KIRREL1 (Kin of IRRE Like 1)
A nephrin-like protein involved in kidney podocyte structure and synaptic adhesion
Gene Information Card
| Symbol | KIRREL1 |
|---|---|
| Full Name | Kin of IRRE Like 1 (Drosophila) |
| Gene Type | protein-coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000143184 |
| UniProt ID | Q96J84 |
| OMIM ID | 604909 |
| HGNC ID | 15719 |
| Aliases | NEPH1, FLJ21908, MGC138290 |
Description
KIRREL1 (Kin of IRRE Like 1) encodes a transmembrane protein belonging to the nephrin-like family. It is a key component of the slit diaphragm in kidney podocytes, essential for glomerular filtration. The protein also functions in cell-cell adhesion and is expressed in neural tissues, where it may play a role in synaptic organization. Mutations in KIRREL1 are associated with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Focal segmental glomerulosclerosis (FSGS) | Loss of KIRREL1 disrupts slit diaphragm integrity, leading to proteinuria and glomerular scarring | ClinVar, OMIM #604909 |
| Nephrotic syndrome, type 2 | Homozygous mutations in KIRREL1 impair podocyte adhesion and filtration barrier function | OMIM #604909, PubMed: 25726036 |
| Steroid-resistant nephrotic syndrome | Biallelic KIRREL1 variants cause early-onset proteinuria and renal failure | ClinVar, PubMed: 25726036 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | High |
| Brain | 8.3 | Medium |
| Testis | 6.1 | Medium |
| Lung | 3.2 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Podocytes (immortalized) | 15.2 | High expression; key for slit diaphragm |
| HEK293 | 4.8 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 6.3 | Neuronal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.214C>T (p.Arg72Cys) | Missense | Rare | Impaired protein trafficking to cell surface; associated with FSGS |
| c.1018G>A (p.Gly340Arg) | Missense | Rare | Disrupted slit diaphragm localization; nephrotic syndrome |
| c.1240_1241del (p.Leu414fs) | Frameshift | Very rare | Loss of function; early-onset proteinuria |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking transmembrane domain, causing loss of slit diaphragm integrity.
Gain of Function (GOF)
No gain-of-function mutations reported for KIRREL1.
Dominant Negative (DN)
Missense mutations (e.g., p.Arg72Cys) may act dominant-negative by interfering with wild-type protein trafficking.
View complete mutation data：
Gene Ontology (GO)
| • cell-cell adhesion | • glomerular filtration |
| • slit diaphragm assembly | • protein homodimerization activity |
| • cell junction |
Pathways
• Slit diaphragm signaling (Reactome: R-HSA-373753)
• Cell-cell junction organization (GO:0045216)
Protein Summary
KIRREL1 (NEPH1) is a 750-amino acid transmembrane protein with extracellular immunoglobulin-like domains and a cytoplasmic tail. It localizes to the slit diaphragm of kidney podocytes, where it interacts with nephrin and podocin to form the filtration barrier. The protein also mediates heterophilic cell adhesion in neural tissues. Structural mutations disrupt podocyte function, leading to proteinuric kidney diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KIRREL1 Knockout HEK293 Cell Line | EDJ-KQ13211 | Human | 55243 | Details Get a Quote |
| KIRREL1 Knockout A-549 Cell Line | EDJ-KQ43852 | Human | 55243 | Details Get a Quote |
| KIRREL1 Knockout HCT 116 Cell Line | EDJ-KQ43854 | Human | 55243 | Details Get a Quote |
| KIRREL1 Knockout HeLa Cell Line | EDJ-KQ43855 | Human | 55243 | Details Get a Quote |
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