TSPYL2

Summary

TSPYL2 (TSPY like 2, HGNC:24358) is a protein-coding gene on chromosome Xp11.22, encoding Testis-specific Y-encoded-like protein 2 (Q9H2G4). Part of the CASK/TBR1/TSPYL2 transcriptional complex which modulates gene expression in response to neuronal synaptic activity, probably by facilitating nucleosome assembly.

This gene encodes a member of the testis-specific protein Y-encoded, TSPY-like/SET/nucleosome assembly protein-1 superfamily. The encoded protein is localized to the nucleolus where it functions in chromatin remodeling and as an inhibitor of cell-cycle progression. This protein may play a role in the suppression of tumor growth.

Source: NCBI Gene 64061 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 152 total — 1 pathogenic
• MANE Select transcript: NM_022117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24358
Approved symbol	TSPYL2
Name	TSPY like 2
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	SE20-4, HRIHFB2216, CTCL, DENTT, CDA1, CINAP, TSPX
Ensembl gene	ENSG00000184205
Ensembl biotype	protein_coding
OMIM	300564
Entrez	64061

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000375442, ENST00000463525, ENST00000553557, ENST00000556808, ENST00000578306, ENST00000579390, ENST00000887607, ENST00000887608, ENST00000887609, ENST00000887610, ENST00000887611, ENST00000912652, ENST00000912653, ENST00000966747, ENST00000966748, ENST00000966749, ENST00000966750, ENST00000966751

RefSeq mRNA: 1 — MANE Select: NM_022117 NM_022117

CCDS: CCDS14350

Canonical transcript exons

ENST00000375442 — 7 exons

Exon	Start	End
ENSE00001306696	53085631	53086310
ENSE00001314590	53084545	53084622
ENSE00001467109	53087776	53088540
ENSE00003491224	53082367	53083305
ENSE00003495392	53084755	53084866
ENSE00003501674	53084954	53085099
ENSE00003541529	53085227	53085321

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1416 / max 753.7421, expressed in 1707 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196403	19.8644	1707
196405	0.1553	67
196404	0.1219	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	99.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.44	gold quality
right ovary	UBERON:0002118	99.40	gold quality
left ovary	UBERON:0002119	99.40	gold quality
cerebellar hemisphere	UBERON:0002245	99.39	gold quality
cerebellar cortex	UBERON:0002129	99.37	gold quality
pituitary gland	UBERON:0000007	99.25	gold quality
right frontal lobe	UBERON:0002810	99.00	gold quality
right testis	UBERON:0004534	99.00	gold quality
left testis	UBERON:0004533	98.98	gold quality
mucosa of stomach	UBERON:0001199	98.92	gold quality
cerebellum	UBERON:0002037	98.85	gold quality
tibial nerve	UBERON:0001323	98.76	gold quality
left uterine tube	UBERON:0001303	98.71	gold quality
endocervix	UBERON:0000458	98.70	gold quality
body of uterus	UBERON:0009853	98.63	gold quality
nucleus accumbens	UBERON:0001882	98.61	gold quality
right adrenal gland cortex	UBERON:0035827	98.60	gold quality
tibial artery	UBERON:0007610	98.59	gold quality
popliteal artery	UBERON:0002250	98.58	gold quality
right adrenal gland	UBERON:0001233	98.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.45	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.39	gold quality
lower esophagus	UBERON:0013473	98.37	gold quality
sural nerve	UBERON:0015488	98.37	gold quality
left adrenal gland cortex	UBERON:0035825	98.29	gold quality
adrenal cortex	UBERON:0001235	98.19	gold quality
left adrenal gland	UBERON:0001234	98.18	gold quality
aorta	UBERON:0000947	98.16	gold quality
cingulate cortex	UBERON:0003027	98.16	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8381	yes	894.61
E-HCAD-4	yes	30.67
E-GEOD-134144	yes	29.52
E-CURD-122	yes	28.87
E-ANND-3	yes	12.68
E-GEOD-84465	yes	6.67
E-MTAB-7606	no	666.45

