TSPYL4

Summary

TSPYL4 (TSPY like 4, HGNC:21559) is a protein-coding gene on chromosome 6q22.1, encoding Testis-specific Y-encoded-like protein 4 (Q9UJ04).

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 23270 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_021648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21559
Approved symbol	TSPYL4
Name	TSPY like 4
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ486I3.2, KIAA0721
Ensembl gene	ENSG00000187189
Ensembl biotype	protein_coding
OMIM	619586
Entrez	23270

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000420283

RefSeq mRNA: 1 — MANE Select: NM_021648 NM_021648

CCDS: CCDS5106

Canonical transcript exons

ENST00000420283 — 1 exons

Exon	Start	End
ENSE00001607063	116249964	116254075

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.6317 / max 617.2054, expressed in 1761 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75246	18.9434	1751
75248	0.6814	252
75247	0.4953	200
75244	0.2938	111
75245	0.2178	88

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	99.37	gold quality
endothelial cell	CL:0000115	99.14	gold quality
cerebellar vermis	UBERON:0004720	99.12	gold quality
superior vestibular nucleus	UBERON:0007227	98.71	gold quality
entorhinal cortex	UBERON:0002728	98.66	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.64	gold quality
superior frontal gyrus	UBERON:0002661	98.62	gold quality
pons	UBERON:0000988	98.61	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.61	gold quality
postcentral gyrus	UBERON:0002581	98.58	gold quality
parietal lobe	UBERON:0001872	98.55	gold quality
middle temporal gyrus	UBERON:0002771	98.23	gold quality
CA1 field of hippocampus	UBERON:0003881	98.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.10	gold quality
primary visual cortex	UBERON:0002436	98.08	gold quality
occipital lobe	UBERON:0002021	98.06	gold quality
substantia nigra pars compacta	UBERON:0001965	98.01	gold quality
medulla oblongata	UBERON:0001896	97.96	gold quality
orbitofrontal cortex	UBERON:0004167	97.82	gold quality
paraflocculus	UBERON:0005351	97.59	gold quality
frontal pole	UBERON:0002795	97.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.26	gold quality
ventral tegmental area	UBERON:0002691	97.24	gold quality
lateral globus pallidus	UBERON:0002476	97.17	gold quality
prefrontal cortex	UBERON:0000451	96.86	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.59	gold quality
hypothalamus	UBERON:0001898	96.49	gold quality
cerebral cortex	UBERON:0000956	96.45	gold quality
cortical plate	UBERON:0005343	96.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	7.01
E-ANND-3	yes	4.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting TSPYL4, 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-1193	100.00	65.93	529
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4728-5P	99.85	69.39	4718

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
mus_musculus	Tspyl4	ENSMUSG00000039485
rattus_norvegicus	Tspyl4	ENSRNOG00000082577
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), 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 4 — Q9UJ04 (reviewed: Q9UJ04)

All UniProt accessions (1): Q9UJ04

UniProt curated annotations — full annotation on UniProt →

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

RefSeq proteins (1): NP_067680* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UJ04-F1	65.77	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 195 (showing top): GCM_MAP4K4, BROWNE_HCMV_INFECTION_6HR_DN, MODULE_451, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, BILD_SRC_ONCOGENIC_SIGNATURE, MODULE_66, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, HFH8_01, ACATTCC_MIR1_MIR206, CAIRO_HEPATOBLASTOMA_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GCM_NF2, RFX1_02

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

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPYL4	NT5DC1	Q5TFE4	507
TSPYL4	ZNF134	P52741	479
TSPYL4	GABRD	O14764	443
TSPYL4	GABRG2	P18507	423
TSPYL4	SCN1B	Q07699	418
TSPYL4	CCDC89	Q8N998	406
TSPYL4	ATXN7L3B	Q96GX2	404
TSPYL4	ERCC6L	Q2NKX8	396
TSPYL4	MAGEB2	O15479	390
TSPYL4	HMG20B	Q9P0W2	382
TSPYL4	EPHX3	Q9H6B9	380
TSPYL4	PCDH18	Q9HCL0	368
TSPYL4	ERICH6	Q7L0X2	364
TSPYL4	DNASE1L1	P49184	361
TSPYL4	GPR155	Q7Z3F1	355

IntAct

85 interactions, top by confidence:

A	B	Type	Score
DFFA	DFFB	psi-mi:“MI:0914”(association)	0.940
MAGEA4	TSPYL4	psi-mi:“MI:0915”(physical association)	0.800
TSPYL4	TRIM38	psi-mi:“MI:0915”(physical association)	0.720
TSPYL4	CDK5RAP3	psi-mi:“MI:0915”(physical association)	0.720
CDK5RAP3	TSPYL4	psi-mi:“MI:0915”(physical association)	0.720
TRIM38	TSPYL4	psi-mi:“MI:0915”(physical association)	0.720
TSPYL4	NAP1L3	psi-mi:“MI:0915”(physical association)	0.560
TSPYL4	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
TFIP11	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
TSPYL4	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
TH	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
ZRANB1	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
CEP57	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	TSPYL4	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	MAGEB16	psi-mi:“MI:0914”(association)	0.530
NAP1L5	RPS2	psi-mi:“MI:0914”(association)	0.530
TSPYL1	GPC3	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530

BioGRID (53): TSPYL4 (Two-hybrid), TSPYL4 (Two-hybrid), TSPYL4 (Two-hybrid), TFIP11 (Two-hybrid), CDK5RAP3 (Two-hybrid), TSPYL4 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), TSPYL4 (Two-hybrid), TSPYL4 (Affinity Capture-MS), TSPYL4 (Two-hybrid), TSPYL4 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), TSPYL4 (Affinity Capture-MS), TSPYL4 (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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 63 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.

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	10	25.5×	3e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

133 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116253707:TCCAG:T	donor_gain	0.7400
6:116250415:TAGG:T	acceptor_gain	0.6900
6:116253512:T:TA	donor_gain	0.6800
6:116253872:A:AC	donor_gain	0.6600
6:116253474:C:CT	donor_gain	0.6400
6:116253475:T:TT	donor_gain	0.6400
6:116253870:CCA:C	donor_gain	0.6200
6:116253873:TC:T	donor_gain	0.5900
6:116253871:CA:C	donor_gain	0.5800
6:116254044:T:TA	donor_gain	0.5800
6:116253868:CGCCA:C	donor_gain	0.5400
6:116253557:T:TA	donor_gain	0.5300
6:116250418:G:C	acceptor_gain	0.5200
6:116250395:T:G	acceptor_gain	0.5000
6:116253473:A:AC	donor_gain	0.5000
6:116253509:C:CA	donor_gain	0.5000
6:116253711:G:T	donor_gain	0.4900
6:116253857:C:CT	donor_gain	0.4900
6:116253858:C:T	donor_gain	0.4900
6:116253855:C:A	donor_gain	0.4800
6:116253356:T:C	donor_gain	0.4700
6:116253874:C:T	donor_gain	0.4600
6:116250419:C:CC	acceptor_gain	0.4400
6:116253361:G:C	donor_gain	0.4400
6:116250382:CAAAA:C	acceptor_gain	0.4200
6:116250383:AAAAA:A	acceptor_gain	0.4200
6:116250393:CCT:C	acceptor_gain	0.4200
6:116253470:TGCAC:T	donor_gain	0.4200
6:116253453:C:CT	donor_gain	0.4100
6:116250373:A:G	acceptor_gain	0.4000

AlphaMissense

2712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:116252940:A:G	W357R	0.999
6:116252940:A:T	W357R	0.999
6:116253070:C:A	K313N	0.999
6:116253070:C:G	K313N	0.999
6:116253249:A:G	W254R	0.999
6:116253249:A:T	W254R	0.999
6:116253250:G:C	F253L	0.999
6:116253250:G:T	F253L	0.999
6:116253252:A:G	F253L	0.999
6:116252938:C:A	W357C	0.998
6:116252938:C:G	W357C	0.998
6:116253015:A:G	W332R	0.998
6:116253015:A:T	W332R	0.998
6:116253092:A:G	F306S	0.998
6:116253109:A:C	F300L	0.998
6:116253109:A:T	F300L	0.998
6:116253111:A:G	F300L	0.998
6:116253116:A:G	F298S	0.998
6:116253122:A:G	F296S	0.998
6:116253164:A:G	L282S	0.998
6:116253247:C:A	W254C	0.998
6:116253247:C:G	W254C	0.998
6:116253251:A:G	F253S	0.998
6:116253280:T:A	R243S	0.998
6:116253280:T:G	R243S	0.998
6:116253281:C:G	R243T	0.998
6:116253313:A:C	F232L	0.998
6:116253313:A:T	F232L	0.998
6:116253315:A:G	F232L	0.998
6:116252891:A:T	I373N	0.997

dbSNP variants (sampled 300 via entrez): RS1000044427 (6:116254783 A>G), RS1000543320 (6:116251719 C>T), RS1001315624 (6:116254457 C>A,G), RS1002052883 (6:116252014 T>C,G), RS1002423617 (6:116252439 T>C), RS1002720480 (6:116255026 G>A,C), RS1003227863 (6:116255532 T>G), RS1003514765 (6:116253080 C>A,T), RS1004628079 (6:116251018 C>T), RS1004969709 (6:116252069 G>A), RS1004999425 (6:116251674 A>G), RS1005058290 (6:116251262 T>A), RS1005730081 (6:116254208 T>A), RS1005974011 (6:116250288 C>A,T), RS1006006554 (6:116249954 C>A,G)

Disease associations

OMIM: gene MIM:619586 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003902_3	Fast beta electroencephalogram	3.000000e-08
GCST007643_3	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	3.000000e-06
GCST009391_1917	Metabolite levels	2.000000e-06
GCST010002_333	Refractive error	2.000000e-36

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0007835	alcohol dependence measurement
EFO:0010464	beta-aminoisobutyric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, affects methylation, affects cotreatment, increases abundance	3
Air Pollutants	increases expression, decreases expression, increases abundance	2
Smoke	decreases expression, increases abundance, increases expression	2
Cyclosporine	decreases expression	2
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1
Cisplatin	increases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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