SEC61G

Chr 7

SEC61 translocon subunit gamma

Also known as: SSS1

NCBI Gene: 23480ENSG00000132432UniProt: P60059

The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the gamma-subunit protein. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

27
ClinVar variants
11
Pathogenic / LP
0.63
pLI score
0
Active trials
Clinical Summary— SEC61G
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.63) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 16 VUS of 27 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
0.93LOEUF
pLI 0.631
Z-score 1.65
OE 0.00 (0.00–0.93)
Moderately constrained

Typical tolerance to LoF variation

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.
1.26Z-score
OE missense 0.42 (0.29–0.64)
16 obs / 37.8 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.0.00 (0.00–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.42 (0.29–0.64)
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.1.20
0≤1.21.6
LoF obs/exp: 0 / 3.2Missense obs/exp: 16 / 37.8Syn Z: -0.52

ClinVar Variant Classifications

27 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS16
10
Pathogenic
1
Likely Pathogenic
16
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
3
13
0
16
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0324027

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

View in ClinVar →

Protein Context — Lollipop Plot

SEC61G · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SEC61G Facilitates Brain Metastases via Antagonizing PGAM1 Ubiquitination and Immune Microenvironment Remodeling in Non-Small Cell Lung Cancer.
Zhou C et al.·Int J Biol Sci
2025Functional
In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies.
Shao Y et al.·Sci Rep
2024
SEC61G identified as a prognostic biomarker of head and neck squamous cell carcinoma.
Shi Y et al.·Eur Arch Otorhinolaryngol
2022
Single-cell analysis reveals exosome-associated biomarkers for prognostic prediction and immunotherapy in lung adenocarcinoma.
Lin S et al.·Aging (Albany NY)
2023
SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.
Zhou C et al.·Acta Biochim Biophys Sin (Shanghai)
2024
Gefitinib Combined with Cetuximab for the Treatment of Lung Adenocarcinoma Harboring the EGFR-Intergenic Region (SEC61G) Fusion and EGFR Amplification.
Zhang G et al.·Oncologist
2021Case report
Focusing on scRNA-seq-Derived T Cell-Associated Genes to Identify Prognostic Signature and Immune Microenvironment Status in Low-Grade Glioma.
Wen J et al.·Mediators Inflamm
2023
Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.
Ren P et al.·Bioengineered
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