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

48 targeting TSPYL2, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-1227-5P	98.65	65.32	1549

Literature-anchored findings (GeneRIF, showing 24)

• This paper characterizes monkey DENTT cDNA and makes a comparison with human and mouse DENTT (PMID:15823505)
• Overexpression of cell division autoantigen-1 (CDA1) slowed parasite growth and induced expression of bradyzoite-specific proteins. Results showed that changes in host cell transcription can influence the molecular environment for bradyzoite development. (PMID:17069459)
• CDA1 induces p53- and MEK/ERK1/2 MAPK-dependent expression of p21 by acting through the p53 responsive element in the p21 promoter and this contributes to its antiproliferative activity (PMID:17317670)
• a role for DENTT as a suppressor of the tumorigenic phenotype. (PMID:18381359)
• knockdown of CINAP expression results in marked reduction of histone transcription, lower levels of U small nuclear RNAs (U1, U2, U4, and U5), and a loss of cell viability (PMID:20186459)
• TSPX is principally expressed in Sertoli cells in the human testis. (PMID:21204751)
• hCINAP may not simply regulate nucleotide homeostasis, but may have broader functionality, including control of Cajal body assembly and disassembly (PMID:22038794)
• More importantly, RPS14 was specifically modified with NEDD8 and hCINAP inhibited RPS14 NEDDylation by recruiting NEDD8-specific protease 1 (PMID:23246961)
• The oncogenic events leading to an ectopic activation of TSPY and/or inactivating mutation/epigenetic silencing of TSPX could collectively contribute to the sexual dimorphism(s) in HCC and related liver cancers in male-biased manners. (PMID:25017435)
• Atrial fibrillation can result in alterations in atrial structure and architecture that make the atrial myocardium more susceptible to the maintenance of the arrhythmia. (PMID:25142742)
• TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFbeta signaling activation (PMID:25613376)
• the extent of the duplicated regions in each case encompassing a minimum of three known disease genes TSPYL2, KDM5C and IQSEC2, is reported. (PMID:26059843)
• Authors demonstrate that human coilin-interacting nuclear ATPase protein (hCINAP) is a novel negative regulator in NF-kappaB signaling by deactivating IkappaB kinase (IKK) complex. (PMID:26089539)
• homozygous Asp3779Asn and a hemizygous Ile262Met mutations in the LRP2 and TSPYL2 genes, respectively, in a Pakistani family with two boys affected with mild nonsyndromic intellectual disability (PMID:26529358)
• Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. (PMID:27477389)
• TSPY and TSPX exert opposing effects on the transactivation functions of AR and AR-Vs important for various physiological and disease processes sensitive to male sex hormone actions, thereby not only affecting the pathogenesis of male-specific prostate cancer but also likely contributing to sex differences in the health and diseases of man. (PMID:28169398)
• Aortic CDA1 expression was downregulated approximately 70% within biopsies from human abdominal aortic aneurysms. (PMID:29311219)
• Here we identify the nucleosome assembly protein TSPY-Like 2 (TSPYL2, also known as TSPX, DENTT, and CDA1) as a novel regulator of SIRT1 and p300 function. We demonstrate that, upon DNA damage, TSPYL2 inhibits SIRT1, disrupting its association with target proteins, and promotes p300 acetylation and activation, finally stimulating p53 acetylation and p53-dependent cell death. (PMID:30050056)
• hCINAP serves a critical role in hypoxiainduced cardiomyocyte apoptosis via modulating lactate production and mitochondrialmediated apoptosis signaling. (PMID:33300073)
• TSPYL2 reduced gefitinib resistance and DNA damage repair via suppressing SIRT1-mediated FOXO3 deacetylation. (PMID:35192400)
• Sex specific regulation of TSPY-Like 2 in the DNA damage response of cancer cells. (PMID:36918555)
• A tumor-suppressing role of TSPYL2 in thyroid cancer: Through interacting with SIRT1 and repressing SIRT1/AKT pathway. (PMID:37696385)
• CRL2[APPBP2]-mediated TSPYL2 degradation counteracts human mesenchymal stem cell senescence. (PMID:38170390)
• TSPYL1 as a Critical Regulator of TGFbeta Signaling through Repression of TGFBR1 and TSPYL2. (PMID:38588050)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	tspy	ENSDARG00000005015
danio_rerio	nap1l4a	ENSDARG00000070560
mus_musculus	Tspyl2	ENSMUSG00000041096
rattus_norvegicus	Tspyl2	ENSRNOG00000061782
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), 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 2 — Q9H2G4 (reviewed: Q9H2G4)

