ATRX

Chr XXLDXLR

ATRX chromatin remodeler

Also known as: JMS, MRX52, RAD54, RAD54L, XH2, XNP, ZNF-HX

The protein encoded by this gene contains an ATPase/helicase domain, and thus it belongs to the SWI/SNF family of chromatin remodeling proteins. This protein is found to undergo cell cycle-dependent phosphorylation, which regulates its nuclear matrix and chromatin association, and suggests its involvement in the gene regulation at interphase and chromosomal segregation in mitosis. Mutations in this gene are associated with X-linked syndromes exhibiting cognitive disabilities as well as alpha-thalassemia (ATRX) syndrome. These mutations have been shown to cause diverse changes in the pattern of DNA methylation, which may provide a link between chromatin remodeling, DNA methylation, and gene expression in developmental processes. Multiple alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2017]

OMIMResearchGenerating clinical summary…
LOFmechanismXLD/XLRLOEUF 0.124 OMIM phenotypes
Clinical SummaryATRX
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Gene-Disease Validity (ClinGen)
ATR-X-related syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.12LOEUF
pLI 1.000
Z-score 8.22
OE 0.06 (0.030.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
3.10Z-score
OE missense 0.70 (0.660.75)
604 obs / 860.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.06 (0.030.12)
00.351.4
Missense OE?0.70 (0.660.75)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 5 / 88.5Missense obs/exp: 604 / 860.0Syn Z: -0.82
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveATRX-related alpha-thalassemia intellectual developmental disorder syndrome non-deletion typeLOFXLR

This gene — mechanism propensity

DN
0.3097th %ile
GOF
0.16100th %ile
LOF
0.77top 5%

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

LOFprediction above median · LOEUF 0.12 · ClinGen HI: Sufficient evidence for dosage pathogenicity

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ATRX · 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