DENND4A Gene (DENN Domain Containing 4A)
A guanine nucleotide exchange factor (GEF) for Rab10 involved in endocytic trafficking and cellular signaling.
Gene Information Card
| Symbol | DENND4A |
|---|---|
| Full Name | DENN domain containing 4A |
| Gene Type | Protein coding |
| Chromosomal Location | 15q22.31 |
| NCBI Gene ID | 10260 ncbi.nlm.nih.gov/gene/10260 |
| Ensembl ID | ENSG00000137807 |
| UniProt ID | Q7Z401 |
| OMIM ID | 610482 |
| HGNC ID | 24419 |
| Aliases | DENND4, FLJ20125, KIAA1090, MGC138207 |
Description
DENND4A encodes a member of the DENN (differentially expressed in normal and neoplastic cells) domain-containing protein family. It functions as a guanine nucleotide exchange factor (GEF) specifically for Rab10, a small GTPase involved in endocytic recycling and vesicle trafficking. The protein contains a DENN domain, a dDENN domain, and a uDENN domain, and is implicated in cellular processes such as membrane transport, cell migration, and signal transduction. Alternative splicing results in multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression and copy number gain of DENND4A may promote tumorigenesis through Rab10-mediated trafficking of growth factor receptors. | COSMIC; PMID: 25344691 |
| Lung cancer | DENND4A amplification observed in non-small cell lung cancer; potential role in cell proliferation. | COSMIC; PMID: 23542377 |
| Colorectal cancer | Altered expression levels associated with poor prognosis; possible involvement in Wnt signaling modulation. | COSMIC; PMID: 27197159 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 8.2 | Medium |
| Brain | 6.5 | Low |
| Breast | 9.1 | Medium |
| Colon | 7.8 | Medium |
| Lung | 10.3 | Medium |
| Ovary | 11.5 | Medium |
| Testis | 14.2 | High |
| Thyroid | 12.0 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 9.5 | Cervical cancer cell line |
| A549 | 11.2 | Lung cancer cell line |
| MCF7 | 10.8 | Breast cancer cell line |
| HCT116 | 8.9 | Colorectal cancer cell line |
| HEK293 | 7.6 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2143G>A (p.Gly715Arg) | Missense | <0.01% (gnomAD) | Unknown functional effect; predicted benign by SIFT |
| c.2876C>T (p.Pro959Leu) | Missense | <0.01% (gnomAD) | Unknown functional effect; predicted damaging by PolyPhen-2 |
| c.3610_3611insA (p.Thr1204Asnfs*2) | Frameshift insertion | Rare | Likely loss of function; truncation of DENN domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.Thr1204Asnfs*2) that truncate the DENN domain are predicted to impair Rab10 GEF activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in COSMIC or ClinVar.
Dominant Negative (DN)
No dominant-negative variants described in the literature.
View complete mutation data：
Gene Ontology (GO)
| • Guanine nucleotide exchange factor activity (GO:0005085) | • Rab10 binding (GO:0031267) |
| • Endocytic recycling (GO:0032456) | • Intracellular protein transport (GO:0006886) |
| • Membrane (GO:0016020) |
Pathways
• Rab10-mediated endocytic recycling (Reactome: R-HSA-8876198)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
DENND4A is a 1,209-amino acid protein that contains a DENN domain, a dDENN domain, and a uDENN domain. It acts as a guanine nucleotide exchange factor (GEF) for Rab10, catalyzing the exchange of GDP for GTP to activate Rab10. The protein localizes to endosomal membranes and regulates endocytic recycling of receptors such as integrins and growth factor receptors. DENND4A is widely expressed, with highest levels in testis and thyroid. Its dysregulation has been linked to several cancers, where it may influence cell migration and proliferation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DENND4A Knockout HEK293 Cell Line | EDJ-KQ6977 | Human | 10260 | Details Get a Quote |
| DENND4A Knockout A-549 Cell Line | EDJ-KQ31675 | Human | 10260 | Details Get a Quote |
| DENND4A Knockout HCT 116 Cell Line | EDJ-KQ31676 | Human | 10260 | Details Get a Quote |
| DENND4A Knockout HeLa Cell Line | EDJ-KQ31677 | Human | 10260 | Details Get a Quote |
