Details of Disease

General Information of Disease (ID: DISFLNLI)

• Disease Name: Hypercholesterolemia, familial, 4
• Synonyms: hypercholesterolemia, autosomal recessive, 2, formerly; FHCB2, formerly; hypercholesterolemia, autosomal recessive, 2; hypercholesterolemia, autosomal recessive; FHCB2; hypercholesterolemia, autosomal recessive, 1; FHCB1, formerly; FHCB1; hypercholesterolemia, autosomal recessive, 1, formerly; ARH1; autosomal recessive hypercholesterolemia 2; autosomal recessive hypercholesterolemia 1; ARH2; familial autosomal recessive hypercholesterolemia; ARH
• Definition: An autosomal recessive condition caused by mutation(s) in the LDLRAP1 gene, encoding low density lipoprotein receptor adaptor protein 1. The phenotype is similar to that of familial hypercholesterolemia, but generally considered to be a milder form of hypercholesterolemia.
• Disease Hierarchy:
  DISVBLBO: Hyperlipoproteinemia
  DISO5FAY: Inborn error of metabolism
  DISFLNLI: Hypercholesterolemia, familial, 4
• Disease Identifiers:
  MONDO ID: MONDO_0011374
  UMLS CUI: C1863512
  OMIM ID: 603813
  MedGen ID: 400313

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LDLR	TTH0DUS	Strong	Genetic Variation	[1]
LPAR6	TTZDAGB	Strong	Biomarker	[2]
PCSK9	TTNIZ2B	Strong	Genetic Variation	[1]

This Disease Is Related to 10 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ADPRH	OTLJ5511	Strong	Biomarker	[3]
ADPRS	OTI1KPN6	Strong	Genetic Variation	[4]
AMN	OTS1TJXG	Strong	Biomarker	[5]
CLTC	OTBFASMA	Strong	Biomarker	[6]
DDHD1	OTWTHOWK	Strong	Genetic Variation	[2]
DSG4	OTWIQDC4	Strong	Biomarker	[2]
KRT25	OT4JMRN6	Strong	Genetic Variation	[7]
LIPH	OTRGYLKL	Strong	Genetic Variation	[7]
PTBP2	OTF4S7NE	Strong	Genetic Variation	[8]
LDLRAP1	OT6QTX7R	Definitive	Autosomal recessive	[9]

References

• [1] A new variant (c.1A>G) in LDLRAP1 causing autosomal recessive hypercholesterolemia: Characterization of the defect and response to PCSK9 inhibition.Atherosclerosis. 2019 May;284:223-229. doi: 10.1016/j.atherosclerosis.2019.01.010. Epub 2019 Jan 25.
• [2] Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis.Hum Mutat. 2010 May;31(5):602-10. doi: 10.1002/humu.21235.
• [3] Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred.J Clin Lipidol. 2018 Jan-Feb;12(1):145-151. doi: 10.1016/j.jacl.2017.10.014. Epub 2017 Oct 27.
• [4] Prevalence and clinical features of heterozygous carriers of autosomal recessive hypercholesterolemia in Sardinia.Atherosclerosis. 2009 Nov;207(1):162-7. doi: 10.1016/j.atherosclerosis.2009.04.027. Epub 2009 May 4.
• [5] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2.Traffic. 2010 May;11(5):706-20. doi: 10.1111/j.1600-0854.2010.01042.x. Epub 2010 Jan 18.
• [6] Premature senescence in cells from patients with autosomal recessive hypercholesterolemia (ARH): evidence for a role for ARH in mitosis.Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2270-7. doi: 10.1161/ATVBAHA.111.232223. Epub 2011 Jul 21.
• [7] Autosomal Recessive Hypotrichosis with Woolly Hair Caused by a Mutation in the Keratin 25 Gene Expressed in Hair Follicles.J Invest Dermatol. 2016 Jun;136(6):1097-1105. doi: 10.1016/j.jid.2016.01.037. Epub 2016 Feb 20.
• [8] A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.Hum Genet. 2005 Jan;116(1-2):114-20. doi: 10.1007/s00439-004-1192-9. Epub 2004 Nov 17.
• [9] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.