SEC61A2

Chr 10

SEC61 translocon subunit alpha 2

NCBI Gene: 55176ENSG00000065665UniProt: Q9H9S3

The protein forms part of the SEC61 translocon complex that mediates transport of signal peptide-containing proteins across the endoplasmic reticulum membrane and serves as a ribosome receptor for cotranslational translocation. Mutations cause autosomal recessive tubular aggregate myopathy with features including progressive muscle weakness, muscle pain, and characteristic tubular aggregates on muscle biopsy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.558), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
20
P/LP submissions
0%
P/LP missense
0.56
LOEUF
DN
Mechanism· predicted
Clinical Summary— SEC61A2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 39 VUS of 76 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
0.56LOEUF
pLI 0.007
Z-score 3.34
OE 0.32 (0.19–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.00Z-score
OE missense 0.49 (0.42–0.56)
131 obs / 269.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.32 (0.19–0.56)
0≤0.351.4
Missense OE0.49 (0.42–0.56)
0≤0.61.4
Synonymous OE0.83
0≤1.21.6
LoF obs/exp: 9 / 28.1Missense obs/exp: 131 / 269.6Syn Z: 1.38
DN
0.77top 25%
GOF
0.5170th %ile
LOF
0.3356th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

76 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
VUS39
Likely Benign1
Benign1
20
Pathogenic
39
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
0
0
0
VUS
0
30
9
0
39
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Total03130061

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

View in ClinVar →

Protein Context — Lollipop Plot

SEC61A2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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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