KIRREL3
Kin of IRRE-like protein 3: A neuronal adhesion molecule implicated in neurodevelopmental disorders
Gene Information Card
| Symbol | KIRREL3 |
|---|---|
| Full Name | Kin of IRRE like 3 (Drosophila) |
| Gene Type | protein-coding |
| Chromosomal Location | 11q24.2 |
| NCBI Gene ID | 84623 ncbi.nlm.nih.gov/gene/84623 |
| Ensembl ID | ENSG00000149480 |
| UniProt ID | Q8IZU9 |
| OMIM ID | 607761 |
| HGNC ID | 23080 |
| Aliases | NEPH3, KIAA1867, MRD4 |
Description
KIRREL3 encodes a member of the immunoglobulin superfamily, structurally related to the Drosophila irregular chiasm C-roughest (IRREC) protein. The protein functions as a cell adhesion molecule at synapses, particularly in the developing and mature nervous system. It is involved in synaptic organization, neurite outgrowth, and neuronal migration. Mutations in KIRREL3 are associated with intellectual disability and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder, autosomal dominant 4 (MRD4) | Loss-of-function mutations disrupt synaptic adhesion and neuronal connectivity | OMIM #607761; ClinVar |
| Autism spectrum disorder | Missense variants impair protein stability or binding to interacting partners | ClinVar; PubMed studies |
| Schizophrenia | Rare variants may contribute to synaptic dysfunction | NCBI Gene; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebral cortex | 15.2 | Medium |
| Cerebellum | 18.7 | Medium |
| Testis | 8.3 | Low |
| Kidney | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.0 | Neuronal model |
| U-87 MG (glioblastoma) | 9.5 | Glial model |
| HEK 293 (embryonic kidney) | 5.2 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Cys) | Missense | <0.01% | Reduced protein stability; associated with autism |
| c.1045G>A (p.Gly349Arg) | Missense | <0.01% | Impaired synaptic localization; intellectual disability |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of translation; severe neurodevelopmental phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and start-loss variants that abolish protein expression or disrupt critical domains (e.g., Ig-like domains) lead to haploinsufficiency and neurodevelopmental disorders.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in KIRREL3.
Dominant Negative (DN)
Missense variants that retain expression but disrupt interactions with nephrin or other synaptic partners may act in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • cell adhesion | • synaptic membrane adhesion |
| • homophilic cell adhesion via plasma membrane adhesion molecules | • neuron projection development |
| • positive regulation of synapse assembly |
Pathways
• Nephrin/Neph family signaling
• Synaptic adhesion and organization
Protein Summary
KIRREL3 (NEPH3) is a single-pass type I membrane protein containing five extracellular immunoglobulin-like domains and a cytoplasmic tail with PDZ-binding motif. It localizes to synaptic junctions and interacts with nephrin and other scaffolding proteins to regulate synapse formation and maintenance. The protein is highly expressed in the brain, particularly in the cerebral cortex and cerebellum.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KIRREL3 Knockout HEK293 Cell Line | EDJ-KQ10134 | Human | 84623 | Details Get a Quote |
| KIRREL3 Knockout A-549 Cell Line | EDJ-KQ36001 | Human | 84623 | Details Get a Quote |
| KIRREL3 Knockout HeLa Cell Line | EDJ-KQ37236 | Human | 84623 | Details Get a Quote |
| KIRREL3 Knockout HCT 116 Cell Line | EDJ-KQ74541 | Human | 84623 | Details Get a Quote |
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