KYNU Gene - Kynureninase
Comprehensive genomic and functional analysis of the KYNU gene, its role in tryptophan metabolism, and associated diseases.
Gene Information Card
| Symbol | KYNU |
|---|---|
| Full Name | Kynureninase |
| Gene Type | Protein coding |
| Chromosomal Location | 2q22.2 |
| NCBI Gene ID | 8942 ncbi.nlm.nih.gov/gene/8942 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q16719 |
| OMIM ID | 605197 |
| HGNC ID | 6469 |
| Aliases | LCCP, MGC88934 |
Description
The KYNU gene encodes kynureninase, a pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine to anthranilic acid and 3-hydroxyanthranilic acid, respectively. This enzyme is a key component of the tryptophan degradation pathway via the kynurenine route, which ultimately leads to the synthesis of NAD+. Mutations in KYNU can cause hydroxykynureninuria, a rare autosomal recessive disorder characterized by intellectual disability and other neurological symptoms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hydroxykynureninuria | Loss-of-function mutations in KYNU impair the conversion of 3-hydroxykynurenine to 3-hydroxyanthranilic acid, leading to accumulation of kynurenine metabolites and neurological dysfunction. | OMIM #236800; multiple case reports with biallelic pathogenic variants |
| NAD+ deficiency disorders | Reduced kynureninase activity disrupts NAD+ biosynthesis from tryptophan, potentially contributing to pellagra-like symptoms. | Inferred from metabolic pathway; limited direct evidence in patients |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Brain | 4.1 | Medium |
| Lung | 2.7 | Low |
| Heart | 1.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| HEK293 | 6.8 | Embryonic kidney cells; moderate expression |
| SH-SY5Y | 3.5 | Neuroblastoma cell line; moderate expression |
| A549 | 2.1 | Lung carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.682C>T (p.Arg228*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1015G>A (p.Gly339Arg) | Missense | Rare | Reduced enzyme activity; associated with hydroxykynureninuria |
| c.1246C>T (p.Arg416Trp) | Missense | Rare | Impaired PLP binding; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported pathogenic variants in KYNU are loss-of-function, leading to reduced or absent kynureninase activity and accumulation of upstream metabolites.
Gain of Function (GOF)
No gain-of-function mutations have been reported for KYNU.
Dominant Negative (DN)
No dominant-negative effects have been described; the disorder is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • kynureninase activity (GO:0030429) | • cytoplasm (GO:0005737) |
| • tryptophan catabolic process (GO:0006569) | • NAD+ biosynthetic process (GO:0034353) |
| • pyridoxal phosphate binding (GO:0030170) |
Pathways
• Tryptophan metabolism (KEGG: hsa00380)
• Nicotinate and nicotinamide metabolism (KEGG: hsa00760)
• NAD+ biosynthesis from tryptophan (Reactome: R-HSA-196807)
Protein Summary
Kynureninase is a 465-amino-acid protein that functions as a homodimer. Each subunit binds one molecule of pyridoxal-5'-phosphate (PLP) as a cofactor. The enzyme catalyzes the hydrolytic cleavage of L-kynurenine and L-3-hydroxykynurenine, producing anthranilic acid and 3-hydroxyanthranilic acid, respectively. It is primarily expressed in liver and kidney, with lower levels in brain and other tissues. Defects in this enzyme lead to hydroxykynureninuria, a rare autosomal recessive disorder.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KYNU Knockout HEK293 Cell Line | EDJ-KQ6412 | Human | 8942 | Details Get a Quote |
| KYNU Knockout A-549 Cell Line | EDJ-KQ30452 | Human | 8942 | Details Get a Quote |
| KYNU Knockout HeLa Cell Line | EDJ-KQ30453 | Human | 8942 | Details Get a Quote |
| KYNU Knockout HCT 116 Cell Line | EDJ-KQ71993 | Human | 8942 | Details Get a Quote |
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