Leukodystrophy, Hypomyelinating, 2 disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 2

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 2:

Name: Leukodystrophy, Hypomyelinating, 2 ⁵⁷ ⁷³ ¹² ⁷¹

Hypomyelinating Leukodystrophy 2 ¹¹ ²⁴ ⁴² ²⁸ ⁵ ¹⁴

Pmld1 ⁵⁷ ¹¹ ²⁴ ⁴² ⁵⁸ ⁷³

Hld2 ⁵⁷ ¹¹ ²⁴ ⁴² ⁷³

Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation ¹¹ ⁵⁸

Pelizaeus-Merzbacher-Like Disease Type 1 ⁴² ⁷³

Pelizaeus-Merzbacher-Like Disease 1 ¹¹ ²⁴

Pelizaeus-Merzbacher-Like Disease Autosomal Recessive Type 1 ⁷³

Pmld - Pelizaeus Merzbacher Like Disease ⁴²

Leukodystrophy, Hypomyelinating, Type 2 ³⁸

Pelizaeus-Merzbacher-Like Disease, 1 ⁵⁷

Pelizaeus-Merzbacher-Like Disease ⁴²

Pelizaeus Merzbacher Like Disease ⁴²

Pmldar1 ⁷³

Characteristics:

Inheritance:

Leukodystrophy, Hypomyelinating, 2: Autosomal recessive ⁵⁷

Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation: Autosomal recessive ⁵⁸

Age Of Onset:

Pelizaeus-Merzbacher-Like Disease Due to Gjc2 Mutation: Infancy,Neonatal ⁵⁸

OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Miscellaneous:
onset in infancy
most children become wheelchair-bound
similar disorder to x-linked pelizaeus-merzbacher disease (pmd, )

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Neuronal diseases Eye diseases Ear diseases Muscle diseases Mental diseases

See all MalaCards categories (disease lists)

ICD10: ³¹ ³²

Endocrine, nutritional and metabolic diseases

Metabolic disorders

Disorders of sphingolipid metabolism and other lipid storage disorders

Other sphingolipidosis

Orphanet: ⁵⁸

Rare neurological diseases

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Summaries for Leukodystrophy, Hypomyelinating, 2

MedlinePlus Genetics: ⁴² Pelizaeus-Merzbacher-like disease type 1 is an inherited condition involving the brain and spinal cord (central nervous system). This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are abnormalities of the nervous system's white matter, which consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In particular, Pelizaeus-Merzbacher-like disease type 1 involves hypomyelination, which means that the nervous system has a reduced ability to form myelin. The signs and symptoms of this condition are very similar to another leukodystrophy called Pelizaeus-Merzbacher disease, but the two disorders have different genetic causes.Beginning in the first few months of life, infants with Pelizaeus-Merzbacher-like disease type 1 typically experience weak muscle tone (hypotonia), involuntary movements of the eyes (nystagmus), and delayed development of speech and motor skills, such as sitting or grasping objects. As children with Pelizaeus-Merzbacher-like disease type 1 get older, hypotonia changes to muscle stiffness (spasticity).During childhood, individuals with Pelizaeus-Merzbacher-like disease type 1 develop problems with movement and balance (ataxia), difficulty with movements that involve judging distance or scale (dysmetria), tremors that occur mainly during movement (intention tremors), and head and neck tremors (titubation). People with this condition have an inability to perform quick, alternating movements (dysdiadochokinesia), such as quickly tapping different fingers. Some develop involuntary tensing of the muscles (dystonia) and jerking (choreiform) movements. Many people with Pelizaeus-Merzbacher-like disease type 1 develop skeletal issues such as an abnormal curvature of the spine (scoliosis) and require wheelchair assistance from childhood.Muscle abnormalities can lead to difficulty swallowing and problems producing speech (expressive language), but affected individuals can understand speech (receptive language). Most individuals with Pelizaeus-Merzbacher-like disease type 1 have normal intelligence. Rarely, hearing loss, optic atrophy, and recurrent seizures (epilepsy) can occur.

MalaCards based summary: Leukodystrophy, Hypomyelinating, 2, also known as hypomyelinating leukodystrophy 2, is related to leukodystrophy, hypomyelinating, 3 and leukodystrophy, hypomyelinating, 4, and has symptoms including ataxia, head titubation and action tremor. An important gene associated with Leukodystrophy, Hypomyelinating, 2 is GJC2 (Gap Junction Protein Gamma 2), and among its related pathways/superpathways are Vesicle-mediated transport and G-protein signaling G-Protein alpha-i signaling cascades. Affiliated tissues include spinal cord, brain and cerebellum, and related phenotypes are nystagmus and ataxia

Disease Ontology: ¹¹ A hypomyelinating leukodystrophy characterized by autosomal recessive inheritance of nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity that has material basis in homozygous or compound heterozygous mutation in the GJC2 gene on chromosome 1q42.

UniProtKB/Swiss-Prot: ⁷³ An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.

