EPB42: Erythrocyte Membrane Protein Band 4.2
Key structural component of the red blood cell membrane skeleton; mutations cause hereditary spherocytosis type 5.
Gene Information Card
| Symbol | EPB42 |
|---|---|
| Full Name | Erythrocyte Membrane Protein Band 4.2 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.2 |
| NCBI Gene ID | 2038 ncbi.nlm.nih.gov/gene/2038 |
| Ensembl ID | ENSG00000137868 |
| UniProt ID | P16452 |
| OMIM ID | 177070 |
| HGNC ID | 3382 |
| Aliases | PA, band 4.2, erythrocyte surface protein band 4.2 |
Description
EPB42 encodes the erythrocyte membrane protein band 4.2, a major component of the red blood cell membrane skeleton. This protein binds to the cytoplasmic domain of band 3 (anion exchanger 1) and to ankyrin, stabilizing the membrane and maintaining erythrocyte shape and deformability. Mutations in EPB42 lead to hereditary spherocytosis type 5 (HS5), an autosomal recessive hemolytic anemia characterized by spherical red cells, reduced membrane stability, and splenomegaly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary spherocytosis type 5 (HS5) | Loss-of-function mutations in EPB42 disrupt band 4.2 protein, impairing membrane-cytoskeleton linkage and causing membrane vesiculation and spherocyte formation. | ClinVar, OMIM #612690 |
| Hemolytic anemia (nonspherocytic) | EPB42 deficiency leads to reduced erythrocyte deformability and increased osmotic fragility. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Spleen | 8.3 | Low |
| Whole Blood | 6.1 | Low |
| Liver | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Erythroleukemia (K562) | 15.0 | High expression; model for erythroid differentiation |
| Lymphoblastoid (GM12878) | 0.5 | Very low expression |
| HeLa | 0.1 | Not expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.772C>T (p.Arg258Ter) | Nonsense | Rare | Premature stop; loss of protein function; causes HS5 |
| c.1190G>A (p.Arg397His) | Missense | Rare | Impaired band 4.2 stability and binding; associated with HS5 |
| c.1462C>T (p.Arg488Trp) | Missense | Rare | Reduced protein expression; pathogenic in HS5 |
Mutation functional classification
Loss of Function (LOF)
Most EPB42 mutations are loss-of-function (nonsense, frameshift, missense) leading to reduced or absent band 4.2 protein, causing hereditary spherocytosis type 5.
Gain of Function (GOF)
No gain-of-function mutations reported for EPB42.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Erythrocyte membrane skeleton (Reactome: R-HSA-5621480)
• Band 3-ankyrin-4.2 complex assembly
Protein Summary
Erythrocyte membrane protein band 4.2 (UniProt P16452) is a 691-amino-acid protein that localizes to the inner leaflet of the red blood cell membrane. It contains a transglutaminase-like domain but lacks enzymatic activity. Band 4.2 binds to the N-terminal cytoplasmic domain of band 3 (SLC4A1) and to ankyrin-1 (ANK1), stabilizing the membrane skeleton. Deficiency leads to reduced membrane deformability and hereditary spherocytosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| EPB42 Knockout HEK293 Cell Line | EDJ-KQ4533 | Human | 2038 | Details Get a Quote |
| EPB42 Knockout HeLa Cell Line | EDJ-KQ53163 | Human | 2038 | Details Get a Quote |
| EPB42 Knockout A-549 Cell Line | EDJ-KQ61639 | Human | 2038 | Details Get a Quote |
| EPB42 Knockout HCT 116 Cell Line | EDJ-KQ70122 | Human | 2038 | Details Get a Quote |
