HDL2
MCID: HNT004
MIFTS: 51

Huntington Disease-Like 2 (HDL2)

Categories: Eye diseases, Genetic diseases, Mental diseases, Muscle 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 25 58 72 29 13 54 6 70
Hdl2 57 12 58 72
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®:

57 (Updated 20-May-2021)
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:

25
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® 57 606438
ICD10 32 G10
ICD10 via Orphanet 33 G10
UMLS via Orphanet 71 C1847987
Orphanet 58 ORPHA98934
MedGen 41 C1847987
UMLS 70 C1847987

Summaries for Huntington Disease-Like 2

UniProtKB/Swiss-Prot : 72 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 huntington disease, 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 Anticholesteremic Agents and Rosuvastatin Calcium have been mentioned in the context of this disorder. Affiliated tissues include heart, liver and eye, and related phenotypes are personality changes and hyperreflexia

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 104)
# Related Disease Score Top Affiliating Genes
1 huntington disease-like 1 30.5 VPS13A TBP JPH3
2 huntington disease 30.3 VPS13A TBP LOC109029536 JPH3 HTT C9orf72
3 choreoacanthocytosis 30.2 VPS13A TBP JPH3
4 myotonic dystrophy 30.2 MBNL1 DMPK CNBP CELF1
5 spinocerebellar ataxia 17 29.9 VPS13A TBP PPP2R2B JPH3 ATXN8OS ATXN7
6 movement disease 29.7 VPS13A TBP HTT C9orf72 ATXN3
7 spinocerebellar ataxia 2 29.7 JPH3 HTT C9orf72 ATXN8OS ATXN7 ATXN3
8 choreatic disease 29.7 VPS13A TBP JPH3 HTT C9orf72 ATXN7
9 dystonia 29.6 VPS13A TBP JPH3 HTT C9orf72 ATXN7
10 dentatorubral-pallidoluysian atrophy 28.4 TWNK TBP PPP2R2B NOP56 MBNL1 JPH3
11 autosomal dominant cerebellar ataxia 28.2 TWNK TBP PPP2R2B NOP56 MBNL1 JPH3
12 huntington disease-like syndrome 11.1
13 huntington disease-like 3 10.9
14 parkinsonism 10.3
15 cerebellar ataxia type 9 10.3 PPP2R2B ATXN7 ATXN10
16 tactile agnosia 10.2 PPP2R2B ATXN7
17 abetalipoproteinemia 10.2
18 muscular disease 10.2 MBNL1 DMPK CNBP
19 coronary heart disease 1 10.2
20 spinocerebellar ataxia 37 10.2 NOP56 ATXN8OS ATXN10
21 myotonic cataract 10.2 TWNK DMPK
22 myotonia 10.2 MBNL1 DMPK CNBP
23 ataxia and polyneuropathy, adult-onset 10.2
24 chorea, childhood-onset, with psychomotor retardation 10.2
25 immature cataract 10.2 DMPK CNBP
26 hypertriglyceridemia, familial 10.2
27 lipoprotein quantitative trait locus 10.2
28 rapidly involuting congenital hemangioma 10.2
29 spinocerebellar ataxia 7 10.1 ATXN8OS ATXN7 ATXN3
30 spinocerebellar ataxia 30 10.1 PPP2R2B NOP56 ATXN7 ATXN10
31 holoprosencephaly 5 10.1 JPH3 ATXN8OS
32 mental retardation, x-linked, with cerebellar hypoplasia and distinctive facial appearance 10.1 ATXN7 ATXN3
33 hypercholesterolemia, familial, 1 10.1
34 heart disease 10.1
35 liver cirrhosis 10.1
36 spinocerebellar ataxia 31 10.1 NOP56 C9orf72 ATXN10
37 oculopharyngeal muscular dystrophy 10.1 MBNL1 DMPK CNBP CELF1
38 lens disease 10.1 MBNL1 DMPK CNBP CELF1
39 familial adult myoclonic epilepsy 10.1 C9orf72 ATXN8OS ATXN10
40 muscle tissue disease 10.0 MBNL1 DMPK CNBP
41 arteries, anomalies of 10.0
42 familial hyperlipidemia 10.0
43 familial hypercholesterolemia 10.0
44 kidney disease 10.0
45 spinocerebellar ataxia 36 10.0 NOP56 C9orf72 ATXN8OS ATXN10
46 subacute delirium 10.0
47 myoclonus 10.0
48 leukodystrophy, hypomyelinating, 2 10.0 VPS13A JPH3
49 dementia 10.0 JPH3 HTT C9orf72 ATXN3
50 mcleod syndrome 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 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
3 gait disturbance 58 31 occasional (7.5%) Occasional (29-5%) HP:0001288
4 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
5 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
6 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
7 weight loss 58 31 occasional (7.5%) Occasional (29-5%) HP:0001824
8 memory impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0002354
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 caudate atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002340
13 primitive reflex 58 31 occasional (7.5%) Occasional (29-5%) HP:0002476
14 depressivity 31 HP:0000716
15 dysarthria 31 HP:0001260
16 behavioral abnormality 58 Occasional (29-5%)
17 hallucinations 31 HP:0000738
18 abnormality of movement 58 Frequent (79-30%)
19 anxiety 31 HP:0000739
20 irritability 31 HP:0000737
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®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
chorea
dystonia
rigidity
more
Growth Weight:
weight loss

Neurologic Behavioral Psychiatric Manifestations:
hallucinations
anxiety
irritability
apathy
delusions
more

Clinical features from OMIM®:

606438 (Updated 20-May-2021)

UMLS symptoms related to Huntington Disease-Like 2:


bradykinesia; action tremor; muscle rigidity

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

26 (show all 24)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-114 9.74 MBNL1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.74 ATXN10
3 Increased shRNA abundance (Z-score > 2) GR00366-A-13 9.74 ATXN10
4 Increased shRNA abundance (Z-score > 2) GR00366-A-139 9.74 CNBP
5 Increased shRNA abundance (Z-score > 2) GR00366-A-151 9.74 ATXN10
6 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.74 ATXN10
7 Increased shRNA abundance (Z-score > 2) GR00366-A-180 9.74 TBP
8 Increased shRNA abundance (Z-score > 2) GR00366-A-187 9.74 ATXN10
9 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.74 ATXN10
10 Increased shRNA abundance (Z-score > 2) GR00366-A-203 9.74 CNBP
11 Increased shRNA abundance (Z-score > 2) GR00366-A-209 9.74 PURA
12 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.74 ATXN10 CNBP
13 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.74 PURA
14 Increased shRNA abundance (Z-score > 2) GR00366-A-29 9.74 CNBP
15 Increased shRNA abundance (Z-score > 2) GR00366-A-3 9.74 PURA
16 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.74 PURA
17 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.74 CNBP
18 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.74 ATXN10 MBNL1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-59 9.74 ATXN10
20 Increased shRNA abundance (Z-score > 2) GR00366-A-6 9.74 MBNL1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-67 9.74 CNBP
22 Increased shRNA abundance (Z-score > 2) GR00366-A-76 9.74 PURA
23 Increased shRNA abundance (Z-score > 2) GR00366-A-81 9.74 PURA
24 Increased shRNA abundance (Z-score > 2) GR00366-A-86 9.74 CNBP

MGI Mouse Phenotypes related to Huntington Disease-Like 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 ATXN3 ATXN7 C9orf72 CNBP HTT JPH3
2 nervous system MP:0003631 9.36 ATXN3 ATXN7 C9orf72 CNBP HTT JPH3

Drugs & Therapeutics for Huntington Disease-Like 2

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

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Anticholesteremic Agents Phase 4
2 Rosuvastatin Calcium Phase 4 147098-20-2
3 Antimetabolites Phase 4
4 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 4
5 Hypolipidemic Agents Phase 4
6 Lipid Regulating Agents Phase 4
7 Calcium, Dietary Phase 4
8
Calcium Nutraceutical Phase 4 7440-70-2 271

Interventional clinical trials:


# 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

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, Eye, Caudate Nucleus, Endothelial, Adipocyte, Smooth Muscle

Publications for Huntington Disease-Like 2

Articles related to Huntington Disease-Like 2:

(show top 50) (show all 2173)
# Title Authors PMID Year
1
A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2. 25 6 57 61 54
11694876 2001
2
Huntington's disease--like 2 can present as chorea-acanthocytosis. 61 57 25 6
14557581 2003
3
Autosomal dominant chorea-acanthocytosis with polyglutamine-containing neuronal inclusions. 6 57 25
11940688 2002
4
CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients. 25 57 6
11914418 2002
5
Huntington's disease--like 2 is associated with CUG repeat-containing RNA foci. 61 57 25
17387722 2007
6
Huntington's Disease-like 2 (HDL2) in North America and Japan. 61 57 25
15468075 2004
7
Huntington's disease-like 2 in Brazil--report of 4 patients. 57 61
18816802 2008
8
Huntington disease-like 2: the first patient with apparent European ancestry. 57 61
18341606 2008
9
Comparison of the Huntington's Disease like 2 and Huntington's Disease Clinical Phenotypes. 25 61
31061838 2019
10
Emerging differences between Huntington's disease-like 2 and Huntington's disease: A comparison using MRI brain volumetry. 61 25
30682531 2019
11
Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3 gene; first reported case from Botswana. 25 61
29066237 2018
12
A Systematic Review of the Huntington Disease-Like 2 Phenotype. 61 25
28339400 2017
13
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. 61 25
26079385 2015
14
Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis. 61 25
22367996 2012
15
Clinical and genetic analysis of 29 Brazilian patients with Huntington's disease-like phenotype. 61 25
21755114 2011
16
An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. 25 61
21555070 2011
17
RNA-mediated neurodegeneration in repeat expansion disorders. 57
20373340 2010
18
A comparison of huntington disease and huntington disease-like 2 neuropathology. 61 25
18379432 2008
19
Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. 61 25
12805114 2003
20
A disorder similar to Huntington's disease is associated with a novel CAG repeat expansion. 57
11761463 2001
21
Juvenile Huntington disease. 57
2942452 1986
22
E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. 25
30409805 2018
23
Huntington's disease-like disorders in Latin America and the Caribbean. 25
29853295 2018
24
Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach. 25
27400454 2016
25
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
26
A South African mixed ancestry family with Huntington disease-like 2: clinical and genetic features. 54 61
17708569 2007
27
Huntington's disease like-2 neuropathology. 25
17516481 2007
28
Phenotypic features of Huntington's disease-like 2. 25
14673892 2003
29
Trinucleotide repeat expansions in the junctophilin-3 gene are not found in Caucasian patients with a Huntington's disease-like phenotype. 25
12112122 2002
30
Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1. 25
11535622 2001
31
Junctophilins: a novel family of junctional membrane complex proteins. 25
10949023 2000
32
Characterization of human junctophilin subtype genes. 25
10891348 2000
33
Patients with features similar to Huntington's disease, without CAG expansion in huntingtin. 25
9674805 1998
34
Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R, C-108T, and L55M polymorphisms. 61
33778169 2021
35
Insulin Rescued MCP-1-Suppressed Cholesterol Efflux to Large HDL2 Particles via ABCA1, ABCG1, SR-BI and PI3K/Akt Activation in Adipocytes. 61
33740174 2021
36
Association between postprandial lipoprotein subclasses and Framingham cardiovascular disease risk stratification. 61
33359967 2021
37
Daily mycoprotein consumption for 1 week does not affect insulin sensitivity or glycaemic control but modulates the plasma lipidome in healthy adults: a randomised controlled trial. 61
32660657 2021
38
The lipid substrate preference of CETP controls the biochemical properties of HDL in fat/cholesterol-fed hamsters. 61
33515552 2021
39
Clinical-epidemiological analysis of HDL2 and HDL3 subfractions in adults from Maracaibo city, Venezuela. 61
33295542 2020
40
Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression. 61
32281547 2020
41
Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration: a proof of concept. 61
32570209 2020
42
Comparison of a novel cholesterol efflux assay using immobilized liposome-bound gel beads with the conventional method. 61
32706025 2020
43
The lipid transfer properties of CETP define the concentration and composition of plasma lipoproteins. 61
32591337 2020
44
HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure. 61
32061870 2020
45
Quantile-specific heritability of high-density lipoproteins with implications for precision medicine. 61
32600822 2020
46
A comparison between the neurocognitive profile of Huntington Disease-Like 2 and Huntington Disease: Exploring the presence of double dissociations. 61
32149528 2020
47
Transcriptomics Reveal Altered Metabolic and Signaling Pathways in Podocytes Exposed to C16 Ceramide-Enriched Lipoproteins. 61
32045989 2020
48
Huntington disease like 2 (HDL-2) with parkinsonism and abnormal DAT-SPECT - A novel observation. 61
32028232 2020
49
Investigations of Huntington's Disease and Huntington's Disease-Like Syndromes in Indian Choreatic Patients. 61
32675418 2020
50
The Neuropsychiatry of Huntington Disease-Like 2: A Comparison with Huntington's Disease. 61
33044188 2020

Variations for Huntington Disease-Like 2

ClinVar genetic disease variations for Huntington Disease-Like 2:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LOC109029536 , JPH3 NM_001271604.4(JPH3):c.431CWG(40_?) Microsatellite Pathogenic 5119 GRCh37: 16:87637894-87637896
GRCh38: 16:87604288-87604290
2 JPH3 NM_020655.4(JPH3):c.955C>T (p.Arg319Trp) SNV Uncertain significance 548586 rs148131421 GRCh37: 16:87678436-87678436
GRCh38: 16:87644830-87644830
3 JPH3 NM_020655.4(JPH3):c.626G>C (p.Ser209Thr) SNV Uncertain significance 779279 rs144296512 GRCh37: 16:87678107-87678107
GRCh38: 16:87644501-87644501
4 LOC109029536 , JPH3 NM_020655.4(JPH3):c.382+760CTG[11] Microsatellite Benign/Likely benign 522262 rs71156237 GRCh37: 16:87637894-87637902
GRCh38: 16:87604288-87604296
5 LOC109029536 , JPH3 NM_020655.4(JPH3):c.382+760CTG[16] Microsatellite Benign 522333 rs71156237 GRCh37: 16:87637893-87637894
GRCh38: 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 11.26 TWNK TBP 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 junctional sarcoplasmic reticulum membrane GO:0014701 9.16 JPH4 JPH3
2 cytoplasmic stress granule GO:0010494 9.13 MBNL1 CELF1 C9orf72
3 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 nervous system development GO:0007399 9.55 VPS13A PURA MBNL1 ATXN3 ATXN10
2 regulation of ryanodine-sensitive calcium-release channel activity GO:0060314 9.37 JPH4 JPH3
3 DNA unwinding involved in DNA replication GO:0006268 9.32 TWNK PURA
4 calcium ion transport into cytosol GO:0060402 9.26 JPH4 JPH3
5 exploration behavior GO:0035640 8.96 JPH3 ATXN3
6 regulation of phosphoprotein phosphatase activity GO:0043666 8.8 PPP2R2B HTT DMPK

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

# Name GO ID Score Top Affiliating Genes
1 single-stranded DNA binding GO:0003697 9.13 TWNK PURA CNBP
2 translation repressor activity, mRNA regulatory element binding GO:0000900 8.62 PURA CELF1

Sources for Huntington Disease-Like 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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