ENY2

Chr 8

ENY2 transcription and export complex 2 subunit

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

NCBI Gene: 56943 ENSG00000120533 UniProt: Q9NPA8 OMIM: 619015

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables transcription coactivator activity. Involved in poly(A)+ mRNA export from nucleus; positive regulation of DNA-templated transcription; and regulation of transcription by RNA polymerase II. Located in mitochondrion and nucleoplasm. Part of SAGA complex and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.44

Clinical Summary— ENY2

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.

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ClinVar Variants

5 VUS of 15 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.875

Z-score 2.41

OE 0.00 (0.00–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.43Z-score

OE missense 0.45 (0.32–0.63)

24 obs / 53.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.44)

0≤0.351.4

Missense OE?0.45 (0.32–0.63)

0≤0.61.4

Synonymous OE?1.37

0≤1.21.6

LoF obs/exp: 0 / 6.8Missense obs/exp: 24 / 53.5Syn Z: -1.24

This gene — mechanism propensity

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

15 submitted variants in ClinVar

ClinVar

Classification Summary

VUS5

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	5	5
Likely Benign	0	0
Benign	0	0
Total	5	5

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

37 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap ENY2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →