FHBL2
MCID: HYP290
MIFTS: 39

Hypobetalipoproteinemia, Familial, 2 (FHBL2)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hypobetalipoproteinemia, Familial, 2

MalaCards integrated aliases for Hypobetalipoproteinemia, Familial, 2:

Name: Hypobetalipoproteinemia, Familial, 2 57 72 29 13 6 70
Fhbl2 57 12 72
Familial Hypobetalipoproteinemia 2 12 15
Combined Hypobetalipoproteinemia Familial 72
Hypobetalipoproteinemia, Familial, Type 2 39
Hypolipidemia, Familial, Combined 57
Combined Familial Hypolipidemia 12

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
heterozygotes have plasma levels of triglycerides and/or hdl cholesterol that are intermediate between homozygotes and unaffected individuals


HPO:

31
hypobetalipoproteinemia, familial, 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111061
OMIM® 57 605019
MeSH 44 D006995
MedGen 41 C1857970
SNOMED-CT via HPO 68 190786004 258211005
UMLS 70 C1857970

Summaries for Hypobetalipoproteinemia, Familial, 2

OMIM® : 57 Hypobetalipoproteinemia (HBL) is defined as permanently low levels, below the 5th percentile of sex- and age-matched individuals in the population, of apolipoprotein B (apoB), total cholesterol, and low-density lipoprotein (LDL) cholesterol; the lipid profile in FHBL2 includes low HDL cholesterol as well. HBL can result from environmental factors such as a strict vegetarian diet, or can be secondary to certain diseases such as intestinal fat malabsorption, chronic pancreatitis, severe liver disease, malnutrition, or hyperthyroidism. Heritable primary causes of HBL include chylomicron retention disease (CMRD; 246700), abetalipoproteinemia (200100), and familial hypobetalipoproteinemia (FHBL) (summary by Martin-Campos et al., 2012). For a discussion of genetic heterogeneity of familial hypobetalipoproteinemia, see FHBL1 (615558). (605019) (Updated 20-May-2021)

MalaCards based summary : Hypobetalipoproteinemia, Familial, 2, also known as fhbl2, is related to defective apolipoprotein b-100 and arcus corneae. An important gene associated with Hypobetalipoproteinemia, Familial, 2 is ANGPTL3 (Angiopoietin Like 3), and among its related pathways/superpathways are Metabolism and Lipoprotein metabolism. Affiliated tissues include heart and liver, and related phenotypes are decreased ldl cholesterol concentration and hypotriglyceridemia

Disease Ontology : 12 A hypobetalipoproteinemia that has material basis in homozygous or compound heterozygous mutation in the ANGPTL3 gene on chromosome 1p31.

UniProtKB/Swiss-Prot : 72 Hypobetalipoproteinemia, familial, 2: A disorder of lipid metabolism characterized by less than 5th percentile age- and sex-specific levels of low density lipoproteins, and dietary fat malabsorption. Affected individuals present with combined hypolipidemia, consisting of extremely low plasma levels of LDL cholesterol, HDL cholesterol, and triglycerides.

Related Diseases for Hypobetalipoproteinemia, Familial, 2

Diseases in the Hypobetalipoproteinemia, Familial, 1 family:

Hypobetalipoproteinemia, Familial, 2

Diseases related to Hypobetalipoproteinemia, Familial, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 defective apolipoprotein b-100 10.1 PCSK9 APOB
2 arcus corneae 10.1 PCSK9 APOB
3 corneal degeneration 10.0 PCSK9 APOB
4 intermediate coronary syndrome 10.0 PCSK9 APOB
5 familial apolipoprotein c-ii deficiency 10.0 APOC3 APOB
6 hyperlipoproteinemia, type v 10.0 APOC3 APOB
7 hypercholesterolemia, familial, 4 10.0 PCSK9 APOB
8 hypertriglyceridemia, familial 10.0 APOC3 APOB
9 coronary stenosis 10.0 PCSK9 APOB
10 sitosterolemia 10.0 PCSK9 APOB
11 peripheral artery disease 9.9 PCSK9 APOB
12 abetalipoproteinemia 9.9 PCSK9 APOB ANGPTL3
13 hyperlipoproteinemia, type iv 9.9 APOC3 APOB ANGPTL3
14 aortic atherosclerosis 9.8 PLTP APOB
15 coronary heart disease 1 9.8 PCSK9 APOC3 APOB
16 inherited metabolic disorder 9.8 PCSK9 APOC3 APOB
17 homozygous familial hypercholesterolemia 9.7 PCSK9 APOB
18 hypobetalipoproteinemia, familial, 1 9.6 PCSK9 APOC3 APOB ANGPTL3
19 familial hypercholesterolemia 9.6 PCSK9 APOC3 APOB ANGPTL3
20 vascular disease 9.6 PCSK9 APOC3 APOB
21 hyperalphalipoproteinemia 1 9.6 PLTP APOC3 APOB
22 hyperlipidemia, familial combined, 3 9.6 PLTP APOC3 APOB
23 nephrotic syndrome 9.6 APOB ANGPTL4 ANGPTL3
24 familial lipoprotein lipase deficiency 9.6 APOC3 APOB ANGPTL4 ANGPTL3
25 tangier disease 9.4 PLTP LIPG APOC3 APOB
26 lipid metabolism disorder 9.4 PLTP LIPG APOC3 APOB
27 cardiovascular system disease 9.2 PLTP PCSK9 LIPG APOC3 APOB
28 hyperlipoproteinemia, type i 9.1 PCSK9 LIPG APOC3 APOB ANGPTL4 ANGPTL3
29 body mass index quantitative trait locus 11 9.0 PLTP LIPG APOC3 APOB ANGPTL4
30 hypolipoproteinemia 9.0 PLTP PCSK9 LIPG APOC3 APOB ANGPTL3
31 atherosclerosis susceptibility 9.0 PLTP PCSK9 LIPG APOC3 APOB ANGPTL3
32 diabetes mellitus 8.6 PLTP PCSK9 APOC3 APOB ANGPTL8 ANGPTL4
33 type 2 diabetes mellitus 8.4 PLTP PCSK9 LIPG APOC3 APOB ANGPTL8

Graphical network of the top 20 diseases related to Hypobetalipoproteinemia, Familial, 2:



Diseases related to Hypobetalipoproteinemia, Familial, 2

Symptoms & Phenotypes for Hypobetalipoproteinemia, Familial, 2

Human phenotypes related to Hypobetalipoproteinemia, Familial, 2:

31
# Description HPO Frequency HPO Source Accession
1 decreased ldl cholesterol concentration 31 HP:0003563
2 hypotriglyceridemia 31 HP:0012153

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Laboratory Abnormalities:
low ldl cholesterol
low triglycerides
low to very low hdl cholesterol
low apolipoprotein
marked hypobetalipoproteinemia
more

Clinical features from OMIM®:

605019 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Hypobetalipoproteinemia, Familial, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.23 ANGPTL3 ANGPTL4 ANGPTL8 APOB DOCK7 LIPG

Drugs & Therapeutics for Hypobetalipoproteinemia, Familial, 2

Search Clinical Trials , NIH Clinical Center for Hypobetalipoproteinemia, Familial, 2

Genetic Tests for Hypobetalipoproteinemia, Familial, 2

Genetic tests related to Hypobetalipoproteinemia, Familial, 2:

# Genetic test Affiliating Genes
1 Hypobetalipoproteinemia, Familial, 2 29 ANGPTL3

Anatomical Context for Hypobetalipoproteinemia, Familial, 2

MalaCards organs/tissues related to Hypobetalipoproteinemia, Familial, 2:

40
Heart, Liver

Publications for Hypobetalipoproteinemia, Familial, 2

Articles related to Hypobetalipoproteinemia, Familial, 2:

(show all 23)
# Title Authors PMID Year
1
Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization. 57 6
22659251 2012
2
Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia. 57 6
22247256 2012
3
Identification of a novel mutation in the ANGPTL3 gene in two families diagnosed of familial hypobetalipoproteinemia without APOB mutation. 6 57
22155345 2012
4
Characterization of three kindreds with familial combined hypolipidemia caused by loss-of-function mutations of ANGPTL3. 57 6
22062970 2012
5
Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. 57 6
20942659 2010
6
Rare loss-of-function mutations in ANGPTL family members contribute to plasma triglyceride levels in humans. 57 6
19075393 2009
7
Genetic heterogeneity in familial hypobetalipoproteinemia: linkage and non-linkage to the apoB gene in Caucasian families. 6 57
9508071 1998
8
Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease. 57
28538136 2017
9
Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides. 57
28538111 2017
10
Evidence for a quantitative trait locus affecting low levels of apolipoprotein B and low density lipoprotein on chromosome 10 in Caucasian families. 57
17890784 2007
11
Linkage of a gene for familial hypobetalipoproteinemia to chromosome 3p21.1-22. 57
10762553 2000
12
A form of familial hypobetalipoproteinaemia not due to a mutation in the apolipoprotein B gene. 57
1995762 1991
13
Hypobetalipoproteinemia and abetalipoproteinemia: liver disease and cardiovascular disease. 61
32039990 2020
14
Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia. 61
29752428 2019
15
ANGPTL3 serum concentration and rare genetic variants in Finnish population. 61
28972399 2017
16
Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and familial combined hypolipidemia. 61
28733173 2017
17
Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins. 61
28633452 2017
18
Association between familial hypobetalipoproteinemia and the risk of diabetes. Is this the other side of the cholesterol-diabetes connection? A systematic review of literature. 61
27804036 2017
19
Effects of angiopoietin-like protein 3 deficiency on postprandial lipid and lipoprotein metabolism. 61
27040449 2016
20
The role of ANGPTL3 in controlling lipoprotein metabolism. 61
26754661 2016
21
Silencing of ANGPTL 3 (angiopoietin-like protein 3) in human hepatocytes results in decreased expression of gluconeogenic genes and reduced triacylglycerol-rich VLDL secretion upon insulin stimulation. 61
25495645 2014
22
Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish. 61
24685482 2014
23
Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis. 61
24058201 2013

Variations for Hypobetalipoproteinemia, Familial, 2

ClinVar genetic disease variations for Hypobetalipoproteinemia, Familial, 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.50_51delinsGA (p.Ser17Ter) Indel Pathogenic 18439 rs267606655 GRCh37: 1:63063287-63063288
GRCh38: 1:62597616-62597617
2 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.385G>T (p.Glu129Ter) SNV Pathogenic 18440 rs200785483 GRCh37: 1:63063622-63063622
GRCh38: 1:62597951-62597951
3 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.1198+1G>T SNV Pathogenic 91863 rs398122985 GRCh37: 1:63069907-63069907
GRCh38: 1:62604236-62604236
4 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.55del (p.Ile19fs) Deletion Pathogenic 91864 rs398122986 GRCh37: 1:63063291-63063291
GRCh38: 1:62597620-62597620
5 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.431_434AACT[2] (p.Thr146_Asn147insTer) Microsatellite Pathogenic 91865 rs398122987 GRCh37: 1:63063668-63063671
GRCh38: 1:62597997-62598000
6 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.883T>C (p.Phe295Leu) SNV Pathogenic 91867 rs398122989 GRCh37: 1:63068003-63068003
GRCh38: 1:62602332-62602332
7 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.358_362CTCAA[1] (p.Asn121fs) Microsatellite Pathogenic 91866 rs398122988 GRCh37: 1:63063593-63063597
GRCh38: 1:62597922-62597926
8 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.1335dup (p.Ser446fs) Duplication Pathogenic 1031835 GRCh37: 1:63070436-63070437
GRCh38: 1:62604765-62604766
9 ANGPTL3 , DOCK7 NM_014495.4(ANGPTL3):c.575del (p.Gln192fs) Deletion Pathogenic 1031836 GRCh37: 1:63064446-63064446
GRCh38: 1:62598775-62598775

Expression for Hypobetalipoproteinemia, Familial, 2

Search GEO for disease gene expression data for Hypobetalipoproteinemia, Familial, 2.

Pathways for Hypobetalipoproteinemia, Familial, 2

GO Terms for Hypobetalipoproteinemia, Familial, 2

Cellular components related to Hypobetalipoproteinemia, Familial, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.7 PLTP PCSK9 LIPG APOC3 APOB ANGPTL4
2 collagen-containing extracellular matrix GO:0062023 9.61 APOC3 ANGPTL4 ANGPTL3
3 extracellular region GO:0005576 9.56 PLTP PCSK9 LIPG APOC3 APOB ANGPTL8
4 high-density lipoprotein particle GO:0034364 9.4 PLTP APOB
5 very-low-density lipoprotein particle GO:0034361 9.37 APOC3 APOB
6 chylomicron GO:0042627 9.32 APOC3 APOB
7 intermediate-density lipoprotein particle GO:0034363 9.26 APOC3 APOB
8 early endosome GO:0005769 9.02 PCSK9 LIPG APOC3 APOB ANGPTL3

Biological processes related to Hypobetalipoproteinemia, Familial, 2 according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.73 PLTP APOC3 APOB
2 lipid catabolic process GO:0016042 9.72 LIPG APOC3 APOB
3 cholesterol metabolic process GO:0008203 9.69 PCSK9 APOB ANGPTL3
4 flagellated sperm motility GO:0030317 9.64 PLTP APOB
5 phospholipid metabolic process GO:0006644 9.63 PCSK9 ANGPTL3
6 retinoid metabolic process GO:0001523 9.63 APOC3 APOB
7 intermembrane lipid transfer GO:0120009 9.62 PLTP APOB
8 triglyceride metabolic process GO:0006641 9.62 PCSK9 APOC3
9 artery morphogenesis GO:0048844 9.61 APOB ANGPTL3
10 cholesterol efflux GO:0033344 9.61 APOC3 APOB
11 low-density lipoprotein particle clearance GO:0034383 9.6 PCSK9 APOB
12 phospholipid catabolic process GO:0009395 9.59 LIPG ANGPTL3
13 reverse cholesterol transport GO:0043691 9.58 LIPG APOC3
14 negative regulation of low-density lipoprotein particle clearance GO:0010989 9.58 PCSK9 APOC3
15 triglyceride catabolic process GO:0019433 9.58 LIPG APOC3 APOB
16 phospholipid homeostasis GO:0055091 9.57 LIPG ANGPTL3
17 very-low-density lipoprotein particle assembly GO:0034379 9.54 APOC3 APOB
18 lipoprotein metabolic process GO:0042157 9.54 PCSK9 APOC3 APOB
19 chylomicron assembly GO:0034378 9.52 APOC3 APOB
20 high-density lipoprotein particle remodeling GO:0034375 9.5 PLTP LIPG APOC3
21 regulation of lipoprotein lipase activity GO:0051004 9.49 ANGPTL8 ANGPTL3
22 chylomicron remodeling GO:0034371 9.48 APOC3 APOB
23 chylomicron remnant clearance GO:0034382 9.46 APOC3 APOB
24 triglyceride homeostasis GO:0070328 9.46 APOC3 ANGPTL8 ANGPTL4 ANGPTL3
25 regulation of lipoprotein metabolic process GO:0050746 9.43 LIPG ANGPTL8
26 negative regulation of lipoprotein lipase activity GO:0051005 9.43 APOC3 ANGPTL4 ANGPTL3
27 cholesterol homeostasis GO:0042632 9.35 PCSK9 LIPG APOC3 APOB ANGPTL3
28 lipid metabolic process GO:0006629 9.23 PLTP PCSK9 LIPG APOC3 APOB ANGPTL8

Molecular functions related to Hypobetalipoproteinemia, Familial, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 enzyme inhibitor activity GO:0004857 9.37 ANGPTL4 ANGPTL3
2 heparin binding GO:0008201 9.33 LIPG APOB ANGPTL3
3 low-density lipoprotein particle receptor binding GO:0050750 9.32 PCSK9 APOB
4 intermembrane cholesterol transfer activity GO:0120020 9.26 PLTP APOB
5 low-density lipoprotein particle binding GO:0030169 8.96 PLTP PCSK9
6 very-low-density lipoprotein particle binding GO:0034189 8.62 PLTP PCSK9

Sources for Hypobetalipoproteinemia, Familial, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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