SPRR1A
protein-codingsmall proline rich protein 1A, the group of Small proline rich proteins
Gene summary
A structural constituent of skin epidermis. Involved in cornification and peptide cross-linking. Located in cornified envelope. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~1.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SPRR1A variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005987.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 15 | 1 | 16 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 15 | 2 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005978.2 | 1 | MANE Select | |
| Ensembl | ENSP00000357751.1 | 1 | MANE Select | |
| RefSeq | NP_001186757.1 | 1 | Standard | |
| Ensembl | ENSP00000512485.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Keratinization
- Developmental Biology
- Formation of the cornified envelope
Biological Process
- epidermis development
- peptide cross-linking
- keratinocyte differentiation
- cornification
Molecular Function
- structural molecule activity
- protein binding
- structural constituent of epidermis
- protein binding, bridging
Cellular Component
- cornified envelope
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307122
- Coding exons
- 1
- Length
- 1733
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125745
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.693 | 59 | 45.8 | 1.29 | 0.00000205 | 565 |
| Missense (PolyPhen) | 21 | 17.794 | 1.1802 | 200 | ||
| Synonymous | -0.342 | 20 | 18.1 | 1.10 | 8.71e-7 | 171 |
| Loss of Function | -0.0565 | 3 | 2.90 | 1.04 | 1.25e-7 | 29 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.;
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- LoFtool
- 0.570
- RVIS EVS
- 0.24
- RVIS percentile EVS
- 68.72
Essentials
- Essential (CRISPR)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.134
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |