EVX2

Chr 2

even-skipped homeobox 2

Also known as: EVX-2

This gene is located at the 5' end of the HOXD gene cluster on chromosome 2. The encoded protein is a homeobox transcription factor that is related to the protein encoded by the Drosophila even-skipped (eve) gene, a member of the pair-rule class of segmentation genes. A 117 kb microdeletion at the 5' end of the HOXD gene cluster, which includes this gene and the HOXD9-HOXD13 genes, causes synpolydactyly, a dominantly inherited disease resulting in limb malformation. [provided by RefSeq, Sep 2009]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.68
Clinical SummaryEVX2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.68LOEUF
pLI 0.400
Z-score 2.22
OE 0.21 (0.090.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.15Z-score
OE missense 0.97 (0.871.09)
208 obs / 214.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.21 (0.090.68)
00.351.4
Missense OE?0.97 (0.871.09)
00.61.4
Synonymous OE?1.07
01.21.6
LoF obs/exp: 2 / 9.3Missense obs/exp: 208 / 214.2Syn Z: -0.51

This gene — mechanism propensity

DN
0.6355th %ile
GOF
0.3887th %ile
LOF
0.71top 10%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EVX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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