ADD3 Gene - Adducin 3
Comprehensive genomic and functional analysis of the ADD3 gene encoding gamma-adducin, a cytoskeletal protein involved in cell shape regulation and associated with cerebral palsy and hypertension.
Gene Information Card
| Symbol | ADD3 |
|---|---|
| Full Name | Adducin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q24.2 |
| NCBI Gene ID | 120 ncbi.nlm.nih.gov/gene/120 |
| Ensembl ID | ENSG00000148700 |
| UniProt ID | Q9UEY8 |
| OMIM ID | 601568 |
| HGNC ID | 245 |
| Aliases | ADDL, gamma-adducin |
Description
The ADD3 gene encodes gamma-adducin, a member of the adducin family of cytoskeletal proteins. Adducins are heteromeric proteins composed of alpha, beta, and gamma subunits that bind to actin filaments and promote the assembly of the spectrin-actin network. Gamma-adducin is ubiquitously expressed and plays a critical role in cell shape regulation, cell motility, and membrane stability. Variants in ADD3 have been associated with susceptibility to essential hypertension and cerebral palsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cerebral palsy, spastic quadriplegic, 3 (CPSQ3) | Loss-of-function mutations in ADD3 disrupt cytoskeletal organization in neurons, leading to impaired neuronal migration and synaptic function. | OMIM #617008; PMID: 28135719 |
| Essential hypertension | ADD3 polymorphisms (e.g., rs3731566) alter adducin expression and actin-binding activity, affecting renal sodium transport and vascular tone. | OMIM #601568; PMID: 10888879 |
| Cholangiocarcinoma | ADD3 overexpression promotes tumor cell migration and invasion via actin cytoskeleton remodeling. | COSMIC; PMID: 25605247 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 18.5 | High |
| Heart | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Kidney | 15.1 | High |
| Lung | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 22.1 | High expression |
| HeLa | 14.5 | Medium expression |
| K562 | 9.8 | Medium expression |
| SH-SY5Y | 25.3 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.220C>T (p.Arg74*) | Nonsense | <0.01% | Loss of function; associated with cerebral palsy |
| c.1019G>A (p.Arg340His) | Missense | 0.02% | Reduced actin-binding affinity; hypertension risk |
| c.1465_1466del (p.Leu489Valfs*12) | Frameshift | <0.01% | Loss of function; cerebral palsy |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg74*, p.Leu489Valfs*12) lead to truncated or degraded protein, impairing cytoskeletal integrity and neuronal function.
Gain of Function (GOF)
Not reported for ADD3.
Dominant Negative (DN)
Not reported for ADD3.
View complete mutation data：
Gene Ontology (GO)
| • actin binding (GO:0003779) | • spectrin binding (GO:0030507) |
| • calmodulin binding (GO:0005516) | • cytoskeleton organization (GO:0007010) |
| • cell shape regulation (GO:0008360) |
Pathways
• Adducin pathway (Reactome: R-HSA-5663205)
• Actin cytoskeleton regulation (KEGG: hsa04810)
Protein Summary
Gamma-adducin (UniProt Q9UEY8) is a 706-amino acid protein that forms heteromeric complexes with alpha- and beta-adducin. It contains an N-terminal head domain, a neck domain, and a C-terminal tail domain with a calmodulin-binding site. The protein binds F-actin and spectrin, promoting the assembly of the membrane skeleton. Post-translational modifications include phosphorylation by protein kinase C and PKA, which regulate its activity and localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADD3 Knockout HEK293 Cell Line | EDJ-KQ2495 | Human | 120 | Details Get a Quote |
| ADD3 Knockout A-549 Cell Line | EDJ-KQ24465 | Human | 120 | Details Get a Quote |
| ADD3 Knockout HCT 116 Cell Line | EDJ-KQ24466 | Human | 120 | Details Get a Quote |
| ADD3 Knockout HeLa Cell Line | EDJ-KQ24467 | Human | 120 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
