VCX3B

Summary

VCX3B (variable charge X-linked 3B, HGNC:31838) is a protein-coding gene on chromosome Xp22.31, encoding Variable charge X-linked protein 3B (Q9H321). May mediate a process in spermatogenesis or may play a role in sex ratio distortion.

This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes, and all are expressed exclusively in male germ cells. The X-linked members are clustered on chromosome Xp22, and the Y-linked members are two identical copies of the gene within a palindromic region on chromosome Yq11. The family members share a high degree of sequence identity, with the exception that a 30-nt unit is tandemly repeated in X-linked members but occurs only once in Y-linked members. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. This family member, as represented by the reference genome allele, contains 14 copies of the 30-nt repeat unit. VCX/Y genes encode small and highly charged proteins containing putative bipartite nuclear localization signals. Although the exact function of this family member has yet to be determined, a role in mRNA stability regulation can be inferred from the ability of the highly similar family member, VCX-A, to inhibit mRNA decapping. A possible role in the regulation of ribosome assembly during spermatogenesis has also been suggested.

Source: NCBI Gene 425054 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 130 total
• MANE Select transcript: NM_001001888

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31838
Approved symbol	VCX3B
Name	variable charge X-linked 3B
Location	Xp22.31
Locus type	gene with protein product
Status	Approved
Aliases	VCX-C
Ensembl gene	ENSG00000205642
Ensembl biotype	protein_coding
OMIM	300981
Entrez	425054

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381032

RefSeq mRNA: 1 — MANE Select: NM_001001888 NM_001001888

CCDS: CCDS48077

Canonical transcript exons

ENST00000381032 — 3 exons

Exon	Start	End
ENSE00001487283	8465745	8466510
ENSE00001667677	8465305	8465552
ENSE00001786778	8464830	8464990

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 89.05.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	89.05	gold quality
left testis	UBERON:0004533	88.04	gold quality
testis	UBERON:0000473	87.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.55	gold quality
apex of heart	UBERON:0002098	55.38	gold quality
metanephros cortex	UBERON:0010533	55.04	gold quality
lower esophagus mucosa	UBERON:0035834	52.75	gold quality
right adrenal gland cortex	UBERON:0035827	51.76	gold quality
left lobe of thyroid gland	UBERON:0001120	47.77	gold quality
thyroid gland	UBERON:0002046	47.30	gold quality
right lobe of thyroid gland	UBERON:0001119	47.17	gold quality
hypothalamus	UBERON:0001898	45.96	gold quality
cortex of kidney	UBERON:0001225	45.80	gold quality
right atrium auricular region	UBERON:0006631	45.69	gold quality
putamen	UBERON:0001874	45.61	gold quality
heart left ventricle	UBERON:0002084	45.51	gold quality
primary visual cortex	UBERON:0002436	45.18	gold quality
right uterine tube	UBERON:0001302	44.61	silver quality
anterior cingulate cortex	UBERON:0009835	44.39	gold quality
amygdala	UBERON:0001876	44.06	gold quality
right adrenal gland	UBERON:0001233	43.99	gold quality
right coronary artery	UBERON:0001625	43.92	gold quality
temporal lobe	UBERON:0001871	43.86	gold quality
caudate nucleus	UBERON:0001873	43.52	gold quality
left adrenal gland cortex	UBERON:0035825	43.12	gold quality
adenohypophysis	UBERON:0002196	43.08	gold quality
heart	UBERON:0000948	43.07	gold quality
adult mammalian kidney	UBERON:0000082	42.80	gold quality
nucleus accumbens	UBERON:0001882	42.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	2775.31
E-GEOD-124263	yes	1231.55
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting VCX3B, 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-2861	95.24	65.47	1056
HSA-MIR-3615	95.04	65.37	109

Cross-species orthologs

0 orthologs

Paralogs (5): VCY1B (ENSG00000129862), VCY (ENSG00000129864), VCX3A (ENSG00000169059), VCX2 (ENSG00000177504), VCX (ENSG00000182583)

Protein

Protein identifiers

Variable charge X-linked protein 3B — Q9H321 (reviewed: Q9H321)

Alternative names: Variably charged protein X-C

All UniProt accessions (1): Q9H321

UniProt curated annotations — full annotation on UniProt →

Function. May mediate a process in spermatogenesis or may play a role in sex ratio distortion.

Tissue specificity. Expressed exclusively in testis.

Similarity. Belongs to the VCX/VCY family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H321-1	1	yes
Q9H321-2	2

RefSeq proteins (1): NP_001001888* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026653	VCX/VCY1	Family

Pfam: PF15231

UniProt features (32 total): repeat 14, compositionally biased region 10, sequence conflict 3, region of interest 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H321-F1	46.84	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 6 (showing top): GOBP_HEAD_DEVELOPMENT, GOCC_NUCLEOLUS, chrXp22, PAX3_TARGET_GENES, FOURATI_BLOOD_TWINRIX_AGE_25_83YO_RESPONDERS_VS_POOR_RESPONDERS_0DY_DN, GOBP_CENTRAL_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (1): brain development (GO:0007420)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
central nervous system development	1
animal organ development	1
head development	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCX3B	ARX	Q96QS3	670
VCX3B	PUDP	Q08623	600
VCX3B	PNPLA4	P41247	580
VCX3B	STS	P08842	516
VCX3B	DCP2	Q8IU60	477
VCX3B	ARSF	P54793	476
VCX3B	HSFX1	Q9UBD0	452
VCX3B	TGIF2LX	Q8IUE1	448
VCX3B	FAM47C	Q5HY64	402
VCX3B	XAGE5	Q8WWM1	391
VCX3B	NLGN4X	Q8N0W4	388
VCX3B	CPXCR1	Q8N123	370
VCX3B	CYLC1	P35663	370
VCX3B	ANOS1	P23352	369
VCX3B	DYDC1	Q8WWB3	366

