ACRV1

Summary

ACRV1 (acrosomal vesicle protein 1, HGNC:127) is a protein-coding gene on chromosome 11q24.2, encoding Acrosomal protein SP-10 (P26436).

This gene encodes a testis-specific, differentiation antigen, acrosomal vesicle protein 1, that arises within the acrosomal vesicle during spermatogenesis, and is associated with the acrosomal membranes and matrix of mature sperm. The acrosomal vesicle protein 1 may be involved in sperm-zona binding or penetration. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 56 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total — 3 pathogenic
• MANE Select transcript: NM_001612

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:127
Approved symbol	ACRV1
Name	acrosomal vesicle protein 1
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	SPACA2, SP-10, D11S4365
Ensembl gene	ENSG00000134940
Ensembl biotype	protein_coding
OMIM	102525
Entrez	56

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000315608, ENST00000527795, ENST00000530048, ENST00000533904

RefSeq mRNA: 4 — MANE Select: NM_001612 NM_001612, NM_020069, NM_020107, NM_020108

CCDS: CCDS44759, CCDS44761, CCDS8460, CCDS8461

Canonical transcript exons

ENST00000533904 — 4 exons

Exon	Start	End
ENSE00000917275	125676359	125676478
ENSE00001338661	125677797	125678297
ENSE00002145060	125671522	125672717
ENSE00002200495	125680729	125680847

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 96.75.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1125 / max 123.1462, expressed in 3 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122999	0.0785	3
123000	0.0228	3
206489	0.0112	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	96.75	gold quality
right testis	UBERON:0004534	96.56	gold quality
testis	UBERON:0000473	93.72	gold quality
sperm	CL:0000019	92.85	gold quality
male germ cell	CL:0000015	91.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.48	gold quality
adult organism	UBERON:0007023	79.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.20	gold quality
pancreatic ductal cell	CL:0002079	75.14	silver quality
ileal mucosa	UBERON:0000331	73.88	gold quality
tibialis anterior	UBERON:0001385	70.13	gold quality
ventricular zone	UBERON:0003053	68.65	gold quality
prefrontal cortex	UBERON:0000451	66.08	gold quality
putamen	UBERON:0001874	65.37	gold quality
caudate nucleus	UBERON:0001873	64.98	gold quality
nucleus accumbens	UBERON:0001882	64.88	gold quality
olfactory bulb	UBERON:0002264	64.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	62.71	gold quality
ganglionic eminence	UBERON:0004023	62.70	gold quality
cingulate cortex	UBERON:0003027	62.08	gold quality
anterior cingulate cortex	UBERON:0009835	62.03	gold quality
right frontal lobe	UBERON:0002810	62.01	gold quality
hypothalamus	UBERON:0001898	61.41	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	60.98	gold quality
cortical plate	UBERON:0005343	60.95	gold quality
upper leg skin	UBERON:0004262	60.23	gold quality
amygdala	UBERON:0001876	60.16	gold quality
neocortex	UBERON:0001950	60.13	gold quality
frontal cortex	UBERON:0001870	59.94	gold quality
telencephalon	UBERON:0001893	58.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, ILF2, ILF3

miRNA regulators (miRDB)

20 targeting ACRV1, 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-3185	99.99	68.12	1959
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-1265	98.36	66.46	598
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-4524B-3P	95.52	64.12	964
HSA-MIR-5586-3P	95.51	67.00	805

Literature-anchored findings (GeneRIF, showing 3)

• GP56 inhibits cell division when expressed in uninfected Bacillus subtilis, without preventing cell growth, DNA synthesis or chromosome segregation, ultimately causing filamentation and loss of viability. (PMID:24210121)
• ACRV1 protein was predominantly located in round and elongated spermatids in testes, indicating that ACRV1 may play an important role in mammalian spermatogenesis (PMID:21488928)
• ACVR1-activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans. (PMID:35442931)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Acrv1	ENSMUSG00000032110
rattus_norvegicus	Acrv1	ENSRNOG00000008508

Paralogs (4): PATE1 (ENSG00000171053), PATE2 (ENSG00000196844), PATE3 (ENSG00000236027), PATE4 (ENSG00000237353)

Protein

Protein identifiers

Acrosomal protein SP-10 — P26436 (reviewed: P26436)

Alternative names: Acrosomal vesicle protein 1

All UniProt accessions (1): P26436

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Testis.

Isoforms (11)

UniProt ID	Names	Canonical?
P26436-1	1	yes
P26436-2	2
P26436-3	3
P26436-4	4
P26436-5	5
P26436-6	6
P26436-7	7
P26436-8	8
P26436-9	9
P26436-10	10
P26436-11	11

RefSeq proteins (4): NP_001603, NP_064454, NP_064492, NP_064493 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016054	LY6_UPA_recep-like	Domain
IPR052671	Acrosomal_SP-10-like	Family

Pfam: PF00021

UniProt features (36 total): repeat 16, splice variant 9, region of interest 4, compositionally biased region 2, signal peptide 1, chain 1, glycosylation site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26436-F1	62.66	0.31

Functional residue map

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

Glycosylation sites (1): 258

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): WANG_CLIM2_TARGETS_UP, GRUETZMANN_PANCREATIC_CANCER_DN, GOCC_SECRETORY_GRANULE, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MALE_GAMETE_GENERATION, BLALOCK_ALZHEIMERS_DISEASE_UP, HP1SITEFACTOR_Q6, GNF2_CCNA1, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOCC_SECRETORY_VESICLE, GOCC_ACROSOMAL_VESICLE, chr11q24, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP

GO Biological Process (1): spermatogenesis (GO:0007283)

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

GO Cellular Component (4): acrosomal vesicle (GO:0001669), cytoplasm (GO:0005737), vesicle (GO:0031982), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
binding	1
secretory granule	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane-bounded organelle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACRV1	SP9	P0CG40	883
ACRV1	ACVR1	Q04771	806
ACRV1	LIPN	Q5VXI9	793
ACRV1	MBD3L2	Q8NHZ7	777
ACRV1	SP6	Q3SY56	773
ACRV1	SP8	Q8IXZ3	662
ACRV1	LRP5	O75197	623
ACRV1	PCSK5	Q92824	595
ACRV1	TEX101	Q9BY14	595
ACRV1	NOG	Q13253	594
ACRV1	SYCP3	Q8IZU3	591
ACRV1	DPM1	O60762	587
ACRV1	SP3	Q02447	572
ACRV1	SLURP1	P55000	544
ACRV1	PATE3	B3GLJ2	533

IntAct

18 interactions, top by confidence:

A	B	Type	Score
ACRV1	PPT1	psi-mi:“MI:0915”(physical association)	0.560
TSC1	ACRV1	psi-mi:“MI:0915”(physical association)	0.560
ACRV1	PANK2	psi-mi:“MI:0915”(physical association)	0.560
ACRV1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
ACRV1	CISD2	psi-mi:“MI:0915”(physical association)	0.560
ACRV1	TRIM68	psi-mi:“MI:0915”(physical association)	0.400
CFTR	ACRV1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): ACRV1 (Affinity Capture-RNA), TRIM68 (Affinity Capture-MS), ACRV1 (PCA)

ESM2 similar proteins: A0JP43, A4H238, A4H239, A6H8Z2, F1LWT0, F6QRE9, O43493, O60721, P01042, P23327, P23499, P24054, P26436, P50289, P53353, P70663, Q06990, Q0P6D6, Q13342, Q14242, Q14515, Q28139, Q29125, Q2EG98, Q30KK3, Q3MIW9, Q5F378, Q5XHX6, Q62170, Q66HD8, Q6A058, Q6P752, Q6P902, Q70KF4, Q7L311, Q7Z5P9, Q7Z7G0, Q8BYU6, Q8C627, Q8CHD8

Diamond homologs: P26436, P50289, P53353, P83106, P83107, Q06990, B3GLJ2, P81827, Q3UN54, Q9QXN2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
147400	GRCh38/hg38 11q24.1-24.2(chr11:122182443-125957977)x1	Pathogenic
154016	GRCh38/hg38 11q24.1-25(chr11:121611476-135068576)x1	Pathogenic
3063186	GRCh37/hg19 11q23.3-24.2(chr11:121183636-127620828)x1	Pathogenic

SpliceAI

340 predictions. Top by Δscore:

Variant	Effect	Δscore
11:125678296:TCC:T	acceptor_loss	0.9800
11:125678298:C:CG	acceptor_loss	0.9800
11:125678299:T:A	acceptor_loss	0.9800
11:125678303:A:C	acceptor_gain	0.9800
11:125678298:C:CC	acceptor_gain	0.9600
11:125678303:A:AC	acceptor_gain	0.9600
11:125678293:TGTTC:T	acceptor_gain	0.9300
11:125678296:TC:T	acceptor_gain	0.9100
11:125678297:CC:C	acceptor_gain	0.9100
11:125680861:T:TA	donor_gain	0.9000
11:125678300:G:C	acceptor_loss	0.8900
11:125680725:TCA:T	donor_loss	0.8900
11:125680726:CAC:C	donor_loss	0.8900
11:125680727:ACCTC:A	donor_loss	0.8900
11:125680728:C:CA	donor_loss	0.8900
11:125678316:A:T	acceptor_loss	0.8800
11:125680721:ACACT:A	donor_loss	0.8800
11:125680723:ACTCA:A	donor_loss	0.8800
11:125680728:CCT:C	donor_gain	0.8500
11:125678295:TTC:T	acceptor_gain	0.8300
11:125678294:GTTC:G	acceptor_gain	0.8200
11:125678177:GTCTC:G	acceptor_gain	0.8000
11:125680727:A:AC	donor_gain	0.7900
11:125680728:C:CC	donor_gain	0.7900
11:125678222:AACTC:A	donor_loss	0.7000
11:125678223:ACTCA:A	donor_loss	0.7000
11:125678224:CTCA:C	donor_loss	0.7000
11:125678225:TCA:T	donor_loss	0.7000
11:125678226:CA:C	donor_loss	0.7000
11:125678228:C:CA	donor_loss	0.7000

AlphaMissense

1720 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:125676382:C:G	C217S	0.999
11:125676383:A:T	C217S	0.999
11:125672675:C:G	C239S	0.998
11:125672676:A:G	C239R	0.998
11:125672676:A:T	C239S	0.998
11:125672687:C:G	C235S	0.998
11:125672688:A:T	C235S	0.998
11:125672701:G:C	F230L	0.998
11:125672701:G:T	F230L	0.998
11:125672703:A:G	F230L	0.998
11:125676383:A:G	C217R	0.998
11:125676427:C:G	C202S	0.998
11:125676428:A:T	C202S	0.998
11:125676381:G:C	C217W	0.997
11:125676428:A:G	C202R	0.997
11:125672628:A:G	C255R	0.996
11:125672674:G:C	C239W	0.996
11:125672687:C:T	C235Y	0.996
11:125672688:A:G	C235R	0.996
11:125672702:A:C	F230C	0.996
11:125676455:A:G	C193R	0.996
11:125672626:G:C	C255W	0.995
11:125672627:C:G	C255S	0.995
11:125672628:A:T	C255S	0.995
11:125672702:A:G	F230S	0.995
11:125676372:C:A	K220N	0.995
11:125676372:C:G	K220N	0.995
11:125676382:C:T	C217Y	0.995
11:125676406:C:G	C209S	0.995
11:125676407:A:T	C209S	0.995

dbSNP variants (sampled 300 via entrez): RS1000038745 (11:125671484 G>A,T), RS1000218137 (11:125672747 A>C), RS1000387485 (11:125677823 C>T), RS1000992894 (11:125676279 C>T), RS1001258052 (11:125676527 G>A), RS1001284945 (11:125671888 T>C), RS1001337152 (11:125671533 T>A), RS1001634445 (11:125681918 A>G), RS1001768535 (11:125681601 C>T), RS1001861672 (11:125674929 G>A,C), RS1002327731 (11:125676701 C>A,T), RS1002668423 (11:125680560 G>C), RS1003158659 (11:125681928 G>A), RS1003217237 (11:125674687 T>C), RS1003299749 (11:125673547 C>T)

Disease associations

OMIM: gene MIM:102525 | disease phenotypes: MIM:614226

GenCC curated gene-disease

Mondo (2): holoprosencephaly 11 (MONDO:0013642), prostate cancer (MONDO:0008315)

Orphanet (2): Holoprosencephaly (Orphanet:2162), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002861_2	Breast cancer (survival)	1.000000e-09
GCST90002402_398	Platelet count	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0000714	survival time
EFO:0004309	platelet count

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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
propionaldehyde	decreases expression	1
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Amphotericin B	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Lead	decreases expression	1
Silicon Dioxide	decreases 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