TSPY4

Summary

TSPY4 (testis specific protein Y-linked 4, HGNC:37287) is a protein-coding gene on chromosome Yp11.2, encoding Testis-specific Y-encoded protein 4 (P0CV99). May be involved in sperm differentiation and proliferation.

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in several processes, including gonadal mesoderm development; nucleosome assembly; and spermatogenesis. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleus.

Source: NCBI Gene 728395 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001164471

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37287
Approved symbol	TSPY4
Name	testis specific protein Y-linked 4
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000233803
Ensembl biotype	protein_coding
Entrez	728395

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000383008, ENST00000426950, ENST00000466036, ENST00000482082, ENST00000640033

RefSeq mRNA: 2 — MANE Select: NM_001164471 NM_001164471, NM_001422086

CCDS: CCDS48202

Canonical transcript exons

ENST00000426950 — 6 exons

Exon	Start	End
ENSE00001494279	9337464	9338013
ENSE00001697845	9339040	9339185
ENSE00001734097	9338827	9338938
ENSE00001897275	9340068	9340278
ENSE00003638561	9338621	9338698
ENSE00003808304	9339292	9339373

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 95.72.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.72	gold quality
right testis	UBERON:0004534	95.65	gold quality
left testis	UBERON:0004533	94.74	gold quality
testis	UBERON:0000473	93.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.30	gold quality
stromal cell of endometrium	CL:0002255	41.28	silver 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
skeletal muscle tissue	UBERON:0001134	35.60	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
monocyte	CL:0000576	35.28	gold quality
leukocyte	CL:0000738	34.59	gold quality
metanephros cortex	UBERON:0010533	34.40	gold quality
duodenum	UBERON:0002114	34.24	gold quality
gall bladder	UBERON:0002110	34.02	gold quality
muscle tissue	UBERON:0002385	32.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
vermiform appendix	UBERON:0001154	31.59	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	29.30	gold quality
cortex of kidney	UBERON:0001225	29.03	silver quality
blood	UBERON:0000178	27.79	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
muscle of leg	UBERON:0001383	25.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	453.00
E-GEOD-134144	yes	211.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting TSPY4, 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), TSPY3 (ENSG00000228927), TSPY8 (ENSG00000229549), SETSIP (ENSG00000230667), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Testis-specific Y-encoded protein 4 — P0CV99 (reviewed: P0CV99)

All UniProt accessions (3): A0A1W2PPS3, A6NEC3, P0CV99

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 (2): NP_001157943, NP_001409015 (=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-P0CV99-F1	73.30	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (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, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, GOMF_CHROMATIN_BINDING, GOMF_HISTONE_BINDING, chrYp11, GOBP_GONADAL_MESODERM_DEVELOPMENT, GOBP_NUCLEOSOME_ORGANIZATION

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

294 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPY4	RBMY1B	A6NDE4	721
TSPY4	RBMY1J	Q15415	668
TSPY4	TGIF2LY	Q8IUE0	545
TSPY4	VCY	O14598	507
TSPY4	CDY2A	Q9Y6F7	445
TSPY4	EIF1AY	O14602	437
TSPY4	CCDC89	Q8N998	436
TSPY4	RPS4Y2	Q8TD47	434
TSPY4	DAZ2	Q13117	420
TSPY4	USP9Y	O00507	414
TSPY4	ZFY	P08048	396
TSPY4	TMSB4Y	O14604	395
TSPY4	PRKY	O43930	375
TSPY4	DDX3Y	O15523	374
TSPY4	TMEM229B	Q8NBD8	366

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1075 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:9338696:GAGG:G	donor_loss	1.0000
Y:9338697:AGGT:A	donor_loss	1.0000
Y:9338699:G:A	donor_loss	1.0000
Y:9338709:G:GT	donor_gain	1.0000
Y:9338816:T:TA	acceptor_gain	1.0000
Y:9338821:T:TA	acceptor_gain	1.0000
Y:9338825:A:AG	acceptor_gain	1.0000
Y:9338825:AG:A	acceptor_gain	1.0000
Y:9338825:AGGT:A	acceptor_gain	1.0000
Y:9338825:AGGTG:A	acceptor_gain	1.0000
Y:9338826:G:GG	acceptor_gain	1.0000
Y:9338826:GG:G	acceptor_gain	1.0000
Y:9338826:GGT:G	acceptor_gain	1.0000
Y:9338826:GGTG:G	acceptor_gain	1.0000
Y:9338826:GGTGG:G	acceptor_gain	1.0000
Y:9338905:G:GG	donor_gain	1.0000
Y:9338917:G:GT	donor_gain	1.0000
Y:9339037:TAG:T	acceptor_loss	1.0000
Y:9339038:A:AG	acceptor_gain	1.0000
Y:9339039:G:GC	acceptor_loss	1.0000
Y:9339039:G:GG	acceptor_gain	1.0000
Y:9339039:GA:G	acceptor_gain	1.0000
Y:9339039:GAAT:G	acceptor_gain	1.0000
Y:9339039:GAATA:G	acceptor_gain	1.0000
Y:9339065:A:AG	acceptor_gain	1.0000
Y:9339183:GAG:G	donor_gain	1.0000
Y:9339186:G:GC	donor_loss	1.0000
Y:9339186:G:GG	donor_gain	1.0000
Y:9339187:T:A	donor_loss	1.0000
Y:9337908:G:GT	donor_gain	0.9900

AlphaMissense

2064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:9338916:G:C	K224N	0.999
Y:9338916:G:T	K224N	0.999
Y:9337999:T:C	F164L	0.998
Y:9338001:C:A	F164L	0.998
Y:9338001:C:G	F164L	0.998
Y:9338894:T:C	F217S	0.998
Y:9339072:T:A	W243R	0.998
Y:9339072:T:C	W243R	0.998
Y:9338002:T:A	W165R	0.997
Y:9338002:T:C	W165R	0.997
Y:9338875:T:C	F211L	0.997
Y:9338877:T:A	F211L	0.997
Y:9338877:T:G	F211L	0.997
Y:9339141:T:A	W266R	0.997
Y:9339141:T:C	W266R	0.997
Y:9338000:T:C	F164S	0.996
Y:9338004:G:C	W165C	0.996
Y:9338004:G:T	W165C	0.996
Y:9338631:A:G	H172R	0.995
Y:9338893:T:C	F217L	0.995
Y:9338895:C:A	F217L	0.995
Y:9338895:C:G	F217L	0.995
Y:9338914:A:G	K224E	0.995
Y:9338920:T:C	Y226H	0.995
Y:9339074:G:C	W243C	0.995
Y:9339074:G:T	W243C	0.995
Y:9338663:G:C	D183H	0.994
Y:9338900:A:T	N219I	0.994
Y:9338921:A:C	Y226S	0.994
Y:9339143:G:C	W266C	0.994

dbSNP variants (sampled 208 via entrez): RS1166223370 (Y:9335763 T>C), RS1173383392 (Y:9340298 G>A), RS1187018460 (Y:9335592 T>C), RS1191181003 (Y:9339914 AT>A), RS1199155386 (Y:9337644 A>G), RS1199647885 (Y:9337966 C>T), RS1219191390 (Y:9340348 GTGTA>G), RS1232314812 (Y:9340425 C>T), RS1246401467 (Y:9337358 G>A), RS1257206373 (Y:9337985 A>C), RS1259762569 (Y:9337927 C>T), RS1275736639 (Y:9337423 C>T), RS1280086160 (Y:9340358 A>T), RS1303761552 (Y:9340328 G>GTGTGTGTGTGTGTCTT), RS1310366762 (Y:9340371 G>A,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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
1-hydroxypyrene	affects cotreatment, increases methylation	1
Arsenic	decreases methylation, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Metals, Heavy	decreases methylation, increases abundance, affects cotreatment, increases methylation	1

Clinical trials (associated diseases)

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