TSPY2

Summary

TSPY2 (testis specific protein Y-linked 2, HGNC:23924) is a protein-coding gene on chromosome Yp11.2, encoding Testis-specific Y-encoded protein 2 (A6NKD2). 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 64591 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_022573

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23924
Approved symbol	TSPY2
Name	testis specific protein Y-linked 2
Location	Yp11.2
Locus type	gene with protein product
Status	Approved
Aliases	TSPYQ1
Ensembl gene	ENSG00000168757
Ensembl biotype	protein_coding
Entrez	64591

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000320701, ENST00000383042, ENST00000429039, ENST00000464674, ENST00000470569

RefSeq mRNA: 1 — MANE Select: NM_022573 NM_022573

CCDS: CCDS35465

Canonical transcript exons

ENST00000320701 — 6 exons

Exon	Start	End
ENSE00001623435	6247562	6247673
ENSE00001642228	6247775	6247920
ENSE00001707785	6246223	6246754
ENSE00001830098	6248803	6249018
ENSE00003546295	6247356	6247433
ENSE00003563383	6248027	6248108

Expression profiles

Bgee: expression breadth broad, 50 present calls, max score 90.32.

Top tissues by expression

116 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	90.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.25	gold quality
right testis	UBERON:0004534	85.22	gold quality
testis	UBERON:0000473	83.39	gold quality
left testis	UBERON:0004533	83.07	gold quality
stromal cell of endometrium	CL:0002255	38.59	gold quality
monocyte	CL:0000576	37.21	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
leukocyte	CL:0000738	36.35	gold quality
sural nerve	UBERON:0015488	36.26	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
apex of heart	UBERON:0002098	34.43	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
primary visual cortex	UBERON:0002436	33.20	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
popliteal artery	UBERON:0002250	31.51	gold quality
tibial artery	UBERON:0007610	31.45	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
prefrontal cortex	UBERON:0000451	30.95	gold quality
lymph node	UBERON:0000029	30.91	gold quality
urinary bladder	UBERON:0001255	30.39	silver quality
right coronary artery	UBERON:0001625	30.01	silver quality
liver	UBERON:0002107	29.41	gold quality
vermiform appendix	UBERON:0001154	29.14	gold quality
descending thoracic aorta	UBERON:0002345	29.12	silver quality
calcaneal tendon	UBERON:0003701	28.59	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting TSPY2, 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), 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), TSPY4 (ENSG00000233803), TSPY10 (ENSG00000236424), TSPY9 (ENSG00000238074), TSPY1 (ENSG00000258992), (ENSG00000293164)

Protein

Protein identifiers

Testis-specific Y-encoded protein 2 — A6NKD2 (reviewed: A6NKD2)

Alternative names: Testis-specific Y-encoded protein Q1

All UniProt accessions (3): A6NKD2, A6NGT6, C9JPU3

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. PubMed:12815422 reports 35 tandemly repeated gene copies on Yp11 originating from one individual.

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

RefSeq proteins (1): NP_072095* (*=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-A6NKD2-F1	75.24	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 31 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MESENCHYME_DEVELOPMENT, CONRAD_GERMLINE_STEM_CELL, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_MESODERM_DEVELOPMENT, GOBP_CHROMATIN_REMODELING, HAMAI_APOPTOSIS_VIA_TRAIL_DN, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, SHEN_SMARCA2_TARGETS_DN, GOBP_DEVELOPMENT_OF_PRIMARY_SEXUAL_CHARACTERISTICS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN

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

GO Molecular Function (3): chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

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
binding	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
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

12 interactions, top by confidence:

A	B	Type	Score
TSPY2	DPY30	psi-mi:“MI:0915”(physical association)	0.560
RSPH1	TSPY2	psi-mi:“MI:0914”(association)	0.350
FAM163B	TSPY2	psi-mi:“MI:0914”(association)	0.350
GDF11	TSPY2	psi-mi:“MI:0914”(association)	0.350
LHX3	TSPY2	psi-mi:“MI:0914”(association)	0.350
CFAP54	TSPY2	psi-mi:“MI:0914”(association)	0.350
PDC	TSPY2	psi-mi:“MI:0914”(association)	0.350
C8orf33	TSPY2	psi-mi:“MI:0914”(association)	0.350
TSPY2	TSPY8	psi-mi:“MI:0914”(association)	0.350
DPY30	TSPY2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): TSPY2 (Two-hybrid), TRIB1 (Affinity Capture-MS), TSPY8 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), TSPY2 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), APP (Reconstituted Complex)

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:6247651:G:C	K218N	0.997
Y:6247651:G:T	K218N	0.997
Y:6246740:T:C	F158L	0.996
Y:6246742:C:A	F158L	0.996
Y:6246742:C:G	F158L	0.996
Y:6247629:T:C	F211S	0.995
Y:6247807:T:A	W237R	0.995
Y:6247807:T:C	W237R	0.995
Y:6247610:T:C	F205L	0.994
Y:6247612:T:A	F205L	0.994
Y:6247612:T:G	F205L	0.994
Y:6247628:T:C	F211L	0.993
Y:6247630:C:A	F211L	0.993
Y:6247630:C:G	F211L	0.993
Y:6247809:G:C	W237C	0.991
Y:6247809:G:T	W237C	0.991
Y:6247635:A:T	N213I	0.990
Y:6246741:T:C	F158S	0.989
Y:6247876:T:A	W260R	0.989
Y:6247876:T:C	W260R	0.989
Y:6246743:T:A	W159R	0.987
Y:6246743:T:C	W159R	0.987
Y:6247655:T:C	Y220H	0.987
Y:6246745:G:C	W159C	0.986
Y:6246745:G:T	W159C	0.986
Y:6247398:G:C	D177H	0.985
Y:6247621:C:A	N208K	0.984
Y:6247621:C:G	N208K	0.984
Y:6247656:A:C	Y220S	0.984
Y:6247611:T:C	F205S	0.983

dbSNP variants (sampled 300 via entrez): RS112253183 (Y:6245919 T>G), RS1156861945 (Y:6247351 A>G), RS1162145295 (Y:6246239 T>TC), RS1162794549 (Y:6247394 C>T), RS1173833231 (Y:6246479 A>ATGGCGGAGGTGGAGGTGG), RS1177434141 (Y:6244445 AG>A), RS1179817091 (Y:6247516 C>T), RS1187454926 (Y:6246406 G>T), RS1189163821 (Y:6246280 G>C), RS1189361916 (Y:6248861 G>A), RS1190770456 (Y:6249055 TTGTGTGTGTGTG>T,TTGTGTG,TTGTGTGTG,TTGTGTGTGTG,TTGTGTGTGTGTGTG,TTGTGTGTGTGTGTGTG), RS1197192701 (Y:6247468 C>CG), RS1199817483 (Y:6248042 C>T), RS1202553295 (Y:6247973 T>A), RS1211825972 (Y:6246363 C>G)

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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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