DUX4

double homeobox 4

Basic information

Region (hg38): 4:190173773-190185942

Links

ENSG00000260596 ∙ NCBI:100288687 ∙ OMIM:606009 ∙ HGNC:50800 ∙ Uniprot:Q9UBX2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Facioscapulohumeral muscular dystrophy, type 2	Digenic	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	Musculoskeletal	23143600
Digenic inheritance has been described involving an SMCHD1 variant and a permissive D4Z4 haplotype

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DUX4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DUX4 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						0
missense			1			1
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	1	0	0

Variants in DUX4

This is a list of pathogenic ClinVar variants found in the DUX4 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-190174726-T-A		not specified	Uncertain significance (May 04, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcriptional regulation. May regulate microRNA (miRNA) expression. {ECO:0000269|PubMed:10433963, ECO:0000269|PubMed:24145033}.
• Disease: DISEASE: Facioscapulohumeral muscular dystrophy 1 (FSHD1) [MIM:158900]: A degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. {ECO:0000269|PubMed:10433963, ECO:0000269|PubMed:19320656}. Note=The gene represented in this entry is involved in disease pathogenesis. The disease is caused by deletion of an integral number of units of a 3.3-kb tandem repeats, termed D4Z4 macrosatellite, located on chromosome 4q35. In unaffected subjects, the D4Z4 array consists of 11-150 repeats, while in FSHD1 patients, the array is reduced to 1-10 repeats (PubMed:19320656). DUX4 is located in D4Z4 macrosatellite which is epigenetically repressed in somatic tissues. D4Z4 chromatin relaxation in FSHD1 results in inefficient epigenetic repression of DUX4 and a variegated pattern of DUX4 protein expression in a subset of skeletal muscle nuclei. Ectopic expression of DUX4 in skeletal muscle activates the expression of stem cell and germline genes, and, when overexpressed in somatic cells, DUX4 can ultimately lead to cell death. {ECO:0000269|PubMed:19320656}.

Haploinsufficiency Scores

• ghis: 0.394

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.189

Gene ontology

• Biological process: apoptotic process;negative regulation of cell population proliferation;positive regulation of transcription by RNA polymerase II;negative regulation of G0 to G1 transition
• Cellular component: nucleus;nucleoplasm;nucleolus;Golgi apparatus;cytosol;nuclear membrane
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding