SZT2

Chr 1AR

SZT2 subunit of KICSTOR complex

Also known as: C1orf84, DEE18, EIEE18, KIAA0467, KICS1, SZT2A, SZT2B

The protein is localized to peroxisomes and lysosomes and functions in resistance to oxidative stress by increasing superoxide dismutase activity. Biallelic mutations cause developmental and epileptic encephalopathy 18, an autosomal recessive disorder characterized by seizures and developmental delay. The pathogenic mechanism involves impaired oxidative stress resistance, which contributes to increased seizure susceptibility and epileptogenesis.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.411 OMIM phenotype
Clinical SummarySZT2
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
40 unique Pathogenic / Likely Pathogenic· 175 VUS of 498 total submissions
📖
GeneReview available — SZT2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.000
Z-score 8.52
OE 0.33 (0.270.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.60Z-score
OE missense 0.84 (0.800.87)
1666 obs / 1992.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.33 (0.270.41)
00.351.4
Missense OE0.84 (0.800.87)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 61 / 186.6Missense obs/exp: 1666 / 1992.2Syn Z: 0.23

ClinVar Variant Classifications

498 submitted variants in ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic11
VUS175
Likely Benign219
Benign4
29
Pathogenic
11
Likely Pathogenic
175
VUS
219
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
26
1
2
0
29
Likely Pathogenic
10
1
0
0
11
VUS
1
163
9
2
175
Likely Benign
0
7
98
114
219
Benign
0
0
4
0
4
Total37172113116438

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

View in ClinVar →

Protein Context — Lollipop Plot

SZT2 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