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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TSSC4
tumor suppressing subtransferable candidate 4
Chromosome 11 · 11p15.5
NCBI Gene: 10078Ensembl: ENSG00000184281.16HGNC: HGNC:12386UniProt: Q9Y5U2
39PubMed Papers
9Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingprotein-containing complex bindingmolecular sequestering activityspliceosomal tri-snRNP complex assemblypneumoniafungal lung infectious diseaseglioblastoma multiformediabetes mellitus
✦AI Summary

TSSC4 is a nuclear protein with dual roles in RNA splicing and cancer suppression. Structurally, TSSC4 is an intrinsically disordered protein that functions as a U5 snRNP assembly and recycling factor 12. It employs conserved regions to bind PRPF8 and SNRNP200 helicase, inhibiting SNRNP200 activity while coordinating U5 snRNP assembly into the functional U4/U6•U5 tri-snRNP complex 23. Beyond spliceosomal function, TSSC4 suppresses cancer through splicing regulation and autophagy inhibition. TSSC4 deficiency causes widespread alterations in alternative splicing patterns and dysregulates tumor-associated genes including oncogenes across multiple cancer cell lines 4. Additionally, TSSC4 inhibits autophagy via interaction with MAP1LC3/LC3, preventing cancer cells from entering death pathways during proliferation 5. This dual mechanism is clinically relevant: TSSC4 suppresses glioblastoma and breast cancer growth, with its expression promoted by oncogenic EGFR and ERBB2 variants 5. A two-gene classifier including TSSC4 achieved 100% accuracy in distinguishing allergic asthma from controls 6, suggesting potential diagnostic applications. TSSC4 is located in the imprinted 11p15 region but itself escapes genomic imprinting 7.

Sources cited
1
TSSC4 is a U5 snRNP component that promotes tri-snRNP formation and interacts with U5-specific proteins PRPF8, EFTUD2, and SNRNP200
PMID: 34131137
2
TSSC4 is an intrinsically disordered protein that inhibits SNRNP200 helicase, acts as a placeholder, and coordinates U5 snRNP assembly through multiple conserved binding regions
PMID: 35188580
3
TSSC4 works with CD2BP2 chaperone in U5 snRNP late biogenesis and recycling, priming U5 snRNP for tri-snRNP formation
PMID: 38467876
4
TSSC4 deficiency causes widespread alterations in splicing patterns and dysregulation of tumor-associated genes including oncogenes in multiple cancer cell lines
PMID: 39697342
5
TSSC4 suppresses cancer cell growth by inhibiting autophagy through interaction with MAP1LC3/LC3 via its conserved LIR domain, and its expression is promoted by ERBB2 and EGFRvIII
PMID: 34530675
6
A two-gene TSSC4-FAM212B classifier achieved 100% accuracy in distinguishing allergic asthma from healthy controls using skin tape-strip transcriptomics
PMID: 38375886
7
TSSC4 is located in the imprinted 11p15 domain but itself escapes genomic imprinting in fetal and extra-embryonic tissues
PMID: 10072438
Disease Associationsⓘ9
pneumoniaOpen Targets
0.05Suggestive
fungal lung infectious diseaseOpen Targets
0.04Suggestive
glioblastoma multiformeOpen Targets
0.03Suggestive
diabetes mellitusOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
cancerOpen Targets
0.01Suggestive
lymphomaOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EFTUD2Protein interaction100%PRPF8Protein interaction100%CRNKL1Protein interaction100%PRPF6Protein interaction100%SNW1Protein interaction100%SNRNP40Protein interaction100%
Tissue Expression6 tissues
Liver
100%
Lung
100%
Bone Marrow
84%
Ovary
80%
Heart
53%
Brain
45%
Gene Interaction Network
Click a node to explore
TSSC4EFTUD2PRPF8CRNKL1PRPF6SNW1SNRNP40
PROTEIN STRUCTURE
Preparing viewer…
PDB7PX3 · 3.05 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.91LoF Tolerant
pLIⓘ
0.06Tolerant
Observed/Expected LoF1.32 [0.43–1.91]
RankingsWhere TSSC4 stands among ~20K protein-coding genes
  • #10,412of 20,598
    Most Researched39
  • #17,353of 17,882
    Most Constrained (LOEUF)1.91
Genes detectedTSSC4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Alternative splicing regulation by tumor suppressing subtransferable candidate 4: a pathway to tumor suppression.
PMID: 39697342
Front Immunol · 2024
1.00
2
The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling.
PMID: 35188580
Nucleic Acids Res · 2022
0.90
3
Autophagy inhibition by TSSC4 (tumor suppressing subtransferable candidate 4) contributes to sustainable cancer cell growth.
PMID: 34530675
Autophagy · 2022
0.80
4
Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities.
PMID: 38375886
Allergy · 2024
0.70
5
TSSC4 is a component of U5 snRNP that promotes tri-snRNP formation.
PMID: 34131137
Nat Commun · 2021
0.60