BPY2B

Summary

BPY2B (basic charge Y-linked 2B, HGNC:25449) is a protein-coding gene on chromosome Yq11.23, encoding Testis-specific basic protein Y 2 (O14599).

This gene is located in the nonrecombining portion of the Y chromosome, and expressed specifically in testis. The encoded protein interacts with ubiquitin protein ligase E3A and may be involved in male germ cell development and male infertility. Three nearly identical copies of this gene exist on chromosome Y; two copies are part of a palindromic region. This record represents the more centromeric copy within the palindrome.

Source: NCBI Gene 442867 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001002760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25449
Approved symbol	BPY2B
Name	basic charge Y-linked 2B
Location	Yq11.23
Locus type	gene with protein product
Status	Approved
Aliases	VCY2B
Ensembl gene	ENSG00000183795
Ensembl biotype	protein_coding
Entrez	442867

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382392, ENST00000602549, ENST00000602770, ENST00000615850

RefSeq mRNA: 1 — MANE Select: NM_001002760 NM_001002760

CCDS: CCDS44029

Canonical transcript exons

ENST00000382392 — 9 exons

Exon	Start	End
ENSE00001619605	24618310	24618432
ENSE00001625788	24638667	24638791
ENSE00001676764	24618004	24618034
ENSE00001689728	24621498	24621634
ENSE00001723611	24638886	24639207
ENSE00001757255	24628222	24628339
ENSE00003463186	24631992	24632116
ENSE00003549506	24626044	24626162
ENSE00003667169	24631194	24631299

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 46.43.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	46.43	gold quality
testis	UBERON:0000473	46.10	gold quality
right testis	UBERON:0004534	44.40	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
metanephros cortex	UBERON:0010533	36.97	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
gall bladder	UBERON:0002110	36.10	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
cortex of kidney	UBERON:0001225	34.56	silver quality
right lobe of liver	UBERON:0001114	33.80	silver quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
kidney	UBERON:0002113	32.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
adult mammalian kidney	UBERON:0000082	31.35	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
islet of Langerhans	UBERON:0000006	29.39	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
skin of abdomen	UBERON:0001416	28.66	gold quality
muscle of leg	UBERON:0001383	28.23	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	27.67	gold quality
leukocyte	CL:0000738	27.67	gold quality
gastrocnemius	UBERON:0001388	27.63	gold quality
lymph node	UBERON:0000029	27.57	gold quality
zone of skin	UBERON:0000014	27.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting BPY2B, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-657	99.48	66.02	848
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-4482-5P	97.53	65.68	598
HSA-MIR-663B	97.40	62.91	664

Literature-anchored findings (GeneRIF, showing 2)

• VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A (PMID:12207887)
• VCY2 was weakly expressed at the spermatogonia and immunonegative in spermatocytes and round spermatids in testicular biopsy specimens with maturation arrest or hypospermatogenesis. (PMID:12724276)

Cross-species orthologs

0 orthologs

Paralogs (2): BPY2 (ENSG00000183753), BPY2C (ENSG00000185894)

Protein

Protein identifiers

Testis-specific basic protein Y 2 — O14599 (reviewed: O14599)

Alternative names: Basic charge, Y-linked 2, Variably charged protein Y 2

All UniProt accessions (2): O14599, R4GMN0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with MAP1S. Interacts with UBE3A (via HECT domain).

Tissue specificity. Expressed exclusively in testis. Expressed in ejaculated spermatozoa of germ cell. Expressed in the nuclei of spermatogonia, spermatocytes, and round spermatids, except elongated spermatids (at protein level).

Similarity. Belongs to the VCX/VCY family.

RefSeq proteins (1): NP_001002760* (*=MANE)

Domains & families (InterPro)

UniProt features (2 total): chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14599-F1	41.56	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION, chrYq11, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, MIR4311, MIR7159_3P, MIR1276, MIR583, MIR6776_5P, MIR7855_5P, MIR5589_5P, MIR6780B_3P, MIR5011_3P

GO Biological Process (2): spermatogenesis (GO:0007283), single fertilization (GO:0007338)

GO Molecular Function (2): HECT domain binding (GO:0032399), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
fertilization	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BPY2B	CDY1	Q9Y6F8	964
BPY2B	CDY2A	Q9Y6F7	948
BPY2B	VCY	O14598	946
BPY2B	PRY	O14603	932
BPY2B	DAZ1	Q9NQZ3	930
BPY2B	DAZ2	Q13117	892
BPY2B	RBMY1A1	P0DJD3	855
BPY2B	UBE3A	P78355	849
BPY2B	E7ERQ6	E7ERQ6	842
BPY2B	USP9Y	O00507	821
BPY2B	RBMY1D	P0C7P1	800
BPY2B	DDX3Y	O15523	799
BPY2B	HSFY1	Q96LI6	762
BPY2B	UTY	O14607	731
BPY2B	TSPY1	P09002	696

IntAct

5 interactions, top by confidence:

A	B	Type	Score
BPY2C	MAP1S	psi-mi:“MI:0915”(physical association)	0.580
MAP1S	BPY2C	psi-mi:“MI:0915”(physical association)	0.580
MAP1S	BPY2C	psi-mi:“MI:0407”(direct interaction)	0.580
BPY2C	PPIA	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): UBE3A (Two-hybrid), MAP1S (Two-hybrid), MAP1S (Reconstituted Complex), PPIA (Proximity Label-MS), UBE3A (Affinity Capture-Western)

ESM2 similar proteins: A0A023PXH2, A8MS09, B0L3A2, B6HUQ5, G2TRK6, G2TRL6, G2TRL8, G3V211, O13536, O14599, O30141, P03935, P05678, P0CE96, P0CE97, P0CE98, P19282, P38296, P38476, P39725, P40211, P53132, P53175, P53229, P53342, P75202, P92561, Q02918, Q03864, Q04434, Q07746, Q0Q027, Q10300, Q12174, Q12225, Q12327, Q3E7B9, Q54UZ5, Q65962, Q6B108

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	7
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
870519	GRCh37/hg19 Yq11.221-11.23(chrY:18546605-28799937)x0	Pathogenic
442918	GRCh37/hg19 Yq11.223-12(chrY:26137299-59336737)x0	Likely pathogenic

SpliceAI

1419 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:24631192:A:AG	acceptor_gain	1.0000
Y:24631192:AGT:A	acceptor_gain	1.0000
Y:24631192:AGTG:A	acceptor_gain	1.0000
Y:24631192:AGTGG:A	acceptor_gain	1.0000
Y:24631193:G:GG	acceptor_gain	1.0000
Y:24631193:GTG:G	acceptor_gain	1.0000
Y:24631193:GTGG:G	acceptor_gain	1.0000
Y:24631193:GTGGG:G	acceptor_gain	1.0000
Y:24621489:T:A	acceptor_gain	0.9900
Y:24621493:A:AG	acceptor_gain	0.9900
Y:24621496:A:AG	acceptor_gain	0.9900
Y:24621497:G:GG	acceptor_gain	0.9900
Y:24622382:A:AG	donor_gain	0.9900
Y:24631190:ATAGT:A	acceptor_gain	0.9900
Y:24631193:GT:G	acceptor_gain	0.9900
Y:24631296:CGAGG:C	donor_loss	0.9900
Y:24631297:GAGG:G	donor_loss	0.9900
Y:24631298:AGG:A	donor_loss	0.9900
Y:24631299:GGT:G	donor_loss	0.9900
Y:24631301:TGAGT:T	donor_loss	0.9900
Y:24631302:G:GT	donor_loss	0.9900
Y:24621490:G:A	acceptor_gain	0.9800
Y:24621497:GT:G	acceptor_gain	0.9800
Y:24632114:GAT:G	donor_gain	0.9800
Y:24632117:G:GG	donor_gain	0.9800
Y:24631188:CCATA:C	acceptor_loss	0.9700
Y:24631189:CATA:C	acceptor_loss	0.9700
Y:24631190:ATAG:A	acceptor_loss	0.9700
Y:24631191:TAG:T	acceptor_loss	0.9700
Y:24631192:A:C	acceptor_loss	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 46 via entrez): RS111237964 (Y:24617647 C>T), RS111441574 (Y:24630993 A>G), RS112996964 (Y:24617782 C>T), RS1227701249 (Y:24634731 A>G), RS1292752573 (Y:24634463 C>G), RS1325496811 (Y:24634468 C>T), RS1556281481 (Y:24617820 CA>C,CAA), RS1556281486 (Y:24626279 C>T), RS1556281495 (Y:24632047 T>C), RS1603606039 (Y:24631019 T>C), RS1603606040 (Y:24634392 T>C), RS1603606041 (Y:24634410 C>A), RS1603606042 (Y:24634417 G>A), RS1603606043 (Y:24634429 A>G), RS1603606044 (Y:24634492 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (2): autism (MONDO:0005260), male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
Benzo(a)pyrene	increases expression	1
Cadmium	increases abundance, decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms