Table 1 Mosaic mutations in genes and their associated signaling pathways and diseases.

Disease abbreviations: CLOVES, Congenital lipomatous overgrowth, vascular malformations, and epidermal nevi; FCD, focal cortical dysplasia; GPCR, G protein–coupled receptor; HME, hemimegalencephaly; MCAP, megalencephaly-capillary malformation-polymicrogyria syndrome; MPPH2, megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-2; NF, neurofibromatosis; RALD, Ras-associated autoimmune leukoproliferative disorder; TSC, tuberous sclerosis complex. Mosaicism abbreviations: G, germline; S, somatic; OS, obligatory somatic; MS, milder somatic; SHS, second-hit somatic.

Gene(s)Signaling
pathway(s)
Disease(s)Cellular
function(s)
Cancer(s)Cancer roleMosaicism
PIK3CA (100104)PI3K-AKT-mTORHME, mosaic
overgrowth syndrome,
type 2 segmental,
CLOVES, MCAP
PI3K subunit,
serine/threonine
kinase
Cervical, various
neoplasms, colorectal
OncogeneOS
AKT1 (105)PI3K-AKT-mTORProteus syndromeSerine/threonine
kinase
Breast, ovarian,
colorectal
OncogeneOS
AKT2 (106)PI3K-AKT-mTORDiabetes mellitusSerine/threonine
kinase
Ovarian, pancreatic,
breast, colorectal,
lung cancer
OncogeneG/S
AKT3 (101, 103, 13, 107)PI3K-AKT-mTORHME, MCAP, MPPH2Serine/threonine
kinase
Melanoma, glioma,
ovarian cancer
OncogeneOS
MTOR (108)PI3K-AKT-mTORFCD type IISerine/threonine
kinase
Carcinoma,
glioblastoma,
melanoma
OncogeneOS
DEPDC5 (109, 110)PI3K-AKT-mTOREpilepsy with FCDmTORC1
repressor
Glioblastoma and
ovarian tumors
Tumor
suppressor
G/S
TSC1 (111, 112)PI3K-AKT-mTORTSCNegative
regulator of
mTORC1
Renal angiomyolipomasTumor
suppressor
SHS
TSC2 (111, 112)PI3K-AKT-mTORTSCNegative
regulator of
mTORC1
Renal angiomyolipomasTumor
suppressor
SHS
NRAS, BRAF,
FGFR3, PIK3CA
(113118)
RAS, PI3K-AKT-
mTOR
Congenital
melanocytic,
other nevi;
seborrheic
keratosis
Cell cycle
regulation
(FGFR3) bladder,
cervical, urothelial
OncogeneG/S
NF2 (119)RAS, PI3K-AKT-
mTOR
NF type 2Negative regulator
of Ras, mTOR
pathways
NeurofibromasTumor
suppressor
G/MS
NF1 (120124)RASNF type 1, Watson
syndrome
Negative regulator
of Ras pathway
Neurofibromas,
leukemia
Tumor
suppressor
SHS
BRAF, NRAS,
KRAS (125)
RASPyogenic granulomaCell cycle
regulation
(KRAS) breast,
colorectal, other;
(NRAS) thyroid,
melanoma, other;
(BRAF) melanoma,
colorectal
OncogeneOS
HRAS, KRAS (126)RASSchimmelpenning-Feuerstein-
Mims syndrome
Cell cycle
regulation
(KRAS) bladder,
breast, colorectal,
pancreatic, other;
(HRAS) Colorectal,
bladder, kidney, other
OncogeneOS
KRAS (127, 128)RASRALDCell cycle
regulation
Breast, bladder, otherOncogeneOS
GNAQ (129)GPCR, MAPKSturge-Weber syndromeG protein
alpha subunit
MelanomaOncogeneOS
GNAQ, GNA11 (130)GPCR, MAPKDermal melanocytosis
and phakomatosis
pigmentovascularis
G protein
alpha subunit
MelanomaOncogeneOS
MAP3K3 (131)MAPKVerrucous venous
malformation
Cell cycle
regulation
Breast, colon,
rectal cancers
OncogeneOS
GNAS (132, 133)GPCRMcCune-Albright
syndrome
G protein alpha
subunit
Adenomas,
carcinomas,
ovarian neoplasms
OncogeneOS
JAK2 (134, 135)JAK-STATMyelofibrosis,
polycythemia vera,
and essential
thrombocythemia
Cell cycle
regulation
LeukemiaOncogeneSHS
SCN1A (136)Sodium channelDravet syndromeNeural excitationG/MS
NLRP3 (137)Caspase/
inflammasome
CINCA syndromeInflammasome
subunit
G/MS
PORCN (138)WntFocal dermal
hypoplasia
O-acyltransferaseG/MS
PIGA (139)HematopoiesisParoxysmal
nocturnal
hemoglobinuria
ER protein
processing
LeukemiaOS