VCX2

Summary

VCX2 (variable charge X-linked 2, HGNC:18158) is a protein-coding gene on chromosome Xp22.31, encoding Variable charge X-linked protein 2 (Q9H322). 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 that are expressed exclusively in male germ cells. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. This gene contains two copies of a 30 nt tandem repeat. Deletion of a nearby member of this family was implicated in cognitive disability.

Source: NCBI Gene 51480 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total — 1 pathogenic
• MANE Select transcript: NM_016378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18158
Approved symbol	VCX2
Name	variable charge X-linked 2
Location	Xp22.31
Locus type	gene with protein product
Status	Approved
Aliases	VCX-2r, VCX-2R
Ensembl gene	ENSG00000177504
Ensembl biotype	protein_coding
OMIM	300532
Entrez	51480

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000317103

RefSeq mRNA: 1 — MANE Select: NM_016378 NM_016378

CCDS: CCDS35200

Canonical transcript exons

ENST00000317103 — 3 exons

Exon	Start	End
ENSE00001237016	8169944	8170349
ENSE00001615353	8171107	8171267
ENSE00001782121	8170542	8170789

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 86.54.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.54	gold quality
left testis	UBERON:0004533	60.20	gold quality
testis	UBERON:0000473	59.57	gold quality
right testis	UBERON:0004534	58.03	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
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	35.21	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
right uterine tube	UBERON:0001302	32.39	gold quality
muscle tissue	UBERON:0002385	32.14	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	29.91	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
tonsil	UBERON:0002372	28.79	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
smooth muscle tissue	UBERON:0001135	27.29	gold quality
islet of Langerhans	UBERON:0000006	27.11	silver quality
muscle of leg	UBERON:0001383	26.89	silver quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.25	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
endometrium	UBERON:0001295	25.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

Cross-species orthologs

0 orthologs

Paralogs (5): VCY1B (ENSG00000129862), VCY (ENSG00000129864), VCX3A (ENSG00000169059), VCX (ENSG00000182583), VCX3B (ENSG00000205642)

Protein

Protein identifiers

Variable charge X-linked protein 2 — Q9H322 (reviewed: Q9H322)

Alternative names: Variable charge protein on X with two repeats, Variably charged protein X-B

All UniProt accessions (1): Q9H322

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 (1): NP_057462* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026653	VCX/VCY1	Family

Pfam: PF15231

UniProt features (14 total): sequence variant 4, compositionally biased region 3, repeat 2, sequence conflict 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H322-F1	62.53	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): GOBP_HEAD_DEVELOPMENT, HAMAI_APOPTOSIS_VIA_TRAIL_DN, chrXp22, GSE10325_BCELL_VS_LUPUS_BCELL_UP, GSE11864_UNTREATED_VS_CSF1_IFNG_PAM3CYS_IN_MAC_DN, GSE17974_CTRL_VS_ACT_IL4_AND_ANTI_IL12_0.5H_CD4_TCELL_UP, GSE29618_PRE_VS_DAY7_POST_TIV_FLU_VACCINE_BCELL_DN, GSE9960_HEALTHY_VS_SEPSIS_PBMC_UP, GSE25088_CTRL_VS_ROSIGLITAZONE_STIM_STAT6_KO_MACROPHAGE_UP, GSE34156_UNTREATED_VS_24H_NOD2_AND_TLR1_TLR2_LIGAND_TREATED_MONOCYTE_DN, GOBP_CENTRAL_NERVOUS_SYSTEM_DEVELOPMENT, GSE42088_2H_VS_24H_LEISHMANIA_INF_DC_DN

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

GO Molecular Function (0):

GO Cellular Component (0):

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

Protein interactions and networks

STRING

316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCX2	STS	P08842	776
VCX2	PUDP	Q08623	665
VCX2	ARX	Q96QS3	647
VCX2	PNPLA4	P41247	641
VCX2	C3orf22	Q8N5N4	479
VCX2	ARSF	P54793	446
VCX2	DCP2	Q8IU60	437
VCX2	RNASE12	Q5GAN4	434
VCX2	C6orf163	Q5TEZ5	432
VCX2	C12orf56	Q8IXR9	432
VCX2	SMIM17	P0DL12	419
VCX2	TGIF2LX	Q8IUE1	418
VCX2	HSFX1	Q9UBD0	418
VCX2	CFAP107	Q8N1D5	417
VCX2	SH2D7	A6NKC9	400

IntAct

0 interactions, top by confidence:

