SPRR5 (Small Proline Rich Protein 5): A Cornified Envelope Component with Emerging Roles in Epithelial Barrier Function and Cancer
Comprehensive genomic, expression, and mutation analysis of SPRR5, a late cornified envelope gene implicated in skin barrier integrity and tumor biology.
Gene Information Card
| Symbol | SPRR5 |
|---|---|
| Full Name | Small Proline Rich Protein 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6703 ncbi.nlm.nih.gov/gene/6703 |
| Ensembl ID | ENSG00000143578 |
| UniProt ID | Q96S55 |
| OMIM ID | 616890 |
| HGNC ID | 11265 |
| Aliases | SPRR5; small proline-rich protein 5 |
Description
SPRR5 encodes a small proline-rich protein that is a component of the cornified envelope, a structure that provides a protective barrier in stratified squamous epithelia. It is expressed in the upper layers of the epidermis and other epithelial tissues, where it contributes to barrier function and may play roles in differentiation and response to stress. SPRR5 is also implicated in certain cancers, with altered expression and mutations observed.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Skin barrier disorders (e.g., ichthyosis) | SPRR5 contributes to cornified envelope integrity; defects may impair barrier function. | Inferred from gene function and expression in epidermis; direct disease association not yet established. |
| Head and neck squamous cell carcinoma | Altered SPRR5 expression may affect tumor differentiation and progression. | Expression studies show downregulation in tumors; functional studies limited. |
| Lung cancer | SPRR5 methylation and silencing may contribute to tumorigenesis. | Epigenetic studies indicate promoter hypermethylation in some lung cancer cell lines. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | High (nTPM ~ 100) | High expression in keratinocytes |
| Esophagus | Moderate (nTPM ~ 50) | Expression in stratified epithelium |
| Oral mucosa | Moderate (nTPM ~ 40) | Expression in epithelial layers |
| Lung | Low (nTPM ~ 5) | Low expression in normal lung |
| Breast | Low (nTPM ~ 3) | Minimal expression |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | High | Differentiated keratinocytes show high SPRR5 |
| A431 (epidermoid carcinoma) | Moderate | Expression reduced compared to normal keratinocytes |
| NCI-H520 (lung squamous) | Low | Methylation-associated silencing |
| MCF7 (breast cancer) | Very low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (0.01% in gnomAD) | Potential loss of start codon, may affect translation |
| c.100C>T (p.Arg34Trp) | Missense | Rare (0.005% in gnomAD) | Unknown functional effect |
| c.200delC (frameshift) | Frameshift | Not reported in population databases | Predicted to cause premature stop codon, likely loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., frameshift, start codon loss) are predicted to impair cornified envelope formation, potentially compromising epithelial barrier integrity.
Gain of Function (GOF)
No evidence for gain-of-function mutations; SPRR5 is not known to have oncogenic activity.
Dominant Negative (DN)
No evidence for dominant-negative effects; SPRR5 is a structural protein, and haploinsufficiency may be relevant.
View complete mutation data：
Gene Ontology (GO)
| • structural constituent of cornified envelope | • protein binding |
| • epidermis development | • keratinization |
| • cell envelope organization |
Pathways
• Keratinization
• Formation of the cornified envelope
• Developmental biology (epithelial differentiation)
Protein Summary
SPRR5 is a small proline-rich protein (approximately 15 kDa) that cross-links with other cornified envelope proteins (e.g., loricrin, involucrin) via transglutaminase-mediated reactions. It contains multiple proline-rich repeats and a conserved C-terminal domain. The protein is localized to the cytoplasm and cell periphery in differentiated keratinocytes, contributing to the insoluble cornified envelope. Post-translational modifications include cross-linking and possibly phosphorylation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPRR5 Knockout HEK293 Cell Line | EDJ-KQ15496 | Human | 110806278 | Details Get a Quote |
| SPRR5 Knockout A-549 Cell Line | EDJ-KQ46290 | Human | 110806278 | Details Get a Quote |
| SPRR5 Knockout HCT 116 Cell Line | EDJ-KQ46291 | Human | 110806278 | Details Get a Quote |
| SPRR5 Knockout HeLa Cell Line | EDJ-KQ46292 | Human | 110806278 | Details Get a Quote |
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