ESX1

Chr XADAR

ESX homeobox 1

Also known as: ESX1L, ESXR1

The ESX1 protein functions as a transcriptional repressor and cell cycle regulator that undergoes proteolytic cleavage to produce nuclear and cytoplasmic fragments involved in controlling cyclin degradation and gene expression. Mutations cause amelogenesis imperfecta type IV, trichodontoosseous syndrome, and metaphyseal anadysplasia 2, affecting dental enamel formation, hair and tooth development, and bone growth. Both autosomal dominant and autosomal recessive inheritance patterns are reported.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Amelogenesis imperfecta, type IVMIM #104510
AD
Trichodontoosseous syndromeMIM #190320
AD
Metaphyseal anadysplasia 2MIM #613073
AR
0
Active trials
0
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.75
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryESX1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.75LOEUF
pLI 0.527
Z-score 1.96
OE 0.16 (0.060.75)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
-0.04Z-score
OE missense 1.01 (0.891.15)
157 obs / 155.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.16 (0.060.75)
00.351.4
Missense OE1.01 (0.891.15)
00.61.4
Synonymous OE1.44
01.21.6
LoF obs/exp: 1 / 6.3Missense obs/exp: 157 / 155.7Syn Z: -2.80
DN
0.7132th %ile
GOF
0.72top 25%
LOF
0.3842th %ile

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

GOFprediction 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

ESX1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