ATRX
ATRX chromatin remodeler, the group of RNA helicases
Basic information
Region (hg38): X:77504880-77786233
Previous symbols: [ "RAD54", "JMS", "MRX52" ]
Links
Phenotypes
GenCC
Source:
- alpha thalassemia-X-linked intellectual disability syndrome (Definitive), mode of inheritance: XLR
- alpha thalassemia-X-linked intellectual disability syndrome (Definitive), mode of inheritance: XL
- intellectual disability-hypotonic facies syndrome, X-linked, 1 (Moderate), mode of inheritance: XL
- alpha thalassemia-X-linked intellectual disability syndrome (Supportive), mode of inheritance: XL
- alpha thalassemia-X-linked intellectual disability syndrome (Definitive), mode of inheritance: XL
- alpha thalassemia-X-linked intellectual disability syndrome (Strong), mode of inheritance: XL
- ATR-X-related syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Alpha-thalassemia/impaired intellectual development syndrome, X-linked; Intellectual disability-hypotonic facies syndrome, X-linked 1 | XL | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic; Renal | 6267462; 6682021; 6711605; 3239563; 1684092; 7726225; 8644709; 10398237; 10398234; 11449489; 11050622; 10751095; 15508018; 16222662; 16100724; 16813605; 16955409; 16688741; 17579672; 19764021; 20301622; 22089611 |
ClinVar
This is a list of variants' phenotypes submitted to
- Alpha thalassemia-X-linked intellectual disability syndrome (23 variants)
- not provided (15 variants)
- Intellectual disability-hypotonic facies syndrome, X-linked, 1 (4 variants)
- ATRX-related disorder (2 variants)
- Adrenal cortex carcinoma (1 variants)
- Global developmental delay (1 variants)
- Ambiguous genitalia;Intellectual disability, severe;Cryptorchidism;Microcephaly;Bone osteosarcoma (1 variants)
- Alpha thalassemia-X-linked intellectual disability syndrome;Intellectual disability-hypotonic facies syndrome, X-linked, 1 (1 variants)
- Inborn genetic diseases (1 variants)
- Intellectual disability-hypotonic facies syndrome, X-linked (1 variants)
- See cases (1 variants)
- Intellectual disability-hypotonic facies syndrome, X-linked, 1;Alpha thalassemia-X-linked intellectual disability syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATRX gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 638 | 39 | 683 | |||
| missense | 39 | 518 | 251 | 76 | 890 | |
| nonsense | 13 | 22 | ||||
| start loss | 3 | |||||
| frameshift | 13 | 16 | ||||
| inframe indel | 34 | 42 | ||||
| splice donor/acceptor (+/-2bp) | 9 | |||||
| splice region | 3 | 2 | 25 | 90 | 9 | 129 |
| non coding | 208 | 54 | 266 | |||
| Total | 38 | 52 | 567 | 1104 | 170 |
Highest pathogenic variant AF is 0.00000892
Variants in ATRX
This is a list of pathogenic ClinVar variants found in the ATRX region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-77508138-G-A | Likely benign (Jul 10, 2018) | |||
| X-77508356-T-C | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Jul 09, 2023) | ||
| X-77508357-TG-T | Alpha thalassemia-X-linked intellectual disability syndrome | Uncertain significance (Dec 05, 2020) | ||
| X-77508362-T-A | Alpha thalassemia-X-linked intellectual disability syndrome | Uncertain significance (Aug 10, 2023) | ||
| X-77508376-C-T | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Feb 03, 2023) | ||
| X-77508391-C-T | Alpha thalassemia-X-linked intellectual disability syndrome | Conflicting classifications of pathogenicity (Aug 02, 2023) | ||
| X-77508394-A-G | Alpha thalassemia-X-linked intellectual disability syndrome • ATRX-related disorder | Benign (Jun 30, 2023) | ||
| X-77508395-T-C | Alpha thalassemia-X-linked intellectual disability syndrome | Conflicting classifications of pathogenicity (Jan 31, 2024) | ||
| X-77508398-G-A | Alpha thalassemia-X-linked intellectual disability syndrome | Benign (Dec 17, 2023) | ||
| X-77508398-G-C | Inborn genetic diseases • Alpha thalassemia-X-linked intellectual disability syndrome • Acquired hemoglobin H disease;Alpha thalassemia-X-linked intellectual disability syndrome;Intellectual disability-hypotonic facies syndrome, X-linked, 1 | Conflicting classifications of pathogenicity (Jan 04, 2024) | ||
| X-77508399-G-A | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Jun 04, 2023) | ||
| X-77508401-G-T | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Jun 25, 2021) | ||
| X-77508402-T-A | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Mar 06, 2021) | ||
| X-77508405-T-C | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Nov 16, 2022) | ||
| X-77508408-A-G | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Aug 23, 2023) | ||
| X-77508409-C-T | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Jul 12, 2022) | ||
| X-77508417-T-C | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (May 05, 2022) | ||
| X-77508422-G-A | Uncertain significance (Dec 11, 2023) | |||
| X-77508424-G-A | Uncertain significance (May 02, 2023) | |||
| X-77508429-C-T | Alpha thalassemia-X-linked intellectual disability syndrome | Benign (Dec 27, 2023) | ||
| X-77508430-A-G | Alpha thalassemia-X-linked intellectual disability syndrome | Likely benign (Sep 03, 2023) | ||
| X-77508434-C-A | not specified | Uncertain significance (Jul 09, 2020) | ||
| X-77508434-C-T | Uncertain significance (Nov 01, 2023) | |||
| X-77508435-AC-A | Pathogenic (Aug 07, 2012) | |||
| X-77508436-CCAGCCACTGGCTGATACATTCCT-C | Uncertain significance (Apr 01, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ATRX | protein_coding | protein_coding | ENST00000373344 | 35 | 281347 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 2.88e-11 | 125711 | 0 | 9 | 125720 | 0.0000358 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.10 | 604 | 860 | 0.702 | 0.0000617 | 16613 |
| Missense in Polyphen | 122 | 360.46 | 0.33846 | 6761 | ||
| Synonymous | -0.824 | 310 | 292 | 1.06 | 0.0000207 | 4376 |
| Loss of Function | 8.22 | 5 | 88.5 | 0.0565 | 0.00000723 | 1648 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000114 | 0.0000985 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000626 | 0.0000462 |
| European (Non-Finnish) | 0.0000738 | 0.0000528 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in transcriptional regulation and chromatin remodeling. Facilitates DNA replication in multiple cellular environments and is required for efficient replication of a subset of genomic loci. Binds to DNA tandem repeat sequences in both telomeres and euchromatin and in vitro binds DNA quadruplex structures. May help stabilizing G-rich regions into regular chromatin structures by remodeling G4 DNA and incorporating H3.3- containing nucleosomes. Catalytic component of the chromatin remodeling complex ATRX:DAXX which has ATP-dependent DNA translocase activity and catalyzes the replication-independent deposition of histone H3.3 in pericentric DNA repeats outside S- phase and telomeres, and the in vitro remodeling of H3.3- containing nucleosomes. Its heterochromatin targeting is proposed to involve a combinatorial readout of histone H3 modifications (specifically methylation states of H3K9 and H3K4) and association with CBX5. Involved in maintaining telomere structural integrity in embryonic stem cells which probably implies recruitment of CBX5 to telomers. Reports on the involvement in transcriptional regulation of telomeric repeat-containing RNA (TERRA) are conflicting; according to a report, it is not sufficient to decrease chromatin condensation at telomers nor to increase expression of telomeric RNA in fibroblasts (PubMed:24500201). May be involved in telomere maintenance via recombination in ALT (alternative lengthening of telomeres) cell lines. Acts as negative regulator of chromatin incorporation of transcriptionally repressive histone H2AFY, particularily at telomeres and the alpha-globin cluster in erythroleukemic cells. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, required for the chromatin occupancy of SMC1 and CTCTF within the H19 imprinting control region (ICR) and involved in esatblishment of histone tails modifications in the ICR. May be involved in brain development and facial morphogenesis. Binds to zinc-finger coding genes with atypical chromatin signatures and regulates its H3K9me3 levels. Forms a complex with ZNF274, TRIM28 and SETDB1 to facilitate the deposition and maintenance of H3K9me3 at the 3' exons of zinc- finger genes (PubMed:27029610). {ECO:0000269|PubMed:12953102, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:21029860, ECO:0000269|PubMed:22391447, ECO:0000269|PubMed:22829774, ECO:0000269|PubMed:24500201, ECO:0000269|PubMed:27029610}.;
- Disease
- DISEASE: Alpha-thalassemia mental retardation syndrome, X-linked (ATRX) [MIM:301040]: A disorder characterized by severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions. {ECO:0000269|PubMed:10204841, ECO:0000269|PubMed:10417298, ECO:0000269|PubMed:10660327, ECO:0000269|PubMed:10995512, ECO:0000269|PubMed:12116232, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:16955409, ECO:0000269|PubMed:21421568, ECO:0000269|PubMed:7697714, ECO:0000269|PubMed:8968741, ECO:0000269|PubMed:9043863, ECO:0000269|PubMed:9326931}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mental retardation, X-linked, syndromic, with hypotonic facies 1 (MRXSHF1) [MIM:309580]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSHF1 is a syndromic mental retardation. Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects. {ECO:0000269|PubMed:10398237, ECO:0000269|PubMed:10751095, ECO:0000269|PubMed:11050622, ECO:0000269|PubMed:15565397, ECO:0000269|PubMed:16222662, ECO:0000269|PubMed:8630485}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]: A disorder characterized by hypochromic, microcytic red blood cells, hemoglobin H detected in peripheral blood, and multilineage myelodysplasia. {ECO:0000269|PubMed:12858175}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Pathways Affected in Adenoid Cystic Carcinoma
(Consensus)
Recessive Scores
- pRec
- 0.563
Intolerance Scores
- loftool
- 0.00517
- rvis_EVS
- -0.93
- rvis_percentile_EVS
- 9.75
Haploinsufficiency Scores
- pHI
- hipred
- Y
- hipred_score
- 0.859
- ghis
- 0.569
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Atrx
- Phenotype
- nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cellular phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- meiotic spindle organization;DNA repair;DNA methylation;nucleosome assembly;DNA replication-independent nucleosome assembly;chromatin remodeling;regulation of transcription, DNA-templated;spermatogenesis;positive regulation of nuclear cell cycle DNA replication;DNA damage response, signal transduction by p53 class mediator;forebrain development;replication fork processing;positive regulation of telomere maintenance;post-embryonic forelimb morphogenesis;multicellular organism growth;positive regulation of transcription by RNA polymerase II;Sertoli cell development;chromosome organization involved in meiotic cell cycle;protein localization to chromosome, telomeric region;seminiferous tubule development;cellular response to hydroxyurea;regulation of histone H3-K9 trimethylation;negative regulation of telomeric RNA transcription from RNA pol II promoter;positive regulation of telomeric RNA transcription from RNA pol II promoter;negative regulation of maintenance of mitotic sister chromatid cohesion, telomeric
- Cellular component
- condensed nuclear chromosome, centromeric region;nuclear chromosome, telomeric region;nucleus;nucleoplasm;nuclear heterochromatin;pericentric heterochromatin;nuclear body;PML body;nuclear pericentric heterochromatin;telomeric heterochromatin;nuclear subtelomeric heterochromatin
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;chromatin binding;helicase activity;protein binding;ATP binding;DNA translocase activity;methylated histone binding;histone binding;metal ion binding;chromo shadow domain binding