• 0
    Haplo
    Score
  • 40
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
VCX3A (HGNC:18159) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
variable charge X-linked 3A
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
VCX3
Alias symbols
VCX-8r, VCX-8R, VCX-A
%HI
94.12(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.31(Read more about gnomAD pLI score)
LOEUF
1.87(Read more about gnomAD LOEUF score)
Cytoband
Xp22.31
Genomic Coordinates
GRCh37/hg19: chrX:6451659-6453159 NCBI Ensembl UCSC
GRCh38/hg38: chrX:6533618-6535118 NCBI Ensembl UCSC
MANE Select Transcript
NM_016379.4 ENST00000381089.7 (Read more about MANE Select)
Function
May mediate a process in spermatogenesis or may play a role in sex ratio distortion. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-7171
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
Dosage Sensitivity Unlikely (40)
Last Evaluated:
10/12/2012

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence Comments:
Focal deletions or loss of function mutations within VCX3A (VCXA) have not been described. Some studies suggest that deletion of VCX3A is responsible for intellectual disability. Fukami et al (2000, PMID:10903929) report deletion mapping of 15 males with and without intellectual disability (ID) who had deletions at Xp22.3. This revealed a deleted interval common to all four individuals with ID and not deleted in individuals without ID which contained only VCX3A. Mutation analysis of 5 patients with XLID and linkage to Xp22 did not reveal mutations. Van Esch et al. (2005, PMID:15888481) established that the recomination site for 1.5 Mb deletion in patient with X-linked ichthyosis (XLI) and ID was between VCX3A and VCXB. Also, based on a patient with an unbalanced t(X;Y), they propose a combined dosage mechanism for all VCX/Y genes. Hosomi et al. (2007, PMID:17113756) report a male with XLI and an IQ of 76, which they consider borderline low, whose deletion included the promoter of VCX3A. However, there are also many reports of individuals with deletions including VCX3A who have normal intelligence. Cuevas-Covarrubias et al. (2008, PMID:18076704) and Gonzalez-Huerta et al. (2009, PMID:19200188) reported many males with XLI and normal intelligence who had a deletion that includes VCX3A. Lesca et al. (2005, PMID:15733277) report a family in which 7 males have XLI due to a deletion that includes VCX3A. Six of the patients had normal intelligence and one had myoclonic epilepsy starting at age 1 month and moderate developmental delay. Turner et al. (2003, PMID:12599187) report a family with a syndromic form of X-linked ID in which linkage studies excluded VCX3A. Additionally, there reports of male individuals with unbalanced X;Y translocation resulting in deletion at Xp22 that involves VCX3A who have normal cognition (PMIDs: 14636323, 11474655) and a report by Palka-Bayard-de-Volo et al (2012, PMID:22583828) of a female with mild ID and other features who had a 6.8 Mb deletion as a result of a de novo der(X)t(X;Y)(p22;q11) that did not include VCX3A. Some studies listed above suggest that the ID in the patients originally reported by Fukami et al. could be explained by deletion of NLGN4X, rather than VCX3A.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
40
TS Evidence Strength:
Dosage Sensitivity Unlikely (Disclaimer)
TS Evidence Comments:
There are several reports in DGV of duplications of VCX3A in control populations, including PMID:17911159, 15895083, and 17116639.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)