MCID: HYP396
MIFTS: 33

Hypercholesterolemia, Autosomal Recessive

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Hypercholesterolemia, Autosomal Recessive

MalaCards integrated aliases for Hypercholesterolemia, Autosomal Recessive:

Name: Hypercholesterolemia, Autosomal Recessive 57 75 29 55 6 73
Hypercholesterolemia, Familial, Autosomal Recessive 57 13 40
Arh 57 12 75
Familial Autosomal Recessive Hypercholesterolemia 12 37
Autosomal Recessive Hypercholesterolemia 1 12 75
Autosomal Recessive Hypercholesterolemia 2 12 75
Fhcb1 12 75
Fhcb2 12 75
Arh1 12 75
Arh2 12 75
Hypercholesterolemia, Autosomal Recessive, 1, Formerly; Arh1, Formerly 57
Hypercholesterolemia, Autosomal Recessive, 2, Formerly; Arh2, Formerly 57
Hypercholesterolemia, Autosomal Recessive, 1, Formerly 57
Hypercholesterolemia, Autosomal Recessive, 2, Formerly 57
Autosomal Recessive Hypercholesterolemia 12
Fhcb1, Formerly 57
Fhcb2, Formerly 57
Arh1, Formerly 57
Arh2, Formerly 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
hypercholesterolemia, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 603813
Disease Ontology 12 DOID:0090105
ICD10 33 E78.0
MedGen 42 C1863512
MeSH 44 D006937
KEGG 37 H01918
UMLS 73 C1863512

Summaries for Hypercholesterolemia, Autosomal Recessive

OMIM : 57 Autosomal recessive hypercholesterolemia is a rare monogenic disease characterized by very high levels of low-density lipoprotein (LDL) cholesterol (usually above 400 mg/dl) and increased risk of premature atherosclerotic cardiovascular disease (summary by Sanchez-Hernandez et al., 2018). (603813)

MalaCards based summary : Hypercholesterolemia, Autosomal Recessive, also known as hypercholesterolemia, familial, autosomal recessive, is related to hypercholesterolemia, familial and homozygous familial hypercholesterolemia. An important gene associated with Hypercholesterolemia, Autosomal Recessive is LDLRAP1 (Low Density Lipoprotein Receptor Adaptor Protein 1), and among its related pathways/superpathways are Endocytosis and Lipoprotein metabolism. Related phenotypes are atherosclerosis and hypercholesterolemia

Disease Ontology : 12 A familial hypercholesterolemia characterized by autosomal inheritance that has material basis in homozygous mutation in the LDLRAP1 gene on chromosome 1p36.

UniProtKB/Swiss-Prot : 75 Hypercholesterolemia, autosomal recessive: A familial condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very- low-density lipoproteins.

Related Diseases for Hypercholesterolemia, Autosomal Recessive

Diseases in the Hypercholesterolemia, Familial family:

Hypercholesterolemia, Autosomal Dominant, Type B Hypercholesterolemia, Autosomal Dominant, 3
Hypercholesterolemia, Autosomal Recessive

Diseases related to Hypercholesterolemia, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hypercholesterolemia, familial 27.9 LDLR LDLRAP1 PCSK9
2 homozygous familial hypercholesterolemia 27.9 LDLR LDLRAP1 PCSK9
3 xanthomatosis 9.1 LDLR LDLRAP1
4 coronary heart disease 1 9.0 LDLR PCSK9
5 arcus corneae 8.7 LDLR LDLRAP1 PCSK9

Graphical network of the top 20 diseases related to Hypercholesterolemia, Autosomal Recessive:



Diseases related to Hypercholesterolemia, Autosomal Recessive

Symptoms & Phenotypes for Hypercholesterolemia, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Skin Nails Hair Skin:
xanthomas

Laboratory Abnormalities:
hypertriglyceridemia
very high low-density lipoprotein (ldl) cholesterol (>400 mg/dl)
high total cholesterol (>600 mg/dl)


Clinical features from OMIM:

603813

Human phenotypes related to Hypercholesterolemia, Autosomal Recessive:

32
# Description HPO Frequency HPO Source Accession
1 atherosclerosis 32 HP:0002621
2 hypercholesterolemia 32 obligate (100%) HP:0003124
3 Increased circulating very-low-density lipoprotein levels 32 HP:0003362
4 tendon xanthomatosis 32 HP:0010874

GenomeRNAi Phenotypes related to Hypercholesterolemia, Autosomal Recessive according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased free cholesterol GR00340-A-2 8.8 LDLR LDLRAP1 PCSK9

Drugs & Therapeutics for Hypercholesterolemia, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Hypercholesterolemia, Autosomal Recessive

Genetic Tests for Hypercholesterolemia, Autosomal Recessive

Genetic tests related to Hypercholesterolemia, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Hypercholesterolemia, Autosomal Recessive 29 LDLRAP1

Anatomical Context for Hypercholesterolemia, Autosomal Recessive

Publications for Hypercholesterolemia, Autosomal Recessive

Articles related to Hypercholesterolemia, Autosomal Recessive:

# Title Authors Year
1
[LDL-apheresis in patients with familial autosomal recessive hypercholesterolemia]. ( 22388845 )
2012

Variations for Hypercholesterolemia, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Hypercholesterolemia, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 LDLRAP1 p.Ser202His VAR_023320 rs386629678

ClinVar genetic disease variations for Hypercholesterolemia, Autosomal Recessive:

6
(show top 50) (show all 57)
# Gene Variation Type Significance SNP ID Assembly Location
1 LDLRAP1 NM_015627.2(LDLRAP1): c.65G> A (p.Trp22Ter) single nucleotide variant Pathogenic rs121908324 GRCh37 Chromosome 1, 25870254: 25870254
2 LDLRAP1 NM_015627.2(LDLRAP1): c.65G> A (p.Trp22Ter) single nucleotide variant Pathogenic rs121908324 GRCh38 Chromosome 1, 25543763: 25543763
3 LDLRAP1 LDLRAP1, 1-BP INS, 432A insertion Pathogenic
4 LDLRAP1 NM_015627.2(LDLRAP1): c.406C> T (p.Gln136Ter) single nucleotide variant Pathogenic rs121908325 GRCh37 Chromosome 1, 25883705: 25883705
5 LDLRAP1 NM_015627.2(LDLRAP1): c.406C> T (p.Gln136Ter) single nucleotide variant Pathogenic rs121908325 GRCh38 Chromosome 1, 25557214: 25557214
6 LDLRAP1 NM_015627.2(LDLRAP1): c.74dup (p.Gly26Trpfs) duplication Pathogenic GRCh37 Chromosome 1, 25870263: 25870263
7 LDLRAP1 NM_015627.2(LDLRAP1): c.74dup (p.Gly26Trpfs) duplication Pathogenic GRCh38 Chromosome 1, 25543772: 25543772
8 LDLRAP1 NM_015627.2(LDLRAP1): c.89-1G> C single nucleotide variant Pathogenic rs755104973 GRCh37 Chromosome 1, 25880412: 25880412
9 LDLRAP1 NM_015627.2(LDLRAP1): c.89-1G> C single nucleotide variant Pathogenic rs755104973 GRCh38 Chromosome 1, 25553921: 25553921
10 LDLRAP1 NM_015627.2(LDLRAP1): c.459+2T> G single nucleotide variant Pathogenic GRCh37 Chromosome 1, 25883760: 25883760
11 LDLRAP1 NM_015627.2(LDLRAP1): c.459+2T> G single nucleotide variant Pathogenic GRCh38 Chromosome 1, 25557269: 25557269
12 LDLRAP1 NM_015627.2(LDLRAP1): c.603dup (p.Ser202Leufs) duplication Pathogenic GRCh37 Chromosome 1, 25889631: 25889631
13 LDLRAP1 NM_015627.2(LDLRAP1): c.603dup (p.Ser202Leufs) duplication Pathogenic GRCh38 Chromosome 1, 25563140: 25563140
14 LDLRAP1 NM_015627.2(LDLRAP1): c.604_605delTCinsCA (p.Ser202His) indel Uncertain significance rs386629678 GRCh37 Chromosome 1, 25889632: 25889633
15 LDLRAP1 NM_015627.2(LDLRAP1): c.604_605delTCinsCA (p.Ser202His) indel Uncertain significance rs386629678 GRCh38 Chromosome 1, 25563141: 25563142
16 LDLRAP1 NM_015627.2(LDLRAP1): c.201G> A (p.Ser67=) single nucleotide variant Conflicting interpretations of pathogenicity rs747011377 GRCh37 Chromosome 1, 25880525: 25880525
17 LDLRAP1 NM_015627.2(LDLRAP1): c.201G> A (p.Ser67=) single nucleotide variant Conflicting interpretations of pathogenicity rs747011377 GRCh38 Chromosome 1, 25554034: 25554034
18 LDLRAP1 NM_015627.2(LDLRAP1): c.654A> G (p.Thr218=) single nucleotide variant Benign rs28969504 GRCh37 Chromosome 1, 25890189: 25890189
19 LDLRAP1 NM_015627.2(LDLRAP1): c.654A> G (p.Thr218=) single nucleotide variant Benign rs28969504 GRCh38 Chromosome 1, 25563698: 25563698
20 LDLRAP1 NM_015627.2(LDLRAP1): c.672C> T (p.Ser224=) single nucleotide variant Conflicting interpretations of pathogenicity rs41291054 GRCh38 Chromosome 1, 25563716: 25563716
21 LDLRAP1 NM_015627.2(LDLRAP1): c.672C> T (p.Ser224=) single nucleotide variant Conflicting interpretations of pathogenicity rs41291054 GRCh37 Chromosome 1, 25890207: 25890207
22 LDLRAP1 NM_015627.2(LDLRAP1): c.284G> A (p.Arg95Gln) single nucleotide variant Uncertain significance rs139877665 GRCh37 Chromosome 1, 25881403: 25881403
23 LDLRAP1 NM_015627.2(LDLRAP1): c.284G> A (p.Arg95Gln) single nucleotide variant Uncertain significance rs139877665 GRCh38 Chromosome 1, 25554912: 25554912
24 LDLRAP1 NM_015627.2(LDLRAP1): c.451C> T (p.Arg151Trp) single nucleotide variant Uncertain significance rs148916767 GRCh37 Chromosome 1, 25883750: 25883750
25 LDLRAP1 NM_015627.2(LDLRAP1): c.451C> T (p.Arg151Trp) single nucleotide variant Uncertain significance rs148916767 GRCh38 Chromosome 1, 25557259: 25557259
26 LDLRAP1 NM_015627.2(LDLRAP1): c.712C> T (p.Arg238Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs41291058 GRCh38 Chromosome 1, 25563756: 25563756
27 LDLRAP1 NM_015627.2(LDLRAP1): c.712C> T (p.Arg238Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs41291058 GRCh37 Chromosome 1, 25890247: 25890247
28 LDLRAP1 NM_015627.2(LDLRAP1): c.115C> T (p.Arg39Trp) single nucleotide variant Uncertain significance rs201179339 GRCh37 Chromosome 1, 25880439: 25880439
29 LDLRAP1 NM_015627.2(LDLRAP1): c.115C> T (p.Arg39Trp) single nucleotide variant Uncertain significance rs201179339 GRCh38 Chromosome 1, 25553948: 25553948
30 LDLRAP1 NM_015627.2(LDLRAP1): c.603_604delCTinsTC (p.Ser202Pro) indel Likely benign rs1060504131 GRCh37 Chromosome 1, 25889631: 25889632
31 LDLRAP1 NM_015627.2(LDLRAP1): c.603_604delCTinsTC (p.Ser202Pro) indel Likely benign rs1060504131 GRCh38 Chromosome 1, 25563140: 25563141
32 LDLRAP1 NM_015627.2(LDLRAP1): c.711G> A (p.Pro237=) single nucleotide variant Likely benign rs112914959 GRCh37 Chromosome 1, 25890246: 25890246
33 LDLRAP1 NM_015627.2(LDLRAP1): c.711G> A (p.Pro237=) single nucleotide variant Likely benign rs112914959 GRCh38 Chromosome 1, 25563755: 25563755
34 LDLRAP1 NM_015627.2(LDLRAP1): c.870C> T (p.Val290=) single nucleotide variant Likely benign rs200433841 GRCh37 Chromosome 1, 25893426: 25893426
35 LDLRAP1 NM_015627.2(LDLRAP1): c.870C> T (p.Val290=) single nucleotide variant Likely benign rs200433841 GRCh38 Chromosome 1, 25566935: 25566935
36 LDLRAP1 NM_015627.2(LDLRAP1): c.71delG (p.Gly24Alafs) deletion Pathogenic GRCh37 Chromosome 1, 25870260: 25870260
37 LDLRAP1 NM_015627.2(LDLRAP1): c.71delG (p.Gly24Alafs) deletion Pathogenic GRCh38 Chromosome 1, 25543769: 25543769
38 LDLRAP1 NM_015627.2(LDLRAP1): c.626C> T (p.Thr209Ile) single nucleotide variant Uncertain significance rs141522360 GRCh38 Chromosome 1, 25563670: 25563670
39 LDLRAP1 NM_015627.2(LDLRAP1): c.626C> T (p.Thr209Ile) single nucleotide variant Uncertain significance rs141522360 GRCh37 Chromosome 1, 25890161: 25890161
40 LDLRAP1 NM_015627.2(LDLRAP1): c.653_654invCA (p.Thr218Met) inversion Benign GRCh38 Chromosome 1, 25563697: 25563698
41 LDLRAP1 NM_015627.2(LDLRAP1): c.653_654invCA (p.Thr218Met) inversion Benign GRCh37 Chromosome 1, 25890188: 25890189
42 LDLRAP1 NM_015627.2(LDLRAP1): c.906G> A (p.Gln302=) single nucleotide variant Likely benign rs777827146 GRCh37 Chromosome 1, 25893462: 25893462
43 LDLRAP1 NM_015627.2(LDLRAP1): c.906G> A (p.Gln302=) single nucleotide variant Likely benign rs777827146 GRCh38 Chromosome 1, 25566971: 25566971
44 LDLRAP1 NM_015627.2(LDLRAP1): c.396C> T (p.Ile132=) single nucleotide variant Conflicting interpretations of pathogenicity rs369497122 GRCh37 Chromosome 1, 25883695: 25883695
45 LDLRAP1 NM_015627.2(LDLRAP1): c.396C> T (p.Ile132=) single nucleotide variant Conflicting interpretations of pathogenicity rs369497122 GRCh38 Chromosome 1, 25557204: 25557204
46 LDLRAP1 NM_015627.2(LDLRAP1): c.653C> T (p.Thr218Ile) single nucleotide variant Pathogenic rs114583297 GRCh37 Chromosome 1, 25890188: 25890188
47 LDLRAP1 NM_015627.2(LDLRAP1): c.653C> T (p.Thr218Ile) single nucleotide variant Pathogenic rs114583297 GRCh38 Chromosome 1, 25563697: 25563697
48 LDLRAP1 NM_015627.2(LDLRAP1): c.863C> T (p.Ser288Leu) single nucleotide variant Pathogenic rs753151497 GRCh37 Chromosome 1, 25893419: 25893419
49 LDLRAP1 NM_015627.2(LDLRAP1): c.863C> T (p.Ser288Leu) single nucleotide variant Pathogenic rs753151497 GRCh38 Chromosome 1, 25566928: 25566928
50 LDLRAP1 NM_015627.2(LDLRAP1): c.713G> A (p.Arg238Gln) single nucleotide variant Likely benign rs148579379 GRCh37 Chromosome 1, 25890248: 25890248

Expression for Hypercholesterolemia, Autosomal Recessive

Search GEO for disease gene expression data for Hypercholesterolemia, Autosomal Recessive.

Pathways for Hypercholesterolemia, Autosomal Recessive

Pathways related to Hypercholesterolemia, Autosomal Recessive according to KEGG:

37
# Name Kegg Source Accession
1 Endocytosis hsa04144

GO Terms for Hypercholesterolemia, Autosomal Recessive

Cellular components related to Hypercholesterolemia, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 early endosome GO:0005769 9.33 LDLR LDLRAP1 PCSK9
2 lysosome GO:0005764 9.32 LDLR PCSK9
3 late endosome GO:0005770 9.26 LDLR PCSK9
4 endolysosome membrane GO:0036020 8.96 LDLR PCSK9
5 PCSK9-LDLR complex GO:1990666 8.62 LDLR PCSK9

Biological processes related to Hypercholesterolemia, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.61 LDLR LDLRAP1 PCSK9
2 steroid metabolic process GO:0008202 9.5 LDLR LDLRAP1 PCSK9
3 receptor-mediated endocytosis GO:0006898 9.49 LDLR LDLRAP1
4 endocytosis GO:0006897 9.48 LDLR LDLRAP1
5 membrane organization GO:0061024 9.46 LDLR LDLRAP1
6 cholesterol metabolic process GO:0008203 9.43 LDLR LDLRAP1 PCSK9
7 cholesterol transport GO:0030301 9.4 LDLR LDLRAP1
8 lipoprotein metabolic process GO:0042157 9.37 LDLR PCSK9
9 receptor-mediated endocytosis involved in cholesterol transport GO:0090118 9.16 LDLR LDLRAP1
10 cholesterol homeostasis GO:0042632 9.13 LDLR LDLRAP1 PCSK9
11 low-density lipoprotein particle clearance GO:0034383 8.8 LDLR LDLRAP1 PCSK9

Molecular functions related to Hypercholesterolemia, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 amyloid-beta binding GO:0001540 9.16 LDLR LDLRAP1
2 low-density lipoprotein particle receptor binding GO:0050750 8.96 LDLRAP1 PCSK9
3 low-density lipoprotein particle binding GO:0030169 8.62 LDLR PCSK9

Sources for Hypercholesterolemia, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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