SEZ6L2

Chr 16

seizure related 6 homolog like 2

Also known as: BSRPA, PSK-1

NCBI Gene: 26470ENSG00000174938UniProt: Q6UXD5

This gene encodes a seizure-related protein that is localized on the cell surface. The gene is located in a region of chromosome 16p11.2 that is thought to contain candidate genes for autism spectrum disorders (ASD), though there is no evidence directly implicating this gene in ASD. Increased expression of this gene has been found in lung cancers, and the protein is therefore considered to be a novel prognostic marker for lung cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

456
ClinVar variants
128
Pathogenic / LP
0.12
pLI score
0
Active trials
Clinical Summary— SEZ6L2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
128 Pathogenic / Likely Pathogenic· 117 VUS of 456 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.
0.42LOEUF
pLI 0.117
Z-score 4.42
OE 0.25 (0.15–0.42)
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.
1.75Z-score
OE missense 0.79 (0.73–0.86)
452 obs / 569.9 exp
Tolerant

Mild missense constraint

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.0.25 (0.15–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.73–0.86)
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.0.98
0≤1.21.6
LoF obs/exp: 10 / 40.3Missense obs/exp: 452 / 569.9Syn Z: 0.24

ClinVar Variant Classifications

456 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic125
Likely Pathogenic3
VUS117
Likely Benign14
Benign9
125
Pathogenic
3
Likely Pathogenic
117
VUS
14
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
125
0
125
Likely Pathogenic
0
0
3
0
3
VUS
0
110
7
0
117
Likely Benign
0
5
0
9
14
Benign
0
2
0
7
9
Total011713516268

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

View in ClinVar →

Protein Context — Lollipop Plot

SEZ6L2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting SEZ6L2 in Colon Cancer: Efficacy of Bexarotene and Implications for Survival.
Zheng H et al.·J Gastrointest Cancer
2024
Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma.
Wang L et al.·Dis Markers
2020
Identification of EPHB4 as a potential causal gene and therapeutic target for endometriosis using Mendelian randomization.
Ling S et al.·Hereditas
2025
Association and mutation analyses of 16p11.2 autism candidate genes.
Kumar RA et al.·PLoS One
2009
Seizure-related 6 homolog like 2 autoimmunity: Neurologic syndrome and antibody effects.
Landa J et al.·Neurol Neuroimmunol Neuroinflamm
2020Case report
A Genome-Wide Association Study in Psoriasis Patients Reveals Variants Associated with Response to Treatment with Interleukin-17A Pathway Inhibitors.
Ioakeimidou D et al.·Genes (Basel)
2025Cohort
Integrated analysis of proteomics and metabolomics in infantile epileptic spasms syndrome.
Chen J et al.·Sci Rep
2025
Duplication 16p11.2 in a child with infantile seizure disorder.
Bedoyan JK et al.·Am J Med Genet A
2010Case report
Towards Precision Medicine in Obesity: Genetic Copy Number Variations Profiling Linked to Specific Metabolic Dysregulation Patterns.
Mitu I et al.·Int J Mol Sci
2025
Transcriptome-based identification of molecular markers related to the development and prognosis of Colon cancer.
Lu J et al.·Nucleosides Nucleotides Nucleic Acids
2021
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