DAXX

death domain associated protein

Basic information

Region (hg38): 6:33318558-33323016

Links

ENSG00000204209 ∙ NCBI:1616 ∙ OMIM:603186 ∙ HGNC:2681 ∙ Uniprot:Q9UER7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DAXX gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAXX 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					1	1
missense			23	6	2	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1		2
Total	0	0	24	7	3

Variants in DAXX

This is a list of pathogenic ClinVar variants found in the DAXX region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-33319046-C-T		not specified	Likely benign (May 23, 2023)
6-33319047-G-A		not specified	Likely benign (Dec 28, 2022)
6-33319055-G-A		not specified	Likely benign (May 14, 2024)
6-33319146-G-A		not specified	Likely benign (Dec 14, 2022)
6-33319202-C-T		not specified	Likely benign (Mar 01, 2024)
6-33319402-C-T		not specified	Uncertain significance (May 08, 2024)
6-33319419-T-G		not specified	Uncertain significance (May 31, 2023)
6-33319503-C-A		not specified	Uncertain significance (May 09, 2023)
6-33319710-G-A		not specified	Uncertain significance (Sep 26, 2023)
6-33319809-T-C		not specified	Uncertain significance (Dec 22, 2023)
6-33319830-A-G		not specified	Likely benign (May 24, 2024)
6-33320019-G-C			Benign (Aug 15, 2018)
6-33320059-C-T		not specified	Uncertain significance (Dec 28, 2023)
6-33320158-C-T		not specified	Uncertain significance (Feb 13, 2024)
6-33320159-G-A			Benign (Jul 18, 2018)
6-33320384-C-T		not specified	Uncertain significance (Nov 20, 2023)
6-33320433-C-G		not specified	Uncertain significance (Aug 16, 2021)
6-33320444-G-A		not specified	Uncertain significance (May 02, 2024)
6-33320452-CT-C		Metastatic pancreatic neuroendocrine tumours	Likely pathogenic (Nov 01, 2017)
6-33320508-C-T			Benign (Jun 18, 2018)
6-33320565-C-T		not specified	Uncertain significance (Jan 06, 2023)
6-33320589-C-T		not specified	Likely benign (May 31, 2023)
6-33320915-C-T		not specified	Uncertain significance (May 26, 2023)
6-33320925-G-A		Metastatic pancreatic neuroendocrine tumours	Likely pathogenic (Nov 01, 2017)
6-33320948-T-C		not specified	Uncertain significance (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAXX	protein_coding	protein_coding	ENST00000374542	7	10712

