NIPAL4 (NIPA-Like Domain Containing 4)
Gene associated with autosomal recessive congenital ichthyosis (ARCI) and skin barrier function
Gene Information Card
| Symbol | NIPAL4 |
|---|---|
| Full Name | NIPA-Like Domain Containing 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q33.3 |
| NCBI Gene ID | 348093 ncbi.nlm.nih.gov/gene/348093 |
| Ensembl ID | ENSG00000172575 |
| UniProt ID | Q5T0J0 |
| OMIM ID | 609383 |
| HGNC ID | 28016 |
| Aliases | ICHTHYIN, ARCI6, NIPA4 |
Description
NIPAL4 encodes ichthyin, a transmembrane protein involved in epidermal lipid metabolism and skin barrier formation. Mutations in this gene cause autosomal recessive congenital ichthyosis (ARCI) type 6, characterized by scaling and erythroderma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive congenital ichthyosis (ARCI) type 6 | Loss-of-function mutations impair lipid processing in the stratum corneum, leading to defective skin barrier | ClinVar, OMIM |
| Ichthyosis, congenital, autosomal recessive, with fine scaling | Same mechanism as ARCI6 | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 15.2 | Medium |
| Esophagus | 8.1 | Low |
| Vagina | 6.5 | Low |
| Breast | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Keratinocytes | 18.5 | High expression |
| Fibroblasts | 2.1 | Low expression |
| Melanocytes | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.527C>A (p.Ala176Asp) | Missense | Common in European ARCI | Loss of function |
| c.853C>T (p.Arg285Trp) | Missense | Rare | Loss of function |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most NIPAL4 mutations are loss-of-function, reducing ichthyin stability or lipid transport.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described for NIPAL4.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • integral component of membrane (GO:0016021) |
| • lipid metabolic process (GO:0006629) | • keratinization (GO:0031424) |
Pathways
• Epidermal differentiation
• Lipid metabolism
Protein Summary
Ichthyin is a 404-amino acid transmembrane protein with 4–6 predicted helices, localized to the endoplasmic reticulum and involved in lipid processing for the epidermal barrier.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NIPAL4 Knockout HEK293 Cell Line | EDJ-KQ14428 | Human | 348938 | Details Get a Quote |
| NIPAL4 Knockout A-549 Cell Line | EDJ-KQ44639 | Human | 348938 | Details Get a Quote |
| NIPAL4 Knockout HeLa Cell Line | EDJ-KQ44640 | Human | 348938 | Details Get a Quote |
| NIPAL4 Knockout HCT 116 Cell Line | EDJ-KQ76680 | Human | 348938 | Details Get a Quote |
