SEPSECS

Chr 4AR

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

ENSG00000109618 UniProt: Q9HD40 OMIM: 613009

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.991 OMIM phenotype

Clinical Summary— SEPSECS

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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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Some data sources returned errors (1)

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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 OE?0.65 (0.44–0.99)

0≤0.351.4

Missense OE?1.00 (0.90–1.10)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 16 / 24.6Missense obs/exp: 269 / 270.0Syn Z: 2.10

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveSEPSECS-related pontocerebellar hypoplasiaLOFAR

This gene — mechanism propensity

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

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.