TSNAXIP1

Summary

TSNAXIP1 (translin associated factor X interacting protein 1, HGNC:18586) is a protein-coding gene on chromosome 16q22.1, encoding Translin-associated factor X-interacting protein 1 (Q2TAA8). Possible role in spermatogenesis.

Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in perinuclear region of cytoplasm. Predicted to be active in cytoplasm.

Source: NCBI Gene 55815 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 130 total
• MANE Select transcript: NM_001288990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18586
Approved symbol	TSNAXIP1
Name	translin associated factor X interacting protein 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	TXI1
Ensembl gene	ENSG00000102904
Ensembl biotype	protein_coding
OMIM	607720
Entrez	55815

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000388833, ENST00000415766, ENST00000431934, ENST00000466164, ENST00000487120, ENST00000561639, ENST00000561654, ENST00000562321, ENST00000562633, ENST00000563363, ENST00000565148, ENST00000565339, ENST00000565558, ENST00000567852, ENST00000568990, ENST00000569504, ENST00000885113

RefSeq mRNA: 7 — MANE Select: NM_001288990 NM_001288990, NM_001288991, NM_001288992, NM_001288993, NM_001288994, NM_001351158, NM_018430

CCDS: CCDS10846, CCDS73903, CCDS73904

Canonical transcript exons

ENST00000561639 — 16 exons

Exon	Start	End
ENSE00001710897	67825667	67825836
ENSE00001721952	67825917	67826076
ENSE00002626189	67806889	67807196
ENSE00003460483	67827473	67827579
ENSE00003468402	67827249	67827375
ENSE00003485303	67823626	67823719
ENSE00003512399	67827753	67828068
ENSE00003532960	67825137	67825272
ENSE00003537327	67826963	67827072
ENSE00003554373	67826437	67826562
ENSE00003576401	67814302	67814401
ENSE00003606639	67821099	67821225
ENSE00003620961	67826692	67826844
ENSE00003646502	67820839	67820951
ENSE00003661877	67824583	67824779
ENSE00003674770	67826152	67826282

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 96.03.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4834 / max 120.4397, expressed in 605 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154678	1.0346	532
154679	0.4488	147

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.03	gold quality
left testis	UBERON:0004533	91.72	gold quality
right testis	UBERON:0004534	91.68	gold quality
epithelium of bronchus	UBERON:0002031	90.59	gold quality
bronchial epithelial cell	CL:0002328	90.26	gold quality
testis	UBERON:0000473	89.28	gold quality
bronchus	UBERON:0002185	89.21	gold quality
sperm	CL:0000019	88.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.31	gold quality
male germ cell	CL:0000015	85.85	gold quality
adenohypophysis	UBERON:0002196	85.20	gold quality
pituitary gland	UBERON:0000007	84.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.99	gold quality
right frontal lobe	UBERON:0002810	80.30	gold quality
caudate nucleus	UBERON:0001873	80.11	gold quality
nucleus accumbens	UBERON:0001882	80.01	gold quality
mucosa of paranasal sinus	UBERON:0005030	77.55	gold quality
anterior cingulate cortex	UBERON:0009835	76.90	gold quality
cingulate cortex	UBERON:0003027	76.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.67	gold quality
ventricular zone	UBERON:0003053	75.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.86	gold quality
putamen	UBERON:0001874	75.73	gold quality
right adrenal gland cortex	UBERON:0035827	75.49	gold quality
cortical plate	UBERON:0005343	75.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.14	gold quality
hypothalamus	UBERON:0001898	75.12	gold quality
prefrontal cortex	UBERON:0000451	75.10	gold quality
right adrenal gland	UBERON:0001233	75.09	gold quality
tendon of biceps brachii	UBERON:0008188	75.09	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• rs1630250 was associated in males w/ methamphetamine dependence in allele analysis. results not significant after Bonferroni correction. findings suggest TSNAX does not play a role in methamphetamine dependence in Japanese population (PMID:21683752)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tsnaxip1	ENSMUSG00000031893
rattus_norvegicus	Tsnaxip1	ENSRNOG00000018954

Protein

Protein identifiers

Translin-associated factor X-interacting protein 1 — Q2TAA8 (reviewed: Q2TAA8)

All UniProt accessions (11): Q2TAA8, B4DXD0, E7ENJ7, H3BNS9, H3BNU6, H3BQ72, I3L1M2, J3KQF4, J3QQL6, J3QS50, J3QSH8

UniProt curated annotations — full annotation on UniProt →

Function. Possible role in spermatogenesis.

Subunit / interactions. Interacts with TSNAX.

Subcellular location. Cytoplasm. Perinuclear region.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2TAA8-1	1	yes
Q2TAA8-2	2

RefSeq proteins (7): NP_001275919, NP_001275920, NP_001275921, NP_001275922, NP_001275923, NP_001338087, NP_060900 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032755	TSNAXIP1_N	Domain

Pfam: PF15739

UniProt features (4 total): coiled-coil region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2TAA8-F1	84.48	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): CREL_01, chr16q22, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, MODULE_511, AACYNNNNTTCCS_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, GGAMTNNNNNTCCY_UNKNOWN, SP1_Q2_01, NFKB_C, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, RFX1_02, AP1FJ_Q2, MARSON_BOUND_BY_FOXP3_STIMULATED, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (2): spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1513 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSNAXIP1	TSNAX	Q99598	878
TSNAXIP1	LRRC23	Q53EV4	570
TSNAXIP1	ZSWIM2	Q8NEG5	563
TSNAXIP1	RSPH14	Q9UHP6	555
TSNAXIP1	RSPH10B	P0C881	537
TSNAXIP1	CCDC146	Q8IYE0	536
TSNAXIP1	CFAP74	Q9C0B2	526
TSNAXIP1	C16orf86	Q6ZW13	502
TSNAXIP1	ADAD1	Q96M93	490
TSNAXIP1	CFAP161	Q6P656	487
TSNAXIP1	MTMR14	Q8NCE2	482
TSNAXIP1	LRRC34	Q8IZ02	480
TSNAXIP1	CFAP52	Q8N1V2	466
TSNAXIP1	CFAP57	Q96MR6	459
TSNAXIP1	N4BP3	O15049	451

IntAct

17 interactions, top by confidence:

A	B	Type	Score
TSNAXIP1	FAM161B	psi-mi:“MI:0915”(physical association)	0.560
CDC7	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.560
TSNAXIP1	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
TSNAXIP1	SPG21	psi-mi:“MI:0915”(physical association)	0.560
TSNAXIP1	PB2	psi-mi:“MI:0915”(physical association)	0.370
HSPB1	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.370
TSNAXIP1	DPP8	psi-mi:“MI:0914”(association)	0.350
FMR1	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.000
FAM161B	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.000
CDC7	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.000
PRPF18	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.000
SPG21	TSNAXIP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): TSNAXIP1 (Two-hybrid), PIBF1 (Affinity Capture-MS), CCDC186 (Affinity Capture-MS), DPP8 (Affinity Capture-MS), FBXW5 (Affinity Capture-MS), USO1 (Affinity Capture-MS), TSNAXIP1 (Affinity Capture-RNA), TSNAXIP1 (Two-hybrid), TSNAXIP1 (Two-hybrid), TSNAXIP1 (Two-hybrid), TSNAXIP1 (Two-hybrid), FAM161B (Two-hybrid), PRPF18 (Two-hybrid), TSNAXIP1 (Affinity Capture-RNA), CCDC186 (Affinity Capture-MS)

ESM2 similar proteins: A0JMQ7, A0JMY4, A2AUM9, A2BDR7, A6NI79, A7MD70, A8KB59, F1QRC1, F1RKB1, O35550, O35551, Q05D60, Q08C53, Q0VFN8, Q0VFX2, Q15276, Q17QH9, Q2TAA8, Q2TBK0, Q3USS3, Q3V079, Q498G2, Q4R703, Q4R7Y8, Q4V7B0, Q5JU67, Q5RA03, Q5U3Z6, Q5XI65, Q5XIR6, Q5ZJ27, Q66KE8, Q6DFC2, Q6IQY5, Q6NRB0, Q6NRC9, Q6NRW2, Q6P0R8, Q6P402, Q80UF4

Diamond homologs: Q2TAA8, Q99P25

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4451 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67814300:A:AG	acceptor_gain	1.0000
16:67814301:G:GG	acceptor_gain	1.0000
16:67814395:G:GT	donor_gain	1.0000
16:67821098:GGA:G	acceptor_gain	1.0000
16:67821211:GAAC:G	donor_gain	1.0000
16:67821223:CAG:C	donor_loss	1.0000
16:67821224:AG:A	donor_loss	1.0000
16:67821225:GGTC:G	donor_loss	1.0000
16:67821226:GTCAG:G	donor_loss	1.0000
16:67821227:T:A	donor_loss	1.0000
16:67824581:A:AG	acceptor_gain	1.0000
16:67824582:G:GG	acceptor_gain	1.0000
16:67824787:G:GT	donor_gain	1.0000
16:67825268:GCCAG:G	donor_gain	1.0000
16:67825271:AG:A	donor_gain	1.0000
16:67825272:GG:G	donor_gain	1.0000
16:67825272:GGT:G	donor_loss	1.0000
16:67825273:G:GG	donor_gain	1.0000
16:67825273:GTA:G	donor_loss	1.0000
16:67825274:T:G	donor_loss	1.0000
16:67825915:A:AG	acceptor_gain	1.0000
16:67825915:AGCT:A	acceptor_gain	1.0000
16:67825916:G:GG	acceptor_gain	1.0000
16:67825916:GCT:G	acceptor_gain	1.0000
16:67825916:GCTG:G	acceptor_gain	1.0000
16:67826073:AAAGG:A	donor_loss	1.0000
16:67826074:AAGG:A	donor_loss	1.0000
16:67826076:GGTGA:G	donor_loss	1.0000
16:67826078:T:A	donor_loss	1.0000
16:67826151:GAT:G	acceptor_gain	1.0000

AlphaMissense

4728 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67826061:T:A	W323R	0.993
16:67826061:T:C	W323R	0.993
16:67826063:G:C	W323C	0.993
16:67826063:G:T	W323C	0.993
16:67823697:G:C	K99N	0.989
16:67823697:G:T	K99N	0.989
16:67826178:T:A	W337R	0.988
16:67826178:T:C	W337R	0.988
16:67821164:T:C	L55P	0.987
16:67823684:T:A	L95Q	0.987
16:67823693:T:A	I98N	0.987
16:67826205:A:C	S346R	0.987
16:67826207:C:A	S346R	0.987
16:67826207:C:G	S346R	0.987
16:67823701:G:C	A101P	0.986
16:67826002:G:C	R303P	0.986
16:67826536:T:A	W405R	0.982
16:67826536:T:C	W405R	0.982
16:67823684:T:C	L95P	0.981
16:67826227:T:C	L353P	0.980
16:67824706:T:C	L148P	0.979
16:67826465:T:C	L381P	0.978
16:67821152:T:C	L51P	0.977
16:67826227:T:A	L353H	0.976
16:67827009:T:C	L480P	0.976
16:67823641:T:C	F81L	0.975
16:67823643:T:A	F81L	0.975
16:67823643:T:G	F81L	0.975
16:67826023:T:C	L310P	0.975
16:67827555:T:C	L571P	0.975

dbSNP variants (sampled 300 via entrez): RS1000009892 (16:67814039 G>A), RS1000051477 (16:67805252 G>C), RS1000185739 (16:67824185 T>C), RS1000277816 (16:67811102 G>A), RS1000317330 (16:67817160 G>GC), RS1000366423 (16:67816806 C>G), RS1000375837 (16:67827040 G>A,C), RS1000468034 (16:67813726 C>G,T), RS1000803072 (16:67822747 G>C), RS1000870500 (16:67824468 G>A), RS1000906719 (16:67806713 C>A,T), RS1000921223 (16:67822394 C>T), RS1000999439 (16:67824075 T>C,G), RS1001001176 (16:67828183 TG>T,TGG), RS1001169202 (16:67814541 G>A,C)

Disease associations

OMIM: gene MIM:607720 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST005751_4	Empathy quotient	9.000000e-07
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14
GCST90020024_744	A body shape index	4.000000e-10
GCST90020025_211	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_23	Waist-hip index	7.000000e-10
GCST90020029_573	Waist circumference adjusted for body mass index	6.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009183	empathy measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sotorasib	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
tetrachlorodian	decreases expression	1
CGP 52608	affects binding, increases reaction	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer