SEPSECS

Chr 4AR

Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase

Also known as: LP, PCH2D, SLA, SLA-p35, SLA/LP, SecS

NCBI Gene: 51091ENSG00000109618UniProt: Q9HD40

The amino acid selenocysteine is the only amino acid that does not have its own tRNA synthetase. Instead, this amino acid is synthesized on its cognate tRNA in a three step process. The protein encoded by this gene catalyzes the third step in the process, the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec).[provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia type 2DMIM #613811
AR
0
Active trials
57
Pathogenic / LP
292
ClinVar variants
8
Pubs (1 yr)
0.0
Missense Z
0.99
LOEUF
Clinical Summary— SEPSECS
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 Pathogenic / Likely Pathogenic· 103 VUS of 292 total submissions
📖
GeneReview available — SEPSECS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.65 (0.44–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.02Z-score
OE missense 1.00 (0.90–1.10)
269 obs / 270.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.44–0.99)
0≤0.351.4
Missense OE1.00 (0.90–1.10)
0≤0.61.4
Synonymous OE0.73
0≤1.21.6
LoF obs/exp: 16 / 24.6Missense obs/exp: 269 / 270.0Syn Z: 2.10
DN
DN
0.74top 25%
GOF
0.3491th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

292 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic22
VUS103
Likely Benign118
Benign13
Conflicting1
35
Pathogenic
22
Likely Pathogenic
103
VUS
118
Likely Benign
13
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
1
15
0
35
Likely Pathogenic
12
3
7
0
22
VUS
1
87
10
5
103
Likely Benign
1
1
52
64
118
Benign
0
0
13
0
13
Conflicting
—1
Total33929769292

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

SEPSECS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SEPSECS-related pontocerebellar hypoplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients