SSR4

Chr X

signal sequence receptor subunit 4

Also known as: CDG1Y, TRAPD

NCBI Gene: 6748ENSG00000180879UniProt: P51571

This gene encodes the delta subunit of the translocon-associated protein complex which is involved in translocating proteins across the endoplasmic reticulum membrane. The encoded protein is located in the Xq28 region and is arranged in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene and both genes are driven by a CpG-embedded bidirectional promoter. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

UniProtCongenital disorder of glycosylation 1Y
245
ClinVar variants
116
Pathogenic / LP
0.87
pLI score
0
Active trials
Clinical Summary— SSR4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
116 Pathogenic / Likely Pathogenic· 73 VUS of 245 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.
0.44LOEUF
pLI 0.875
Z-score 2.41
OE 0.00 (0.00–0.44)
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.
0.90Z-score
OE missense 0.71 (0.57–0.89)
55 obs / 77.3 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.0.00 (0.00–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.71 (0.57–0.89)
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.1.25
0≤1.21.6
LoF obs/exp: 0 / 6.8Missense obs/exp: 55 / 77.3Syn Z: -1.18

ClinVar Variant Classifications

245 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic108
Likely Pathogenic8
VUS73
Likely Benign41
Benign13
Conflicting2
108
Pathogenic
8
Likely Pathogenic
73
VUS
41
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
104
0
108
Likely Pathogenic
3
0
5
0
8
VUS
1
52
20
0
73
Likely Benign
1
1
25
14
41
Benign
0
1
11
1
13
Conflicting
—2
Total95416515245

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

View in ClinVar →

Protein Context — Lollipop Plot

SSR4 · 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.

📖
GeneReview available — SSR4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Unveiling SSR4: a promising biomarker in esophageal squamous cell carcinoma.
Zhang J et al.·Front Immunol
2025
SSR4 as a prognostic biomarker and related with immune infiltration cells in colon adenocarcinoma.
He W et al.·Expert Rev Mol Diagn
2022
SSR4-CDG, an ultra-rare X-linked congenital disorder of glycosylation affecting the TRAP complex: Review of 22 affected individuals including the first adult patient.
Johnsen C et al.·Mol Genet Metab
2024Review
Expanding the phenotype of X-linked SSR4-CDG: Connective tissue implications.
Castiglioni C et al.·Hum Mutat
2021
The TRAP complex (SSR1-SSR4): mechanistic roles and therapeutic opportunities.
Zhang J et al.·Ann Med
2026Review
Expanding the Molecular and Clinical Phenotype of SSR4-CDG.
Ng BG et al.·Hum Mutat
2015Case report
Clinical and genetic characterization of congenital disorders of glycosylation in 20 Chinese patients.
Zhao P et al.·Orphanet J Rare Dis
2025Cohort
Single-cell RNA-seq combined with bulk RNA-seq analysis identifies necroptosis-related genes as therapeutic targets for periodontitis.
Zhu F et al.·BMC Med Genomics
2025
Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.
Zemet R et al.·Mol Genet Metab
2024Natural history
[Analysis of SSR4 gene variant in a child with congenital glycosylation type 1y in conjunct with congenital dysplasia of external auditory canal].
Wu R et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2022
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