SEPSECS

Chr 4AR

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

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

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]

GeneReviewsOMIMResearchGenerating clinical summary…
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.
📋
ClinVar Variants
111 unique Pathogenic / Likely Pathogenic· 186 VUS of 686 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
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 OE?0.65 (0.440.99)
00.351.4
Missense OE?1.00 (0.901.10)
00.61.4
Synonymous OE?0.73
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

This gene — mechanism propensity

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

686 submitted variants in ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic68
VUS186
Likely Benign329
Benign35
Conflicting17
43
Pathogenic
68
Likely Pathogenic
186
VUS
329
Likely Benign
35
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
35
2
6
0
43
Likely Pathogenic
60
5
3
0
68
VUS
2
129
49
6
186
Likely Benign
1
3
147
178
329
Benign
0
2
33
0
35
Conflicting
17
Total98141238184678

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

View in ClinVar →

31 pathogenic / likely-pathogenic (of 33) ClinVar copy-number / structural variants overlap SEPSECS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

SEPSECS · protein map & ClinVar variants

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