ENY2

Chr 8

ENY2 transcription and export complex 2 subunit

Also known as: DC6, Sus1, e(y)2

ENY2 encodes a transcription coactivator that functions within both the SAGA histone modification complex and the TREX-2 mRNA export complex, playing essential roles in gene transcription activation and nuclear mRNA export. The gene is highly constrained against loss-of-function variants (pLI 0.87, LOEUF 0.44), suggesting mutations would likely cause severe disease, though specific associated disorders have not yet been established in the literature. Given its fundamental role in transcription and mRNA processing, mutations would be expected to cause neurodevelopmental phenotypes affecting multiple organ systems.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
37
P/LP submissions
P/LP missense
0.44
LOEUF
LOF
Mechanism· predicted
Clinical SummaryENY2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 9 VUS of 57 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.44LOEUF
pLI 0.875
Z-score 2.41
OE 0.00 (0.000.44)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.43Z-score
OE missense 0.45 (0.320.63)
24 obs / 53.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.44)
00.351.4
Missense OE0.45 (0.320.63)
00.61.4
Synonymous OE1.37
01.21.6
LoF obs/exp: 0 / 6.8Missense obs/exp: 24 / 53.5Syn Z: -1.24
DN
0.5280th %ile
GOF
0.3491th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.44

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

57 submitted variants in ClinVar

Classification Summary

Pathogenic37
VUS9
Likely Benign1
37
Pathogenic
9
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
37
Likely Pathogenic
0
VUS
9
Likely Benign
1
Benign
0
Total47

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ENY2 · 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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Clinical Literature
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