Table 2.

Diseases associated with the SH3 family.

SH3DCP	Mutation	Disease	Refs.
AHI1	FsX1103	Joubert syndrome	[241]
	Deletion of the SH3 domain	Leukemia and lymphomas	[242]
MYO7A	Missense mutation (A1628S) and truncation/deletion mutations (c.4838delA, c.5146-5148delGAG)	Usher Syndrome or nonsyndromic deafness (DFNB2)	[243,244]
FRK	R64Q	Cervix and vulva cancer	[245]
YES1	K113Q	Breast and colon cancer	[245]
ACK1	M393T, M409I	Colon, Gastric adenocarcinoma	[245,246,247,248]
AMPH	Q434X, K436X, Q573X, K575X	Centronuclear Myopathy	[249,250]
ARHGAP10	Lacking the RHOGAP and SH3 domains	Schizophrenia	[251]
ARHGEF9	G55A	Hzperekplexia, seizures or epilepsy, developmental Delay, or intellectual disability	[252]
ARHGEF23	Missense and nonsense mutations	Neurodevelopmental disorders	[253]
ARHGEF30	V5668A	Breast cancer	[101]
	A5660V	Cardiomyopathies	[254]
CD2AP	K301M	Sporadic nephrotic syndrome and focal segmental glomerulosclerosis (FSGS)	[255]
BIN1	Q434X, K436X, Q573X, K575X, P593HfsX54, X594DfsX53	Centronuclear myopathy (CNM)	[249,256]
	rs138047593 (K358 R (KR))	Alzheimer’s disease	[257,258]
BLK	A71T	Autoimmune diseases, (e.g., systemic lupus erythematosus (SLE))	[259]
BTK	Deletion of C-terminal 14 aa residues of SH3 domain	X-linked agammaglobulinemia (XLA)	[260,261]
LYN	SH3 mutations (transformative and non-transformative)	Cancer (uterine, sarcoma, thyroid, liver, head and neck, melanoma, lung, glioma, kidney, breast, hematologic)	[39]
MIA	High expression	Melanoma development, progression and metastasis	[74]
MYO15A	G2909S, G2941Vfs*94, W2931Gfs*103, R2923*, P2880Rfs*19, R2903*, R2924H, G2938R, V2940fs*3034	Human Deafness	[262,263]
NPHP1	2q13	Autosomal recessive cystic kidney disease	[264]
	L180P	Familial Juvenile Nephronophthisis	[265]
PEX13	Missense mutation at SH3, nonsense mutation of W234ter, temperature sensitive mutation of I326T, W313G	Peroxisome-biogenesis disorders (PBDs) including Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease	[266,267,268,269]
PLC-γ1	Substitution mutations	Adult T cell leukemia/lymphoma, angioimmunoblastic T-cell lymphomas, T-cell prolymphocytic leukemia, Sézary Syndrome, PLAID, autoinflammation, immune deficiency	[270,271,272,273]
PSTPIP1	D384G, G403E, G403R, R405C	Autoinflammatory diseases (most notably in the PAPA syndrome; pyogenic sterile arthritis, pyoderma gangrenosum, and acne) and CVID (common variable immunodeficiency)	[274,275]
PTK6	L16F	Cancer	[276]
RASA1	Missense, nonsense, frame shift, and splice site mutation	Cancer, capillary malformation (CM)	[277,278]
RIMBP1	G1808S	Autosomal recessive dystonia	[279]
SASH1	S587R, M595T, E617K, I586M, S587R, M595T	DUH (dyschromatosis universalis hereditaria) and lentiginous phenotype	[280,281]
SH3PXD2B	Non-synonymous coding sequence variations (G245R, E396K, G481R)	Axenfeld–Rieger syndrome	[282]
	BDCS3 deletion (deletion of two C-terminus SH3 domains)	Borrone dermato-cardio-skeletal syndrome	[283]
SHANK1	R874H	Autism spectrum disorder	[284]
SHANK2	S557N, R569H	Autism spectrum disorder	[285]
SHANK3	Lacking parts of the SH3 domain in case of G1527A	Autism spectrum disorder and intellectual disability (ID)	[286]
SPTAN1	D2303_L2305dup	Epileptic encephalopathy	[287]
VAV1	L801P	Cancer	[288]
STAC3	W > S substitution	Native American myopathy	[289]
	P269R, N281S, W284S, F295L, H311R, K329N	Native American myopathy, dystrophin-deficient muscles	[289,290,291,292]
OBSCN	V5668A	Breast cancer	[293]
CASK	G659D	Severe intellectual disability (ID), microcephaly and pontine, and cerebellar hypoplasia in girls (MICPCH)	[294]