LRPAP1
protein-codingLDL receptor related protein associated protein 1
Gene summary
This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
- A2MRAP
- RAP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014183
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014183
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0014183
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LRPAP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002337.4. 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 | 7 | 3 | 10 | |||
| missense | 83 | 14 | 2 | 99 | ||
| nonsense | 2 | 1 | 3 | |||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 3 | 4 | 87 | 21 | 5 | 120 |
Highest pathogenic variant AF is 0.000001430824
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002328.1 | 8 | MANE Select | |
| Ensembl | ENSP00000497444.1 | 8 | MANE Select | |
| Ensembl | ENSP00000421648.1 | 2 | Standard | |
| Ensembl | ENSP00000496947.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cholesterol metabolism - Homo sapiens (human)
- integrin signaling pathway
- Reelin signaling pathway
- Lissencephaly gene (LIS1) in neuronal migration and development
- Signaling events mediated by the Hedgehog family
Biological Process
- negative regulation of receptor internalization
- negative regulation of very-low-density lipoprotein particle clearance
- negative regulation of protein binding
- transcytosis
- regulation of receptor-mediated endocytosis
Molecular Function
- amyloid-beta binding
- signaling receptor binding
- protein binding
- heparin binding
- lipase binding
Cellular Component
- extracellular region
- endosome
- endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000500728
- Coding exons
- 8
- Length
- 26184
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.03 | 272 | 228 | 1.19 | 0.0000147 | 2303 |
| Missense (PolyPhen) | 85 | 79.651 | 1.0672 | 902 | ||
| Synonymous | -1.07 | 122 | 108 | 1.13 | 0.00000798 | 681 |
| Loss of Function | 1.05 | 12 | 16.6 | 0.721 | 7.08e-7 | 198 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00030 | 0.00029 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Molecular chaperone for LDL receptor-related proteins that may regulate their ligand binding activity along the secretory pathway. {ECO:0000269|PubMed:7774585}.;
- Disease
- DISEASE: Myopia 23, autosomal recessive (MYP23) [MIM:615431]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:23830514}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.123
Intolerance Scores
- LoFtool
- 0.551
- RVIS EVS
- 0.6
- RVIS percentile EVS
- 82.83
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.802
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |