LRPAP1

Chr 4AR

LDL receptor related protein associated protein 1

Also known as: A2MRAP, A2RAP, HBP44, MYP23, RAP, alpha-2-MRAP

This gene encodes a molecular chaperone that facilitates proper folding and localization of LDL receptor-related proteins and prevents premature ligand binding along the secretory pathway. Mutations cause autosomal recessive myopia 23, affecting vision development. The gene shows low constraint to loss-of-function variation (pLI near 0, LOEUF >1), consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Myopia 23, autosomal recessiveMIM #615431
AR
0
Active trials
6
Pubs (1 yr)
128
P/LP submissions
0%
P/LP missense
1.17
LOEUF
LOF
Mechanism· G2P
Clinical SummaryLRPAP1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
126 unique Pathogenic / Likely Pathogenic· 85 VUS of 254 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.17LOEUF
pLI 0.000
Z-score 1.05
OE 0.72 (0.461.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.03Z-score
OE missense 1.19 (1.081.32)
272 obs / 228.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.72 (0.461.17)
00.351.4
Missense OE1.19 (1.081.32)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 12 / 16.6Missense obs/exp: 272 / 228.3Syn Z: -1.07
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLRPAP1-related myopia, extremeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6840th %ile
GOF
0.6052th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

254 submitted variants in ClinVar

Classification Summary

Pathogenic119
Likely Pathogenic7
VUS85
Likely Benign20
Benign9
119
Pathogenic
7
Likely Pathogenic
85
VUS
20
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
116
0
119
Likely Pathogenic
1
0
6
0
7
VUS
0
81
4
0
85
Likely Benign
0
13
3
4
20
Benign
0
3
0
6
9
Total49712910240

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LRPAP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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