BioGRID (9): VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), VCX2 (Two-hybrid), STAC3 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTR3, A0A7H0DN82, A7RR34, E9PVX6, O14598, O60356, O60829, O94243, P04605, P04614, P05909, P0C1K0, P0C765, P0C766, P0DPH9, P17285, P17759, P18098, P19416, P20290, P24109, P46012, P46583, Q06428, Q07555, Q08561, Q09821, Q1L9C7, Q32PF3, Q3KP22, Q5M948, Q5M951, Q5MJ08, Q5RCI9, Q6P8I4, Q758T8, Q76632, Q7M2N1, Q7TP40, Q80WR5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	2
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4683030	GRCh37/hg19 Xp22.32-22.31(chrX:5723890-8448373)x1	Pathogenic

SpliceAI

175 predictions. Top by Δscore:

Variant	Effect	Δscore
X:8170541:CCTT:C	donor_gain	0.9600
X:8170538:TCA:T	donor_loss	0.9500
X:8170539:CA:C	donor_loss	0.9500
X:8170540:A:AT	donor_loss	0.9500
X:8170540:A:AC	donor_gain	0.9400
X:8170541:C:CC	donor_gain	0.9400
X:8171165:C:A	donor_gain	0.9400
X:8170350:C:CC	acceptor_gain	0.9100
X:8171190:TA:T	donor_gain	0.8900
X:8171212:T:TA	donor_gain	0.8900
X:8171187:TGCTA:T	donor_gain	0.8700
X:8170583:T:TA	donor_gain	0.8500
X:8170540:AC:A	donor_gain	0.8400
X:8170541:CC:C	donor_gain	0.8400
X:8171172:T:A	donor_gain	0.8400
X:8170541:CCT:C	donor_gain	0.8300
X:8171182:T:TA	donor_gain	0.8300
X:8170360:A:T	acceptor_gain	0.8200
X:8170349:TCT:T	acceptor_loss	0.8100
X:8170350:C:T	acceptor_loss	0.8100
X:8170348:GT:G	acceptor_gain	0.8000
X:8170540:ACCTT:A	donor_gain	0.8000
X:8170541:CCTTC:C	donor_gain	0.8000
X:8171126:A:AC	donor_gain	0.8000
X:8171127:C:CC	donor_gain	0.8000
X:8170348:GTCT:G	acceptor_gain	0.7800
X:8171106:T:C	donor_gain	0.7800
X:8170346:TAGT:T	acceptor_gain	0.7700
X:8170345:GTAGT:G	acceptor_gain	0.7500
X:8170362:C:CT	acceptor_gain	0.7500

AlphaMissense

906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:8170296:C:A	K52N	0.830
X:8170296:C:G	K52N	0.830
X:8170275:C:A	M59I	0.818
X:8170275:C:G	M59I	0.818
X:8170275:C:T	M59I	0.818
X:8170278:C:A	K58N	0.807
X:8170278:C:G	K58N	0.807
X:8170305:T:A	R49S	0.766
X:8170305:T:G	R49S	0.766
X:8170548:C:A	K32N	0.751
X:8170548:C:G	K32N	0.751
X:8170294:T:A	K53I	0.749
X:8170293:T:A	K53N	0.748
X:8170293:T:G	K53N	0.748
X:8170638:A:C	S2R	0.744
X:8170638:A:T	S2R	0.744
X:8170640:T:G	S2R	0.744
X:8170297:T:A	K52M	0.736
X:8170059:A:C	F131L	0.734
X:8170059:A:T	F131L	0.734
X:8170061:A:G	F131L	0.734
X:8170632:C:A	K4N	0.700
X:8170632:C:G	K4N	0.700
X:8170328:C:G	G42R	0.697
X:8170328:C:T	G42R	0.697
X:8170323:T:A	K43N	0.694
X:8170323:T:G	K43N	0.694
X:8170329:C:A	K41N	0.693
X:8170329:C:G	K41N	0.693
X:8170332:C:A	K40N	0.692

dbSNP variants (sampled 300 via entrez): RS1008750347 (X:8171279 A>G), RS1008781271 (X:8171688 G>A), RS1013220331 (X:8172368 T>C), RS1013299039 (X:8172553 A>C,G), RS1013380752 (X:8170866 G>GC,GT,GTA), RS1018756778 (X:8171280 T>A,G), RS1018871672 (X:8171705 A>T), RS1022486596 (X:8171734 A>G), RS1023268427 (X:8172371 T>TA), RS1024998552 (X:8172116 G>GT,GTT), RS1026260589 (X:8171249 C>T), RS1027932135 (X:8172695 A>G), RS1030734817 (X:8172350 A>G), RS1040343842 (X:8171943 G>T), RS1040350966 (X:8172279 A>G)

Disease associations

OMIM: gene MIM:300532 | 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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
propionaldehyde	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1
Phenobarbital	affects expression	1
Plant Oils	increases expression	1
Valproic Acid	decreases methylation	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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