DEAF1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the DEAF1 gene, its protein product, associated diseases, expression patterns, and mutational landscape.
Gene Information Card
| Symbol | DEAF1 |
|---|---|
| Full Name | DEAF1 transcription factor |
| Gene Type | Protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 10522 ncbi.nlm.nih.gov/gene/10522 |
| Ensembl ID | ENSG00000177030 |
| UniProt ID | O75398 |
| OMIM ID | 602635 |
| HGNC ID | 2710 |
| Aliases | DEAF-1, NUDR, SPN, ZMYND5 |
Description
The DEAF1 gene encodes a transcription factor involved in chromatin remodeling and transcriptional regulation. It contains a SAND domain and a MYND zinc finger domain, which mediate DNA binding and protein-protein interactions. DEAF1 plays critical roles in neurodevelopment, immune function, and cellular differentiation. Mutations in DEAF1 are associated with neurodevelopmental disorders, including intellectual disability and developmental and epileptic encephalopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy (DEE) | Pathogenic variants in DEAF1 lead to altered transcriptional regulation, affecting neuronal development and function. | ClinVar; PMID: 29276005 |
| Intellectual disability, autosomal dominant 24 | Dominant mutations cause haploinsufficiency or dominant-negative effects, disrupting normal neurodevelopment. | OMIM #617171; PMID: 29276005 |
| Deafness, autosomal dominant 1 (DFNA1) | Rare missense variants in DEAF1 have been linked to hearing loss, though the mechanism is not fully defined. | ClinVar; PMID: 29276005 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Testis | Medium | Medium |
| Lung | Medium | Medium |
| Kidney | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal model |
| HeLa (cervical carcinoma) | Medium | Common cell line |
| HEK293 (embryonic kidney) | Medium | Transformed cell line |
| Jurkat (T-cell leukemia) | Low | Immune cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.826C>T (p.Arg276Trp) | Missense | Rare | Pathogenic; associated with DEE |
| c.1018C>T (p.Arg340Cys) | Missense | Rare | Pathogenic; associated with intellectual disability |
| c.1A>G (p.Met1Val) | Start-loss | Rare | Likely pathogenic; loss of function |
| c.1252C>T (p.Arg418Ter) | Nonsense | Rare | Pathogenic; truncating variant |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) reduce DEAF1 protein levels, leading to haploinsufficiency, which is a major mechanism in autosomal dominant intellectual disability.
Gain of Function (GOF)
Gain-of-function mutations are not well documented for DEAF1; most pathogenic variants are loss-of-function or dominant-negative.
Dominant Negative (DN)
Missense mutations in the SAND domain can exert dominant-negative effects by interfering with DNA binding or protein-protein interactions, disrupting transcriptional regulation.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • transcription factor activity |
| • chromatin binding | • zinc ion binding |
| • regulation of transcription by RNA polymerase II | • nervous system development |
Pathways
• Transcriptional regulation by DEAF1
• Chromatin remodeling
• Neurodevelopmental pathways
Protein Summary
The DEAF1 protein (UniProt O75398) is a 565-amino acid transcription factor with a SAND domain (residues 220-300) that binds to the DEAF1 response element (DRE) in DNA, and a MYND zinc finger domain (residues 1-60) involved in protein-protein interactions. It functions as a transcriptional activator or repressor depending on context. DEAF1 is essential for embryonic development, particularly of the nervous system, and is involved in immune regulation. Mutations in DEAF1 disrupt its nuclear localization, DNA binding, or protein interactions, leading to neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DEAF1 Knockout HEK293 Cell Line | EDJ-KQ7081 | Human | 10522 | Details Get a Quote |
| DEAF1 Knockout A-549 Cell Line | EDJ-KQ31912 | Human | 10522 | Details Get a Quote |
| DEAF1 Knockout HCT 116 Cell Line | EDJ-KQ31913 | Human | 10522 | Details Get a Quote |
| DEAF1 Knockout HeLa Cell Line | EDJ-KQ31914 | Human | 10522 | Details Get a Quote |
