SEPSECS

Chr 4AR

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

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

This enzyme converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec), which is essential for selenoprotein biosynthesis. Biallelic mutations cause pontocerebellar hypoplasia type 2D, an autosomal recessive neurodevelopmental disorder affecting the brainstem and cerebellum. The gene shows very low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.991 OMIM phenotype
Clinical SummarySEPSECS
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SEPSECS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.65 (0.440.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.02Z-score
OE missense 1.00 (0.901.10)
269 obs / 270.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.440.99)
00.351.4
Missense OE1.00 (0.901.10)
00.61.4
Synonymous OE0.73
01.21.6
LoF obs/exp: 16 / 24.6Missense obs/exp: 269 / 270.0Syn Z: 2.10
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSEPSECS-related pontocerebellar hypoplasiaLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.74top 25%
GOF
0.3491th %ile
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SEPSECS · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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