LRPAP1

LDL receptor related protein associated protein 1

Basic information

Region (hg38): 4:3503611-3532446

Previous symbols: [ "A2MRAP", "RAP" ]

Links

ENSG00000163956 ∙ NCBI:4043 ∙ OMIM:104225 ∙ HGNC:6701 ∙ Uniprot:P30533 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopia 23, autosomal recessive (Limited), mode of inheritance: AR
• myopia 23, autosomal recessive (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 23, autosomal recessive	AR	General	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	Ophthalmologic	23830514; 25525168

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRPAP1 gene.

• Inborn genetic diseases (24 variants)
• not provided (17 variants)
• Myopia 23, autosomal recessive (1 variants)
• Rare isolated myopia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRPAP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	5	9
missense			25	3	3	31
nonsense		1				1
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	1	1	25	8	8

Variants in LRPAP1

This is a list of pathogenic ClinVar variants found in the LRPAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-3512969-T-C		LRPAP1-related disorder	Likely benign (Aug 08, 2023)
4-3512979-G-A		not specified	Uncertain significance (Nov 03, 2022)
4-3512988-G-C		not specified	Uncertain significance (Apr 08, 2022)
4-3512991-G-A		not specified	Uncertain significance (Jun 28, 2023)
4-3514774-C-T		LRPAP1-related disorder	Likely benign (Sep 05, 2023)
4-3514816-C-T		not specified	Likely benign (Jan 24, 2024)
4-3514817-G-A		not specified	Uncertain significance (Mar 12, 2024)
4-3514824-G-A			Benign (Jul 23, 2018)
4-3514898-CGA-C		Myopia 23, autosomal recessive	Likely pathogenic (Mar 29, 2024)
4-3516119-G-T		not specified	Likely benign (Sep 01, 2021)
4-3516141-G-A		not specified	Uncertain significance (Oct 03, 2022)
4-3516145-G-A		not specified	Likely benign (Sep 20, 2022)
4-3516147-T-G		not specified	Uncertain significance (May 10, 2022)
4-3516151-C-T		not specified	Uncertain significance (May 27, 2022)
4-3516207-G-T		LRPAP1-related disorder	Likely benign (Jul 12, 2019)
4-3518035-A-G		LRPAP1-related disorder	Benign (Apr 30, 2019)
4-3518057-T-C		not specified	Uncertain significance (Oct 06, 2021)
4-3518076-GGTCC-G		Myopia 23, autosomal recessive	Pathogenic (Mar 22, 2022)
4-3518094-T-C			Uncertain significance (Sep 27, 2022)
4-3518120-G-A		not specified	Uncertain significance (Jul 26, 2022)
4-3518121-T-G		not specified	Uncertain significance (Dec 09, 2023)
4-3518147-T-G		not specified	Uncertain significance (Dec 02, 2022)
4-3518154-C-T		LRPAP1-related disorder	Likely benign (Jul 05, 2023)
4-3518170-G-A			Likely benign (Dec 31, 2019)
4-3518179-GT-G		Myopia 23, autosomal recessive	Pathogenic (Aug 08, 2013)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRPAP1	protein_coding	protein_coding	ENST00000500728	8	26184

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.50e-7	0.626	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.03	272	228	1.19	0.0000147	2303
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000212
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000133	0.000123
Middle Eastern	0.000109	0.000109
South Asian	0.000304	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.551
• rvis_EVS: 0.6
• rvis_percentile_EVS: 82.83

Haploinsufficiency Scores

• pHI: 0.128
• hipred: N
• hipred_score: 0.197
• ghis: 0.422

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.802

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lrpap1
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); renal/urinary system phenotype

Gene ontology

• 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;negative regulation of cell death;extracellular negative regulation of signal transduction;negative regulation of amyloid-beta clearance;positive regulation of amyloid-beta clearance
• Cellular component: extracellular region;endosome;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;Golgi apparatus;Golgi lumen;cis-Golgi network;plasma membrane;cell surface;endosome lumen;rough endoplasmic reticulum lumen
• Molecular function: amyloid-beta binding;signaling receptor binding;protein binding;heparin binding;lipase binding;receptor antagonist activity;low-density lipoprotein particle receptor binding;very-low-density lipoprotein particle receptor binding