Alternative names: Cell division autoantigen 1, Cutaneous T-cell lymphoma-associated antigen se20-4, Differentially-expressed nucleolar TGF-beta1 target protein, Nuclear protein of 79 kDa

All UniProt accessions (3): Q9H2G4, J3KS33, J3KST2

UniProt curated annotations — full annotation on UniProt →

Function. Part of the CASK/TBR1/TSPYL2 transcriptional complex which modulates gene expression in response to neuronal synaptic activity, probably by facilitating nucleosome assembly. May inhibit cell proliferation by inducing p53-dependent CDKN1A expression.

Subunit / interactions. Interacts with histones. Interacts with CASK. Part of a complex containing CASK, TBR1 and TSPYL2.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed, with highest levels in brain, testis and heart, and lowest levels in liver and pancreas.

Post-translational modifications. Phosphorylation at Ser-20 and/or Thr-340 impairs function on cell proliferation.

Induction. Up-regulated in growth-arrested T-cells. Induced by TGFB1 and all-trans retinoic acid (ATRA) in lung cancer cells (at protein level).

Miscellaneous. Synaptic activity down-regulates TSPYL2 protein levels by inducing rapid proteasomal degradation. Subject to X inactivation.

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

RefSeq proteins (1): NP_071400* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002164	NAP	Family
IPR037231	NAP-like_sf	Homologous_superfamily

Pfam: PF00956

UniProt features (29 total): compositionally biased region 7, modified residue 6, region of interest 5, sequence conflict 4, cross-link 3, mutagenesis site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H2G4-F1	58.59	0.19

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 (9): 18, 20, 340, 658, 668, 671, 11, 163, 165

Mutagenesis-validated functional residues (2):

Position	Phenotype
20	impairs effect on cell proliferation; when associated with a-340.
340	impairs effect on cell proliferation; when associated with a-20.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-381038	XBP1(S) activates chaperone genes

MSigDB gene sets: 203 (showing top): REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, CCAWYNNGAAR_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, FOXO1_01, MODULE_66, FREAC3_01, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN

GO Biological Process (7): nucleosome assembly (GO:0006334), negative regulation of DNA replication (GO:0008156), regulation of signal transduction (GO:0009966), negative regulation of cell growth (GO:0030308), negative regulation of cell cycle (GO:0045786), regulation of protein kinase activity (GO:0045859), chromatin organization (GO:0006325)

GO Molecular Function (4): rDNA binding (GO:0000182), chromatin binding (GO:0003682), histone binding (GO:0042393), protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
IRE1alpha activates chaperones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
negative regulation of cellular process	2
binding	2
nuclear lumen	2
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
DNA replication	1
regulation of DNA replication	1
negative regulation of DNA metabolic process	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
cell cycle	1
regulation of cell cycle	1
regulation of protein phosphorylation	1
protein kinase activity	1
regulation of kinase activity	1
cellular component organization	1
sequence-specific double-stranded DNA binding	1
protein binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPYL2	TBR1	Q16650	687
TSPYL2	CDK1	P06493	572
TSPYL2	RPS4X	P12631	528
TSPYL2	RELN	P78509	501
TSPYL2	PSMD3	O43242	495
TSPYL2	ARSF	P54793	486
TSPYL2	GRIN2B	Q13224	461
TSPYL2	CDK4	P11802	450
TSPYL2	RBMY1A1	P0DJD3	443
TSPYL2	AMELX	Q99217	443
TSPYL2	DAZL	Q92904	437
TSPYL2	POPDC3	Q9HBV1	431
TSPYL2	CDK2	P24941	426
TSPYL2	CENPVL1	A0A0U1RR11	419
TSPYL2	GYG2	O15488	418

IntAct

180 interactions, top by confidence:

A	B	Type	Score
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
CSNK2A2	EIF3J	psi-mi:“MI:0914”(association)	0.790
CSNK2A1	TSPYL2	psi-mi:“MI:0915”(physical association)	0.740
TSPYL2	NOP53	psi-mi:“MI:0915”(physical association)	0.740
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
TSPYL2	ABT1	psi-mi:“MI:0915”(physical association)	0.670
ZNF687	TSPYL2	psi-mi:“MI:0915”(physical association)	0.670
CSNK2B	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
SINHCAF	TNRC18	psi-mi:“MI:0914”(association)	0.640
TSPYL1	PCM1	psi-mi:“MI:0914”(association)	0.640
TSPYL6	USP12	psi-mi:“MI:0914”(association)	0.640
TSPYL2	XAGE1A	psi-mi:“MI:0915”(physical association)	0.560
SNIP1	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
TNNT1	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
ZNF280C	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
RPS25	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
INO80B	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB24	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
AEBP2	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
TSPYL2	ZNF835	psi-mi:“MI:0915”(physical association)	0.560
ZFP91	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
TSPYL2	ZNF286A	psi-mi:“MI:0915”(physical association)	0.560
ZNF329	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
RNF151	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560
ZFP1	TSPYL2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (138): TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS), TSPYL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YY54, A0A494C086, A0A494C0Z2, A0A494C191, A6NHP3, A6NIY4, A6NJR5, A6NNV3, B4DH59, F6SZT2, P0C6Y7, P0CI01, P0DKJ7, P0DKJ8, P0DTA3, P0DUD1, P0DUD2, P0DUD3, P0DUD4, P0DUX0, P0DUX1, P0DV79, P79386, Q08AG5, Q13342, Q16666, Q3BBV2, Q495Y8, Q587J8, Q5JRC9, Q5QGU6, Q5RD14, Q5RKG3, Q63HK3, Q6ITT4, Q7TQI8, Q86T75, Q8IWY8, Q8N660, Q8NFV5

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

2 interactions.

A	Effect	B	Mechanism
CyclinA2/CDK2	“up-regulates activity”	TSPYL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 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
Formation of a pool of free 40S subunits	12	18.2×	8e-10
Peptide chain elongation	10	17.1×	2e-08
Viral mRNA Translation	10	17.1×	2e-08
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	10	17.0×	2e-08
L13a-mediated translational silencing of Ceruloplasmin expression	12	16.4×	1e-09
GTP hydrolysis and joining of the 60S ribosomal subunit	12	16.2×	1e-09
Selenocysteine synthesis	10	16.2×	2e-08
Eukaryotic Translation Termination	10	16.2×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	10	17.0×	2e-07
translation	10	9.4×	3e-05
rRNA processing	6	7.8×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	11
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59190	GRCh38/hg38 Xp22.33-11.1(chrX:253129-58271563)x1	Pathogenic

SpliceAI

933 predictions. Top by Δscore:

Variant	Effect	Δscore
X:53083289:GCTTC:G	donor_gain	1.0000
X:53083298:TCA:T	donor_gain	1.0000
X:53085222:A:AG	acceptor_gain	1.0000
X:53085223:A:G	acceptor_gain	1.0000
X:53085225:A:AG	acceptor_gain	1.0000
X:53085226:G:GC	acceptor_gain	1.0000
X:53085226:G:T	acceptor_loss	1.0000
X:53085226:GA:G	acceptor_gain	1.0000
X:53085226:GAT:G	acceptor_gain	1.0000
X:53085226:GATT:G	acceptor_gain	1.0000
X:53085226:GATTA:G	acceptor_gain	1.0000
X:53086306:GGAAG:G	donor_gain	1.0000
X:53086307:GAAGG:G	donor_gain	1.0000
X:53086308:A:T	donor_gain	1.0000
X:53086308:AAGGT:A	donor_loss	1.0000
X:53086309:AGGT:A	donor_loss	1.0000
X:53086310:GGTG:G	donor_loss	1.0000
X:53086312:T:G	donor_loss	1.0000
X:53087758:T:A	acceptor_gain	1.0000
X:53087771:T:TA	acceptor_gain	1.0000
X:53087772:GCAG:G	acceptor_loss	1.0000
X:53087773:CA:C	acceptor_loss	1.0000
X:53087774:A:AG	acceptor_gain	1.0000
X:53087774:AG:A	acceptor_gain	1.0000
X:53087775:G:GC	acceptor_gain	1.0000
X:53087775:GG:G	acceptor_gain	1.0000
X:53087775:GGC:G	acceptor_gain	1.0000
X:53087775:GGCA:G	acceptor_gain	1.0000
X:53083303:GCA:G	donor_gain	0.9900
X:53083306:G:GG	donor_gain	0.9900

AlphaMissense

4700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:53083217:T:C	L240P	1.000
X:53084803:T:C	F312L	1.000
X:53084804:T:C	F312S	1.000
X:53084805:C:A	F312L	1.000
X:53084805:C:G	F312L	1.000
X:53084821:T:C	F318L	1.000
X:53084822:T:C	F318S	1.000
X:53084823:C:A	F318L	1.000
X:53084823:C:G	F318L	1.000
X:53084844:G:C	K325N	1.000
X:53084844:G:T	K325N	1.000
X:53084986:T:A	W344R	1.000
X:53084986:T:C	W344R	1.000
X:53084988:G:C	W344C	1.000
X:53084988:G:T	W344C	1.000
X:53083175:T:C	L226P	0.999
X:53083195:G:C	A233P	0.999
X:53083207:T:C	F237L	0.999
X:53083209:C:A	F237L	0.999
X:53083209:C:G	F237L	0.999
X:53083228:T:C	F244L	0.999
X:53083229:T:C	F244S	0.999
X:53083230:C:A	F244L	0.999
X:53083230:C:G	F244L	0.999
X:53083263:A:C	R255S	0.999
X:53083263:A:T	R255S	0.999
X:53083291:T:C	F265L	0.999
X:53083292:T:C	F265S	0.999
X:53083293:C:A	F265L	0.999
X:53083293:C:G	F265L	0.999

dbSNP variants (sampled 300 via entrez): RS1000151289 (X:53084999 A>G), RS1000479665 (X:53084497 C>A,T), RS1002373876 (X:53086551 G>C), RS1002926853 (X:53082587 C>T), RS1003072425 (X:53088820 C>T), RS1003998814 (X:53084393 G>A), RS1006265626 (X:53086026 A>G), RS1006776170 (X:53082228 C>A), RS1006940272 (X:53088600 C>G), RS1007344690 (X:53087709 A>G,T), RS1007915809 (X:53083404 G>A,C), RS1010122394 (X:53085603 C>G), RS1010193443 (X:53087129 A>G), RS1010585682 (X:53080895 C>T), RS1011252257 (X:53086808 C>T)

Disease associations

OMIM: gene MIM:300564 | 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

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	4
Cyclosporine	increases expression	3
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, affects methylation, decreases methylation	2
Doxorubicin	decreases expression, increases expression, affects reaction	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	affects expression	1
cobaltous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	increases expression	1
Amiodarone	increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D9V5	Ubigene HEK293 TSPYL2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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