Genes associated with “macrocephaly

235 genes foundHPO: MacrocephalyOpen Targets: Macrocephaly14632 ClinVar P/LP variants
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:
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Strong Candidates

16 genes
1
NF1

neurofibromin 1

38
score
ClinGen: DefinitiveGTR ↑

neurofibromatosis type 1

Frequency
38%
n=128
P/LP Variants
12
OT Score
0.27
2
PTEN

phosphatase and tensin homolog

37
score
ClinGen: DefinitiveACMG SFP2G #2GTR ↑

macrocephaly-autism syndrome

Frequency
100%
n=3
P/LP Variants
25
OT Score
0.52
35
score
ClinGen: DefinitiveGTR ↑

mucopolysaccharidosis type 2

Frequency
88%
n=131
P/LP Variants
6
OT Score
-
4
PTCH1

patched 1

30
score
ClinGen: DefinitiveP2G #9GTR ↑
Frequency
-
P/LP Variants
169
OT Score
0.33
5
CHD3

chromodomain helicase DNA binding protein 3

30
score
ClinGen: DefinitiveGTR ↑

Snijders Blok-Campeau syndrome

Frequency
61%
n=31
P/LP Variants
2
OT Score
0.37
6
CHD8

chromodomain helicase DNA binding protein 8

29
score
ClinGen: DefinitiveGTR ↑
Frequency
-
P/LP Variants
10
OT Score
0.41
28
score
ClinGen: DefinitiveP2G #5GTR ↑

Weaver syndrome

Frequency
100%
n=3
P/LP Variants
35
OT Score
-
26
score
P2G #3GTR ↑

polydactyly, postaxial, type A1

Frequency
0%
n=10
P/LP Variants
9
OT Score
-
9
BRWD3

bromodomain and WD repeat domain containing 3

26
score
ClinGen: DefinitiveGTR ↑
Frequency
-
P/LP Variants
6
OT Score
0.37
25TRIO
Def

intellectual developmental disorder, autosomal dominant 63, with macrocephaly

24CHD4
Def

Sifrim-Hitz-Weiss syndrome

23WDFY3
Def

WD repeat and FYVE domain containing 3

23NFIA
Def

nuclear factor I A

23NFIX
Def
22GUSB
Def

mucopolysaccharidosis type 7

20SUFU
Def

basal cell nevus syndrome 2

Consider

61 genes

macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin

20NFIB
Def

nuclear factor I B

19NSD1
Def#7

Sotos syndrome

19DICER1
Def
19SPRED1
Def
18FGFR3
Def#1

achondroplasia

17ASPA
Def#12

Canavan disease

16KIF7
#4

acrocallosal syndrome

14PIK3CA
Def#13

megalencephaly-capillary malformation-polymicrogyria syndrome

14MTOR
Def

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

13HEPACAM
Def

megalencephalic leukoencephalopathy with subcortical cysts 2A

13ERF
Def

craniosynostosis 4

13HSD17B4
Def

d-bifunctional protein deficiency

COLOBOMA, OSTEOPETROSIS, MICROPHTHALMIA, MACROCEPHALY, ALBINISM, AND DEAFNESS; COMMAD

INTELLECTUAL DEVELOPMENTAL DISORDER WITH AUTISM AND MACROCEPHALY; IDDAM

INTELLECTUAL DEVELOPMENTAL DISORDER WITH MACROCEPHALY, SEIZURES, AND SPEECH DELAY; IDDMSSD

MACROCEPHALY, ACQUIRED, WITH IMPAIRED INTELLECTUAL DEVELOPMENT; MACID

MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION; MDFPMR

MACROCEPHALY, NEURODEVELOPMENTAL DELAY, LYMPHOID HYPERPLASIA, AND PERSISTENT FETAL HEMOGLOBIN; MNDLFH

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 63, WITH MACROCEPHALY; MRD63

13DNMT3A
Def

Tatton-Brown-Rahman overgrowth syndrome

12HMGA2
Def
12KPTN
Def
12ASXL2
Def

Shashi-Pena syndrome

12MED12
Def

X-linked intellectual disability with marfanoid habitus

12MLC1
Def

modulator of VRAC current 1

12RAF1
Def

Noonan syndrome 5

12FBN1
DefSF

progeroid and marfanoid aspect-lipodystrophy syndrome

11TRIP12
Def
11SOX9
Def

campomelic dysplasia

11PTPN11
Def

LEOPARD syndrome 1

11EED
Mod

Cohen-Gibson syndrome

11PTCH2
Lim
11TET3
Def
11SHANK3
Def

Phelan-McDermid syndrome

11KRAS
Def#6

Toriello-Lacassie-Droste syndrome

11AKT3
Def

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2

10STXBP1
Def

syntaxin binding protein 1

10RPS6KA3
Def

ribosomal protein S6 kinase A3

10SATB2
Def

SATB homeobox 2

10KMT2E
Def

O'Donnell-Luria-Rodan syndrome

10CACNA1E
Def

calcium voltage-gated channel subunit alpha1 E

10OFD1
Def

Simpson-Golabi-Behmel syndrome type 2

macrocephaly/megalencephaly syndrome, autosomal recessive

10SOS1
Def

Noonan syndrome 4

10IDUA
Def
9BRAF
Def

LEOPARD syndrome 3

9CHD7
Def
9FLNA
Def
9TCIRG1
Def

autosomal recessive osteopetrosis 1

neurodevelopmental disorder with alopecia and brain abnormalities

8IGF2
Def

Silver-Russell syndrome 3

8SMAD4
DefSF

Myhre syndrome

8CTSK
Def

cathepsin K

8GPC4
#19

Keipert syndrome

8EXT2
Def

seizures-scoliosis-macrocephaly syndrome

8TAOK1
Def

developmental delay with or without intellectual impairment or behavioral abnormalities

8HRAS
DefSF#11

Costello syndrome

8ABCC9
Def

ATP binding cassette subfamily C member 9

8RPL5
Def

ribosomal protein L5

8NRAS
Def

Noonan syndrome 6

Possible

113 genes — click to expand
8CTR9
Mod

CTR9 component of Paf1/RNA polymerase II complex

8SHOC2
Def

Noonan syndrome-like disorder with loose anagen hair 1

8L1CAM
Def

X-linked hydrocephalus with stenosis of the aqueduct of Sylvius

8PPP1CB
Def

Noonan syndrome-like disorder with loose anagen hair 2

7MITF
Def

coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness

7OPHN1
Def

X-linked intellectual disability-cerebellar hypoplasia syndrome

mitogen-activated protein kinase 1

autosomal dominant Robinow syndrome 2

intellectual developmental disorder with macrocephaly, seizures, and speech delay

7ABCC8
Def

ATP binding cassette subfamily C member 8

7PUF60
Def
7TRIT1
Def

tRNA isopentenyltransferase 1

7FGD1
Def

Aarskog-Scott syndrome, X-linked

7PEX1
Def

peroxisome biogenesis disorder 1A (Zellweger)

7MT-CYB
Def

mitochondrially encoded cytochrome b

7DEPDC5
Def

developmental and epileptic encephalopathy 111

7HEXB
Def

Sandhoff disease

7KDM6B
Def

neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities

7ASH1L
Def

intellectual disability, autosomal dominant 52

7SON
Def

ZTTK syndrome

7DHCR24
Def

desmosterolosis

polyhydramnios, megalencephaly, and symptomatic epilepsy

opsismodysplasia

6PHF21A
Def

intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures

neurexin 3

Chopra-Amiel-Gordon syndrome

Joubert syndrome 2

6UPF3B
Def

syndromic X-linked intellectual disability 14

6EML1
Def

band heterotopia of brain

6GFAP
Def

Alexander disease

6MECP2
Def

syndromic X-linked intellectual disability Lubs type

6GNB1
Def

intellectual disability, autosomal dominant 42

eukaryotic translation elongation factor 2

6LBR
Mod

Greenberg dysplasia

5PLG
Def

hypoplasminogenemia

5EIF2B1
Def

leukoencephalopathy with vanishing white matter 1

5CSF1R
Def

brain abnormalities, neurodegeneration, and dysosteosclerosis

coiled-coil domain containing 186

divergent protein kinase domain 1A

procollagen-lysine,2-oxoglutarate 5-dioxygenase 1

5MT-ND4
Def

mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4

5COL2A1
Def

platyspondylic dysplasia, Torrance type

MACROCEPHALY/MEGALENCEPHALY SYNDROME, AUTOSOMAL RECESSIVE; MGCPH

5SETD2
Def

intellectual developmental disorder, autosomal dominant 70

5SYN1
Def

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

glycogen synthase kinase 3 alpha

RAB5 interacting factor

zinc finger protein 526

5LAMA5
Def

bent bone dysplasia syndrome 2

craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1

5ALG13
Def

developmental and epileptic encephalopathy, 36

5GAN
Def

giant axonal neuropathy 1

5HECW2
Def

neurodevelopmental disorder with hypotonia, seizures, and absent language

5IFT74
Def

Bardet-Biedl syndrome 22

5RIN2
Def

RIN2 syndrome

4CCDC22
Mod

Ritscher-Schinzel syndrome 2

4PDSS1
Mod

deafness-encephaloneuropathy-obesity-valvulopathy syndrome

4ZFX
Str

intellectual developmental disorder, X-linked, syndromic 37

4TRAF7
Def

cardiac, facial, and digital anomalies with developmental delay

4STT3A
Def

congenital disorder of glycosylation, type Iw, autosomal dominant

4GRIA3
Def

syndromic X-linked intellectual disability 94

4NDUFV1
Def

mitochondrial complex I deficiency, nuclear type 4

4TFE3
Def

intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies

4WNT5A
Mod

autosomal dominant Robinow syndrome 1

4RERE
Def

neurodevelopmental disorder with or without anomalies of the brain, eye, or heart

4SMPD1
Def

Niemann-Pick disease type A

BICD cargo adaptor 2

polypeptide N-acetylgalactosaminyltransferase 8

potassium voltage-gated channel subfamily A member 6

4JARID2
Def

developmental delay with variable intellectual disability and dysmorphic facies

B4GALT1-congenital disorder of glycosylation

4BGN
Lim

Meester-Loeys syndrome

Imagawa-Matsumoto syndrome

4CAMK2A
Def

intellectual disability, autosomal dominant 53

family with sequence similarity 177 member A1

autosomal dominant Robinow syndrome 3

mitochondrial complex I deficiency, nuclear type 18

4UBE2A
Def

syndromic X-linked intellectual disability Nascimento type

4USP9X
Def

intellectual disability, X-linked 99

4APC2
Str

intellectual developmental disorder, autosomal recessive 74

4MRAS
Mod

Noonan syndrome 11

4SRCAP
Def

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

4MSX2
Def

parietal foramina 1

4GAD1
Def

developmental and epileptic encephalopathy 89

3BICRA
Def

Coffin-Siris syndrome 12

neurodevelopmental disorder with speech impairment and dysmorphic facies

craniometadiaphyseal osteosclerosis with hip dysplasia

3MAN2C1
Mod

congenital disorder of deglycosylation 2

3CAMK2G
Lim

intellectual developmental disorder 59

acroosteolysis-keloid-like lesions-premature aging syndrome

Cole-Carpenter syndrome 2

3BBS1
Def

Bardet-Biedl syndrome 1

3CCND2
Def

megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3

3CRPPA
Def

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

3D2HGDH
Def

D-2-hydroxyglutaric aciduria 1

3DOCK6
Def

Adams-Oliver syndrome 2

short-rib thoracic dysplasia 8 with or without polydactyly

3ETFB
Def

multiple acyl-CoA dehydrogenase deficiency

autosomal dominant Kenny-Caffey syndrome

3HUWE1
Def

intellectual disability, X-linked syndromic, Turner type

3LRP4
Def

sclerosteosis 2

3MAN2B1
Def

alpha-mannosidosis

3MOCS1
Def

sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

3PIGN
Def

multiple congenital anomalies-hypotonia-seizures syndrome 1

3PIGT
Def

multiple congenital anomalies-hypotonia-seizures syndrome 3

D,L-2-hydroxyglutaric aciduria

3SMO
Def

congenital hypothalamic hamartoma syndrome

3SNX14
Def

autosomal recessive spinocerebellar ataxia 20

3TMEM94
Def

intellectual developmental disorder with cardiac defects and dysmorphic facies

3TRIP11
Def

odontochondrodysplasia 1

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