ATRX

Chr XXLDXLR

ATRX chromatin remodeler

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

NCBI Gene: 546 ENSG00000085224 UniProt: P46100 OMIM: 300032

The ATRX protein is a chromatin remodeling ATPase/helicase that regulates gene expression and chromosomal segregation through cell cycle-dependent nuclear matrix and chromatin associations. Mutations cause X-linked alpha-thalassemia/intellectual disability syndrome and related conditions characterized by cognitive disabilities, alpha-thalassemia, and distinctive facial features through loss-of-function mechanisms that alter DNA methylation patterns. The condition follows X-linked inheritance with both dominant and recessive patterns reported.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

LOFmechanismXLD/XLRLOEUF 0.124 OMIM phenotypes

Clinical Summary— ATRX

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Gene-Disease Validity (ClinGen)

ATR-X-related syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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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

7 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint

0.12LOEUF

pLI 1.000

Z-score 8.22

OE 0.06 (0.03–0.12)

Highly constrained

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

Missense Constraint

3.10Z-score

OE missense 0.70 (0.66–0.75)

604 obs / 860.0 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios

LoF OE0.06 (0.03–0.12)

0≤0.351.4

Missense OE0.70 (0.66–0.75)

0≤0.61.4

Synonymous OE1.06

0≤1.21.6

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

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

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

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.

3D Protein StructureAlphaFold

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Small Cell Lung CancerAdvanced Solid Malignant Tumor

Chiauranib for Advanced Solid Malignant Tumors and Relapsed/Refractory SCLC.

RECRUITING

NCT05271292Phase PHASE1, PHASE2Chipscreen Biosciences, Ltd.Started 2022-08-26

Chiauranib

Pancreatic Neuroendocrine Tumor

ATRX/DAXX in EUS-FNB Specimens of Pan-NETs

ACTIVE NOT RECRUITING

NCT06406387Azienda Ospedaliera Universitaria Integrata VeronaStarted 2024-06-01

ATRX/DAXX immunohistochemistry

Neuroendocrine Carcinoma MetastaticPancreatic Tumors

FTT PET/CT in Pancreatic Neuroendocrine Tumors

RECRUITING

NCT07114939Phase PHASE1Abramson Cancer Center at Penn MedicineStarted 2025-10-01

[18F]FluorThanatrace

16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING

NCT01238250Simons SearchlightStarted 2010-10

Gastric CancerGastroEsophageal Cancer

Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers

ACTIVE NOT RECRUITING

NCT05379972Phase PHASE2University of Colorado, DenverStarted 2023-01-12

PembrolizumabOlaparibStereotactic Body Radiation Therapy

Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING

NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01

Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;

Multiple Myeloma of Bone

Predicting Response to Selinexor-Based Therapy in Relapsed/Refractory Multiple Myeloma: A Multicenter Prospective Study

RECRUITING

NCT07514052Shanxi Bethune HospitalStarted 2026-01-01

Selinexor-Based Regimen

Clinical Literature

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Landmark / reviewRecent case evidence

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