Genes associated with “leukodystrophy

148 genes foundHPO: LeukodystrophyOpen Targets: leukodystrophy4385 ClinVar P/LP variants2 PanelApp panels
How are genes scored? (0–100 composite)
-5–15
ClinGen
0–15
HPO Freq
0–15
Open Targets
0–12
Phen2Gene
0–10
ClinVar
0–8
Constraint
0–8
Dosage
0–8
OMIM CS
0–8
PanelApp
0–5
OMIM
0–5
G2P
0–4
Breadth
Tiers:Strong Candidates (≥20)Consider (≥8)Possible (≥3)
Evidence dots:
HPOClinVarPhen2GeneOpen TargetsPanelApp
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Strong Candidates

58 genes
1
PLP1

proteolipid protein 1

54
score
ClinGen: DefinitivePanel: Green (2)P2G #3GTR ↑

Pelizeaus-Merzbacher spectrum disorder

Frequency
-
P/LP Variants
65
OT Score
0.89
2
ARSA

arylsulfatase A

54
score
ClinGen: DefinitivePanel: Green (2)GTR ↑
Frequency
-
P/LP Variants
34
OT Score
0.89
3
AIMP1

aminoacyl tRNA synthetase complex interacting multifunctional protein 1

51
score
ClinGen: DefinitivePanel: GreenGTR ↑

hypomyelinating leukodystrophy 3

Frequency
-
P/LP Variants
4
OT Score
0.83
4
GJC2

gap junction protein gamma 2

51
score
ClinGen: DefinitivePanel: Green (2)GTR ↑

hypomyelinating leukodystrophy 2

Frequency
-
P/LP Variants
19
OT Score
0.86
5
DEGS1

delta 4-desaturase, sphingolipid 1

43
score
ClinGen: DefinitivePanel: GreenGTR ↑
Frequency
-
P/LP Variants
3
OT Score
0.84
6
TUBB4A

tubulin beta 4A class IVa

41
score
ClinGen: DefinitivePanel: Green (2)GTR ↑

hypomyelinating leukodystrophy 6

Frequency
100%
n=11
P/LP Variants
3
OT Score
0.77
7
ABCD1

ATP binding cassette subfamily D member 1

41
score
ClinGen: DefinitivePanel: Green (2)GTR ↑
Frequency
-
P/LP Variants
80
OT Score
0.88
8
HSPD1

heat shock protein family D (Hsp60) member 1

40
score

hypomyelinating leukodystrophy 4

Frequency
100%
n=8
P/LP Variants
3
OT Score
0.83
9
ADAR

adenosine deaminase RNA specific

39
score
ClinGen: DefinitivePanel: Green (2)P2G #12GTR ↑

Aicardi-Goutieres syndrome 6

Frequency
79%
n=14
P/LP Variants
1
OT Score
0.85
39PEX1
DefP:G×2

peroxisome biogenesis disorder 1B

38PEX16
DefP:G×2

peroxisome biogenesis disorder 8B

38POLR3A
DefP:G×2

Wiedemann-Rautenstrauch syndrome

36PSAP
DefP:G×2
36SAMHD1
DefP:G×2#10

Aicardi-Goutieres syndrome 5

36TREX1
DefP:G×2#13

three prime repair exonuclease 1

36PEX10
DefP:G×2

peroxisome biogenesis disorder 6B

35PEX6
DefP:G×2

peroxisomal biogenesis factor 6

35GALC
DefP:G×2

galactosylceramidase

35ASPA
DefP:G×2

aspartoacylase

35PEX12
DefP:G×2

peroxisomal biogenesis factor 12

35PEX5
DefP:G×2

peroxisomal biogenesis factor 5

33LMNB1
DefP:G×2

leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical

33PYCR2
P:G

hypomyelinating leukodystrophy 10

33HIKESHI
DefP:G

hypomyelinating leukodystrophy 13

33PEX26
DefP:G×2

peroxisomal biogenesis factor 26

33FA2H
DefP:G#2

hereditary spastic paraplegia 35

32EIF2B4
DefP:G×2

eukaryotic translation initiation factor 2B subunit delta

31TMEM106B
DefP:G

leukodystrophy, hypomyelinating, 16

29GFAP
DefP:G×2

glial fibrillary acidic protein

29CYP27A1
DefP:G×2

cytochrome P450 family 27 subfamily A member 1

29POLR3B
DefP:G×2

hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism

29RNASEH2A
DefP:G×2#11

Aicardi-Goutieres syndrome 4

29EIF2B1
DefP:G×2

eukaryotic translation initiation factor 2B subunit alpha

28PEX3
DefP:G×2

peroxisomal biogenesis factor 3

28AARS2
DefP:G×2

alanyl-tRNA synthetase 2, mitochondrial

28RNASEH2B
DefP:G×2#15

ribonuclease H2 subunit B

28RNASEH2C
DefP:G×2#14

ribonuclease H2 subunit C

26DARS2
DefP:G×2

aspartyl-tRNA synthetase 2, mitochondrial

25POLR1C
DefP:G×2

hypomyelinating leukodystrophy 11

24IFIH1
DefP:G

interferon induced with helicase C domain 1

24ISCA2
DefP:G

multiple mitochondrial dysfunctions syndrome 4

24HYCC1
Def

hypomyelinating leukodystrophy 5

24SLC16A2
DefP:G#1

Allan-Herndon-Dudley syndrome

24PEX2
DefP:G×2

peroxisomal biogenesis factor 2

24PEX13
DefP:G×2

peroxisomal biogenesis factor 13

24EIF2B5
DefP:G×2

eukaryotic translation initiation factor 2B subunit epsilon

24HEPACAM
DefP:G×2

hepatic and glial cell adhesion molecule

24EIF2B2
DefP:G×2

eukaryotic translation initiation factor 2B subunit beta

23CSF1R
DefP:G×2

colony stimulating factor 1 receptor

23PEX7
DefP:G×2

peroxisomal biogenesis factor 7

23PEX19
DefP:G×2

peroxisomal biogenesis factor 19

23PEX14
DefP:G×2

peroxisomal biogenesis factor 14

23EIF2B3
DefP:G×2

eukaryotic translation initiation factor 2B subunit gamma

23PEX11B
DefP:G×2

peroxisomal biogenesis factor 11 beta

22AIMP2
DefP:A

leukodystrophy, hypomyelinating, 17

22MLC1
DefP:G

modulator of VRAC current 1

20ALDH3A2
P:G×2

aldehyde dehydrogenase 3 family member A2

20CLCN2
RefP:G×2

chloride voltage-gated channel 2

Consider

76 genes
20RNASET2
P:G×2

ribonuclease T2

NK6 homeobox 2

19KCNT1
DefP:G
19SUMF1
DefP:G
18LAMB1
ModP:G×2
18CTC1
DefP:G×2#7

cerebroretinal microangiopathy with calcifications and cysts 1

18SOX10
DefP:G#8

PCWH syndrome

18ACOX1
DefP:G#4

peroxisomal acyl-CoA oxidase deficiency

17SLC25A12
ModP:G
17NDUFB11
DefP:G#20
17PI4KA
P:G

gastrointestinal defects and immunodeficiency syndrome 2

16ACER3
P:G

alkaline ceramidase 3 deficiency

16NADK2
ModP:G

progressive encephalopathy with leukodystrophy due to DECR deficiency

16TMEM63A
P:G

leukodystrophy, hypomyelinating, 19, transient infantile

16FBXL4
DefP:G

mitochondrial DNA depletion syndrome 13

15NOTCH3
LimP:G×2
15PIDD1
DefP:G
15ASXL3
DefP:G
15DYRK1A
DefP:G
15GATAD2B
DefP:G
15KIF5A
DefP:G×2
15TCF20
DefP:G
14NDUFV1
DefP:G

mitochondrial complex I deficiency, nuclear type 4

14NUBPL
DefP:G

mitochondrial complex I deficiency, nuclear type 21

14NDUFS1
DefP:G

mitochondrial complex I deficiency, nuclear type 5

13NDUFS4
DefP:G

mitochondrial complex I deficiency, nuclear type 1

13ACBD5
DefP:G

Leukodystrophy, demyelinating, adult-onset, autosomal dominant, typical

13DEPDC5
DefP:G
13GAN
DefP:G

LEUKODYSTROPHY, HYPOMYELINATING, 10; HLD10

LEUKODYSTROPHY, HYPOMYELINATING, 11; HLD11

LEUKODYSTROPHY, HYPOMYELINATING, 12; HLD12

LEUKODYSTROPHY, HYPOMYELINATING, 13; HLD13

LEUKODYSTROPHY, HYPOMYELINATING, 3; HLD3

LEUKODYSTROPHY, HYPOMYELINATING, 4; HLD4

LEUKODYSTROPHY, HYPOMYELINATING, 8, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD8

LEUKODYSTROPHY, HYPOMYELINATING, 9; HLD9

LEUKODYSTROPHY AND ACQUIRED MICROCEPHALY WITH OR WITHOUT DYSTONIA; LDAMD

METACHROMATIC LEUKODYSTROPHY DUE TO SAPOSIN B DEFICIENCY; MLDSAPB

NEURODEVELOPMENTAL DISORDER WITH SPASTICITY, HYPOMYELINATING LEUKODYSTROPHY, AND BRAIN ABNORMALITIES; NEDSPLB

SPONDYLOEPIMETAPHYSEAL DYSPLASIA, X-LINKED, WITH HYPOMYELINATING LEUKODYSTROPHY; SEMDHL

13SKI
DefP:G
13SLC17A5
DefP:G
13SDHB
DefSFP:G

mitochondrial complex 2 deficiency, nuclear type 4

12EDNRB
ModP:R#5

Waardenburg syndrome type 4A

12ABAT
ModP:G

GABA aminotransaminase deficiency

12HTRA1
P:G×2
12MAP1B
StrP:G
12RNF216
P:G×2
12DAG1
DefP:G

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9

12BOLA3
DefP:G

multiple mitochondrial dysfunctions syndrome 2

12IBA57
DefP:G

multiple mitochondrial dysfunctions syndrome 3

12TAOK1
DefP:G

developmental delay with or without intellectual impairment or behavioral abnormalities

11COX6B1
DefP:G

mitochondrial complex IV deficiency, nuclear type 7

11ERCC6
DefP:G

de Sanctis-Cacchione syndrome

11SYNE1
DefP:R
11FBP2
P:R

leukodystrophy, childhood-onset, remitting

11LIAS
ModP:G

lipoic acid synthetase deficiency

11ISCA1
P:G

multiple mitochondrial dysfunctions syndrome 5

leukodystrophy, hypomyelinating, 15

11PNPT1
ModP:G

combined oxidative phosphorylation defect type 13

11TUFM
ModP:G

combined oxidative phosphorylation defect type 4

10POLR1A
P:R

leukodystrophy, hypomyelinating, 27

10SLC35B2
P:A

leukodystrophy, hypomyelinating, 26, with chondrodysplasia

hypomyelinating leukodystrophy 9

10CELF2
P:G
10CST3
P:G
10PGK1
P:G
9GATAD1
Lim

leukodystrophy and acquired microcephaly with or without dystonia;

9GLRX5
P:G

spasticity-ataxia-gait anomalies syndrome

8SPTBN1
StrP:G

developmental delay, impaired speech, and behavioral abnormalities

8LSM7
P:A

Possible

10 genes — click to expand
8ATP11A
ModP:A

leukodystrophy, hypomyelinating, 24

7ATRIP
Lim
7COA8
Def

mitochondrial complex IV deficiency, nuclear type 17

7YARS1
Def

LEUKODYSTROPHY, HYPOMYELINATING, 26, WITH CHONDRODYSPLASIA; HLD26

LEUKODYSTROPHY, HYPOMYELINATING, 6; HLD6

LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; HLD7

Data aggregated from HPO/Monarch, ClinVar, OMIM (phenotypes + clinical synopsis), Open Targets, PanelApp, Phen2Gene, and Gene2Phenotype. Click a gene to view full details.