Human genetic diseases and Wnt signaling components

There are many cases of genetic diseases due to mutations in Wnt signaling components. Among these are several where multiple Wnt signaling components have been found as mutated in families. These diseases include abnormalities in bone density, tooth development and the retina. Another example is Robinow syndrome, associated with mutations in three different Wnt signaling components: ROR2 (Van Bokhoven et al, 2000) , WNT5A and DVL1

The table lists many of these diseases and the genes mutated. 

See for reviews:

Moon, RT et al, WNT and beta-catenin signalling: diseases and therapies. Nat Rev Genet. 2004 Sep;5(9):691-701

Clevers, H and Nusse, R. Wnt/β-Catenin Signaling and Disease.Cell. 2012 Jun 8;149(6):1192-205.


Anastas, JN and Moon, RT WNT signalling pathways as therapeutic targets in cancer.Nature Rev Cancer 13 2013:11-26





APC Polyposis coli Kinzler et al 1991, Nishisho et al 1991

Bone Density defects

Vascular defects in the eye (Osteoperosis-pseudoglioma Syndrome, OPPG)

Gong, 2001 Little, 2002, Boyden, 2002
LRP5 Familial Exudative Vitreoretinopathy Toomes et al, 2004

Qin 2005

LRP6 early coronary disease Mani, 2007
LRP6 Late onset Alzheimer De Ferrari 2007
LRP6Autosomal-Dominant Oligodontia (Massink, 2015)

Familial Exudative Vitreoretinopathy:

retinal angiogenesis

Robitaille, 2002

Qin 2005

FZD9Williams Syndrome

Wang 1997

Chailangkarn 2016

Norrin Familial Exudative Vitreoretinopathy Xu et al, 2004
WNT1Osteogenesis imperfecta


Tetra-Amelia Niemann et al 2004
WNT4 Mullerian-duct regression and virilization Biason-Lauber 2004
WNT4 SERKAL syndrome Mandel, 2008
WNT5ARobinow syndrome (Person 2010)
WNT5B Type II diabetes Kanazawa 2004
WNT7A Fuhrmann syndrome Woods 2006
WNT10A Odonto-onycho-dermal dysplasia Adaimy, 2007
WNT10B Obesity Christodoulides 2006
WNT10B Split-Hand/Foot Malformation Ugur, 2008
WNT10BOligodontiaYu, 2016
WNT16Bone density Zheng et al, 2012
DVL1Robinow Syndrome. (White et al, 2015)
AXIN1 caudal duplication Oates, 2006
TCF7L2 (TCF4) Type II diabetes
Grant 2006
Florez 2006
O'Rahilly 2006
AXIN2 Tooth agenesis Lammli et al, 2004 Marvin et al, 2011
WTX Wilms tumor Major, 2007, Rivera, 2007
WTX skeletal dysplasia Jenkins, 2009
PORCN Focal dermal hypoplasia Grzeschik 2007

Wang 2007

RSPO1Palmoplantar hyperkeratosisParma 2006
RSPO2Tetra-amelia Szenker-Ravi, 2018
RSPO4 autosomal recessive anonychia Bergmann 2006, Blaydon 2006
LGR4Bone Density defectsStyrkarsdottir et al, 2013
VANGL1 Neural tube defects Kibar, 2007

Sclerosteosis and Van Buchem disease 

Balemans, 2001, 2002Brunkow, 2001


Pyle's disease (Bone density) 

Simsek Kiper 2016


Robinow syndrome

Van Bokhoven et al, 2000

WLS (Wntless)

Pleiotropic Multiorgan Condition 

Chai et al, 2021