More information from OMIM: 608804 PS312080

GeneReviews: NBK470716

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Related Diseases for Leukodystrophy, Hypomyelinating, 2

Diseases in the Hypomyelinating Leukodystrophy family:

Leukodystrophy, Hypomyelinating, 3	Leukodystrophy, Hypomyelinating, 2
Leukodystrophy, Hypomyelinating, 5	Leukodystrophy, Hypomyelinating, 4
Leukodystrophy, Hypomyelinating, 6	Leukodystrophy, Hypomyelinating, 9
Leukodystrophy, Hypomyelinating, 10	Leukodystrophy, Hypomyelinating, 11
Leukodystrophy, Hypomyelinating, 12	Leukodystrophy, Hypomyelinating, 13
Leukodystrophy, Hypomyelinating, 14	Leukodystrophy, Hypomyelinating, 15
Leukodystrophy, Hypomyelinating, 16	Leukodystrophy, Hypomyelinating, 17
Leukodystrophy, Hypomyelinating, 18	Leukodystrophy, Hypomyelinating, 19, Transient Infantile
Leukodystrophy, Hypomyelinating, 20	Leukodystrophy, Hypomyelinating, 21
Leukodystrophy, Hypomyelinating, 22	Leukodystrophy, Hypomyelinating, 24

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

(show top 50) (show all 72)

#	Related Disease	Score	Top Affiliating Genes
1	leukodystrophy, hypomyelinating, 3	32.8	PLP1 GJC2
2	leukodystrophy, hypomyelinating, 4	32.6	PLP1 GJC2
3	pelizaeus-merzbacher-like disease	31.2	PLP1 GJC2
4	hypomyelinating leukoencephalopathy	30.7	PLP1 GJC2
5	spastic paraplegia 44, autosomal recessive	30.7	PLP1 GJC2 GJB1
6	spastic paraplegia 2, x-linked	30.5	PLP1 GJC2 FA2H
7	leukodystrophy	30.4	PLP1 MBP GJC2 FA2H ASPA
8	hereditary spastic paraplegia	30.3	PLP1 GJC2 GJB1 FA2H
9	pelizaeus-merzbacher disease	30.1	PLP1 MBP GJC2 GJB1 FA2H
10	hypomyelinating leukodystrophy	29.9	PLP1 MBP GJC2 GJB1 GJA1 FA2H
11	47 xxx syndrome	10.5
12	scoliosis	10.4
13	pathologic nystagmus	10.4
14	hypotonia	10.4
15	spasticity	10.4
16	congenital nystagmus	10.3
17	charcot-marie-tooth disease, axonal, type 2q	10.3	GJB1 GCDH
18	hereditary neuropathies	10.3	PLP1 GJB1
19	spastic paraplegia 75, autosomal recessive	10.2	PLP1 GJC2
20	3-methylglutaconic aciduria, type iii	10.2
21	movement disease	10.2
22	dystonia	10.2
23	paraplegia	10.2
24	tremor	10.2
25	keratitis-ichthyosis-deafness syndrome, autosomal dominant	10.2	GJB6 GJA1
26	testicular thecoma	10.2	GJD3 GJC3
27	peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease	10.2	PLP1 GJC2 GJB1
28	down syndrome	10.2
29	niemann-pick disease, type c1	10.2
30	spastic paraplegia 20, autosomal recessive	10.2
31	allan-herndon-dudley syndrome	10.2
32	aceruloplasminemia	10.2
33	leukodystrophy, hypomyelinating, 9	10.2
34	sensorineural hearing loss	10.2
35	tubb4a-related leukodystrophy	10.2
36	athetosis	10.2
37	maternal uniparental disomy of chromosome 1	10.2
38	maternal uniparental disomy	10.2
39	complex hereditary spastic paraplegia	10.2
40	syndactyly, type iii	10.2	GJC1 GJA1
41	central pontine myelinolysis	10.2	MBP GJC2
42	leukodystrophy, hypomyelinating, 5	10.2	PLP1 GJC2
43	megalencephalic leukoencephalopathy with subcortical cysts 1	10.2	GJC2 GCDH ASPA
44	chromosome 18q deletion syndrome	10.2	MBP GJC2
45	leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism	10.2	PLP1 GJC2
46	craniometaphyseal dysplasia, autosomal dominant	10.1	GJC1 GJA4 GJA1
47	metachromatic leukodystrophy	10.1	PLP1 MBP GJC2
48	spastic cerebral palsy	10.1	PLP1 GCDH FA2H
49	charcot-marie-tooth disease type x	10.1	GJC3 GJC2 GJB6 GJB1
50	spastic paraplegia 10, autosomal dominant	10.1	PLP1 GJC2 FA2H

Graphical network of the top 20 diseases related to Leukodystrophy, Hypomyelinating, 2:

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Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

Human phenotypes related to Leukodystrophy, Hypomyelinating, 2:

³⁰ (show all 30)

#	Description	HPO Frequency	HPO Source Accession
1	nystagmus ³⁰	Very rare (1%)	HP:0000639
2	ataxia ³⁰	Very rare (1%)	HP:0001251
3	dysarthria ³⁰	Very rare (1%)	HP:0001260
4	facial palsy ³⁰	Very rare (1%)	HP:0010628
5	motor delay ³⁰	Very rare (1%)	HP:0001270
6	poor head control ³⁰	Very rare (1%)	HP:0002421
7	choreoathetosis ³⁰	Very rare (1%)	HP:0001266
8	spastic paraparesis ³⁰	Very rare (1%)	HP:0002313
9	focal impaired awareness seizure ³⁰	Very rare (1%)	HP:0002384
10	focal aware seizure ³⁰	Very rare (1%)	HP:0002349
11	seizure ³⁰		HP:0001250
12	global developmental delay ³⁰		HP:0001263
13	optic atrophy ³⁰		HP:0000648
14	cognitive impairment ³⁰		HP:0100543
15	myopia ³⁰		HP:0000545
16	dystonia ³⁰		HP:0001332
17	decreased motor nerve conduction velocity ³⁰		HP:0003431
18	progressive spasticity ³⁰		HP:0002191
19	babinski sign ³⁰		HP:0003487
20	leukodystrophy ³⁰		HP:0002415
21	rigidity ³⁰		HP:0002063
22	cerebral atrophy ³⁰		HP:0002059
23	intention tremor ³⁰		HP:0002080
24	poor speech ³⁰		HP:0002465
25	cerebral hypomyelination ³⁰		HP:0006808
26	head titubation ³⁰		HP:0002599
27	sensory axonal neuropathy ³⁰		HP:0003390
28	demyelinating motor neuropathy ³⁰		HP:0007220
29	rotary nystagmus ³⁰		HP:0001583
30	axial hypotonia ³⁰		HP:0008936

Symptoms via clinical synopsis from OMIM®:

⁵⁷ (Updated 08-Dec-2022)

Neurologic Central Nervous System:
ataxia
dysarthria
dystonia
rigidity
choreoathetosis
more

Head And Neck Head:
head titubation

Head And Neck Face:
facial weakness

Head And Neck Eyes:
optic atrophy
myopia
rotary nystagmus

Neurologic Peripheral Nervous System:
demyelinating motor neuropathy
axonal sensory neuropathy
decreased motor nerve conduction velocities (ncv)
peripheral neuropathy, mild (less common)

Clinical features from OMIM®:

608804 (Updated 08-Dec-2022)

UMLS symptoms related to Leukodystrophy, Hypomyelinating, 2:

ataxia; head titubation; action tremor; seizures; muscle rigidity; facial paresis; paraparesis, spastic

GenomeRNAi Phenotypes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

²⁵

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	no effect	GR00402-S-1	10.19	ACY3 ASPA FA2H GCDH GJA1 GJA4
2	no effect	GR00402-S-2	10.19	ACY3 ASPA FA2H GCDH GJA1 GJB4

MGI Mouse Phenotypes related to Leukodystrophy, Hypomyelinating, 2:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	nervous system	MP:0003631	10.2	ASPA FA2H GCDH GJA1 GJB1 GJB6
2	vision/eye	MP:0005391	9.85	ASPA FA2H GJA1 GJB1 GJC1 GJC2
3	hearing/vestibular/ear	MP:0005377	9.8	ASPA GJA1 GJB6 GJC3 MBP PLP1
4	hematopoietic system	MP:0005397	9.7	ACY3 ASPA GJA1 GJB1 GJB4 GJC1
5	mortality/aging	MP:0010768	9.47	ASPA GCDH GJA1 GJA4 GJB1 GJC1

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Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 2

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 2

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Genetic Tests for Leukodystrophy, Hypomyelinating, 2

Genetic tests related to Leukodystrophy, Hypomyelinating, 2:

#	Genetic test	Affiliating Genes
1	Hypomyelinating Leukodystrophy 2 ²⁸	GJC2

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Anatomical Context for Leukodystrophy, Hypomyelinating, 2

Organs/tissues related to Leukodystrophy, Hypomyelinating, 2:

MalaCards : Spinal Cord, Brain, Cerebellum, Endothelial

ODiseA: Peripheral Nerve, Brain

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Publications for Leukodystrophy, Hypomyelinating, 2

Articles related to Leukodystrophy, Hypomyelinating, 2:

(show top 50) (show all 101)

#	Title	Authors	PMID	Year
1	GJC2 promoter mutations causing Pelizaeus-Merzbacher-like disease. ⁶² ²⁴ ⁵⁷ ⁵	Gotoh L...Vanderver A	24374284	2014
2	Expanded spectrum of Pelizaeus-Merzbacher-like disease: literature revision and description of a novel GJC2 mutation in an unusually severe form. ⁶² ²⁴ ⁵⁷ ⁵	Biancheri R...Filocamo M	22669416	2013
3	GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease. ⁶² ²⁴ ⁵⁷ ⁵	Henneke M...Gartner J	18094336	2008
4	Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination. ⁶² ²⁴ ⁵⁷ ⁵	Wolf NI...Woodward KJ	16969684	2007
5	Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease. ⁶² ²⁴ ⁵⁷ ⁵	Uhlenberg B...Gartner J	15192806	2004
6	A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease. ⁶² ⁵⁷ ⁵	Salviati L...Laverda A	17031678	2007
7	A new mutation in GJC2 associated with subclinical leukodystrophy. ⁶² ²⁴ ⁵	Abrams CK...Salsano E	25059390	2014
8	"Pelizaeus-Merzbacher-like disease" presenting as complicated hereditary spastic paraplegia. ⁶² ²⁴ ⁵	Zittel S...Kohlschutter A	22833003	2012
9	Relevance of GJC2 promoter mutation in Pelizaeus-Merzbacher-like disease. ⁶² ²⁴ ⁵	Combes P...Vaurs-Barriere C	21246605	2012
10	Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease. ⁶² ²⁴ ⁵	Osaka H...Inoue K	20695017	2010
11	Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease. ⁶² ²⁴ ⁵⁷	Henneke M...Brockmann K	20513814	2010
12	GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy. ⁶² ²⁴ ⁵⁷	Bugiani M...Zeviani M	16707726	2006
13	Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. ⁶² ⁵	Orthmann-Murphy JL...Scherer SS	17344063	2007
14	Pelizaeus-Merzbacher-like disease: female case report. ⁶² ⁵	Nezu A...Kawanishi C	8733901	1996
15	NGS in Hereditary Ataxia: When Rare Becomes Frequent. ⁵	Galatolo D...Santorelli FM	34445196	2021
16	Hypomyelinating leukodystrophies in adults: Clinical and genetic features. ⁵	Di Bella D...Salsano E	33190326	2021
17	Exome sequencing & homozygosity mapping for identification of genetic aetiology for spastic ataxia in a consanguineous family. ⁵	Dalal A...Phadke SR	26354221	2015
18	Pelizaeus-Merzbacher-Like Disease in a Family With Variable Phenotype and a Novel Splicing GJC2 Mutation. ⁶² ²⁴	Al-Yahyaee SA...Chand P	23143715	2013
19	A novel homozygous mutation of GJC2 derived from maternal uniparental disomy in a female patient with Pelizaeus-Merzbacher-like disease. ⁶² ²⁴	Shimojima K...Yamamoto T	23684670	2013
20	The distribution and functional properties of Pelizaeus-Merzbacher-like disease-linked Cx47 mutations on Cx47/Cx47 homotypic and Cx47/Cx43 heterotypic gap junctions. ⁶² ²⁴	Kim MS...Bai D	23544880	2013
21	Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease. ⁶² ²⁴	Kammoun Jellouli N...Tunisian Network on Mental Retardation Study	23142375	2013
22	Promoter mutation is a common variant in GJC2-associated Pelizaeus-Merzbacher-like disease. ⁶² ²⁴	Meyer E...Maher ER	21959080	2011
23	Pathologic and phenotypic alterations in a mouse expressing a connexin47 missense mutation that causes Pelizaeus-Merzbacher-like disease in humans. ⁶² ²⁴	Tress O...Willecke K	21750683	2011
24	Magnetic resonance imaging pattern recognition in hypomyelinating disorders. ⁶² ²⁴	Steenweg ME...van der Knaap MS	20881161	2010
25	Pelizaeus-Merzbacher-like disease is caused not only by a loss of connexin47 function but also by a hemichannel dysfunction. ⁶² ²⁴	Diekmann S...Gartner J	20442743	2010
26	Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus-Merzbacher-like disease. ⁶² ²⁴	Wang J...Jiang Y	19423250	2010
27	Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. ⁶² ²⁴	Orthmann-Murphy JL...Pareyson D	19056803	2009
28	Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. ⁶² ²⁴	Orthmann-Murphy JL...Abrams CK	18094232	2007
29	Consensus statement on preventive and symptomatic care of leukodystrophy patients. ²⁴	Van Haren K...GLIA Consortium	25577286	2015
30	A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. ²⁴	Parikh S...GLIA Consortium	25655951	2015
31	A de novo mutation in the β-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum. ²⁴	Simons C...Vanderver A	23582646	2013
32	Cx32 and Cx47 mediate oligodendrocyte:astrocyte and oligodendrocyte:oligodendrocyte gap junction coupling. ²⁴	Wasseff SK...Scherer SS	21396451	2011
33	Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32. ²⁴	Maglione M...Kettenmann H	20468052	2010
34	GJC2 missense mutations cause human lymphedema. ²⁴	Ferrell RE...Finegold DN	20537300	2010
35	Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity. ²⁴	Menichella DM...Paul DL	17065440	2006
36	Expression of connexin47 in oligodendrocytes is regulated by the Sox10 transcription factor. ²⁴	Schlierf B...Wegner M	16822525	2006
37	Connexin 47 (Cx47)-deficient mice with enhanced green fluorescent protein reporter gene reveal predominant oligodendrocytic expression of Cx47 and display vacuolized myelin in the CNS. ²⁴	Odermatt B...Willecke K	12805295	2003
38	Structural and functional diversity of connexin genes in the mouse and human genome. ²⁴	Willecke K...Sohl G	12108537	2002
39	Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. ²⁴	Rash JE...Nagy JI	11245683	2001
40	A novel mutation in GJC2 associated with hypomyelinating leukodystrophy type 2 disorder. ⁶²	Komachali SR...Salehi M	35794704	2022
41	Activation of the unfolded protein response by Connexin47 mutations associated with Pelizaeus-Merzbacher-like disease. ⁶²	Flores-Obando RE...Abrams CK	35276347	2022
42	Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report. ⁶²	Javadikooshesh S...Ebadi N	34840390	2021
43	Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease. ⁶²	Li G...Zhou XL	33515434	2021
44	Investigating oligodendrocyte connexins: Heteromeric interactions between Cx32 and mutant or wild-type forms of Cx47 do not contribute to or modulate gap junction function. ⁶²	Abrams CK...Freidin MM	33835612	2021
45	Genetic testing of leukodystrophies unraveling extensive heterogeneity in a large cohort and report of five common diseases and 38 novel variants. ⁶²	Mahdieh N...Rabbani B	33547378	2021
46	The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data. ⁶²	Alfadhel M...Tabarki B	34055681	2021
47	Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report. ⁶²	Fu H...Liu H	33727856	2021
48	An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. ⁶²	Ashrafi MR...Tavasoli AR	31829048	2020
49	Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD). ⁶²	Llaci L...Rangasamy S	31748968	2019
50	Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. ⁶²	Yan H...Wolf NI	31587869	2019

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Genes for Leukodystrophy, Hypomyelinating, 2

Genes/enhancers related to Leukodystrophy, Hypomyelinating, 2 (3 elite genes):

(show all 21)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubMed IDs
1	GJC2	Gap Junction Protein Gamma 2	Protein Coding	1691.12	Molecular basis known ⁵⁷ Pathogenic ⁵ Causative germline mutation ⁵⁸ Causative variation ⁷³ Genetic Tests ²⁸ Likely pathogenic ⁵ DISEASES inferred ¹⁴ GeneCards inferred via : Disorders (show sections)	8733901 15192806 16969684 (more) 17031678 17344063 18094336 20695017 21246605 22669416 24374284 22833003 25059390 26354221 33190326 34445196
1	GJC2::GH01J228147	TSS distance: +1.8kb Elite enhancer with elite association with GJC2			Curated enhancer-disease association ²³ ( 27569544)	20695017
2	GCDH	Glutaryl-CoA Dehydrogenase	Protein Coding	400	Pathogenic ⁵
3	SNAP29	Synaptosome Associated Protein 29	Protein Coding	400	Pathogenic ⁵
4	GJB1	Gap Junction Protein Beta 1	Protein Coding	6.83	DISEASES inferred ¹⁴
5	PLP1	Proteolipid Protein 1	Protein Coding	6.41	DISEASES inferred ¹⁴
6	GJC1	Gap Junction Protein Gamma 1	Protein Coding	5.86	DISEASES inferred ¹⁴
7	GJA1	Gap Junction Protein Alpha 1	Protein Coding	5.58	DISEASES inferred ¹⁴
8	GJB6	Gap Junction Protein Beta 6	Protein Coding	5.28	DISEASES inferred ¹⁴
9	GJD3	Gap Junction Protein Delta 3	Protein Coding	5.21	DISEASES inferred ¹⁴
10	GJC3	Gap Junction Protein Gamma 3	Protein Coding	5.12	DISEASES inferred ¹⁴
11	GJA4	Gap Junction Protein Alpha 4	Protein Coding	5.07	DISEASES inferred ¹⁴
12	YBX3	Y-Box Binding Protein 3	Protein Coding	5.02	DISEASES inferred ¹⁴
13	ASPA	Aspartoacylase	Protein Coding	4.93	DISEASES inferred ¹⁴
14	SMTNL2	Smoothelin Like 2	Protein Coding	4.74	DISEASES inferred ¹⁴
15	MBP	Myelin Basic Protein	Protein Coding	4.68	DISEASES inferred ¹⁴
16	GJB4	Gap Junction Protein Beta 4	Protein Coding	4.59	DISEASES inferred ¹⁴
17	FA2H	Fatty Acid 2-Hydroxylase	Protein Coding	4.54	DISEASES inferred ¹⁴
18	RNF10	Ring Finger Protein 10	Protein Coding	4.45	DISEASES inferred ¹⁴
19	SP2	Sp2 Transcription Factor	Protein Coding	4.44	DISEASES inferred ¹⁴
20	ACY3	Aminoacylase 3	Protein Coding	4.36	DISEASES inferred ¹⁴
21	SOX10	SRY-Box Transcription Factor 10	Protein Coding	4.31	DISEASES inferred ¹⁴

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Variations for Leukodystrophy, Hypomyelinating, 2

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

⁵ (show all 42)

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	GJC2	NM_020435.4(GJC2):c.268C>T (p.Pro90Ser)	SNV	Pathogenic	2072	rs74315312	GRCh37: 1:228345727-228345727 GRCh38: 1:228158026-228158026
2	GJC2	NM_020435.4(GJC2):c.989del (p.Pro330fs)	DEL	Pathogenic	2073	rs796065027	GRCh37: 1:228346446-228346446 GRCh38: 1:228158745-228158745
3	GJC2	NM_020435.4(GJC2):c.814T>G (p.Tyr272Asp)	SNV	Pathogenic	2075	rs74315314	GRCh37: 1:228346273-228346273 GRCh38: 1:228158572-228158572
4	GJC2	NM_020435.4(GJC2):c.914_947del (p.Pro305fs)	DEL	Pathogenic	2076	rs796065028	GRCh37: 1:228346360-228346393 GRCh38: 1:228158659-228158692
5	GJC2	NM_020435.4(GJC2):c.695_696insG (p.Tyr232Ter)	INSERT	Pathogenic	2077	rs796065029	GRCh37: 1:228346154-228346155 GRCh38: 1:228158453-228158454
6	GJC2	NM_020435.4(GJC2):c.787G>A (p.Glu263Lys)	SNV	Pathogenic	60683	rs397514734	GRCh37: 1:228346246-228346246 GRCh38: 1:228158545-228158545
7	GJC2	NM_020435.4(GJC2):c.219_220del (p.Leu74fs)	DEL	Pathogenic	1027507		GRCh37: 1:228345676-228345677 GRCh38: 1:228157975-228157976
8	GJC2	NM_020435.4(GJC2):c.575dup (p.Thr195fs)	DUP	Pathogenic	873005	rs1064795865	GRCh37: 1:228346030-228346031 GRCh38: 1:228158329-228158330
9	GJC2	NM_020435.4(GJC2):c.472_481dup (p.Ala161fs)	DUP	Pathogenic	1525995		GRCh37: 1:228345929-228345930 GRCh38: 1:228158228-228158229
10	GJC2	NM_020435.4(GJC2):c.760G>A (p.Val254Met)	SNV	Pathogenic	1180631		GRCh37: 1:228346219-228346219 GRCh38: 1:228158518-228158518
11	GCDH	NM_000159.4(GCDH):c.1156C>T (p.Arg386Ter)	SNV	Pathogenic	235616	rs752127949	GRCh37: 19:13008590-13008590 GRCh38: 19:12897776-12897776
12	GJC2	NM_020435.4(GJC2):c.718C>T (p.Arg240Ter)	SNV	Pathogenic	2074	rs74315313	GRCh37: 1:228346177-228346177 GRCh38: 1:228158476-228158476
13	SNAP29	NM_004782.4(SNAP29):c.2T>C (p.Met1Thr)	SNV	Pathogenic	279894	rs886041240	GRCh37: 22:21213400-21213400 GRCh38: 22:20859112-20859112
14	SNAP29	NM_004782.4(SNAP29):c.354dup (p.Leu119fs)	DUP	Pathogenic	279932	rs751575036	GRCh37: 22:21224735-21224736 GRCh38: 22:20870447-20870448
15	GJC2	NM_020435.4(GJC2):c.857T>C (p.Met286Thr)	SNV	Pathogenic	2071	rs74315311	GRCh37: 1:228346316-228346316 GRCh38: 1:228158615-228158615
16	GJC2	NM_020435.4(GJC2):c.970_971dup (p.Ala325fs)	DUP	Pathogenic	426207	rs1085307499	GRCh37: 1:228346428-228346429 GRCh38: 1:228158727-228158728
17	GJC2	NM_020435.3(GJC2):c.-167A>G	SNV	Pathogenic	30759	rs587776888	GRCh37: 1:228337561-228337561 GRCh38: 1:228149860-228149860
18	GJC2	NM_020435.3(GJC2):c.-170A>G	SNV	Pathogenic	139577	rs587777496	GRCh37: 1:228337558-228337558 GRCh38: 1:228149857-228149857
19	GJC2	NM_020435.4(GJC2):c.49dup (p.His17fs)	DUP	Likely Pathogenic	983451	rs2034704908	GRCh37: 1:228345506-228345507 GRCh38: 1:228157805-228157806
20	GJC2	NM_020435.4(GJC2):c.107del (p.Ile36fs)	DEL	Likely Pathogenic	625200	rs1571907430	GRCh37: 1:228345566-228345566 GRCh38: 1:228157865-228157865
21	GJC2	NM_020435.4(GJC2):c.302G>T (p.Arg101Leu)	SNV	Likely Pathogenic	1027431		GRCh37: 1:228345761-228345761 GRCh38: 1:228158060-228158060
22	GJC2	NM_020435.4(GJC2):c.1134_1144del (p.Ala379fs)	DEL	Likely Pathogenic	656694	rs1571908452	GRCh37: 1:228346584-228346594 GRCh38: 1:228158883-228158893
23	GJC2	NM_020435.4(GJC2):c.1175C>G (p.Ser392Cys)	SNV	Likely Pathogenic	435326	rs1356633840	GRCh37: 1:228346634-228346634 GRCh38: 1:228158933-228158933
24	GJC2	NM_020435.4(GJC2):c.193_195del (p.Asn65del)	DEL	Likely Pathogenic	634512	rs1558119525	GRCh37: 1:228345650-228345652 GRCh38: 1:228157949-228157951
25	GJC2	NM_020435.4(GJC2):c.254T>C (p.Val85Ala)	SNV	Likely Pathogenic	1027508		GRCh37: 1:228345713-228345713 GRCh38: 1:228158012-228158012
26	GJC2	NM_020435.4(GJC2):c.371_392dup (p.His132fs)	DUP	Likely Pathogenic	1339504		GRCh37: 1:228345828-228345829 GRCh38: 1:228158127-228158128
27	GJC2	NM_020435.4(GJC2):c.755A>G (p.His252Arg)	SNV	Likely Pathogenic	1339505		GRCh37: 1:228346214-228346214 GRCh38: 1:228158513-228158513
28	GJC2	NM_020435.4(GJC2):c.78del (p.Trp27fs)	DEL	Likely Pathogenic	266108	rs886039904	GRCh37: 1:228345537-228345537 GRCh38: 1:228157836-228157836
29	GJC2	NM_020435.4(GJC2):c.217C>A (p.Pro73Thr)	SNV	Likely Pathogenic	801628	rs1330596542	GRCh37: 1:228345676-228345676 GRCh38: 1:228157975-228157975
30	GJC2	NM_020435.4(GJC2):c.1155del (p.Arg386fs)	DEL	Likely Pathogenic	801629	rs1196278287	GRCh37: 1:228346609-228346609 GRCh38: 1:228158908-228158908
31	GJC2	NM_020435.4(GJC2):c.883C>T (p.Gln295Ter)	SNV	Likely Pathogenic	870536	rs1375875748	GRCh37: 1:228346342-228346342 GRCh38: 1:228158641-228158641
32	GJC2	NM_020435.4(GJC2):c.733T>A (p.Cys245Ser)	SNV	Likely Pathogenic	872979	rs1571908056	GRCh37: 1:228346192-228346192 GRCh38: 1:228158491-228158491
33	GJC2	NM_020435.4(GJC2):c.118G>C (p.Ala40Pro)	SNV	Likely Pathogenic	872977	rs1302747902	GRCh37: 1:228345577-228345577 GRCh38: 1:228157876-228157876
34	GJC2	NM_020435.4(GJC2):c.571_572insG (p.Thr191fs)	INSERT	Uncertain Significance	981047	rs2034716505	GRCh37: 1:228346030-228346031 GRCh38: 1:228158329-228158330
35	GJC2	NM_020435.4(GJC2):c.1096dup (p.Asp366fs)	DUP	Uncertain Significance	981049	rs1391047082	GRCh37: 1:228346551-228346552 GRCh38: 1:228158850-228158851
36	GJC2	NM_020435.4(GJC2):c.907_923del (p.Gly303fs)	DEL	Uncertain Significance	932966	rs1423370842	GRCh37: 1:228346362-228346378 GRCh38: 1:228158661-228158677
37	GJC2	NM_020435.4(GJC2):c.768C>G (p.Cys256Trp)	SNV	Uncertain Significance	800511	rs1571908096	GRCh37: 1:228346227-228346227 GRCh38: 1:228158526-228158526
38	GJC2	NM_020435.4(GJC2):c.62C>T (p.Thr21Ile)	SNV	Uncertain Significance	982030	rs2034705112	GRCh37: 1:228345521-228345521 GRCh38: 1:228157820-228157820
39	GJC2	NM_020435.4(GJC2):c.445G>A (p.Gly149Ser)	SNV	Uncertain Significance	695528	rs577325764	GRCh37: 1:228345904-228345904 GRCh38: 1:228158203-228158203
40	GJC2	NM_020435.4(GJC2):c.293C>A (p.Ala98Asp)	SNV	Uncertain Significance	1705684		GRCh37: 1:228345752-228345752 GRCh38: 1:228158051-228158051
41	GJC2	NM_020435.4(GJC2):c.1234C>T (p.His412Tyr)	SNV	Uncertain Significance Uncertain Significance	445910	rs200334298	GRCh37: 1:228346693-228346693 GRCh38: 1:228158992-228158992
42	GJC2	NM_020435.4(GJC2):c.436_462del (p.Pro146_Glu154del)	DEL	Not Provided	943603	rs779077705	GRCh37: 1:228345879-228345905 GRCh38: 1:228158178-228158204

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

⁷³

#	Symbol	AA change	Variation ID	SNP ID
1	GJC2	p.Pro90Ser	VAR_023754	rs74315312
2	GJC2	p.Tyr272Asp	VAR_023755	rs74315314
3	GJC2	p.Met286Thr	VAR_023756	rs74315311

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Expression for Leukodystrophy, Hypomyelinating, 2

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 2.

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Pathways for Leukodystrophy, Hypomyelinating, 2

Pathways related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

#	Super pathways	Score	Top Affiliating Genes
1	Vesicle-mediated transport ⁶⁶ Show member pathways Membrane Trafficking ⁶⁶	13.03	SNAP29 GJD3 GJC2 GJC1 GJB6 GJB4
2	G-protein signaling G-Protein alpha-i signaling cascades ²² Show member pathways Development Beta-adrenergic receptors regulation of ERK ²² G-protein signaling G-Protein alpha-s signaling cascades ²² G-protein signaling G-Protein beta/gamma signaling cascades ²² Signaling in Gap Junctions ⁶⁴	12.29	GJC2 GJC1 GJB6 GJB4 GJB1 GJA4
3	Myometrial relaxation and contraction pathways ⁷⁴ Show member pathways Calcium regulation in cardiac cells ⁷⁴	11.99	GJC2 GJC1 GJB6 GJB4 GJB1 GJA4
4	Gap junction trafficking ⁶⁶ Show member pathways Cell adhesion Gap junctions ²² Entry of Influenza Virion into Host Cell via Endocytosis ⁶⁶ Formation of annular gap junctions ⁶⁶ Gap junction assembly ⁶⁶ Gap junction degradation ⁶⁶ Gap junction trafficking and regulation ⁶⁶ Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane ⁶⁶ Regulation of gap junction activity ⁶⁶ Transport of connexons to the plasma membrane ⁶⁶	11.63	GJD3 GJC2 GJC1 GJB6 GJB4 GJB1
5	Glial cell differentiation ⁷⁴	10.27	PLP1 MBP
6	Transport of connexins along the secretory pathway ⁶⁶ Show member pathways Oligomerization of connexins into connexons ⁶⁶	10.1	GJB1 GJA1

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GO Terms for Leukodystrophy, Hypomyelinating, 2

Cellular components related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	myelin sheath	GO:0043209	9.86	PLP1 MBP GJC3 GJC2
2	anchoring junction	GO:0070161	9.81	GJD3 GJC3 GJC2 GJC1 GJB6 GJB4
3	gap junction	GO:0005921	9.8	GJA1 GJA4 GJB1 GJB4 GJB6 GJC1
4	connexin complex	GO:0005922	9.58	GJA1 GJA4 GJB1 GJB4 GJB6 GJC1

Biological processes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

(show all 13)

#	Name	GO ID	Score	Top Affiliating Genes
1	transmembrane transport	GO:0055085	10.13	GJA1 GJA4 GJB1 GJB4 GJB6 GJC1
2	cell-cell signaling	GO:0007267	10.11	GJA1 GJA4 GJB1 GJB4 GJB6 GJC1
3	maintenance of blood-brain barrier	GO:0035633	9.91	GJA1 GJB6 MBP
4	myelination	GO:0042552	9.89	PLP1 MBP GJC3
5	cell communication by electrical coupling	GO:0010644	9.85	GJC2 GJB6 GJA1
6	central nervous system myelination	GO:0022010	9.83	PLP1 ASPA
7	atrial cardiac muscle cell action potential	GO:0086014	9.81	GJC1 GJA1
8	axon ensheathment	GO:0008366	9.78	PLP1 MBP
9	gap junction-mediated intercellular transport	GO:1990349	9.76	GJB6 GJB4
10	AV node cell to bundle of His cell communication by electrical coupling	GO:0086053	9.72	GJD3 GJC3 GJC1
11	positive regulation of calcium ion transmembrane transport	GO:1904427	9.71	PLP1 GJC2
12	gap junction assembly	GO:0016264	9.65	GJD3 GJC1 GJB6 GJB1 GJA1
13	cell communication	GO:0007154	9.32	GJD3 GJC3 GJC2 GJC1 GJB6 GJB4

Molecular functions related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

#	Name	GO ID	Score	Top Affiliating Genes
1	hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	GO:0016811	9.71	ASPA ACY3
2	structural constituent of myelin sheath	GO:0019911	9.67	PLP1 MBP
3	gap junction channel activity involved in cell communication by electrical coupling	GO:1903763	9.63	GJC2 GJB6 GJA1
4	aminoacylase activity	GO:0004046	9.62	ASPA ACY3
5	gap junction channel activity	GO:0005243	9.58	GJD3 GJC3 GJC2 GJC1 GJB6 GJB4
6	gap junction channel activity involved in cardiac conduction electrical coupling	GO:0086075	9.43	GJD3 GJA1
7	gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling	GO:0086077	9.26	GJC1 GJC3 GJD3

Sources

Sources for Leukodystrophy, Hypomyelinating, 2

¹ BitterDB

² CDC

³ Cell Signaling Technology

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⁸ Cosmic

⁹ dbSNP

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³¹ ICD10

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⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubChem

⁶² PubMed

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⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

HLD2 MCID: LKD010 MIFTS: 51	Leukodystrophy, Hypomyelinating, 2 (HLD2) Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases	Data Licensing For inquiries, contact: [email protected]
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes Expand all tables

Leukodystrophy, Hypomyelinating, 2 (HLD2)

Aliases & Classifications for Leukodystrophy, Hypomyelinating, 2

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 2:

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Inheritance:

Age Of Onset:

OMIM®:

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Summaries for Leukodystrophy, Hypomyelinating, 2

Related Diseases for Leukodystrophy, Hypomyelinating, 2

Diseases in the Hypomyelinating Leukodystrophy family:

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Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

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Variations for Leukodystrophy, Hypomyelinating, 2

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 2:

Expression for Leukodystrophy, Hypomyelinating, 2

Pathways for Leukodystrophy, Hypomyelinating, 2

Pathways related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

GO Terms for Leukodystrophy, Hypomyelinating, 2

Cellular components related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

Biological processes related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

Molecular functions related to Leukodystrophy, Hypomyelinating, 2 according to GeneCards Suite gene sharing:

Sources for Leukodystrophy, Hypomyelinating, 2