ARH
MCID: HYP396
MIFTS: 43

Hypercholesterolemia, Autosomal Recessive (ARH)

Categories: Blood diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Rare diseases, Skin 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
Autosomal Recessive Hypercholesterolemia 12 15
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
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 homozygous familial hypercholesterolemia and hypercholesterolemia, familial. 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 Neuroscience. Affiliated tissues include skin and pancreas, and related phenotypes are hypertriglyceridemia 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

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

Skin Nails Hair Skin:
xanthomas


Clinical features from OMIM:

603813

Human phenotypes related to Hypercholesterolemia, Autosomal Recessive:

32
# Description HPO Frequency HPO Source Accession
1 hypertriglyceridemia 32 HP:0002155
2 hypercholesterolemia 32 obligate (100%) HP:0003124
3 atherosclerosis 32 HP:0002621
4 tendon xanthomatosis 32 HP:0010874
5 increased vldl cholesterol concentration 32 HP:0003362

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

26 (show all 16)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.58 LEP
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.58 PDSS1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.58 LEP PCSK9 PDSS1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-145 9.58 PDSS1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.58 PCSK9
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-153 9.58 PDSS1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.58 PDSS1
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.58 LEP
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.58 LEP PCSK9
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.58 PCSK9
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.58 LEP
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-62 9.58 PDSS1
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-77 9.58 PDSS1
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-87 9.58 PDSS1
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-95 9.58 PDSS1
16 Decreased free cholesterol GR00340-A-2 9.13 LDLR LDLRAP1 PCSK9

MGI Mouse Phenotypes related to Hypercholesterolemia, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.86 AGRP FDXR LDLR LEP NPY OPRL1
2 homeostasis/metabolism MP:0005376 9.85 AGRP DAB2 LDLR LDLRAP1 LEP NPY
3 adipose tissue MP:0005375 9.72 AGRP LDLR LEP NPY POMC
4 liver/biliary system MP:0005370 9.43 AGRP LDLR LEP NPY PCSK9 POMC
5 nervous system MP:0003631 9.23 AGRP FDXR LDLR LEP NPY OPRL1

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

MalaCards organs/tissues related to Hypercholesterolemia, Autosomal Recessive:

41
Skin, Pancreas

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 68)
# 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 NM_015627.2(LDLRAP1): c.432_433insA (p.Ala145Serfs) insertion Pathogenic GRCh37 Chromosome 1, 25883731: 25883732
4 LDLRAP1 NM_015627.2(LDLRAP1): c.432_433insA (p.Ala145Serfs) insertion Pathogenic GRCh38 Chromosome 1, 25557240: 25557241
5 LDLRAP1 NM_015627.2(LDLRAP1): c.406C> T (p.Gln136Ter) single nucleotide variant Pathogenic rs121908325 GRCh37 Chromosome 1, 25883705: 25883705
6 LDLRAP1 NM_015627.2(LDLRAP1): c.406C> T (p.Gln136Ter) single nucleotide variant Pathogenic rs121908325 GRCh38 Chromosome 1, 25557214: 25557214
7 LDLRAP1 NM_015627.2(LDLRAP1): c.605C> A (p.Ser202Tyr) single nucleotide variant Uncertain significance rs121908326 GRCh37 Chromosome 1, 25889633: 25889633
8 LDLRAP1 NM_015627.2(LDLRAP1): c.605C> A (p.Ser202Tyr) single nucleotide variant Uncertain significance rs121908326 GRCh38 Chromosome 1, 25563142: 25563142
9 LDLRAP1 NM_015627.2(LDLRAP1): c.74dup (p.Gly26Trpfs) duplication Pathogenic GRCh37 Chromosome 1, 25870263: 25870263
10 LDLRAP1 NM_015627.2(LDLRAP1): c.74dup (p.Gly26Trpfs) duplication Pathogenic GRCh38 Chromosome 1, 25543772: 25543772
11 LDLRAP1 NM_015627.2(LDLRAP1): c.89-1G> C single nucleotide variant Pathogenic rs755104973 GRCh37 Chromosome 1, 25880412: 25880412
12 LDLRAP1 NM_015627.2(LDLRAP1): c.89-1G> C single nucleotide variant Pathogenic rs755104973 GRCh38 Chromosome 1, 25553921: 25553921
13 LDLRAP1 NM_015627.2(LDLRAP1): c.459+2T> G single nucleotide variant Pathogenic GRCh37 Chromosome 1, 25883760: 25883760
14 LDLRAP1 NM_015627.2(LDLRAP1): c.459+2T> G single nucleotide variant Pathogenic GRCh38 Chromosome 1, 25557269: 25557269
15 LDLRAP1 NM_015627.2(LDLRAP1): c.603dup (p.Ser202Leufs) duplication Pathogenic GRCh37 Chromosome 1, 25889631: 25889631
16 LDLRAP1 NM_015627.2(LDLRAP1): c.603dup (p.Ser202Leufs) duplication Pathogenic GRCh38 Chromosome 1, 25563140: 25563140
17 LDLRAP1 NM_015627.2(LDLRAP1): c.604_605delTCinsCA (p.Ser202His) indel Uncertain significance rs386629678 GRCh37 Chromosome 1, 25889632: 25889633
18 LDLRAP1 NM_015627.2(LDLRAP1): c.604_605delTCinsCA (p.Ser202His) indel Uncertain significance rs386629678 GRCh38 Chromosome 1, 25563141: 25563142
19 LDLRAP1 NM_015627.2(LDLRAP1): c.201G> A (p.Ser67=) single nucleotide variant Conflicting interpretations of pathogenicity rs747011377 GRCh37 Chromosome 1, 25880525: 25880525
20 LDLRAP1 NM_015627.2(LDLRAP1): c.201G> A (p.Ser67=) single nucleotide variant Conflicting interpretations of pathogenicity rs747011377 GRCh38 Chromosome 1, 25554034: 25554034
21 LDLRAP1 NM_015627.2(LDLRAP1): c.654A> G (p.Thr218=) single nucleotide variant Benign rs28969504 GRCh38 Chromosome 1, 25563698: 25563698
22 LDLRAP1 NM_015627.2(LDLRAP1): c.654A> G (p.Thr218=) single nucleotide variant Benign rs28969504 GRCh37 Chromosome 1, 25890189: 25890189
23 LDLRAP1 NM_015627.2(LDLRAP1): c.672C> T (p.Ser224=) single nucleotide variant Conflicting interpretations of pathogenicity rs41291054 GRCh38 Chromosome 1, 25563716: 25563716
24 LDLRAP1 NM_015627.2(LDLRAP1): c.672C> T (p.Ser224=) single nucleotide variant Conflicting interpretations of pathogenicity rs41291054 GRCh37 Chromosome 1, 25890207: 25890207
25 LDLRAP1 NM_015627.2(LDLRAP1): c.284G> A (p.Arg95Gln) single nucleotide variant Uncertain significance rs139877665 GRCh37 Chromosome 1, 25881403: 25881403
26 LDLRAP1 NM_015627.2(LDLRAP1): c.284G> A (p.Arg95Gln) single nucleotide variant Uncertain significance rs139877665 GRCh38 Chromosome 1, 25554912: 25554912
27 LDLRAP1 NM_015627.2(LDLRAP1): c.451C> T (p.Arg151Trp) single nucleotide variant Uncertain significance rs148916767 GRCh37 Chromosome 1, 25883750: 25883750
28 LDLRAP1 NM_015627.2(LDLRAP1): c.451C> T (p.Arg151Trp) single nucleotide variant Uncertain significance rs148916767 GRCh38 Chromosome 1, 25557259: 25557259
29 LDLRAP1 NM_015627.2(LDLRAP1): c.712C> T (p.Arg238Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs41291058 GRCh38 Chromosome 1, 25563756: 25563756
30 LDLRAP1 NM_015627.2(LDLRAP1): c.712C> T (p.Arg238Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs41291058 GRCh37 Chromosome 1, 25890247: 25890247
31 LDLRAP1 NM_015627.2(LDLRAP1): c.115C> T (p.Arg39Trp) single nucleotide variant Uncertain significance rs201179339 GRCh37 Chromosome 1, 25880439: 25880439
32 LDLRAP1 NM_015627.2(LDLRAP1): c.115C> T (p.Arg39Trp) single nucleotide variant Uncertain significance rs201179339 GRCh38 Chromosome 1, 25553948: 25553948
33 LDLRAP1 NM_015627.2(LDLRAP1): c.603_604delCTinsTC (p.Ser202Pro) indel Likely benign rs1060504131 GRCh37 Chromosome 1, 25889631: 25889632
34 LDLRAP1 NM_015627.2(LDLRAP1): c.603_604delCTinsTC (p.Ser202Pro) indel Likely benign rs1060504131 GRCh38 Chromosome 1, 25563140: 25563141
35 LDLRAP1 NM_015627.2(LDLRAP1): c.711G> A (p.Pro237=) single nucleotide variant Likely benign rs112914959 GRCh37 Chromosome 1, 25890246: 25890246
36 LDLRAP1 NM_015627.2(LDLRAP1): c.711G> A (p.Pro237=) single nucleotide variant Likely benign rs112914959 GRCh38 Chromosome 1, 25563755: 25563755
37 LDLRAP1 NM_015627.2(LDLRAP1): c.870C> T (p.Val290=) single nucleotide variant Likely benign rs200433841 GRCh37 Chromosome 1, 25893426: 25893426
38 LDLRAP1 NM_015627.2(LDLRAP1): c.870C> T (p.Val290=) single nucleotide variant Likely benign rs200433841 GRCh38 Chromosome 1, 25566935: 25566935
39 LDLRAP1 NM_015627.2(LDLRAP1): c.71delG (p.Gly24Alafs) deletion Pathogenic GRCh37 Chromosome 1, 25870260: 25870260
40 LDLRAP1 NM_015627.2(LDLRAP1): c.71delG (p.Gly24Alafs) deletion Pathogenic GRCh38 Chromosome 1, 25543769: 25543769
41 LDLRAP1 NM_015627.2(LDLRAP1): c.626C> T (p.Thr209Ile) single nucleotide variant Uncertain significance rs141522360 GRCh37 Chromosome 1, 25890161: 25890161
42 LDLRAP1 NM_015627.2(LDLRAP1): c.626C> T (p.Thr209Ile) single nucleotide variant Uncertain significance rs141522360 GRCh38 Chromosome 1, 25563670: 25563670
43 LDLRAP1 NM_015627.2(LDLRAP1): c.653_654invCA (p.Thr218Met) inversion Benign GRCh38 Chromosome 1, 25563697: 25563698
44 LDLRAP1 NM_015627.2(LDLRAP1): c.653_654invCA (p.Thr218Met) inversion Benign GRCh37 Chromosome 1, 25890188: 25890189
45 LDLRAP1 NM_015627.2(LDLRAP1): c.906G> A (p.Gln302=) single nucleotide variant Likely benign rs777827146 GRCh38 Chromosome 1, 25566971: 25566971
46 LDLRAP1 NM_015627.2(LDLRAP1): c.906G> A (p.Gln302=) single nucleotide variant Likely benign rs777827146 GRCh37 Chromosome 1, 25893462: 25893462
47 LDLRAP1 NM_015627.2(LDLRAP1): c.396C> T (p.Ile132=) single nucleotide variant Conflicting interpretations of pathogenicity rs369497122 GRCh38 Chromosome 1, 25557204: 25557204
48 LDLRAP1 NM_015627.2(LDLRAP1): c.396C> T (p.Ile132=) single nucleotide variant Conflicting interpretations of pathogenicity rs369497122 GRCh37 Chromosome 1, 25883695: 25883695
49 LDLRAP1 NM_015627.2(LDLRAP1): c.653C> T (p.Thr218Ile) single nucleotide variant Pathogenic rs114583297 GRCh37 Chromosome 1, 25890188: 25890188
50 LDLRAP1 NM_015627.2(LDLRAP1): c.653C> T (p.Thr218Ile) single nucleotide variant Pathogenic rs114583297 GRCh38 Chromosome 1, 25563697: 25563697

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 Golgi apparatus GO:0005794 9.63 AGRP CD79B LDLR NPY PCSK9 PRNP
2 endolysosome membrane GO:0036020 8.96 LDLR PCSK9
3 PCSK9-LDLR complex GO:1990666 8.62 LDLR PCSK9

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

(show all 21)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.88 FDXR LDLR LDLRAP1 LEP PCSK9
2 regulation of signaling receptor activity GO:0010469 9.83 AGRP LEP NPY PCSK9 POMC
3 receptor-mediated endocytosis GO:0006898 9.77 DAB2 LDLR LDLRAP1
4 endocytosis GO:0006897 9.75 DAB2 LDLR LDLRAP1
5 membrane organization GO:0061024 9.71 DAB2 LDLR LDLRAP1
6 cholesterol homeostasis GO:0042632 9.67 LDLR LDLRAP1 PCSK9
7 steroid metabolic process GO:0008202 9.67 FDXR LDLR LDLRAP1 PCSK9
8 regulation of blood pressure GO:0008217 9.63 LEP NPY POMC
9 feeding behavior GO:0007631 9.59 AGRP NPY
10 long-term memory GO:0007616 9.58 LDLR PRNP
11 cholesterol transport GO:0030301 9.57 LDLR LDLRAP1
12 positive regulation of endocytosis GO:0045807 9.56 DAB2 LDLR
13 lipoprotein metabolic process GO:0042157 9.55 LDLR PCSK9
14 ubiquinone biosynthetic process GO:0006744 9.52 FDXR PDSS1
15 central nervous system neuron development GO:0021954 9.51 LEP NPY
16 eating behavior GO:0042755 9.5 AGRP LEP OPRL1
17 neuropeptide signaling pathway GO:0007218 9.46 AGRP NPY OPRL1 POMC
18 low-density lipoprotein particle clearance GO:0034383 9.43 LDLR LDLRAP1 PCSK9
19 receptor-mediated endocytosis involved in cholesterol transport GO:0090118 9.4 LDLR LDLRAP1
20 adult feeding behavior GO:0008343 9.13 AGRP LEP NPY
21 cholesterol metabolic process GO:0008203 9.02 FDXR LDLR LDLRAP1 LEP PCSK9

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

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.62 AGRP LEP NPY POMC
2 neuropeptide hormone activity GO:0005184 9.4 AGRP NPY
3 low-density lipoprotein particle receptor binding GO:0050750 9.37 LDLRAP1 PCSK9
4 hormone activity GO:0005179 9.33 LEP NPY POMC
5 low-density lipoprotein particle binding GO:0030169 9.26 LDLR PCSK9
6 clathrin adaptor activity GO:0035615 8.96 DAB2 LDLRAP1
7 amyloid-beta binding GO:0001540 8.8 LDLR LDLRAP1 PRNP

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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