BPY2C

Summary

BPY2C (basic charge Y-linked 2C, HGNC:18225) 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 telomeric copy within the palindrome.

Source: NCBI Gene 442868 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total — 1 pathogenic
• MANE Select transcript: NM_001002761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18225
Approved symbol	BPY2C
Name	basic charge Y-linked 2C
Location	Yq11.23
Locus type	gene with protein product
Status	Approved
Aliases	VCY2C
Ensembl gene	ENSG00000185894
Ensembl biotype	protein_coding
Entrez	442868

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000382287, ENST00000602559, ENST00000602680, ENST00000618574

RefSeq mRNA: 1 — MANE Select: NM_001002761 NM_001002761

CCDS: CCDS44030

Canonical transcript exons

ENST00000382287 — 9 exons

Exon	Start	End
ENSE00001643163	25052074	25052104
ENSE00001711311	25041769	25041886
ENSE00001740581	25030901	25031222
ENSE00001764403	25031317	25031441
ENSE00001775879	25051676	25051798
ENSE00001797093	25048474	25048610
ENSE00003506422	25037992	25038116
ENSE00003547967	25038809	25038914
ENSE00003604811	25043946	25044064

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 50.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
testis	UBERON:0000473	50.87	gold quality
left testis	UBERON:0004533	50.85	gold quality
right testis	UBERON:0004534	50.29	gold quality
metanephros cortex	UBERON:0010533	47.55	gold quality
bone marrow cell	CL:0002092	38.66	gold quality
cortex of kidney	UBERON:0001225	38.28	gold quality
kidney	UBERON:0002113	38.06	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
adult mammalian kidney	UBERON:0000082	36.46	gold quality
gall bladder	UBERON:0002110	35.99	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
liver	UBERON:0002107	33.45	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
right lobe of liver	UBERON:0001114	31.35	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
islet of Langerhans	UBERON:0000006	29.96	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
skin of abdomen	UBERON:0001416	28.05	gold quality
lymph node	UBERON:0000029	27.57	gold quality
gastrocnemius	UBERON:0001388	27.54	silver quality
leukocyte	CL:0000738	27.46	gold quality
monocyte	CL:0000576	27.45	silver quality
zone of skin	UBERON:0000014	27.42	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 BPY2C, 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 3)

• 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)
• The AC006262.5-miR-7855-5p-BPY2C axis facilitates hepatocellular carcinoma proliferation and migration. (PMID:32956593)

Cross-species orthologs

0 orthologs

Paralogs (2): BPY2 (ENSG00000183753), BPY2B (ENSG00000183795)

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_001002761* (*=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: 19 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION, chrYq11, MIR4311, MIR7159_3P, MIR1276, MIR583, MIR6776_5P, MIR7855_5P, MIR5589_5P, MIR6780B_3P, MIR5011_3P, MIR7108_5P

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
BPY2C	CDY1	Q9Y6F8	964
BPY2C	CDY2A	Q9Y6F7	948
BPY2C	VCY	O14598	946
BPY2C	PRY	O14603	932
BPY2C	DAZ1	Q9NQZ3	930
BPY2C	DAZ2	Q13117	892
BPY2C	RBMY1A1	P0DJD3	855
BPY2C	UBE3A	P78355	849
BPY2C	E7ERQ6	E7ERQ6	842
BPY2C	USP9Y	O00507	821
BPY2C	RBMY1D	P0C7P1	800
BPY2C	DDX3Y	O15523	799
BPY2C	HSFY1	Q96LI6	762
BPY2C	UTY	O14607	731
BPY2C	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

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816447	GRCh37/hg19 Yq11.23-12(chrY:26241299-59336737)x0	Pathogenic

SpliceAI

1444 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:25038910:GCCCA:G	acceptor_gain	1.0000
Y:25038911:CCCA:C	acceptor_gain	1.0000
Y:25038911:CCCAC:C	acceptor_gain	1.0000
Y:25038912:CCA:C	acceptor_gain	1.0000
Y:25038912:CCAC:C	acceptor_gain	1.0000
Y:25038913:CAC:C	acceptor_gain	1.0000
Y:25038915:C:CC	acceptor_gain	1.0000
Y:25037990:A:AC	donor_gain	0.9900
Y:25037991:C:CC	donor_gain	0.9900
Y:25038802:AACTC:A	donor_loss	0.9900
Y:25038803:ACTCA:A	donor_loss	0.9900
Y:25038804:CTC:C	donor_loss	0.9900
Y:25038805:T:TA	donor_loss	0.9900
Y:25038806:C:CG	donor_loss	0.9900
Y:25038807:A:C	donor_loss	0.9900
Y:25038808:C:CG	donor_loss	0.9900
Y:25038913:CA:C	acceptor_gain	0.9900
Y:25047725:A:AC	donor_gain	0.9900
Y:25048611:C:CC	acceptor_gain	0.9900
Y:25048614:T:TC	acceptor_gain	0.9900
Y:25048618:C:CT	acceptor_gain	0.9900
Y:25048619:A:T	acceptor_gain	0.9900
Y:25037991:CAT:C	donor_gain	0.9800
Y:25038801:CAACT:C	donor_loss	0.9800
Y:25044685:A:AC	donor_gain	0.9800
Y:25048609:CA:C	acceptor_gain	0.9800
Y:25048618:C:T	acceptor_gain	0.9800
Y:25038914:AC:A	acceptor_loss	0.9700
Y:25038915:C:A	acceptor_loss	0.9700
Y:25038916:T:A	acceptor_loss	0.9700

AlphaMissense

673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:25043952:A:C	F24L	0.805
Y:25043952:A:T	F24L	0.805
Y:25043954:A:G	F24L	0.805
Y:25038889:T:A	K74N	0.767
Y:25038889:T:G	K74N	0.767
Y:25038841:C:A	M90I	0.743
Y:25038841:C:G	M90I	0.743
Y:25038841:C:T	M90I	0.743
Y:25041775:A:G	S64P	0.742
Y:25041854:G:C	C37W	0.734
Y:25041856:A:G	C37R	0.717
Y:25041852:A:G	L38S	0.695
Y:25038887:A:G	L75P	0.683
Y:25038900:A:C	Y71D	0.680
Y:25038842:A:G	M90T	0.677
Y:25041834:T:A	D44V	0.676
Y:25041780:A:G	L62P	0.675
Y:25041859:A:G	Y36H	0.669
Y:25038912:C:G	G67R	0.656
Y:25038836:A:G	L92S	0.649
Y:25041859:A:C	Y36D	0.647
Y:25041770:T:A	K65N	0.642
Y:25041770:T:G	K65N	0.642
Y:25041836:A:C	S43R	0.640
Y:25041836:A:T	S43R	0.640
Y:25041838:T:G	S43R	0.640
Y:25038873:C:A	V80L	0.622
Y:25038873:C:G	V80L	0.622
Y:25041835:C:G	D44H	0.617
Y:25038885:A:C	Y76D	0.614

dbSNP variants (sampled 50 via entrez): RS1214589876 (Y:25043937 CAA>C), RS1280192362 (Y:25039658 C>T), RS1444749114 (Y:25043964 G>A), RS1556282430 (Y:25032510 T>TA), RS1556282433 (Y:25038061 A>G), RS1556282438 (Y:25041913 A>C), RS1556282453 (Y:25050219 G>C), RS1556282455 (Y:25051571 T>TG), RS1603607175 (Y:25035326 A>G), RS1603607176 (Y:25035331 C>G), RS1603607177 (Y:25035365 C>T), RS1603607178 (Y:25035377 T>C), RS1603607179 (Y:25035384 T>G), RS1603607180 (Y:25043309 A>T), RS1603607181 (Y:25043367 T>C)

Disease associations

OMIM: gene `` | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	increases reaction, affects binding	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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