HDL2
MCID: HNT004
MIFTS: 48

Huntington Disease-Like 2 (HDL2)

Categories: Eye diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Huntington Disease-Like 2

MalaCards integrated aliases for Huntington Disease-Like 2:

Name: Huntington Disease-Like 2 57 12 24 59 74 29 13 55 6 72
Hdl2 57 12 59 74
Huntington's Disease-Like 2 12 15
Huntington Disease-Like, Type 2 40

Characteristics:

Orphanet epidemiological data:

59
huntington disease-like 2
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
mean age of onset 35-40 years
normal alleles contain 6 to 28 repeats
pathogenic alleles contain greater than 41 repeats


HPO:

32
huntington disease-like 2:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance For ethical reasons, only a few unaffected individuals from families with hdl2 have been tested; therefore, the penetrance is unknown, though as noted above, one individual with a repeat of 44 triplets did not have evidence of hdl2 at age 65, suggesting the possibility of reduced penetrance in some individuals.

Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0090104
OMIM 57 606438
ICD10 33 G10
ICD10 via Orphanet 34 G10
UMLS via Orphanet 73 C1847987
Orphanet 59 ORPHA98934
MedGen 42 C1847987
UMLS 72 C1847987

Summaries for Huntington Disease-Like 2

UniProtKB/Swiss-Prot : 74 Huntington disease-like 2: Huntington disease (HD) is a neurodegenerative disorder resulting primarily from the loss of medium spiny projection neurons in the striatum, especially in the caudate nucleus, and, to a lesser extent, atrophy of mesencephalic and cortical structures. The typical clinical picture of HD combines familial adult onset chorea and subcortical dementia that usually begin during the fourth decade of life.

MalaCards based summary : Huntington Disease-Like 2, also known as hdl2, is related to huntington disease and dentatorubral-pallidoluysian atrophy, and has symptoms including action tremor, bradykinesia and muscle rigidity. An important gene associated with Huntington Disease-Like 2 is JPH3 (Junctophilin 3). The drugs Atorvastatin and Calcium have been mentioned in the context of this disorder. Affiliated tissues include heart, liver and testes, and related phenotypes are personality changes and gait disturbance

Disease Ontology : 12 A neurodegenerative disease characterized by involuntary movements and abnormalities of voluntary movements, psychiatric symptoms, weight loss, and dementia with onset in the fourth decade and death about 20 years after disease onset, and has material basis in autosomal dominant inheritance of heterozygous expansion of a CAG/CTG repeat in the junctophilin-3 gene (JPH3) on chromosome 16q24.

More information from OMIM: 606438
GeneReviews: NBK1529

Related Diseases for Huntington Disease-Like 2

Diseases in the Huntington Disease family:

Huntington Disease-Like 1 Huntington Disease-Like 3
Huntington Disease-Like 2 Juvenile Huntington Disease
Huntington Disease-Like Syndrome Huntington Disease-Like Syndrome Due to C9orf72 Expansions

Diseases related to Huntington Disease-Like 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 65)
# Related Disease Score Top Affiliating Genes
1 huntington disease 30.5 LOC109029536 JPH3 HTT
2 dentatorubral-pallidoluysian atrophy 29.6 JPH3 HTT
3 choreatic disease 29.3 VPS13A JPH3 HTT
4 mcleod syndrome 29.0 XK VPS13A
5 choreoacanthocytosis 28.8 XK VPS13A JPH3
6 huntington disease-like syndrome 11.4
7 huntington disease-like 3 11.0
8 coronary heart disease 1 10.4
9 rapidly involuting congenital hemangioma 10.3
10 arteries, anomalies of 10.3
11 hyperlipoproteinemia, type iii 10.3
12 coronary artery anomaly 10.3
13 abetalipoproteinemia 10.2
14 hypercholesterolemia, familial, 1 10.2
15 familial hypercholesterolemia 10.2
16 liver disease 10.2
17 ataxia and polyneuropathy, adult-onset 10.2
18 huntington disease-like 1 10.2
19 spinocerebellar ataxia 17 10.2
20 chorea, childhood-onset, with psychomotor retardation 10.2
21 autosomal dominant cerebellar ataxia 10.2
22 dystonia 10.1
23 atherosclerosis susceptibility 10.1
24 hypertriglyceridemia, familial 10.1
25 heart disease 10.1
26 familial hyperlipidemia 10.1
27 arteriosclerosis 10.1
28 liver cirrhosis 10.1
29 kidney disease 10.1
30 fatty liver disease 10.1
31 spinocerebellar ataxia 2 10.0
32 movement disease 10.0
33 subacute delirium 10.0
34 myoclonus 10.0
35 spinocerebellar ataxia 36 10.0
36 myotonic dystrophy 10.0
37 myotonia atrophica 10.0
38 diabetes mellitus, noninsulin-dependent 10.0
39 hyperlipoproteinemia, type iv 10.0
40 hypertension, essential 10.0
41 leukodystrophy, hypomyelinating, 3 10.0
42 body mass index quantitative trait locus 11 10.0
43 myocardial infarction 10.0
44 microvascular complications of diabetes 3 10.0
45 microvascular complications of diabetes 4 10.0
46 microvascular complications of diabetes 6 10.0
47 microvascular complications of diabetes 7 10.0
48 beta-thalassemia 10.0
49 peripheral vascular disease 10.0
50 angina pectoris 10.0

Graphical network of the top 20 diseases related to Huntington Disease-Like 2:



Diseases related to Huntington Disease-Like 2

Symptoms & Phenotypes for Huntington Disease-Like 2

Human phenotypes related to Huntington Disease-Like 2:

59 32 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 personality changes 59 32 frequent (33%) Frequent (79-30%) HP:0000751
2 gait disturbance 59 32 occasional (7.5%) Occasional (29-5%) HP:0001288
3 hyperreflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001347
4 chorea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002072
5 weight loss 59 32 occasional (7.5%) Occasional (29-5%) HP:0001824
6 memory impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0002354
7 dystonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001332
8 cerebral cortical atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002120
9 dementia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000726
10 parkinsonism 59 32 occasional (7.5%) Occasional (29-5%) HP:0001300
11 functional motor deficit 59 32 occasional (7.5%) Occasional (29-5%) HP:0004302
12 caudate atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0002340
13 primitive reflex 59 32 occasional (7.5%) Occasional (29-5%) HP:0002476
14 depressivity 32 HP:0000716
15 dysarthria 32 HP:0001260
16 behavioral abnormality 59 Occasional (29-5%)
17 hallucinations 32 HP:0000738
18 abnormality of movement 59 Frequent (79-30%)
19 irritability 32 HP:0000737
20 anxiety 32 HP:0000739
21 rigidity 32 HP:0002063
22 involuntary movements 59 Occasional (29-5%)
23 action tremor 32 HP:0002345
24 bradykinesia 32 HP:0002067
25 apathy 32 HP:0000741
26 delusions 32 HP:0000746
27 abnormal corpus striatum morphology 59 Occasional (29-5%)
28 abnormality of the cerebrum 59 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
dysarthria
hyperreflexia
chorea
dystonia
rigidity
more
Growth Weight:
weight loss

Neurologic Behavioral Psychiatric Manifestations:
hallucinations
irritability
anxiety
apathy
delusions
more

Clinical features from OMIM:

606438

UMLS symptoms related to Huntington Disease-Like 2:


action tremor, bradykinesia, muscle rigidity

Drugs & Therapeutics for Huntington Disease-Like 2

Drugs for Huntington Disease-Like 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 44)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Atorvastatin Approved Phase 4 134523-00-5 60823
2
Calcium Approved, Nutraceutical Phase 4 7440-70-2 271
3 Rosuvastatin Calcium Phase 4 147098-20-2
4 Calcium, Dietary Phase 4
5 Lipid Regulating Agents Phase 4
6 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 4
7 Hypolipidemic Agents Phase 4
8 Anticholesteremic Agents Phase 4
9 Antimetabolites Phase 4
10
Metformin Approved Phase 3 657-24-9 4091 14219
11
Pioglitazone Approved, Investigational Phase 3 111025-46-8 4829
12 Hypoglycemic Agents Phase 3
13
Norelgestromin Approved, Investigational Phase 2 53016-31-2 13752005
14
Ethinyl Estradiol Approved Phase 2 57-63-6 5991
15
Norgestimate Approved, Investigational Phase 2 35189-28-7 6540478
16
Moxifloxacin Approved, Investigational Phase 2 354812-41-2, 151096-09-2 152946
17
Estradiol Approved, Investigational, Vet_approved Phase 2 50-28-2 5757
18
Polyestradiol phosphate Approved Phase 2 28014-46-2
19 Contraceptives, Oral Phase 2
20 Estrogens Phase 2
21 Contraceptives, Oral, Combined Phase 2
22 Ortho Evra Phase 2
23 Norgestimate, ethinyl estradiol drug combination Phase 2
24 Hormones Phase 2
25 Antioxidants Phase 2
26 Contraceptive Agents Phase 2
27 Estradiol 17 beta-cypionate Phase 2
28 Anti-Bacterial Agents Phase 2
29 Anti-Infective Agents Phase 2
30 Topoisomerase Inhibitors Phase 2
31 Hormone Antagonists Phase 2
32 Estradiol 3-benzoate Phase 2
33 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
34 Tranquilizing Agents Phase 2
35 Omega 3 Fatty Acid Phase 2
36 Soy Bean Phase 2
37 Antidepressive Agents Phase 2
38 Central Nervous System Depressants Phase 2
39 Antipsychotic Agents Phase 2
40 Psychotropic Drugs Phase 2
41 Antimanic Agents Phase 2
42 Olive
43 insulin
44 Insulin, Globin Zinc

Interventional clinical trials:

(show all 15)
# Name Status NCT ID Phase Drugs
1 Effect of Rosuvastatin Therapy on HDL2 Level and Antiatherosclerotic Reverse Cholesterol Transport Process in Chinses CAD Patients With Hyperlipidemia Unknown status NCT02593487 Phase 4 Rosuvastatin 10mg/d group;Rosuvastatin 20mg/d group
2 Atorvastatin Action on Oxidative Stress and Inflammation in Type II Diabetes: The HDL Particle Protection Study Completed NCT02125682 Phase 4 atovastatin 10 mg/day;Atorvastatin 80 mg/day
3 Effects of Pioglitazone on Reverse Cholesterol Transport and HDL Function in Persons With Diabetes Completed NCT01156597 Phase 3 pioglitazone
4 Comparison of Oral and Patch Forms of Hormonal Contraception on Plasma Lipoproteins, Glycemia, Clotting Factors, Indices of Inflammation and Vascular Reactivity Unknown status NCT00439972 Phase 2 Ortho-Cyclen (R);Ortho Evra (R);extended use of Ortho Evra (R)
5 CAD Risk in Schizophrenia: Effect of Omega-3 Fatty Acid Supplementation Completed NCT00167310 Phase 2 Eicosapentaenoic acid (omega-3 fatty acid);Placebo
6 Lipoprotein Subfractions and Coronary Heart Disease During 25 Year Follow-up Completed NCT00005215
7 Genetic Epidemiology of CHD Risk Factors in Blacks Completed NCT00005364
8 Adipose Distribution and Atherosclerosis Completed NCT00005348
9 Clinical Study to Assess the Acute and Chronic Effects of a High-DHA Fish Oil on Fasting and Post-Prandial Biomarkers of Cardiovascular Disease Risk in Adults on Statin Therapy. Completed NCT01690312
10 Effects of CHD Prevention on Lipoprotein Subclasses Completed NCT00005426
11 Cardiovascular Risk Profile Among Mexican-Americans Completed NCT00005187
12 Dietary Fat, Plasma Lipids, and Other CHD Risk Factors Completed NCT00005532
13 Epidemiology of Genetic Factors in Lipid Metabolism Completed NCT00005214
14 The Association of SAA With Apolipoprotein B Affects Cardiovascular Risk Completed NCT02770872
15 Study on the Relationship Between the Change of Cholesterol Efflux Capacity and the Prognosis of Coronary Artery Disease in Real Clinical Practice Not yet recruiting NCT03389529

Search NIH Clinical Center for Huntington Disease-Like 2

Genetic Tests for Huntington Disease-Like 2

Genetic tests related to Huntington Disease-Like 2:

# Genetic test Affiliating Genes
1 Huntington Disease-Like 2 29 JPH3

Anatomical Context for Huntington Disease-Like 2

MalaCards organs/tissues related to Huntington Disease-Like 2:

41
Heart, Liver, Testes, Adipocyte, Caudate Nucleus, Endothelial, Thyroid

Publications for Huntington Disease-Like 2

Articles related to Huntington Disease-Like 2:

(show top 50) (show all 2152)
# Title Authors PMID Year
1
A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. 9 38 4 8 71
11694876 2001
2
Huntington's disease--like 2 can present as chorea-acanthocytosis. 38 4 8 71
14557581 2003
3
Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions. 4 8 71
11940688 2002
4
CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients. 4 8 71
11914418 2002
5
Huntington's disease--like 2 is associated with CUG repeat-containing RNA foci. 38 4 8
17387722 2007
6
Huntington's Disease-like 2 (HDL2) in North America and Japan. 38 4 8
15468075 2004
7
Huntington's disease-like 2 in Brazil--report of 4 patients. 38 8
18816802 2008
8
Huntington disease-like 2: the first patient with apparent European ancestry. 38 8
18341606 2008
9
Huntington Disease-Like 2 38 71
20301701 2004
10
Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes. 38 4
31061838 2019
11
Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry. 38 4
30682531 2019
12
Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3 gene; first reported case from Botswana. 38 4
29066237 2018
13
A Systematic Review of the Huntington Disease-Like 2 Phenotype. 38 4
28339400 2017
14
Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. 38 4
26079385 2015
15
Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis. 38 4
22367996 2012
16
Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype. 38 4
21755114 2011
17
An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. 38 4
21555070 2011
18
RNA-mediated neurodegeneration in repeat expansion disorders. 8
20373340 2010
19
A comparison of huntington disease and huntington disease-like 2 neuropathology. 38 4
18379432 2008
20
Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. 38 4
12805114 2003
21
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. 8
11761463 2001
22
Juvenile Huntington disease. 8
2942452 1986
23
E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. 4
30409805 2018
24
Huntington's disease-like disorders in Latin America and the Caribbean. 4
29853295 2018
25
Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach. 4
27400454 2016
26
Searching for mutation in the JPH3, ATN1 and TBP genes in Polish patients suspected of Huntington's disease and without mutation in the IT15 gene. 9 38
18651325 2008
27
A South African mixed ancestry family with Huntington disease-like 2: clinical and genetic features. 9 38
17708569 2007
28
Huntington's disease like-2 neuropathology. 4
17516481 2007
29
Phenotypic features of Huntington's disease-like 2. 4
14673892 2003
30
Trinucleotide repeat expansions in the junctophilin-3 gene are not found in Caucasian patients with a Huntington's disease-like phenotype. 4
12112122 2002
31
Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1. 4
11535622 2001
32
Characterization of human junctophilin subtype genes. 4
10891348 2000
33
Junctophilins: a novel family of junctional membrane complex proteins. 4
10949023 2000
34
Patients with features similar to Huntington's disease, without CAG expansion in huntingtin. 4
9674805 1998
35
HDL subclasses and mortality in acute heart failure patients. 38
30578754 2019
36
Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension. 38
30302964 2019
37
Lipoprotein Subfractions and Glucose Homeostasis in Prediabetes and Diabetes in Taiwan. 38
30726792 2019
38
Current state of knowledge in Chorea-Acanthocytosis as core Neuroacanthocytosis syndrome. 38
29253590 2018
39
The association between Hepcidin and arterial stiffness in a community-dwelling population. 38
30373612 2018
40
HDL impairs osteoclastogenesis and induces osteoclast apoptosis via upregulation of ABCG1 expression. 38
30060101 2018
41
Activity of paraoxonase 1 (PON1) on HDL2 and HDL3 subclasses in renal disease. 38
30130521 2018
42
Pathophysiology of Diabetic Dyslipidemia. 38
29998913 2018
43
A study of Huntington disease-like syndromes in black South African patients reveals a single SCA2 mutation and a unique distribution of normal alleles across five repeat loci. 38
29801887 2018
44
Acute coronary syndrome remodels the antiplatelet aggregation properties of HDL particle subclasses. 38
29543379 2018
45
Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention. 38
29391013 2018
46
Association of High-Density Lipoprotein Subclasses with Carotid Intima-Media Thickness: Shimane CoHRE Study. 38
28450678 2018
47
Small dense HDLs display potent vasorelaxing activity, reflecting their elevated content of sphingosine-1-phosphate. 38
29150495 2018
48
High-density lipoprotein 3 cholesterol is a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. 38
29304861 2018
49
The Drosophila junctophilin gene is functionally equivalent to its four mammalian counterparts and is a modifier of a Huntingtin poly-Q expansion and the Notch pathway. 38
29208631 2018
50
Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory Changes in Circulating TRAIL and Glutathione Redox Capacity. 38
30104982 2018

Variations for Huntington Disease-Like 2

ClinVar genetic disease variations for Huntington Disease-Like 2:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 JPH3 NM_001271604.2(JPH3): c.431_433CTG(6_27) (p.Ala150_Ala157del) NT expansion Pathogenic rs71156237 16:87637894-87637896 16:87604288-87604290
2 JPH3 NM_020655.4(JPH3): c.955C> T (p.Arg319Trp) single nucleotide variant Uncertain significance rs148131421 16:87678436-87678436 16:87644830-87644830
3 JPH3 NM_020655.4(JPH3): c.382+760CTG[11] short repeat Benign/Likely benign rs71156237 16:87637927-87637935 16:87604321-87604329
4 JPH3 NM_020655.4(JPH3): c.382+760CTG[16] short repeat Benign rs71156237 16:87637930-87637935 16:87604324-87604329

Expression for Huntington Disease-Like 2

Search GEO for disease gene expression data for Huntington Disease-Like 2.

Pathways for Huntington Disease-Like 2

GO Terms for Huntington Disease-Like 2

Cellular components related to Huntington Disease-Like 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 junctional sarcoplasmic reticulum membrane GO:0014701 8.96 JPH3 JPH1
2 junctional membrane complex GO:0030314 8.62 JPH3 JPH1

Biological processes related to Huntington Disease-Like 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 release of sequestered calcium ion into cytosol GO:0051209 9.16 JPH3 JPH1
2 regulation of ryanodine-sensitive calcium-release channel activity GO:0060314 8.96 JPH3 JPH1
3 calcium ion transport into cytosol GO:0060402 8.62 JPH3 JPH1

Molecular functions related to Huntington Disease-Like 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium-release channel activity GO:0015278 8.62 JPH3 JPH1

Sources for Huntington Disease-Like 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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