HDL2
MCID: HNT004
MIFTS: 50

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 56 12 24 58 73 29 13 54 6 71
Hdl2 56 12 58 73
Huntington's Disease-Like 2 12 15
Huntington Disease-Like, Type 2 39

Characteristics:

Orphanet epidemiological data:

58
huntington disease-like 2
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

56
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:

31
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: 58  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:0090104
OMIM 56 606438
ICD10 32 G10
ICD10 via Orphanet 33 G10
UMLS via Orphanet 72 C1847987
Orphanet 58 ORPHA98934
MedGen 41 C1847987
UMLS 71 C1847987

Summaries for Huntington Disease-Like 2

UniProtKB/Swiss-Prot : 73 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-like 1 and mcleod syndrome, and has symptoms including bradykinesia, action tremor and muscle rigidity. An important gene associated with Huntington Disease-Like 2 is JPH3 (Junctophilin 3), and among its related pathways/superpathways is Spinocerebellar ataxia. The drugs Atorvastatin and Rosuvastatin 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 98)
# Related Disease Score Top Affiliating Genes
1 huntington disease-like 1 30.6 XK VPS13A JPH3
2 mcleod syndrome 30.4 XK VPS13A
3 choreoacanthocytosis 30.2 XK VPS13A JPH3 HTT
4 choreatic disease 30.0 XK VPS13A JPH3 HTT ATXN7
5 spinocerebellar ataxia 36 29.9 NOP56 ATXN8OS ATXN10
6 spinocerebellar ataxia 17 29.8 PPP2R2B JPH3 ATXN7 ATXN3
7 huntington disease 29.7 XK VPS13A LOC109029536 JPH3 HTT ATXN7
8 myotonic dystrophy 29.1 MBNL1 DMPK CNBP CELF1
9 dentatorubral-pallidoluysian atrophy 29.0 PPP2R2B JPH3 HTT ATXN7 ATXN3 ATXN10
10 dystonia 29.0 XK VPS13A JPH3 HTT ATXN7 ATXN3
11 spinocerebellar ataxia 2 29.0 JPH3 HTT ATXN8OS ATXN7 ATXN3 ATXN10
12 autosomal dominant cerebellar ataxia 26.2 PPP2R2B NOP56 MBNL1 JPH3 HTT DMPK
13 huntington disease-like syndrome 11.4
14 huntington disease-like 3 11.0
15 coronary heart disease 1 10.4
16 arteries, anomalies of 10.3
17 hyperlipoproteinemia, type iii 10.3
18 lipoprotein quantitative trait locus 10.3
19 rapidly involuting congenital hemangioma 10.3
20 abetalipoproteinemia 10.2
21 holoprosencephaly 5 10.2 JPH3 ATXN8OS
22 hypercholesterolemia, familial, 1 10.2
23 familial hypercholesterolemia 10.2
24 liver disease 10.2
25 ataxia and polyneuropathy, adult-onset 10.2
26 chorea, childhood-onset, with psychomotor retardation 10.2
27 leukodystrophy, hypomyelinating, 2 10.2 XK VPS13A JPH3
28 neurodegeneration with brain iron accumulation 1 10.2 XK VPS13A JPH3
29 neurodegeneration with brain iron accumulation 10.2 XK VPS13A JPH3
30 tactile agnosia 10.1 PPP2R2B ATXN7
31 atherosclerosis susceptibility 10.1
32 hypertriglyceridemia, familial 10.1
33 heart disease 10.1
34 familial hyperlipidemia 10.1
35 arteriosclerosis 10.1
36 liver cirrhosis 10.1
37 kidney disease 10.1
38 fatty liver disease 10.1
39 cerebellar ataxia type 9 10.1 PPP2R2B ATXN7 ATXN10
40 movement disease 10.0
41 subacute delirium 10.0
42 myoclonus 10.0
43 spinocerebellar ataxia 31 10.0 NOP56 ATXN10
44 lingual-facial-buccal dyskinesia 10.0 XK VPS13A
45 diabetes mellitus, noninsulin-dependent 10.0
46 hyperlipoproteinemia, type iv 10.0
47 hypertension, essential 10.0
48 body mass index quantitative trait locus 11 10.0
49 microvascular complications of diabetes 3 10.0
50 microvascular complications of diabetes 4 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:

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 personality changes 58 31 frequent (33%) Frequent (79-30%) HP:0000751
2 gait disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0001288
3 weight loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0001824
4 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
5 memory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002354
6 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
7 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
8 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
9 dementia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000726
10 functional motor deficit 58 31 occasional (7.5%) Occasional (29-5%) HP:0004302
11 parkinsonism 58 31 occasional (7.5%) Occasional (29-5%) HP:0001300
12 primitive reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002476
13 caudate atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002340
14 behavioral abnormality 58 Occasional (29-5%)
15 hallucinations 31 HP:0000738
16 irritability 31 HP:0000737
17 abnormality of movement 58 Frequent (79-30%)
18 anxiety 31 HP:0000739
19 depressivity 31 HP:0000716
20 dysarthria 31 HP:0001260
21 involuntary movements 58 Occasional (29-5%)
22 rigidity 31 HP:0002063
23 apathy 31 HP:0000741
24 abnormal corpus striatum morphology 58 Occasional (29-5%)
25 bradykinesia 31 HP:0002067
26 abnormal cerebral morphology 58 Occasional (29-5%)
27 action tremor 31 HP:0002345
28 delusions 31 HP:0000746

Symptoms via clinical synopsis from OMIM:

56
Neurologic Behavioral Psychiatric Manifestations:
hallucinations
irritability
anxiety
apathy
delusions
more
Neurologic Central Nervous System:
hyperreflexia
dysarthria
dystonia
chorea
rigidity
more
Growth Weight:
weight loss

Clinical features from OMIM:

606438

UMLS symptoms related to Huntington Disease-Like 2:


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

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 Effects of CHD Prevention on Lipoprotein Subclasses Completed NCT00005426
10 Cardiovascular Risk Profile Among Mexican-Americans Completed NCT00005187
11 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
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:

40
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 2162)
# Title Authors PMID Year
1
A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. 54 24 56 6 61
11694876 2001
2
Huntington's disease--like 2 can present as chorea-acanthocytosis. 56 24 6 61
14557581 2003
3
Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions. 24 6 56
11940688 2002
4
CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients. 24 56 6
11914418 2002
5
Huntington's disease--like 2 is associated with CUG repeat-containing RNA foci. 24 56 61
17387722 2007
6
Huntington's Disease-like 2 (HDL2) in North America and Japan. 24 56 61
15468075 2004
7
Huntington's disease-like 2 in Brazil--report of 4 patients. 56 61
18816802 2008
8
Huntington disease-like 2: the first patient with apparent European ancestry. 56 61
18341606 2008
9
Huntington Disease-Like 2 61 6
20301701 2004
10
Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes. 61 24
31061838 2019
11
Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry. 24 61
30682531 2019
12
Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3 gene; first reported case from Botswana. 24 61
29066237 2018
13
A Systematic Review of the Huntington Disease-Like 2 Phenotype. 24 61
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. 24 61
26079385 2015
15
Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis. 61 24
22367996 2012
16
Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype. 61 24
21755114 2011
17
An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. 61 24
21555070 2011
18
RNA-mediated neurodegeneration in repeat expansion disorders. 56
20373340 2010
19
A comparison of huntington disease and huntington disease-like 2 neuropathology. 24 61
18379432 2008
20
Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. 24 61
12805114 2003
21
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. 56
11761463 2001
22
Juvenile Huntington disease. 56
2942452 1986
23
E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. 24
30409805 2018
24
Huntington's disease-like disorders in Latin America and the Caribbean. 24
29853295 2018
25
Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach. 24
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. 61 54
18651325 2008
27
A South African mixed ancestry family with Huntington disease-like 2: clinical and genetic features. 54 61
17708569 2007
28
Huntington's disease like-2 neuropathology. 24
17516481 2007
29
Phenotypic features of Huntington's disease-like 2. 24
14673892 2003
30
Trinucleotide repeat expansions in the junctophilin-3 gene are not found in Caucasian patients with a Huntington's disease-like phenotype. 24
12112122 2002
31
Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1. 24
11535622 2001
32
Characterization of human junctophilin subtype genes. 24
10891348 2000
33
Junctophilins: a novel family of junctional membrane complex proteins. 24
10949023 2000
34
Patients with features similar to Huntington's disease, without CAG expansion in huntingtin. 24
9674805 1998
35
HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure. 61
32061870 2020
36
Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration - a proof of concept. 61
32570209 2020
37
Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression. 61
32281547 2020
38
A comparison between the neurocognitive profile of Huntington Disease-Like 2 and Huntington Disease: Exploring the presence of double dissociations. 61
32149528 2020
39
Huntington disease like 2 (HDL-2) with parkinsonism and abnormal DAT-SPECT - A novel observation. 61
32028232 2020
40
Transcriptomics Reveal Altered Metabolic and Signaling Pathways in Podocytes Exposed to C16 Ceramide-Enriched Lipoproteins. 61
32045989 2020
41
The neuropsychological deficits and dissociations in Huntington Disease-Like 2: A series of case-control studies. 61
31704316 2020
42
Single case-control design for the study of the neuropsychological deficits and dissociations in Huntington's disease-like 2. 61
32021824 2020
43
Lipoprotein Subfractions and Glucose Homeostasis in Prediabetes and Diabetes in Taiwan. 61
30726792 2019
44
The cardiovascular phenotype of adult patients with phenylketonuria. 61
31492166 2019
45
1H NMR spectroscopy quantifies visibility of lipoproteins, subclasses, and lipids at varied temperatures and pressures. 61
31239285 2019
46
HDL subclasses and mortality in acute heart failure patients. 61
30578754 2019
47
Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension. 61
30302964 2019
48
Current state of knowledge in Chorea-Acanthocytosis as core Neuroacanthocytosis syndrome. 61
29253590 2018
49
The association between Hepcidin and arterial stiffness in a community-dwelling population. 61
30373612 2018
50
HDL impairs osteoclastogenesis and induces osteoclast apoptosis via upregulation of ABCG1 expression. 61
30060101 2018

Variations for Huntington Disease-Like 2

ClinVar genetic disease variations for Huntington Disease-Like 2:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 JPH3 NM_001271604.2(JPH3):c.431_433CTG(6_27) (p.Ala150_Ala157del)NT expansion Pathogenic 5119 rs71156237 16:87637894-87637896 16:87604288-87604290
2 JPH3 NM_020655.4(JPH3):c.955C>T (p.Arg319Trp)SNV Uncertain significance 548586 rs148131421 16:87678436-87678436 16:87644830-87644830
3 JPH3 NM_020655.4(JPH3):c.382+760CTG[11]short repeat Benign/Likely benign 522262 rs71156237 16:87637894-87637902 16:87604288-87604296
4 JPH3 NM_020655.4(JPH3):c.382+760CTG[16]short repeat Benign 522333 rs71156237 16:87637893-87637894 16:87604287-87604288

Expression for Huntington Disease-Like 2

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

Pathways for Huntington Disease-Like 2

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

# Super pathways Score Top Affiliating Genes
1 11.05 NOP56 ATXN8OS ATXN3 ATXN10

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 cell GO:0005623 9.63 XK VPS13A JPH4 JPH3 HTT DMPK
2 mitochondrial outer membrane GO:0005741 9.5 VPS13A PPP2R2B DMPK
3 mitochondrial membrane GO:0031966 9.43 VPS13A DMPK ATXN3
4 junctional sarcoplasmic reticulum membrane GO:0014701 8.96 JPH4 JPH3
5 junctional membrane complex GO:0030314 8.62 JPH4 JPH3

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

# Name GO ID Score Top Affiliating Genes
1 regulation of ryanodine-sensitive calcium-release channel activity GO:0060314 9.26 JPH4 JPH3
2 exploration behavior GO:0035640 9.16 JPH3 ATXN3
3 calcium ion transport into cytosol GO:0060402 8.96 JPH4 JPH3
4 regulation of phosphoprotein phosphatase activity GO:0043666 8.8 PPP2R2B HTT DMPK

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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