SEPSECS: Selenocysteine Synthase Gene
Key regulator of selenoprotein biosynthesis and tRNA selenocysteine modification
Gene Information Card
| Symbol | SEPSECS |
|---|---|
| Full Name | Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase |
| Gene Type | Protein coding |
| Chromosomal Location | 4p15.2 |
| NCBI Gene ID | 51091 ncbi.nlm.nih.gov/gene/51091 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q9HD40 |
| OMIM ID | 613009 |
| HGNC ID | 30605 |
| Aliases | SLA, LP, PCHD, SECS, TRNA-SEC, SECSYS |
Description
The SEPSECS gene encodes the enzyme selenocysteine synthase, which catalyzes the conversion of O-phosphoserine (Sep) to selenocysteine (Sec) on the tRNA[Ser]Sec molecule. This is a critical step in the biosynthesis of selenoproteins, which contain the rare amino acid selenocysteine. The enzyme requires pyridoxal phosphate (PLP) as a cofactor and is essential for the incorporation of selenium into proteins. Mutations in SEPSECS cause pontocerebellar hypoplasia type 2D (PCH2D), a severe neurodegenerative disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pontocerebellar hypoplasia type 2D (PCH2D) | Loss-of-function mutations in SEPSECS impair selenocysteine incorporation, leading to defective selenoprotein synthesis and neurodegeneration | ClinVar, OMIM |
| Autosomal recessive intellectual disability | Biallelic SEPSECS variants disrupt brain development via selenoprotein deficiency | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 7.1 | Low |
| Testis | 6.9 | Low |
| Thyroid | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney cells |
| SH-SY5Y | 9.4 | Neuroblastoma cells |
| HepG2 | 7.8 | Hepatocellular carcinoma cells |
| K562 | 6.5 | Leukemia cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.656G>A (p.Arg219His) | Missense | Rare | Loss of catalytic activity; associated with PCH2D |
| c.1168C>T (p.Arg390*) | Nonsense | Rare | Premature truncation; loss of function |
| c.334_335del (p.Leu112Valfs*3) | Frameshift | Rare | Loss of function; PCH2D |
| c.1073T>C (p.Leu358Pro) | Missense | Rare | Impaired protein stability; PCH2D |
Mutation functional classification
Loss of Function (LOF)
Most SEPSECS mutations are loss-of-function, reducing or abolishing selenocysteine synthase activity, leading to selenoprotein deficiency and neurodegeneration.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Selenocysteine biosynthesis (R-HSA-2408522)
• Selenoamino acid metabolism (R-HSA-2408528)
• tRNA processing (R-HSA-72306)
Protein Summary
SEPSECS (selenocysteine synthase) is a 501-amino acid protein localized to the cytoplasm. It catalyzes the conversion of O-phosphoserine to selenocysteine on the tRNA[Ser]Sec molecule using pyridoxal phosphate as a cofactor. This enzyme is essential for the incorporation of selenium into selenoproteins, which have antioxidant and redox functions. Defects in SEPSECS lead to pontocerebellar hypoplasia type 2D, characterized by severe motor and cognitive impairment.
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