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0U1RQI7, A0A1D9BZF0, A6NJU9, A6NKU9, A6NNC1, A6QL64, A8MRT5, B2SU53, B4DH59, B5DUH6, C9JG80, E5RHQ5, F8W0I5, P01068, P02895, P06916, P07907, P0DKL2, P0DPF3, P0DRJ4, P13208, P14417, P32072, P83060, Q26755, Q3BBV0, Q3BBV2, Q4ZJY7, Q4ZJZ0, Q4ZJZ1, Q4ZJZ3, Q5TAG4, Q5TI25, Q6P3W6, Q6RY98, Q7T3L1, Q86SG3, Q86T75

Diamond homologs: O14598, Q9H320, Q9H321, Q9H322, Q9NNX9

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	96
Likely benign	27
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

231 predictions. Top by Δscore:

Variant	Effect	Δscore
X:8465370:T:TA	acceptor_gain	0.9300
X:8464905:GT:G	donor_gain	0.9100
X:8465371:G:A	acceptor_gain	0.9000
X:8465549:GAAG:G	donor_gain	0.8700
X:8465551:AGG:A	donor_loss	0.8600
X:8465552:GGT:G	donor_loss	0.8600
X:8465553:G:GG	donor_gain	0.8600
X:8464932:G:T	donor_gain	0.8500
X:8465742:CAG:C	acceptor_loss	0.8500
X:8465743:A:AG	acceptor_gain	0.8500
X:8465743:AG:A	acceptor_loss	0.8500
X:8465744:G:GC	acceptor_loss	0.8500
X:8465744:G:GG	acceptor_gain	0.8500
X:8465554:T:A	donor_loss	0.8400
X:8465731:T:TA	acceptor_gain	0.8300
X:8465734:T:A	acceptor_gain	0.8200
X:8465744:GA:G	acceptor_gain	0.8200
X:8465744:GACT:G	acceptor_gain	0.8100
X:8465200:G:C	acceptor_gain	0.8000
X:8465510:G:GT	donor_gain	0.8000
X:8465742:CAGA:C	acceptor_gain	0.8000
X:8464884:G:GT	donor_gain	0.7900
X:8465551:AG:A	donor_gain	0.7900
X:8465552:GG:G	donor_gain	0.7900
X:8465378:CGAG:C	acceptor_gain	0.7800
X:8465550:AAG:A	donor_gain	0.7800
X:8465741:CCAGA:C	acceptor_gain	0.7800
X:8465744:GACTA:G	acceptor_gain	0.7700
X:8465744:GAC:G	acceptor_gain	0.7600
X:8465548:AGAAG:A	donor_gain	0.7500

AlphaMissense

1642 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:8466135:A:C	S165R	0.924
X:8466137:T:A	S165R	0.924
X:8466137:T:G	S165R	0.924
X:8466165:A:C	S175R	0.920
X:8466167:T:A	S175R	0.920
X:8466167:T:G	S175R	0.920
X:8466105:A:C	S155R	0.915
X:8466107:T:A	S155R	0.915
X:8466107:T:G	S155R	0.915
X:8466195:A:C	S185R	0.913
X:8466197:T:A	S185R	0.913
X:8466197:T:G	S185R	0.913
X:8466225:A:C	S195R	0.906
X:8466227:T:A	S195R	0.906
X:8466227:T:G	S195R	0.906
X:8466255:A:C	S205R	0.892
X:8466257:T:A	S205R	0.892
X:8466257:T:G	S205R	0.892
X:8466075:A:C	S145R	0.887
X:8466077:T:A	S145R	0.887
X:8466077:T:G	S145R	0.887
X:8466174:A:C	S178R	0.880
X:8466176:C:A	S178R	0.880
X:8466176:C:G	S178R	0.880
X:8466045:A:C	S135R	0.876
X:8466047:T:A	S135R	0.876
X:8466047:T:G	S135R	0.876
X:8466144:A:C	S168R	0.871
X:8466146:C:A	S168R	0.871
X:8466146:C:G	S168R	0.871

dbSNP variants (sampled 300 via entrez): RS1003055612 (X:8464536 A>G), RS1006713455 (X:8464651 A>C,G), RS1010434601 (X:8463365 T>C), RS1010490710 (X:8464026 T>C), RS1016659249 (X:8464293 TTG>T), RS1020395042 (X:8462882 A>G), RS1020447338 (X:8463370 G>A,C), RS1020499716 (X:8464063 A>C,G), RS1030221104 (X:8464743 G>A), RS1034400450 (X:8463469 C>T), RS1034451205 (X:8464241 A>G), RS1036125300 (X:8463052 G>A,C), RS1041995679 (X:8464508 T>C), RS1046068525 (X:8465233 C>CA,CG), RS1050089064 (X:8463081 G>A)

Disease associations

OMIM: gene MIM:300981 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000477_16	Cognitive performance	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Thapsigargin	increases expression	1
Copper Sulfate	increases expression	1

Clinical trials (associated diseases)

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