VCX

Summary

VCX (variable charge X-linked, HGNC:12667) is a protein-coding gene on chromosome Xp22.31, encoding Variable charge X-linked protein 1 (Q9H320). 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 Y-linked members are two identical copies of the gene within a palindromic region on Yq11. The family members share a high degree of sequence identity, with the exception that a 30-bp 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. VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. This gene contains 10 repeats of the 30-bp unit.

Source: NCBI Gene 26609 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 19 total — 4 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001393662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12667
Approved symbol	VCX
Name	variable charge X-linked
Location	Xp22.31
Locus type	gene with protein product
Status	Approved
Aliases	VCX1, VCX10R, VCX-10r, VCX-B1
Ensembl gene	ENSG00000182583
Ensembl biotype	protein_coding
OMIM	300229
Entrez	26609

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000341408, ENST00000381059, ENST00000620630, ENST00000688183, ENST00000692567

RefSeq mRNA: 2 — MANE Select: NM_001393662 NM_001393662, NM_013452

CCDS: CCDS14128

Canonical transcript exons

ENST00000688183 — 2 exons

Exon	Start	End
ENSE00001487372	7843498	7844143
ENSE00003932811	7843171	7843305

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 93.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1509 / max 20.8486, expressed in 53 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195436	0.1509	53

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	93.84	gold quality
left testis	UBERON:0004533	93.75	gold quality
testis	UBERON:0000473	92.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.73	gold quality
ventricular zone	UBERON:0003053	50.76	gold quality
putamen	UBERON:0001874	48.87	gold quality
right uterine tube	UBERON:0001302	46.67	gold quality
primary visual cortex	UBERON:0002436	45.82	gold quality
nucleus accumbens	UBERON:0001882	45.70	gold quality
duodenum	UBERON:0002114	45.57	gold quality
amygdala	UBERON:0001876	45.39	gold quality
temporal lobe	UBERON:0001871	45.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	44.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	44.59	gold quality
caudate nucleus	UBERON:0001873	44.32	gold quality
right frontal lobe	UBERON:0002810	44.27	gold quality
Ammon’s horn	UBERON:0001954	44.23	gold quality
anterior cingulate cortex	UBERON:0009835	43.79	gold quality
superior frontal gyrus	UBERON:0002661	43.44	gold quality
body of stomach	UBERON:0001161	42.79	gold quality
cerebral cortex	UBERON:0000956	42.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	41.96	gold quality
metanephros cortex	UBERON:0010533	41.80	silver quality
tibial nerve	UBERON:0001323	41.25	gold quality
hypothalamus	UBERON:0001898	41.04	gold quality
brain	UBERON:0000955	40.86	gold quality
stomach	UBERON:0000945	39.94	gold quality
cortex of kidney	UBERON:0001225	39.79	gold quality
substantia nigra	UBERON:0002038	39.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	4056.72
E-GEOD-134144	yes	3258.71
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting VCX, 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

Literature-anchored findings (GeneRIF, showing 4)

• Human VCX/Y, SPANX, and CSAG2 gene families together with the murine SPANX gene and the CYPT family may share a common ancestor. (PMID:17342728)
• Identified members of the VCX/Y gene family as novel CT antigens. (PMID:24970476)
• Increasing copy number of VCX could upregulate the gene expression and regulate cell proliferation and apoptosis during spermatogenesis in non-obstructive azoospermia. (PMID:27705943)
• SNPs and DNA methylation at the CHR X: 7810800 locus cooperatively regulate VCX expression in chronic hepatitis B (CHB). The upregulated VCX expression in female CHB patients might represent a mechanism of protection from more severe liver dysfunction and extensive fibrosis, as observed in male CHB patients. (PMID:31161555)

Cross-species orthologs

0 orthologs

Paralogs (5): VCY1B (ENSG00000129862), VCY (ENSG00000129864), VCX3A (ENSG00000169059), VCX2 (ENSG00000177504), VCX3B (ENSG00000205642)

Protein

Protein identifiers

Variable charge X-linked protein 1 — Q9H320 (reviewed: Q9H320)

Alternative names: Variable charge protein on X with ten repeats, Variably charged protein X-B1

All UniProt accessions (4): A0A087X1S4, Q9H320, A0A8I5QKN2, J3KNW2

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.

RefSeq proteins (2): NP_001380591, NP_038480 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026653	VCX/VCY1	Family

Pfam: PF15231

UniProt features (24 total): repeat 10, compositionally biased region 7, region of interest 2, sequence variant 2, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H320-F1	51.19	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_RIBOSOME_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, GOBP_ORGANELLE_ASSEMBLY, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOBP_HEAD_DEVELOPMENT, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, HAMAI_APOPTOSIS_VIA_TRAIL_DN, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, GOMF_CHROMATIN_BINDING, GOCC_NUCLEOLUS, chrXp22, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING

GO Biological Process (4): chromatin organization (GO:0006325), spermatogenesis (GO:0007283), brain development (GO:0007420), ribosome assembly (GO:0042255)

GO Molecular Function (1): chromatin binding (GO:0003682)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular component organization	1
developmental process involved in reproduction	1
male gamete generation	1
central nervous system development	1
animal organ development	1
head development	1
ribosome biogenesis	1
membraneless organelle assembly	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

534 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCX	STS	P08842	776
VCX	ARX	Q96QS3	648
VCX	PAGE3	Q5JUK9	507
VCX	DCP2	Q8IU60	490
VCX	C12orf54	Q6X4T0	446
VCX	SCX	Q7RTU7	445
VCX	CALML6	Q8TD86	378
VCX	CALML3	P27482	378
VCX	CALML5	Q9NZT1	378
VCX	CALML4	Q96GE6	378
VCX	CALM1	P02593	368
VCX	TMEM165	Q9HC07	358
VCX	PPP3R1	P06705	334
VCX	PUDP	Q08623	318
VCX	VAC14	Q08AM6	311

IntAct

0 interactions, top by confidence:

BioGRID (5): VCX (Two-hybrid), VCX (Two-hybrid), VCX (Two-hybrid), FAM9A (Two-hybrid), VCX (Affinity Capture-MS)

ESM2 similar proteins: A0A1D9BZF0, A6QL64, B4DH59, B5DUH6, D3YZV8, E9Q6E9, O43493, O46383, O77733, P06916, P08116, P0C758, P0DKJ7, P0DKJ8, P0DPF3, P31568, P62521, Q01033, Q01042, Q1HVF7, Q2W8Q7, Q3BBV2, Q42626, Q42627, Q4ZJZ1, Q4ZJZ3, Q5JPF3, Q5MJ10, Q6AXX0, Q6GX35, Q6IC83, Q6P3W6, Q6PGQ1, Q7M4S9, Q7M732, Q86T75, Q8BP27, Q8IZU1, Q8N2N9, Q96QF7

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	3
Likely benign	10
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
202223	GRCh37/hg19 Xp22.31(chrX:6456777-8119329)x1	Pathogenic
564755	GRCh37/hg19 Xp22.31(chrX:6448751-8135644)x1	Pathogenic
816248	GRCh37/hg19 Xp22.33-22.31(chrX:168546-8503210)x1	Pathogenic
816293	GRCh37/hg19 Xp22.31(chrX:6896604-7887498)x1	Pathogenic
929373	GRCh37/hg19 Xp22.31(chrX:6476350-8135053)x3	Likely pathogenic

SpliceAI

319 predictions. Top by Δscore:

Variant	Effect	Δscore
X:7842364:G:T	donor_gain	0.9800
X:7842327:TCCTC:T	donor_gain	0.9500
X:7842357:A:T	donor_gain	0.9500
X:7843302:GAAG:G	donor_gain	0.9500
X:7842346:G:GT	donor_gain	0.9300
X:7843304:AGG:A	donor_loss	0.9300
X:7843305:GGT:G	donor_loss	0.9300
X:7843306:G:GG	donor_gain	0.9300
X:7843306:GTG:G	donor_loss	0.9300
X:7842316:G:GT	donor_gain	0.9200
X:7843307:T:A	donor_loss	0.9000
X:7842281:G:GT	donor_gain	0.8900
X:7843123:T:TA	acceptor_gain	0.8900
X:7843124:G:A	acceptor_gain	0.8900
X:7843496:A:AG	acceptor_gain	0.8900
X:7843497:G:GG	acceptor_gain	0.8900
X:7843495:CAGA:C	acceptor_gain	0.8600
X:7842364:G:GT	donor_gain	0.8500
X:7843304:AG:A	donor_gain	0.8500
X:7843305:GG:G	donor_gain	0.8500
X:7843494:CCAG:C	acceptor_loss	0.8500
X:7843495:CAGAC:C	acceptor_loss	0.8500
X:7843496:A:C	acceptor_loss	0.8500
X:7843497:G:A	acceptor_loss	0.8500
X:7843303:AAG:A	donor_gain	0.8400
X:7843497:GA:G	acceptor_gain	0.8400
X:7842323:A:G	donor_gain	0.8300
X:7842347:A:T	donor_gain	0.8300
X:7843301:AGAAG:A	donor_gain	0.8300
X:7843302:GAAGG:G	donor_gain	0.8300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1006706523 (X:7840746 C>A,G), RS1018161806 (X:7840436 G>C), RS1018554642 (X:7840762 G>A,C), RS1020216756 (X:7840825 G>A), RS1026771676 (X:7840373 G>A), RS1039584648 (X:7844598 G>A,T), RS1046056633 (X:7840699 T>C), RS1046509202 (X:7840351 C>A,T), RS1048098148 (X:7840738 G>A,T), RS1055350166 (X:7840263 T>A), RS1103931 (X:7844478 G>A), RS111462905 (X:7842611 G>A), RS112068586 (X:7844583 A>G), RS112105768 (X:7844306 G>T), RS112517702 (X:7844305 G>A,T)

Disease associations

OMIM: gene MIM:300229 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, affects expression	1
Diethylnitrosamine	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Plant Oils	increases expression	1

Clinical trials (associated diseases)

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