SSR1

Chr 6

signal sequence receptor subunit 1

Also known as: TRAPA

NCBI Gene: 6745ENSG00000124783UniProt: P43307

The signal sequence receptor (SSR) is a glycosylated endoplasmic reticulum (ER) membrane receptor associated with protein translocation across the ER membrane. The SSR consists of 2 subunits, a 34-kD glycoprotein encoded by this gene and a 22-kD glycoprotein. This gene generates several mRNA species as a result of complex alternative polyadenylation. This gene is unusual in that it utilizes arrays of polyA signal sequences that are mostly non-canonical. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

68
ClinVar variants
31
Pathogenic / LP
0.27
pLI score
0
Active trials
Clinical Summary— SSR1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 36 VUS of 68 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.
0.55LOEUF
pLI 0.271
Z-score 2.86
OE 0.24 (0.12–0.55)
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.
1.45Z-score
OE missense 0.66 (0.56–0.79)
97 obs / 146.3 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.0.24 (0.12–0.55)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.56–0.79)
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.1.03
0≤1.21.6
LoF obs/exp: 4 / 16.5Missense obs/exp: 97 / 146.3Syn Z: -0.17

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic28
Likely Pathogenic3
VUS36
Likely Benign1
28
Pathogenic
3
Likely Pathogenic
36
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
28
0
28
Likely Pathogenic
0
0
3
0
3
VUS
0
23
13
0
36
Likely Benign
0
0
1
0
1
Benign
0
0
0
0
0
Total02345068

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

View in ClinVar →

Protein Context — Lollipop Plot

SSR1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The TRAP complex (SSR1-SSR4): mechanistic roles and therapeutic opportunities.
Zhang J et al.·Ann Med
2026Review
Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell lung cancers.
Nomura M et al.·PLoS Med
2007
Combined assessment of EGFR-related molecules to predict outcome of 1st-line cetuximab-containing chemotherapy for metastatic colorectal cancer.
Sunakawa Y et al.·Cancer Biol Ther
2016
Highly mutable tandem DNA repeats generate a cell wall protein variant more frequent in disease-causing Candida albicans isolates than in commensal isolates.
Zhou Z et al.·PLoS One
2017
Expanding the phenotype associated with interstitial 6p25.1p24.3 microdeletion: a new case and review of the literature.
Tassano E et al.·J Genet
2021Review
Comprehensive bioinformatics analysis reveals the hub genes and pathways associated with multiple myeloma.
Zhao S et al.·Hematology
2022
Changes in the liver of Tinca tinca under successive domestication using an integrated multi-omics approach.
Hou X et al.·Comp Biochem Physiol Part D Genomics Proteomics
2023
CA-SSR1 Polymorphism in Intron 1 of the EGFR Gene in Patients with Malignant Tumors Who Develop Acneiform Rash Associated with the Use of Cetuximab.
Jarząbek T et al.·Mol Diagn Ther
2015Cohort
Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer.
Brugger W et al.·J Clin Oncol
2011Clinical trial
The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-small-cell lung cancer.
Ichihara S et al.·Int J Cancer
2007Cohort
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