IEMbase 0370: LDLRAP1-related autosomal recessive hypercholesterolemia
Scope
| Field | Value |
|---|---|
| IEMbase ID | 370 |
| Nosology | 15.1.02.01 |
| Gene | LDLRAP1 |
| External IDs | OMIM:603813; OMIM:605747; ORPHA:391665 |
| Generated mapping | UNMAPPED; low candidate Familial_Hypercholesterolemia.yaml |
| Candidate DisMech targets | Familial_Hypercholesterolemia.yaml#LDLRAP1-Related LDL Uptake Defect |
| Review date | 2026-07-07 |
IEMbase phenotype signal
IEMbase represents autosomal recessive hypercholesterolemia caused by LDLRAP1, also listed as ARH1. Inheritance is autosomal recessive.
Characteristic rows include arcus cornealis, xanthelasma, tendon xanthomas, plasma LDL cholesterol, plasma HDL cholesterol, serum triglyceride, and plasma Apo B. Clinical rows include carotid bruits, femoral bruits, and myocardial ischemia. Treatment rows include ezetimibe, lomitapide, PCSK9 inhibitors, and statins.
DisMech phenotype coverage
The generated UNMAPPED status is a false negative. DisMech has a Familial Hypercholesterolemia file that explicitly covers biallelic LDLRAP1 loss of function as a recessive route into the LDL receptor pathway. The local mechanism describes LDLRAP1 as the adaptor required for LDLR-LDL internalization through clathrin-coated pits, with biallelic deficiency reducing hepatic LDL uptake and converging on the same LDL-clearance defect as FH.
Local coverage is stronger for the receptor-internalization mechanism and FH treatment framework. IEMbase is stronger for bruits and specific treatment rows for this record.
Concordance and completeness
Judgement: false negative; resolve to the local familial hypercholesterolemia LDLRAP1/autosomal recessive hypercholesterolemia context.
The resources agree on LDLRAP1 identity, recessive inheritance, impaired LDL clearance, elevated LDL cholesterol, tendon xanthomas, corneal arcus, xanthelasma, and premature ischemic cardiovascular disease. IEMbase treatment rows overlap with local LDL-lowering therapy, but lomitapide and PCSK9 inhibitors should be reviewed in the LDLRAP1-specific clinical context before import.
Curation actions
- Map this record to
Familial_Hypercholesterolemia.yaml, specifically the LDLRAP1-related LDL uptake defect and autosomal recessive FH context. - Consider future enrichment with carotid bruits, femoral bruits, Apo B, HDL cholesterol, LDL cholesterol, triglyceride rows, and LDLRAP1-specific treatment nuance.
- Preserve autosomal recessive inheritance and avoid merging this record into heterozygous LDLR/APOB/PCSK9 FH subtypes.