Genes associated with “developmental regression

267 genes foundHPO: Developmental regressionOpen Targets: Developmental regression2881 ClinVar P/LP variants1 PanelApp panel
Some sources returned errors (2)

omim: Error: OMIM search: 429

omimClinSyn: Error: OMIM CS: 429

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
hover for details

Strong Candidates

21 genes
1
SCN8A

sodium voltage-gated channel alpha subunit 8

30
score
ClinGen: DefinitiveGTR ↑

developmental and epileptic encephalopathy, 13

Frequency
44%
n=9
P/LP Variants
4
OT Score
0.33
30
score
ClinGen: DefinitiveGTR ↑
Frequency
-
P/LP Variants
1
OT Score
-
3
MECP2

methyl-CpG binding protein 2

29
score
ClinGen: DefinitiveGTR ↑

syndromic X-linked intellectual disability Lubs type

Frequency
40%
n=10
P/LP Variants
11
OT Score
0.43
4
GNB1

G protein subunit beta 1

28
score
ClinGen: DefinitiveP2G #42GTR ↑

intellectual disability, autosomal dominant 42

Frequency
23%
n=13
P/LP Variants
3
OT Score
0.42
27
score
ClinGen: DefinitiveGTR ↑

developmental and epileptic encephalopathy 94

Frequency
100%
n=6
P/LP Variants
1
OT Score
-
6
GALC

galactosylceramidase

25
score
ClinGen: DefinitiveP2G #7GTR ↑
Frequency
-
P/LP Variants
1
OT Score
0.33
25
score
ClinGen: DefinitiveP2G #10GTR ↑
Frequency
-
P/LP Variants
43
OT Score
-
23
score
ClinGen: DefinitiveGTR ↑

early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation

Frequency
54%
n=35
P/LP Variants
77
OT Score
-
23
score
ClinGen: DefinitiveGTR ↑

developmental and epileptic encephalopathy, 12

Frequency
100%
n=1
P/LP Variants
-
OT Score
-
22IFIH1
DefP:G

Aicardi-Goutieres syndrome 7

22ST3GAL5
Def

ST3 beta-galactoside alpha-2,3-sialyltransferase 5

22PLA2G6
Def#3

neurodegeneration with brain iron accumulation 2A

21CAD
Def

developmental and epileptic encephalopathy, 50

21TCF20
Def
20SGSH
Def

N-sulfoglucosamine sulfohydrolase

20CACNA1E
Def
20FGF12
Def

developmental and epileptic encephalopathy, 47

20FRRS1L
Def

developmental and epileptic encephalopathy, 37

20SLC1A2
Def

developmental and epileptic encephalopathy, 41

20TANC2
Def

intellectual developmental disorder with autistic features and language delay, with or without seizures

20UBTF
Def

childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder

Consider

49 genes
19NDUFAF6
Def

mitochondrial complex I deficiency, nuclear type 17

19EBF3
Def

EBF transcription factor 3

19SLC12A5
Lim
18FOXG1
Def

FOXG1 disorder

18ACOX1
Def#6

peroxisomal acyl-CoA oxidase deficiency

18HEXB
Def

Sandhoff disease

17CACNA1B
Mod

neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements

17TBCK
Def

hypotonia, infantile, with psychomotor retardation and characteristic facies 3

16ASPA
Def
16CDKL5
Def

developmental and epileptic encephalopathy, 2

15HTT
Def#13

Lopes-Maciel-Rodan syndrome

15BRPF1
Def
13POLR3A
Def

leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism

13ECHS1
Def
13GNS
Def
13HGSNAT
Def
13NAGLU
Def
12SURF1
Def

mitochondrial complex IV deficiency, nuclear type 1

11VHL
DefSF

spastic paraplegia 82, autosomal recessive

11AFG3L2
Def
11SCN1A
Def

developmental and epileptic encephalopathy, 6A

11EARS2
Def

leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome

11KCTD7
DefP:R

progressive myoclonic epilepsy type 3

10POLR3B
Def

leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism

10ABAT
Mod
10GM2A
Def
10KARS1
Lim

leukoencephalopathy, progressive, infantile-onset, with or without deafness

10SERAC1
Def

3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome

10OPA3
ModP:R

outer mitochondrial membrane lipid metabolism regulator OPA3

9ATP2B2
Def
9FANCD2
Def
9GRIP1
DefP:R
9KMT2E
Def
9CHD8
Def

intellectual developmental disorder with autism and macrocephaly

nucleoporin 214

9PIGA
Def

multiple congenital anomalies-hypotonia-seizures syndrome 2

9TUBB4A
Def

hypomyelinating leukodystrophy 6

9FDXR
Def

multiple mitochondrial dysfunctions syndrome 9b

9TPP1
DefP:R

neuronal ceroid lipofuscinosis 2

9NFU1
Def

spastic paraplegia 93, autosomal recessive

8SMPD1
Def

Niemann-Pick disease type A

8CLN5
DefP:R

neuronal ceroid lipofuscinosis 5

8EIF2B1
Def

leukoencephalopathy with vanishing white matter 1

8EHMT1
Def

Kleefstra syndrome 1

8AGA
Def

aspartylglucosaminuria

Possible

145 genes — click to expand
8NDUFV1
Def

mitochondrial complex I deficiency, nuclear type 4

8PSAP
Def

Gaucher disease due to saposin C deficiency

intellectual disability, autosomal dominant 5

8SDHA
Def

mitochondrial complex II deficiency, nuclear type 1

8SDHD
DefSF

mitochondrial complex 2 deficiency, nuclear type 3

8GCDH
Def

glutaryl-CoA dehydrogenase deficiency

8SDHAF1
Def

mitochondrial complex 2 deficiency, nuclear type 2

7CRELD1
Lim
7HIBCH
Def

3-hydroxyisobutyryl-CoA hydrolase deficiency

7AARS2
Def

leukoencephalopathy, progressive, with ovarian failure

psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome

7CUX2
Mod

developmental and epileptic encephalopathy, 67

7HMGA2
Def

d-bifunctional protein deficiency

7MSRB3
Def
7PMM2
Def
7RXYLT1
Def
7TBK1
Def
7USP7
Def
7MT-ND1
Def

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1

7NDUFS1
Def

mitochondrial complex I deficiency, nuclear type 5

7SON
Def

ZTTK syndrome

7NMNAT1
Def

nicotinamide nucleotide adenylyltransferase 1

7AHDC1
Def

AHDC1-related intellectual disability - obstructive sleep apnea - mild dysmorphism syndrome

developmental and epileptic encephalopathy, 8

7NDUFS2
Def

mitochondrial complex I deficiency, nuclear type 6

7ZBTB18
Def

intellectual disability, autosomal dominant 22

7LYRM7
Def

mitochondrial complex III deficiency nuclear type 8

7TBCD
Def

early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome

6SGPL1
Def

nephrotic syndrome 14

6GFAP
Def

Alexander disease

6NDUFS4
Def

mitochondrial complex I deficiency, nuclear type 1

6NDUFS7
Def

mitochondrial complex I deficiency, nuclear type 3

6MTRFR
Def

combined oxidative phosphorylation defect type 7

biotin-responsive basal ganglia disease

HSD10 mitochondrial disease

6ISCA2
Def

multiple mitochondrial dysfunctions syndrome 4

6NAXD
Def

NAD(P)HX dehydratase deficiency

6CD40LG
Def

hyper-IgM syndrome type 1

6PIGT
Def

multiple congenital anomalies-hypotonia-seizures syndrome 3

6POLG
Lim

mitochondrial DNA depletion syndrome 4a

intellectual developmental disorder, autosomal recessive 83

6NBEA
Def

neurodevelopmental disorder with or without early-onset generalized epilepsy

developmental and epileptic encephalopathy, 64

6ETHE1
Def

ethylmalonic encephalopathy

6ROGDI
Def

amelocerebrohypohidrotic syndrome

5AIFM1
Def

severe X-linked mitochondrial encephalomyopathy

5ATP5MK
Mod

mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6

5NDUFA2
Def

mitochondrial complex I deficiency, nuclear type 13

intellectual disability, X-linked, syndromic, Bain type

interleukin 1 receptor accessory protein like 1

5NRXN1
Def

Pitt-Hopkins-like syndrome 2

5PCDH19
Def

developmental and epileptic encephalopathy, 9

5UNC13A
Lim

unc-13 homolog A

5HPDL
Mod

neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities

5MFF
Mod

encephalopathy due to defective mitochondrial and peroxisomal fission 2

alkaline ceramidase 3 deficiency

neurodevelopmental disorder with motor regression, progressive spastic paraplegia, and oromotor dysfunction

5LIFR
Def

LIF receptor subunit alpha

5LMNA
DefSF

lamin A/C

5NDUFB3
Def

NADH:ubiquinone oxidoreductase subunit B3

5PIGY
Lim

hyperphosphatasia with intellectual disability syndrome 6

5COX15
Def

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2

5GLB1
Def

GM1 gangliosidosis type 2

5HNRNPU
Def

developmental and epileptic encephalopathy, 54

5IQSEC2
Def

intellectual disability, X-linked 1

5MPV17
Def

mitochondrial DNA depletion syndrome 6 (hepatocerebral type)

5NGLY1
Def

congenital disorder of deglycosylation 1

5WARS2
Def

parkinsonism-dystonia 3, childhood-onset

4SATB1
Def

Kohlschutter-Tonz syndrome-like

neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures

neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction

4KCNT1
Def

developmental and epileptic encephalopathy, 14

4MED27
Str

neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia

4EIF3F
Def

intellectual developmental disorder, autosomal recessive 67

4PPP2CA
Def

Houge-Janssens syndrome 3

4TTC19
Def

mitochondrial complex III deficiency nuclear type 2

multiple mitochondrial dysfunctions syndrome 6

4GFM1
Mod

G elongation factor mitochondrial 1

4ATP1A2
Def

alternating hemiplegia of childhood 1

4GAMT
Def

guanidinoacetate methyltransferase deficiency

4ATP11A
Mod

leukodystrophy, hypomyelinating, 24

neurodegeneration, childhood-onset, with cerebellar ataxia and cognitive decline

4GABBR2
Mod

neurodevelopmental disorder with poor language and loss of hand skills

4GABRB1
Lim

developmental and epileptic encephalopathy, 45

4LIPT1
Mod

lipoyl transferase 1 deficiency

4LRPPRC
Def

congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

3BICRA
Def

Coffin-Siris syndrome 12

3COX4I1
Lim

mitochondrial complex IV deficiency, nuclear type 16

leukodystrophy, hypomyelinating, 15

3PET117
Lim

mitochondrial complex IV deficiency, nuclear type 19

developmental and epileptic encephalopathy 114

3NUP62
Dis

familial infantile bilateral striatal necrosis

hypermanganesemia with dystonia 2

3LINS1
Def

lines homolog 1

neurodegeneration, childhood-onset, with cerebellar atrophy

3BSCL2
Def

severe neurodegenerative syndrome with lipodystrophy

3FITM2
Def

Siddiqi syndrome

3FOLR1
Def

neurodegenerative syndrome due to cerebral folate transport deficiency

3GTPBP2
Def

Jaberi-Elahi syndrome

3IBA57
Def

multiple mitochondrial dysfunctions syndrome 3

3ITPR1
Def

spinocerebellar ataxia type 29

3L2HGDH
Def

L-2-hydroxyglutaric aciduria

3NAGA
Def

alpha-N-acetylgalactosaminidase deficiency type 1

3NARS2
Def

combined oxidative phosphorylation defect type 24

3SEMA6B
Def

epilepsy, progressive myoclonic, 11

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