VCX2

Chr X

variable charge X-linked 2

Also known as: VCX-2r, VCX2R, VCXB

NCBI Gene: 51480 ENSG00000177504 UniProt: Q9H322 OMIM: 300532

VCX2 encodes a protein that may mediate processes in spermatogenesis and belongs to a polymorphic gene family expressed exclusively in male germ cells. Deletions in nearby family members have been implicated in cognitive disability, though the specific inheritance pattern and clinical consequences of VCX2 mutations remain unclear. The gene shows low constraint to loss-of-function variation, suggesting tolerance to disruption.

OMIM ResearchSummary from RefSeq, UniProt

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. [provided by RefSeq, Feb 2015]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.94

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.94LOEUF

pLI 0.058

Z-score -1.82

OE 5.68 (0.41–1.94)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-4.99Z-score

OE missense 3.07 (1.89–2.00)

142 obs / 46.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?5.68 (0.41–1.94)

0≤0.351.4

Missense OE?3.07 (1.89–2.00)

0≤0.61.4

Synonymous OE?2.50

0≤1.21.6

LoF obs/exp: 1 / 0.2Missense obs/exp: 142 / 46.3Syn Z: -5.72

Background carrier burden — how many people carry a rare variant somewhere in VCX2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

116 rare PASS variants

Rare truncating (LoF)

1 in 910

16 rare PASS variants

Rare synonymous (reference)

1 in 260

49 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for VCX2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 150	1 in 700
South Asian	~36k	1 in 400	none seen
Remaining (unassigned)	~31k	1 in 240	≈ 1 in 31,000
European (Finnish)	~26k	1 in 830	≈ 1 in 26,000
Admixed American	~23k	1 in 170	none seen
East Asian	~20k	1 in 230	none seen
African / African American	~18k	1 in 260	1 in 1,100
Ashkenazi Jewish	~13k	1 in 490	none seen
Middle Eastern	~2,551	1 in 390	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 1 of 2 coding exons well covered in gnomAD exomes; exon 2 poorly covered. Genomes: 0 of 2 (exons 2, 3 below).? see exons ↓