SEZ6L

Chr 22

seizure related 6 homolog like

Also known as: SEZ6L1

NCBI Gene: 23544ENSG00000100095UniProt: Q9BYH1

Predicted to be involved in synapse maturation. Predicted to act upstream of or within activation of protein kinase C activity; adult locomotory behavior; and cerebellar Purkinje cell layer development. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in several cellular components, including glutamatergic synapse; neuronal cell body; and postsynaptic membrane. [provided by Alliance of Genome Resources, Jul 2025]

220
ClinVar variants
20
Pathogenic / LP
0.51
pLI score
0
Active trials
Clinical Summary— SEZ6L
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 167 VUS of 220 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.
0.37LOEUF
pLI 0.507
Z-score 4.90
OE 0.22 (0.13–0.37)
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.
1.47Z-score
OE missense 0.83 (0.77–0.90)
495 obs / 595.9 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.0.22 (0.13–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.90)
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.1.01
0≤1.21.6
LoF obs/exp: 10 / 45.7Missense obs/exp: 495 / 595.9Syn Z: -0.09

ClinVar Variant Classifications

220 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic1
VUS167
Likely Benign12
Benign7
19
Pathogenic
1
Likely Pathogenic
167
VUS
12
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
1
0
1
VUS
0
163
4
0
167
Likely Benign
0
7
1
4
12
Benign
0
2
1
4
7
Total0172268206

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

View in ClinVar →

Protein Context — Lollipop Plot

SEZ6L · 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
SEZ6-LIKE PROTEIN; SEZ6L
MIM #607021 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Incorporation of a genetic factor into an epidemiologic model for prediction of individual risk of lung cancer: the Liverpool Lung Project.
Raji OY et al.·Cancer Prev Res (Phila)
2010Functional
Not all roads lead to the immune system: the genetic basis of multiple sclerosis severity.
Jokubaitis VG et al.·Brain
2023
Seizure 6-like (SEZ6L) gene and risk for lung cancer.
Gorlov IP et al.·Cancer Res
2007
Characterization of Different Subtypes of Immune Cell Infiltration in Glioblastoma to Aid Immunotherapy.
Feng P et al.·Front Immunol
2022
IL-10 and integrin signaling pathways are associated with head and neck cancer progression.
Bornstein S et al.·BMC Genomics
2016
RNAi-based functional profiling of loci from blood lipid genome-wide association studies identifies genes with cholesterol-regulatory function.
Blattmann P et al.·PLoS Genet
2013Functional
Whole exome sequencing in extended families with autism spectrum disorder implicates four candidate genes.
Chapman NH et al.·Hum Genet
2015
A 6‑gene risk score system constructed for predicting the clinical prognosis of pancreatic adenocarcinoma patients.
Liu Y et al.·Oncol Rep
2019Cohort
Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers.
Shah T et al.·Circ Cardiovasc Genet
2013
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