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0986	0.901	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	343	430	0.798	0.0000266	4785
Missense in Polyphen		99	147.83	0.66967		1818
Synonymous	0.233	165	169	0.977	0.00000924	1543
Loss of Function	3.51	7	26.5	0.264	0.00000151	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000208	0.000208
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.0000708	0.0000703
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription corepressor known to repress transcriptional potential of several sumoylated transcription factors. Down-regulates basal and activated transcription. Its transcription repressor activity is modulated by recruiting it to subnuclear compartments like the nucleolus or PML/POD/ND10 nuclear bodies through interactions with MCSR1 and PML, respectively. Seems to regulate transcription in PML/POD/ND10 nuclear bodies together with PML and may influence TNFRSF6-dependent apoptosis thereby. Inhibits transcriptional activation of PAX3 and ETS1 through direct protein-protein interactions. Modulates PAX5 activity; the function seems to involve CREBBP. Acts as an adapter protein in a MDM2-DAXX-USP7 complex by regulating the RING-finger E3 ligase MDM2 ubiquitination activity. Under non-stress condition, in association with the deubiquitinating USP7, prevents MDM2 self-ubiquitination and enhances the intrinsic E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and subsequent proteasomal degradation. Upon DNA damage, its association with MDM2 and USP7 is disrupted, resulting in increased MDM2 autoubiquitination and consequently, MDM2 degradation, which leads to TP53 stabilization. Acts as histone chaperone that facilitates deposition of histone H3.3. Acts as targeting 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. Does not affect the ATPase activity of ATRX but alleviates its transcription repression activity. Upon neuronal activation associates with regulatory elements of selected immediate early genes where it promotes deposition of histone H3.3 which may be linked to transcriptional induction of these genes. Required for the recruitment of histone H3.3:H4 dimers to PML-nuclear bodies (PML- NBs); the process is independent of ATRX and facilitated by ASF1A; PML-NBs are suggested to function as regulatory sites for the incorporation of newly synthesized histone H3.3 into chromatin. In case of overexpression of centromeric histone variant CENPA (as found in various tumors) is involved in its mislocalization to chromosomes; the ectopic localization involves a heterotypic tetramer containing CENPA, and histones H3.3 and H4 and decreases binding of CTCF to chromatin. Proposed to mediate activation of the JNK pathway and apoptosis via MAP3K5 in response to signaling from TNFRSF6 and TGFBR2. Interaction with HSPB1/HSP27 may prevent interaction with TNFRSF6 and MAP3K5 and block DAXX-mediated apoptosis. In contrast, in lymphoid cells JNC activation and TNFRSF6-mediated apoptosis may not involve DAXX. Shows restriction activity towards human cytomegalovirus (HCMV). Plays a role as a positive regulator of the heat shock transcription factor HSF1 activity during the stress protein response (PubMed:15016915). {ECO:0000269|PubMed:12140263, ECO:0000269|PubMed:14990586, ECO:0000269|PubMed:15016915, ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17081986, ECO:0000269|PubMed:17942542, ECO:0000269|PubMed:20504901, ECO:0000269|PubMed:20651253, ECO:0000269|PubMed:23222847, ECO:0000269|PubMed:24200965, ECO:0000269|PubMed:24530302}.
• Pathway: Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);TGF-Ncore;EGF-Ncore;Androgen receptor signaling pathway;Apoptosis Modulation and Signaling;Amyotrophic lateral sclerosis (ALS);Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;MAPK Signaling Pathway;p38 MAPK Signaling Pathway;Gene expression (Transcription);hiv-1 nef: negative effector of fas and tnf;stress induction of hsp regulation;keratinocyte differentiation;Generic Transcription Pathway;Fas;RNA Polymerase II Transcription;fas signaling pathway (cd95);AndrogenReceptor;regulation of transcriptional activity by pml;TGF_beta_Receptor;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;IL6;HIV-1 Nef: Negative effector of Fas and TNF-alpha;p53 pathway (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.0616
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.88

Haploinsufficiency Scores

• pHI: 0.880
• hipred: Y
• hipred_score: 0.743
• ghis: 0.509

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Daxx
• Phenotype: embryo phenotype; normal phenotype; 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); 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); growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: positive regulation of protein phosphorylation;nucleosome assembly;chromatin remodeling;regulation of transcription, DNA-templated;apoptotic process;activation of JUN kinase activity;extrinsic apoptotic signaling pathway via death domain receptors;viral process;androgen receptor signaling pathway;regulation of protein ubiquitination;cellular response to heat;cellular response to unfolded protein;positive regulation of protein kinase activity;negative regulation of transcription, DNA-templated;cellular response to cadmium ion;cellular response to copper ion;cellular response to diamide;positive regulation of neuron death;positive regulation of nucleic acid-templated transcription;cellular response to sodium arsenite
• Cellular component: chromosome, centromeric region;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;nuclear body;PML body
• Molecular function: p53 binding;transcription coactivator activity;transcription corepressor activity;protein binding;enzyme binding;protein kinase binding;protein kinase activator activity;heat shock protein binding;ubiquitin protein ligase binding;SUMO binding;histone binding;protein heterodimerization activity;protein N-terminus binding;androgen receptor binding