PRELP
protein-codingproline and arginine rich end leucine rich repeat protein, the group of Small leucine rich repeat proteoglycans
Gene summary
The protein encoded by this gene is a leucine-rich repeat protein present in connective tissue extracellular matrix. This protein functions as a molecule anchoring basement membranes to the underlying connective tissue. This protein has been shown to bind type I collagen to basement membranes and type II collagen to cartilage. It also binds the basement membrane heparan sulfate proteoglycan perlecan. This protein is suggested to be involved in the pathogenesis of Hutchinson-Gilford progeria (HGP), which is reported to lack the binding of collagen in basement membranes and cartilage. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 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 PRELP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002725.4. 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 | 2 | 2 | 4 | |||
| missense | 52 | 1 | 53 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 52 | 3 | 2 | 57 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002716.1 | 2 | MANE Select | |
| Ensembl | ENSP00000343924.2 | 2 | MANE Select | |
| RefSeq | NP_958505.1 | 2 | Standard | |
| Ensembl | ENSP00000534952.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of carbohydrates
- Keratan sulfate biosynthesis
- Keratan sulfate/keratin metabolism
- Glycosaminoglycan metabolism
- Metabolism
Biological Process
- skeletal system development
- cell aging
- keratan sulfate biosynthetic process
- keratan sulfate catabolic process
Molecular Function
- extracellular matrix structural constituent
- heparin binding
- extracellular matrix structural constituent conferring compression resistance
Cellular Component
- extracellular region
- Golgi lumen
- extracellular matrix
- lysosomal lumen
- collagen-containing extracellular matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000343110
- Coding exons
- 2
- Length
- 15525
- Individuals with no LoFs
- 125721
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 27
- Defined
- 125748
- p
- 0.000107
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.741 | 193 | 224 | 0.861 | 0.0000139 | 2498 |
| Missense (PolyPhen) | 64 | 77.169 | 0.82935 | 904 | ||
| Synonymous | -1.22 | 119 | 103 | 1.15 | 0.00000677 | 813 |
| Loss of Function | 0.899 | 8 | 11.3 | 0.711 | 8.51e-7 | 108 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.000068 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May anchor basement membranes to the underlying connective tissue. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.465
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.826
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |