SEZ6L2

Chr 16

seizure related 6 homolog like 2

Also known as: BSRPA, PSK-1

NCBI Gene: 26470ENSG00000174938UniProt: Q6UXD5OMIM: 616667

The protein contributes to specialized endoplasmic reticulum functions in neurons and is localized on the cell surface. Mutations in this gene cause neurodevelopmental disorders with autism spectrum features, with the gene located in the chromosome 16p11.2 region associated with autism spectrum disorders. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.42), suggesting intolerance to complete protein loss.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.42
Clinical Summary— SEZ6L2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
279 unique Pathogenic / Likely Pathogenic· 123 VUS of 455 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
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
1.75Z-score
OE missense 0.79 (0.73–0.86)
452 obs / 569.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.25 (0.15–0.42)
0≤0.351.4
Missense OE0.79 (0.73–0.86)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 10 / 40.3Missense obs/exp: 452 / 569.9Syn Z: 0.24
DN
0.6647th %ile
GOF
0.77top 25%
LOF
0.3355th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

455 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic236
Likely Pathogenic43
VUS123
Likely Benign15
Benign9
236
Pathogenic
43
Likely Pathogenic
123
VUS
15
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
236
0
236
Likely Pathogenic
0
0
43
0
43
VUS
0
111
12
0
123
Likely Benign
0
6
0
9
15
Benign
0
2
0
7
9
Total011929116426

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients