SEC22C

Chr 3

SEC22 homolog C, vesicle trafficking protein

Also known as: SEC22L3

NCBI Gene: 9117ENSG00000093183UniProt: Q9BRL7OMIM: 604028

The protein is involved in vesicle transport between the endoplasmic reticulum and Golgi complex as part of the SEC22 family of vesicle trafficking proteins. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and progressive microcephaly. This gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.22
Clinical Summary— SEC22C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 48 VUS of 78 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.22LOEUF
pLI 0.000
Z-score 0.90
OE 0.76 (0.48–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.84Z-score
OE missense 0.82 (0.71–0.94)
137 obs / 167.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.48–1.22)
0≤0.351.4
Missense OE0.82 (0.71–0.94)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 12 / 15.9Missense obs/exp: 137 / 167.5Syn Z: 0.50
DN
0.5869th %ile
GOF
0.6345th %ile
LOF
0.3259th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

78 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS48
Likely Benign3
6
Pathogenic
1
Likely Pathogenic
48
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
43
5
0
48
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total04612058

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

View in ClinVar →

Protein Context — Lollipop Plot

SEC22C · 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 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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