TSPYL6

Summary

TSPYL6 (TSPY like 6, HGNC:14521) is a protein-coding gene on chromosome 2p16.2, encoding Testis-specific Y-encoded-like protein 6 (Q8N831).

Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in nucleosome assembly. Predicted to be active in chromatin and nucleus.

Source: NCBI Gene 388951 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001003937

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14521
Approved symbol	TSPYL6
Name	TSPY like 6
Location	2p16.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178021
Ensembl biotype	protein_coding
Entrez	388951

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000317802

RefSeq mRNA: 1 — MANE Select: NM_001003937 NM_001003937

CCDS: CCDS42682

Canonical transcript exons

ENST00000317802 — 1 exons

Exon	Start	End
ENSE00001237961	54253178	54256229

Expression profiles

Bgee: expression breadth broad, 16 present calls, max score 90.28.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4377 / max 69.4671, expressed in 61 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28377	0.3551	59
28376	0.0423	18
28378	0.0404	21

Top tissues by expression

213 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	90.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.37	gold quality
right testis	UBERON:0004534	83.36	gold quality
testis	UBERON:0000473	83.22	gold quality
left testis	UBERON:0004533	82.39	gold quality
adult organism	UBERON:0007023	80.89	gold quality
sperm	CL:0000019	74.24	gold quality
sural nerve	UBERON:0015488	60.30	silver quality
buccal mucosa cell	CL:0002336	60.10	silver quality
colonic epithelium	UBERON:0000397	59.29	gold quality
lower lobe of lung	UBERON:0008949	57.80	silver quality
bone marrow cell	CL:0002092	55.25	gold quality
hindlimb stylopod muscle	UBERON:0004252	54.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.62	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
pancreatic ductal cell	CL:0002079	51.54	silver quality
myocardium	UBERON:0002349	50.25	gold quality
middle temporal gyrus	UBERON:0002771	48.89	gold quality
skeletal muscle tissue	UBERON:0001134	48.46	gold quality
tibialis anterior	UBERON:0001385	48.45	silver quality
muscle tissue	UBERON:0002385	47.93	gold quality
deltoid	UBERON:0001476	47.76	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
ileal mucosa	UBERON:0000331	46.59	silver quality
quadriceps femoris	UBERON:0001377	46.58	gold quality
vastus lateralis	UBERON:0001379	45.66	gold quality
skin of hip	UBERON:0001554	45.57	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

92 targeting TSPYL6, 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-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 2)

• Findings indicate a significant association between single nucleotide polymorphisms (SNPs) in the testis-specific Y-encoded-like protein 6 (TSPYL6) gene and breast cancer (BC) risk in a Han Chinese population. (PMID:27458158)
• genetic polymorphisms of ACYP2 and TSPYL6 are associated with increased risk of developing ischemic stroke (PMID:27686078)

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), 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-like protein 6 — Q8N831 (reviewed: Q8N831)

All UniProt accessions (2): A0A140VJY4, Q8N831

UniProt curated annotations — full annotation on UniProt →

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

RefSeq proteins (1): NP_001003937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (9 total): sequence variant 4, region of interest 2, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N831-F1	65.14	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 9

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_CHROMATIN_REMODELING, GOMF_CHROMATIN_BINDING, GOMF_HISTONE_BINDING, GOBP_NUCLEOSOME_ORGANIZATION, ARHGAP35_TARGET_GENES, ASH1L_TARGET_GENES, DIDO1_TARGET_GENES, ZNF184_TARGET_GENES, ZNF282_TARGET_GENES, MIR548N, LET_7C_3P, MIR4482_3P, MIR6124, MIR589_3P

GO Biological Process (1): nucleosome assembly (GO:0006334)

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

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
protein binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPYL6	ACYP2	P14621	696
TSPYL6	CIMIP6	Q8N5S3	506
TSPYL6	SPATA31D4	Q6ZUB0	504
TSPYL6	SMIM12	Q96EX1	447
TSPYL6	SPANXN5	Q5MJ07	413
TSPYL6	CLIP4	Q8N3C7	390
TSPYL6	FBXO36	Q8NEA4	380
TSPYL6	TOGARAM2	Q6ZUX3	371
TSPYL6	TMPRSS12	Q86WS5	370
TSPYL6	XAGE3	Q8WTP9	368
TSPYL6	RGSL1	A5PLK6	364
TSPYL6	TTC27	Q6P3X3	358
TSPYL6	PLEKHH2	Q8IVE3	352
TSPYL6	KRTAP2-3	P0C7H8	349
TSPYL6	CT47A11	Q5JQC4	348
TSPYL6	MCTS2	A0A3B3IRV3	348

IntAct

41 interactions, top by confidence:

A	B	Type	Score
MAGEA6	TSPYL6	psi-mi:“MI:0915”(physical association)	0.670
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
KRTAP6-3	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
TSPYL6	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
TSPYL6	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRTAP13-2	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-6	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
KANK2	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-5	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
TSPYL6	DVL3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP8-1	TSPYL6	psi-mi:“MI:0915”(physical association)	0.560
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
HEATR1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
HEATR1	DUSP14	psi-mi:“MI:0914”(association)	0.530
TSPYL6	MYL12B	psi-mi:“MI:0914”(association)	0.350
TSPYL6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
YTHDF1	H1-1	psi-mi:“MI:0914”(association)	0.350
TSPYL6	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	RBPMS	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	MDFI	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	MAGEA6	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	KRTAP13-2	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	KRTAP19-6	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.000
KANK2	TSPYL6	psi-mi:“MI:0915”(physical association)	0.000
TSPYL6	KRTAP19-5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (107): TSPYL6 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), USP46 (Affinity Capture-MS), USP12 (Affinity Capture-MS), WDR20 (Affinity Capture-MS), DMXL2 (Affinity Capture-MS), KDM5B (Affinity Capture-MS), DDX24 (Affinity Capture-MS), AMER1 (Affinity Capture-MS), TTC28 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), TRAF7 (Affinity Capture-MS), WDR48 (Affinity Capture-MS), NSMCE4A (Affinity Capture-MS)

ESM2 similar proteins: A0A087WVF3, A0A087WXS9, A0A087X179, A0A087X1G2, A6NDS4, A6NER0, A6QPT6, B9A6J9, M3WHG5, O14771, O15482, O15553, O19110, O76081, P0C7X1, P0C7X3, P0C7X4, P35125, P48778, P48967, P79209, Q13670, Q15697, Q2TBC4, Q3T191, Q3UZD7, Q4R2Z8, Q5DRQ5, Q5SSQ6, Q5XFX8, Q69ZB3, Q6DHY5, Q6IPX1, Q6ZMN8, Q8BLR5, Q8BWA8, Q8IYF1, Q8IZP1, Q8JZW5, Q8N7G0

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 20 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
Keratinization	6	23.9×	4e-06

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	2
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

54 predictions. Top by Δscore:

Variant	Effect	Δscore
2:54255940:A:T	donor_gain	0.8000
2:54253416:A:T	acceptor_gain	0.7600
2:54255551:G:GA	donor_gain	0.7300
2:54255550:T:TA	donor_gain	0.7200
2:54255943:G:GG	donor_gain	0.7100
2:54255942:A:AG	donor_gain	0.6900
2:54255937:TGGA:T	donor_gain	0.6800
2:54254888:CCTT:C	acceptor_gain	0.5900
2:54254889:CTTC:C	acceptor_gain	0.5900
2:54254890:TTCT:T	acceptor_gain	0.5900
2:54255938:GGAA:G	donor_gain	0.5800
2:54255540:G:GT	donor_gain	0.5700
2:54255544:TTC:T	donor_gain	0.5500
2:54255989:G:GT	donor_gain	0.4800
2:54254889:CTT:C	acceptor_gain	0.4300
2:54254903:ATTCC:A	acceptor_gain	0.3800
2:54254771:T:G	acceptor_gain	0.3600
2:54253337:G:C	acceptor_gain	0.3500
2:54254886:AACCT:A	acceptor_gain	0.3400
2:54255552:G:A	donor_gain	0.3300
2:54253332:A:C	acceptor_gain	0.3200
2:54255939:G:GT	donor_gain	0.3200
2:54255243:G:GG	donor_gain	0.3100
2:54255635:C:G	acceptor_gain	0.3100
2:54255242:A:AG	donor_gain	0.3000
2:54255170:T:TC	acceptor_gain	0.2900
2:54253423:A:T	acceptor_gain	0.2800
2:54254770:TTCAG:T	acceptor_gain	0.2800
2:54254887:ACCT:A	acceptor_gain	0.2800
2:54254901:T:A	acceptor_gain	0.2800

AlphaMissense

2707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:54255399:G:C	F251L	0.991
2:54255399:G:T	F251L	0.991
2:54255401:A:G	F251L	0.991
2:54255258:A:C	F298L	0.985
2:54255258:A:T	F298L	0.985
2:54255260:A:G	F298L	0.985
2:54255219:C:A	K311N	0.981
2:54255219:C:G	K311N	0.981
2:54255271:A:G	F294S	0.978
2:54255313:A:G	L280S	0.977
2:54255400:A:G	F251S	0.974
2:54255095:A:G	W353R	0.973
2:54255095:A:T	W353R	0.973
2:54255398:A:G	W252R	0.973
2:54255398:A:T	W252R	0.973
2:54255241:A:G	F304S	0.971
2:54255240:G:C	F304L	0.970
2:54255240:G:T	F304L	0.970
2:54255242:A:G	F304L	0.970
2:54255249:G:C	N301K	0.970
2:54255249:G:T	N301K	0.970
2:54255396:C:A	W252C	0.970
2:54255396:C:G	W252C	0.970
2:54255235:T:A	N306I	0.968
2:54255270:A:C	F294L	0.968
2:54255270:A:T	F294L	0.968
2:54255272:A:G	F294L	0.968
2:54255265:A:G	F296S	0.967
2:54255375:G:C	H259Q	0.964
2:54255375:G:T	H259Q	0.964

dbSNP variants (sampled 300 via entrez): RS1000030514 (2:54257697 A>G), RS1000146248 (2:54258036 C>G), RS1000790371 (2:54257314 C>A), RS1001315617 (2:54253336 T>C), RS1001922085 (2:54254591 C>T), RS1002291143 (2:54254367 A>G), RS1002365468 (2:54256666 C>G,T), RS1002464895 (2:54256288 C>A,T), RS1002591345 (2:54256528 T>A,C,G), RS1003035584 (2:54254715 G>A,C), RS1003866615 (2:54254529 G>C), RS1004903721 (2:54257302 G>A), RS1005274715 (2:54255787 C>G,T), RS1005343402 (2:54257572 A>G,T), RS1005443333 (2:54253581 T>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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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