DMXL2: A WD Repeat Protein Implicated in Neurodevelopment and Cancer
Comprehensive genomic and functional analysis of DMXL2, a regulator of Notch signaling and vesicular trafficking.
Gene Information Card
| Symbol | DMXL2 |
|---|---|
| Full Name | DmX-like 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q21.2 |
| NCBI Gene ID | 23312 ncbi.nlm.nih.gov/gene/23312 |
| Ensembl ID | ENSG00000104081 |
| UniProt ID | Q8TDJ6 |
| OMIM ID | 612186 |
| HGNC ID | 2938 |
| Aliases | DMX, DmX-like protein 2, FLJ20032, KIAA0856 |
Description
DMXL2 encodes a WD repeat-containing protein that functions as a component of the RAB6-interacting complex and regulates Notch signaling via endosomal trafficking. It is involved in neurodevelopment, and mutations are associated with intellectual disability and epilepsy. The protein also plays a role in cancer through altered expression and somatic mutations.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 57 | Loss-of-function mutations impair Notch signaling and neuronal development | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile | De novo missense variants disrupt protein function | ClinVar, OMIM |
| Ovarian cancer | Somatic mutations and altered expression affect tumor progression | COSMIC |
| Breast cancer | Overexpression linked to poor prognosis | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Ovary | 6.1 | Low |
| Lung | 4.7 | Low |
| Liver | 3.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| SH-SY5Y | 11.8 | Neuronal model |
| HeLa | 9.4 | Cervical cancer |
| MCF7 | 7.1 | Breast cancer |
| A549 | 5.3 | Lung cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Trp) | Missense | Rare | Loss of function, associated with intellectual disability |
| c.1234G>A (p.Gly412Arg) | Missense | Rare | De novo, epileptic encephalopathy |
| c.3456_3457insA | Frameshift | Somatic | Truncation, loss of function in ovarian cancer |
| c.5678A>G (p.Asn1893Ser) | Missense | Somatic | Unknown significance in breast cancer |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay, observed in intellectual disability and cancer.
Gain of Function (GOF)
Not well characterized; some missense variants may alter protein interactions but evidence is limited.
Dominant Negative (DN)
Possible for missense variants that disrupt WD repeat domain function, but not confirmed.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• RAB6-mediated vesicular transport (Reactome: R-HSA-8873719)
• Endosomal trafficking (Reactome: R-HSA-5653656)
Protein Summary
DMXL2 is a 3057-amino acid WD repeat protein localized to the cytoplasm and perinuclear region. It interacts with RAB6 and is involved in endosomal trafficking and Notch receptor recycling. The protein contains multiple WD40 domains that mediate protein-protein interactions. It is highly expressed in brain and testis, and its dysfunction contributes to neurodevelopmental disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DMXL2 Knockout HEK293 Cell Line | EDJ-KQ7956 | Human | 23312 | Details Get a Quote |
| DMXL2 Knockout A-549 Cell Line | EDJ-KQ32302 | Human | 23312 | Details Get a Quote |
| DMXL2 Knockout HCT 116 Cell Line | EDJ-KQ33634 | Human | 23312 | Details Get a Quote |
| DMXL2 Knockout HeLa Cell Line | EDJ-KQ33635 | Human | 23312 | Details Get a Quote |
