DMXL1: A WD40 Repeat-Containing Protein Implicated in Vesicular Trafficking and Neurodevelopment
Comprehensive genomic and functional overview of DMXL1, a gene encoding a putative Rabconnectin-3 complex subunit with roles in endosomal acidification and neuronal function.
Gene Information Card
| Symbol | DMXL1 |
|---|---|
| Full Name | DmX-like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q23.1 |
| NCBI Gene ID | 1657 ncbi.nlm.nih.gov/gene/1657 |
| Ensembl ID | ENSG00000113522 |
| UniProt ID | Q9Y4W6 |
| OMIM ID | 618171 |
| HGNC ID | 2938 |
| Aliases | DMX, DmX, FLJ20071, KIAA0852 |
Description
DMXL1 encodes a large WD40 repeat-containing protein that is a component of the Rabconnectin-3 complex, which regulates vesicular acidification and neurotransmitter release. The protein is involved in endosomal trafficking, synaptic vesicle recycling, and neuronal development. Mutations in DMXL1 have been associated with autosomal recessive intellectual disability and other neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 71 (MRT71) | Loss-of-function mutations impair endosomal acidification and synaptic function | OMIM #618171; ClinVar; multiple case reports |
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Disruption of Rabconnectin-3 complex leads to defective vesicle trafficking | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.2 | Medium |
| Thyroid | 6.1 | Medium |
| Adrenal gland | 5.4 | Medium |
| Liver | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal model |
| HEK293 (embryonic kidney) | 7.8 | Common cell line |
| HeLa (cervical carcinoma) | 5.6 | Epithelial model |
| K562 (leukemia) | 3.2 | Hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1234G>A (p.Gly412Arg) | Missense | Rare | Impaired protein stability |
| c.3456_3457del (p.Glu1152Aspfs*3) | Frameshift | Rare | Loss of function; nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, disrupting Rabconnectin-3 complex assembly and endosomal acidification.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rabconnectin-3 complex mediated endosomal acidification
• Synaptic vesicle cycle
• V-ATPase assembly and regulation
Protein Summary
DMXL1 is a large WD40 repeat-containing protein (approx. 200 kDa) that forms part of the Rabconnectin-3 complex, which interacts with the V-ATPase to regulate endosomal and lysosomal acidification. It is highly expressed in brain and plays a critical role in synaptic vesicle recycling and neurotransmitter release. Loss-of-function mutations cause autosomal recessive intellectual disability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DMXL1 Knockout HEK293 Cell Line | EDJ-KQ4434 | Human | 1657 | Details Get a Quote |
| DMXL1 Knockout A-549 Cell Line | EDJ-KQ26980 | Human | 1657 | Details Get a Quote |
| DMXL1 Knockout HCT 116 Cell Line | EDJ-KQ26981 | Human | 1657 | Details Get a Quote |
| DMXL1 Knockout HeLa Cell Line | EDJ-KQ26982 | Human | 1657 | Details Get a Quote |
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