SEPHS2

Chr 16

selenophosphate synthetase 2

The protein is a selenophosphate synthase that generates the selenium donor required for selenocysteine biosynthesis, catalyzing the formation of selenophosphate from selenide and ATP. Mutations cause autosomal recessive pontocerebellar hypoplasia type 2D, a severe neurodevelopmental disorder affecting the brainstem and cerebellum. The gene shows minimal constraint to loss-of-function variants (pLI 0.002, LOEUF 0.998), which is consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.00
Clinical SummarySEPHS2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.00LOEUF
pLI 0.002
Z-score 1.58
OE 0.51 (0.281.00)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.76Z-score
OE missense 0.69 (0.610.79)
184 obs / 264.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.281.00)
00.351.4
Missense OE0.69 (0.610.79)
00.61.4
Synonymous OE0.82
01.21.6
LoF obs/exp: 6 / 11.9Missense obs/exp: 184 / 264.8Syn Z: 1.51
DN
0.6551th %ile
GOF
0.6052th %ile
LOF
0.3649th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SEPHS2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