SZT2

Chr 1AR

SZT2 subunit of KICSTOR complex

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

NCBI Gene: 23334ENSG00000198198UniProt: Q5T011

The protein encoded by this gene is expressed in the brain, predominantly in the parietal and frontal cortex as well as in dorsal root ganglia. It is localized to the peroxisome, and is implicated in resistance to oxidative stress. It likely functions by increasing superoxide dismutase (SOD) activity, but itself has no direct SOD activity. Studies in mice show that this gene confers low seizure threshold, and may also enhance epileptogenesis. [provided by RefSeq, Jun 2011]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 18MIM #615476
AR
3664
ClinVar variants
48
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SZT2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
48 Pathogenic / Likely Pathogenic· 183 VUS of 3664 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.000
Z-score 8.52
OE 0.33 (0.27–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.60Z-score
OE missense 0.84 (0.80–0.87)
1666 obs / 1992.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.27–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.80–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 61 / 186.6Missense obs/exp: 1666 / 1992.2Syn Z: 0.23

ClinVar Variant Classifications

3664 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic13
VUS183
Likely Benign302
Benign5
35
Pathogenic
13
Likely Pathogenic
183
VUS
302
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
1
18
0
35
Likely Pathogenic
10
1
2
0
13
VUS
1
170
7
5
183
Likely Benign
0
6
134
162
302
Benign
0
0
5
0
5
Total27178166167538

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.

Gene2Phenotype Curations

SZT2-related infantile encephalopathy with epilepsy and dysmorphic corpus callosum

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 18

MIM #615476

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical phenotype and genetic characteristics of SZT2 related diseases: A case report and literature review.
Zhang X et al.·Seizure
2024Review
Genetic analysis of developmental and epileptic encephalopathy caused by novel biallelic SZT2 gene mutations in three Chinese Han infants: a case series and literature review.
Yang S et al.·Neurol Sci
2022Review
mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion.
Calhoun JD et al.·Brain
2022Functional
A novel hypoxia-induced lncRNA, SZT2-AS1, boosts HCC progression by mediating HIF heterodimerization and histone trimethylation under a hypoxic microenvironment.
Liu R et al.·Cell Death Differ
2025
Developmental and epileptic encephalopathy due to SZT2 genomic variants: Emerging features of a syndromic condition.
Trivisano M et al.·Epilepsy Behav
2020Review
Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.
Buchert R et al.·Am J Hum Genet
2025
mTOR Signalling in Head and Neck Cancer: Heads Up.
Tan FH et al.·Cells
2019Review
Compound heterozygous SZT2 mutations in two siblings with early-onset epilepsy, intellectual disability and macrocephaly.
Domingues FS et al.·Seizure
2019
Mutations in SZT2 result in early-onset epileptic encephalopathy and leukoencephalopathy.
Pizzino A et al.·Am J Med Genet A
2018Case report
[Clinical pathological and genetic mutation characteristics of conjunctival lymphoepithelial carcinoma].
Wang YC et al.·Zhonghua Yan Ke Za Zhi
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools