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
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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:

Orphanet: 58  
Rare neurological diseases


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

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:



Diseases related to Leukodystrophy, Hypomyelinating, 2

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 2

Human phenotypes related to Leukodystrophy, Hypomyelinating, 2:

30 (show all 30)
# Description HPO Frequency Orphanet 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

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 2

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

Genetic Tests for Leukodystrophy, Hypomyelinating, 2

Genetic tests related to Leukodystrophy, Hypomyelinating, 2:

# Genetic test Affiliating Genes
1 Hypomyelinating Leukodystrophy 2 28 GJC2

Anatomical Context for Leukodystrophy, Hypomyelinating, 2

Organs/tissues related to Leukodystrophy, Hypomyelinating, 2:

MalaCards : Spinal Cord, Brain, Cerebellum, Endothelial
ODiseA: Peripheral Nerve, Brain

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
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
22669416 2013
3
GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease. 62 24 57 5
18094336 2008
4
Frameshift mutation in GJA12 leading to nystagmus, spastic ataxia and CNS dys-/demyelination. 62 24 57 5
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
15192806 2004
6
A novel deletion in the GJA12 gene causes Pelizaeus-Merzbacher-like disease. 62 57 5
17031678 2007
7
A new mutation in GJC2 associated with subclinical leukodystrophy. 62 24 5
25059390 2014
8
"Pelizaeus-Merzbacher-like disease" presenting as complicated hereditary spastic paraplegia. 62 24 5
22833003 2012
9
Relevance of GJC2 promoter mutation in Pelizaeus-Merzbacher-like disease. 62 24 5
21246605 2012
10
Disrupted SOX10 regulation of GJC2 transcription causes Pelizaeus-Merzbacher-like disease. 62 24 5
20695017 2010
11
Clinical neurophysiology in GJA12-related hypomyelination vs Pelizaeus-Merzbacher disease. 62 24 57
20513814 2010
12
GJA12 mutations in children with recessive hypomyelinating leukoencephalopathy. 62 24 57
16707726 2006
13
Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus-Merzbacher-like disease. 62 5
17344063 2007
14
Pelizaeus-Merzbacher-like disease: female case report. 62 5
8733901 1996
15
NGS in Hereditary Ataxia: When Rare Becomes Frequent. 5
34445196 2021
16
Hypomyelinating leukodystrophies in adults: Clinical and genetic features. 5
33190326 2021
17
Exome sequencing & homozygosity mapping for identification of genetic aetiology for spastic ataxia in a consanguineous family. 5
26354221 2015
18
Pelizaeus-Merzbacher-Like Disease in a Family With Variable Phenotype and a Novel Splicing GJC2 Mutation. 62 24
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
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
23544880 2013
21
Molecular confirmation of founder mutation c.-167A>G in Tunisian patients with PMLD disease. 62 24
23142375 2013
22
Promoter mutation is a common variant in GJC2-associated Pelizaeus-Merzbacher-like disease. 62 24
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
21750683 2011
24
Magnetic resonance imaging pattern recognition in hypomyelinating disorders. 62 24
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
20442743 2010
26
Two novel gap junction protein alpha 12 gene mutations in two Chinese patients with Pelizaeus-Merzbacher-like disease. 62 24
19423250 2010
27
Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations. 62 24
19056803 2009
28
Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins. 62 24
18094232 2007
29
Consensus statement on preventive and symptomatic care of leukodystrophy patients. 24
25577286 2015
30
A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies. 24
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
23582646 2013
32
Cx32 and Cx47 mediate oligodendrocyte:astrocyte and oligodendrocyte:oligodendrocyte gap junction coupling. 24
21396451 2011
33
Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32. 24
20468052 2010
34
GJC2 missense mutations cause human lymphedema. 24
20537300 2010
35
Genetic and physiological evidence that oligodendrocyte gap junctions contribute to spatial buffering of potassium released during neuronal activity. 24
17065440 2006
36
Expression of connexin47 in oligodendrocytes is regulated by the Sox10 transcription factor. 24
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
12805295 2003
38
Structural and functional diversity of connexin genes in the mouse and human genome. 24
12108537 2002
39
Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons. 24
11245683 2001
40
A novel mutation in GJC2 associated with hypomyelinating leukodystrophy type 2 disorder. 62
35794704 2022
41
Activation of the unfolded protein response by Connexin47 mutations associated with Pelizaeus-Merzbacher-like disease. 62
35276347 2022
42
Pelizaeus-Merzbacher-Like Disease 1 Caused by a Novel Mutation in GJC2 Gene: A Case Report. 62
34840390 2021
43
Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease. 62
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
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
33547378 2021
46
The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data. 62
34055681 2021
47
Novel Mutations in NPC1 are Associated with Pelizaeus-Merzbacher-Like Disease: A Case Report. 62
33727856 2021
48
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. 62
31829048 2020
49
Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD). 62
31748968 2019
50
Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. 62
31587869 2019

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

Expression for Leukodystrophy, Hypomyelinating, 2

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

Pathways for Leukodystrophy, Hypomyelinating, 2

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.03 SNAP29 GJD3 GJC2 GJC1 GJB6 GJB4
2
Show member pathways
12.29 GJC2 GJC1 GJB6 GJB4 GJB1 GJA4
3
Show member pathways
11.99 GJC2 GJC1 GJB6 GJB4 GJB1 GJA4
4
Show member pathways
11.63 GJD3 GJC2 GJC1 GJB6 GJB4 GJB1
5 10.27 PLP1 MBP
6
Show member pathways
10.1 GJB1 GJA1

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 for Leukodystrophy, Hypomyelinating, 2

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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