ADD1 Gene - Adducin 1
Genetics, Function, and Clinical Significance of the ADD1 Gene
Gene Information Card
| Symbol | ADD1 |
|---|---|
| Full Name | Adducin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 4p16.3 |
| NCBI Gene ID | 118 ncbi.nlm.nih.gov/gene/118 |
| Ensembl ID | ENSG00000069275 |
| UniProt ID | P35611 |
| OMIM ID | 102680 |
| HGNC ID | 243 |
| Aliases | ADDA, alpha-adducin |
Description
The ADD1 gene encodes the alpha subunit of adducin, a cytoskeletal protein that promotes the assembly of spectrin-actin networks. Adducin is a heteromeric protein composed of alpha, beta, and gamma subunits, and alpha-adducin is expressed in various tissues, particularly in the kidney and brain. ADD1 plays a role in cell shape, cell motility, and signal transduction. Genetic variants in ADD1 have been associated with essential hypertension and salt-sensitive hypertension, likely through effects on renal sodium transport.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Essential Hypertension | The Gly460Trp polymorphism (rs4961) is associated with increased risk of hypertension, possibly by altering renal sodium reabsorption and sodium pump activity. | Multiple case-control studies and meta-analyses (e.g., Liu et al., 2018) show a modest but significant association. |
| Salt-Sensitive Hypertension | The 460Trp allele is linked to salt sensitivity, with increased blood pressure response to sodium intake, likely due to altered adducin function in renal tubular cells. | Clinical studies and animal models support a role in salt-sensitive hypertension. |
| Cardiovascular Disease | ADD1 variants may contribute to stroke and coronary artery disease risk, though findings are inconsistent. | Some meta-analyses suggest a weak association with stroke, but not all studies confirm. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High | High expression in renal tubular epithelial cells. |
| Brain | High | Widely expressed in neurons and glial cells. |
| Liver | Medium | Moderate expression in hepatocytes. |
| Heart | Medium | Expressed in cardiac myocytes. |
| Lung | Low | Low expression in lung tissue. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | High | Commonly used for functional studies of ADD1 variants. |
| HeLa | Medium | Cervical cancer cell line with moderate expression. |
| A549 | Low | Lung carcinoma cell line with low expression. |
| HepG2 | Medium | Liver cancer cell line with moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Gly460Trp (rs4961) | SNP (missense) | ~20-30% in Caucasian populations | Associated with hypertension and salt sensitivity; may alter adducin function in renal sodium handling. |
| Arg546Trp (rs121912715) | SNP (missense) | Rare | Reported in some hypertensive individuals; functional impact unclear. |
| c.429C>T (p.Ser143Ser) | Synonymous | Low | No known functional effect. |
Mutation functional classification
Loss of Function (LOF)
No clear loss-of-function mutations have been characterized; most variants are missense with subtle functional effects.
Gain of Function (GOF)
The 460Trp variant may be considered a gain-of-function in terms of increased sodium reabsorption, but this is not a classic gain-of-function in a signaling sense.
Dominant Negative (DN)
No evidence for dominant-negative effects.
View complete mutation data：
Gene Ontology (GO)
| • actin binding | • cytoskeletal protein binding |
| • protein heterodimerization activity | • structural constituent of cytoskeleton |
| • calmodulin binding |
Pathways
• Adducin and spectrin-actin assembly
• Regulation of actin cytoskeleton
• Ion transport by P-type ATPases (indirect)
Protein Summary
Adducin 1 (alpha-adducin) is a cytoskeletal protein that binds to spectrin and actin, promoting the assembly of the spectrin-actin network. It is a heteromeric protein composed of alpha, beta, and gamma subunits. Alpha-adducin is widely expressed, with high levels in the kidney and brain. It plays a role in cell shape, cell motility, and signal transduction. In the kidney, adducin is involved in the regulation of sodium transport, and variants such as Gly460Trp have been linked to hypertension and salt sensitivity. The protein contains a globular head domain, a neck domain, and a tail domain, and undergoes phosphorylation by protein kinase C and other kinases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ADD1 Knockout HEK293 Cell Line | EDJ-KQ4009 | Human | 118 | Details Get a Quote |
| ADD1 Knockout A-549 Cell Line | EDJ-KQ26331 | Human | 118 | Details Get a Quote |
| ADD1 Knockout HCT 116 Cell Line | EDJ-KQ26332 | Human | 118 | Details Get a Quote |
| ADD1 Knockout HeLa Cell Line | EDJ-KQ26333 | Human | 118 | Details Get a Quote |
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