EBAG9

Chr 8

estrogen receptor binding site associated antigen 9

Also known as: EB9, PDAF

NCBI Gene: 9166 ENSG00000147654 UniProt: O00559 OMIM: 605772

The EBAG9 protein may participate in suppressing cell proliferation and inducing apoptotic cell death through activation of interleukin-1-beta converting enzyme-like proteases. Currently, no established Mendelian diseases have been definitively linked to mutations in this gene in pediatric patients. This gene shows relatively low constraint against loss-of-function variants (pLI 0.08, LOEUF 0.73), suggesting it may tolerate some degree of functional variation.

OMIM ResearchSummary from RefSeq, UniProt

This gene was identified as an estrogen-responsive gene. Regulation of transcription by estrogen is mediated by estrogen receptor, which binds to the estrogen-responsive element found in the 5'-flanking region of this gene. The encoded protein is a tumor-associated antigen that is expressed at high frequency in a variety of cancers. Alternate splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 10. [provided by RefSeq, Jul 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.73

Clinical Summary— EBAG9

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

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ClinVar Variants

28 VUS of 41 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.73LOEUF

pLI 0.077

Z-score 2.24

OE 0.32 (0.16–0.73)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.97Z-score

OE missense 0.73 (0.61–0.89)

76 obs / 103.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.16–0.73)

0≤0.351.4

Missense OE?0.73 (0.61–0.89)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 4 / 12.6Missense obs/exp: 76 / 103.8Syn Z: -0.35

This gene — mechanism propensity

0.6161th %ile

GOF

0.5954th %ile

LOF

0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

41 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign1

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	28	0	0	28
Likely Benign	0	0	1	1
Benign	0	1	0	1
Total	28	1	1	30

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap EBAG9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →