Huntington disease-like 2 (HDL2) is a severe neurodegenerative disorder considered part of the neuroacanthocytosis syndromes characterized by a triad of movement, psychiatric, and cognitive abnormalities¹.

Prevalence

<1/1,000,000². Largely in individuals of African ancestry³, where a possible JPH3 founder mutation has been identified⁴.

Age of Onset

Typical: 30-52; Range: 12-66³.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr16:87637888-87637935

hg38 chr16:87604282-87604329

t2t chr16:93675723-93675776

Details

Intermediate alleles (29-39) may either be premutations or associated with reduced penetrance; the longest pathogenic expansion (40+ motifs) to date is 60 repeats³

Mechanism

LoF/GoF

Non-mutually exclusive mechanisms include loss of function from RNA sequestration and gain of function from toxic transcripts and increased protein expression³

Detection

Year

2001⁵

Location in Gene

Coding Exon 2

Gene Strand

Alleles

Ref. Motif

CTG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

CTG

Pathogenic (gene)

CTG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

Ontology Lookup Service (OLS)

mondo:0011671

Vérification de la connexion...

orphanet:98934

Huntington Disease-Like 2

David G.,Anderson, Amanda,Krause, Russell L.,Margolis

GeneReviews® · 1993-01-01

genereviews:NBK1529

West-Central African Ancestry of the Repeat-Expansion Founder Mutation on the JPH3 Gene in Mexican Patients With Huntington's Disease-Like 2.

Miguel Ángel,Ramírez-García, Petra,Yescas-Gómez, Julio César Misael,Monroy-González, María Teresa,Villarreal-Molina, Karina,Díaz-Barba, Luis Rodrigo,Macias-Kauffer, Gabriela,Castañeda-López, Sandra,Romero-Hidalgo

Archives of medical research · 2025-04-05

pmid:40187026

A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.

S E,Holmes, E,O'Hearn, A,Rosenblatt, C,Callahan, H S,Hwang, R G,Ingersoll-Ashworth, A,Fleisher, G,Stevanin, A,Brice, N T,Potter, C A,Ross, R L,Margolis

Nature genetics · 2001-12-01

pmid:11694876

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Unraveling the genetic architecture of non-Huntington chorea: a biobank-scale study of rare variants and repeat expansions.

Fulya,Akçimen, Monica,Diez-Fairen, Ignacio,Alvarez, Victor,Puente, Spencer,Grant, Jorge,Hernandez-Vara, Marzieh,Khani, Mariateresa,Buongiorno, Félix Javier,Jiménez-Jiménez, José A G,Agúndez, Miquel,Aguilar, Esther,Cubo, Jesus,Perez, Javier,Pagonabarraga, Núria,Caballol, Asuncion,Avila, Jinhui,Ding, Elena,García-Martín, Hortensia,Alonso-Navarro, Yaroslau,Compta, Carlos,Cruchaga, Katrin,Beyer, J Raphael,Gibbs, Andrew,Singleton, Sara,Bandres-Ciga, Pau,Pastor

NPJ genomic medicine · 2026-04-09

pmid:41957010

Huntington's Disease and Huntington's Disease-like 2 (HDL2) in Martinique.

Ignacio,Antolin-Sanfeliz, Anna-Gaelle,Giguet-Valard, Sophie,Duclos, Cécile,Cazeneuve, Chloé,Angelini, Aïssatou,Signaté, Russell L,Margolis, Cyril,Goizet, Rémi,Bellance

Movement disorders clinical practice · 2025-10-11

pmid:41074680

Huntington's disease-like 2 patients' profile in a Brazilian cohort.

Dayany Leonel,Boone, Vitor,Tumas, Gabriel,Vilela, Vanderci,Borges, Roberta Arb Saba,Rodrigues Pinto, Mariana Cavalcanti,Costa, Henrique Ballalai,Ferraz

Parkinsonism & related disorders · 2025-09-03

pmid:40914005

NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.

Jonathan L,Chen, Amirhossein,Taghavi, Alexander J,Frank, Matthew A,Fountain, Shruti,Choudhary, Soma,Roy, Jessica L,Childs-Disney, Matthew D,Disney

bioRxiv : the preprint server for biology · 2024-06-22

pmid:38948793

Atypical Presentations of Huntington Disease-like 2 in South African Individuals.

Heena,Narotam-Jeena, Mark,Guttman, Ludo,van Hillegondsberg, Riaan,van Coller, Amanda,Krause, Jonathan,Carr

Movement disorders clinical practice · 2024-05-09

pmid:38725192

The First Case of Huntington's Disease like 2 in Mali, West Africa.

Abdoulaye,Bocoum, Madani,Ouologuem, Lassana,Cissé, Fahmida,Essop, Souleymane,Dit Papa Coulibaly, Nadine,Botha, Cheick A K,Cissé, Alassane,Dit Baneye Maiga, Amanda,Krause, Guida,Landouré

Tremor and other hyperkinetic movements (New York, N.Y.) · 2024-04-02

pmid:38617831

Genetic screening for Huntington disease phenocopies in Sweden: A tertiary center case series focused on short tandem repeat (STR) disorders.

Martin,Paucar, José,Laffita-Mesa, Valter,Niemelä, Helena,Malmgren, Inger,Nennesmo, Kristina,Lagerstedt-Robinson, Magnus,Nordenskjöld, Per,Svenningsson

Journal of the neurological sciences · 2023-06-10

pmid:37379724

Clinical and Molecular Findings of Intermediate Allele Carriers in the HTT Gene from the Mexican Mestizo Population.

Miguel Ángel,Ramírez-García, David José,Dávila-Ortiz de Montellano, Leticia,Martínez-Ruano, Adriana,Ochoa-Morales, Sandra,Romero-Hidalgo, Juan Carlos,Zenteno, Petra,Yescas-Gómez

Neuro-degenerative diseases · 2022-08-04

pmid:35926480

Allelic and phenotypic heterogeneity in Junctophillin-3 related neurodevelopmental and movement disorders.

Thomas,Bourinaris, Alkyoni,Athanasiou, Stephanie,Efthymiou, Sarah,Wiethoff, Vincenzo,Salpietro, Henry,Houlden

European journal of human genetics : EJHG · 2021-04-06

pmid:33824468

Locus HDL2 JPH3

Disease

Locus

Alleles

gnomAD

References

Additional Literature