000
Y:9399764:A:AG	acceptor_gain	1.0000
Y:9399764:AG:A	acceptor_gain	1.0000
Y:9399764:AGGT:A	acceptor_gain	1.0000
Y:9399764:AGGTG:A	acceptor_gain	1.0000
Y:9399765:G:GT	acceptor_gain	1.0000
Y:9399765:GG:G	acceptor_gain	1.0000
Y:9399765:GGT:G	acceptor_gain	1.0000
Y:9399765:GGTG:G	acceptor_gain	1.0000
Y:9399765:GGTGG:G	acceptor_gain	1.0000
Y:9399844:G:GG	donor_gain	1.0000
Y:9399856:G:GT	donor_gain	1.0000
Y:9399977:A:AG	acceptor_gain	1.0000
Y:9399978:G:GG	acceptor_gain	1.0000
Y:9399978:G:T	acceptor_loss	1.0000
Y:9399978:GA:G	acceptor_gain	1.0000
Y:9399978:GAAT:G	acceptor_gain	1.0000
Y:9399978:GAATA:G	acceptor_gain	1.0000
Y:9400122:GAG:G	donor_gain	1.0000
Y:9400124:GGTG:G	donor_loss	1.0000
Y:9400125:G:GG	donor_gain	1.0000
Y:9400125:GTGA:G	donor_loss	1.0000
Y:9400126:T:G	donor_loss	1.0000
Y:9398847:G:GT	donor_gain	0.9900
Y:9399635:G:GT	donor_gain	0.9900

AlphaMissense

2026 scored. Top likely-pathogenic:

dbSNP variants (sampled 130 via entrez): RS1159000632 (Y:9399651 G>A), RS1166895573 (Y:9400081 G>A), RS1179056320 (Y:9400053 C>T), RS1219141147 (Y:9399817 C>T), RS1224356028 (Y:9400035 G>A), RS1241359213 (Y:9400019 G>A), RS1252105335 (Y:9401287 GTGTA>G), RS1274579311 (Y:9396825 G>A), RS1284922374 (Y:9397165 C>T), RS1291834713 (Y:9400308 G>A), RS1295365422 (Y:9399908 A>G), RS1305003860 (Y:9397040 T>G), RS1308939808 (Y:9400031 G>T), RS1319631261 (Y:9396640 G>T), RS1350936206 (Y:9397154 G>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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