Table 1.

Genes regulating spindle orientation and mutated in diseases

Gene name – species Cellular function Associated disease Molecular characteristics 
Vertebrate Fly Worm  
lis1 lis1 lis-1 Dynein-based movement, nucleokinesis (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome alignment (vertebrate), centrosome separation (fly, worm) spindle positioning (worm) (Swan et al., 1999; Dawe et al., 2001; Cockell et al., 2004; Siller and Doe, 2008; Wynshaw-Boris et al., 2010) Lissencephaly (Reiner et al., 1993; Lo Nigro et al., 1997) Coiled-coil domain, WD40 repeats 
dcx CG17528a zyg-8 Microtubule polymerization (vertebrate, worm), spindle orientation (vertebrate), spindle positioning (worm) (Gönczy et al., 2001; Pramparo et al., 2010; Wynshaw-Boris et al., 2010) Lissencephaly (des Portes et al., 1998; Gleeson et al., 1998) Doublecortin domain, kinase domain 
nde1 nudE nud-2 Centrosome duplication and maturation, chromosome alignment, spindle orientation, nucleokinesis (vertebrate), kinetochore function, chromosome congression, centrosome behavior (fly), nuclear migration (worm) (Wainman et al., 2009; Fridolfsson et al., 2010; Chansard et al., 2011) Microlissencephaly (Alkuraya et al., 2011; Bakircioglu et al., 2011) Coiled-coil domain 
Gαi1, Gαi2, Gαi3 Gαi1 goa-1, gpa-16 Spindle orientation (vertebrate, fly), ACD (fly, worm), spindle positioning, chromosome segregation (worm) (Srinivasan et al., 2003; Morin and Bellaïche, 2011) – GTPase subunit of heterotrimeric G proteins 
numa mud lin-5 ACD, chromosome segregation (vertebrate, fly, worm), spindle orientation, spindle pole integrity (vertebrate, fly), spindle positioning, cytokinesis (worm) (Lorson et al., 2000; Radulescu and Cleveland, 2010; Capalbo et al., 2011; Morin and Bellaïche, 2011; Kolano et al., 2012) Leukemia (Wells et al., 1997) Coiled-coil domain 
pins/lgn/gpsm2/ags3 pins gpr-1, gpr-2 ACD (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation (vertebrate, worm), spindle positioning (worm) (Du et al., 2001; Srinivasan et al., 2003; Morin and Bellaïche, 2011) Non-syndromic deafness (Walsh et al., 2010), brain malformations and deafness in Chudley-McCullough syndrome (Doherty et al., 2012) GoLoco motif, tetratricopeptide (TPR) domains 
insc insc – Spindle orientation (vertebrate, fly), asymmetric cell division (fly) (Morin and Bellaïche, 2011) – Armadillo repeats 
htt htt F21G4.6a Neuronal transport, spindle orientation (vertebrate, fly) (Gunawardena et al., 2003; Godin and Humbert, 2011) The Huntington’s Disease Collaborative Research Group (1993)  Polyglutamine tract, polyproline sequence, HEAT repeats 
magoh mago mag-1 RNA processing (vertebrate, fly worm), RNA localization (vertebrate, fly), spindle orientation and integrity, genomic stability (vertebrate), cytoskeleton organization (fly) (Li et al., 2000; Kataoka et al., 2001; Palacios, 2002; Le Hir and Andersen, 2008; Silver et al., 2010) – Mago nashi domain 
apc apc1, apc2 apr-1 Wnt signaling, ACD, microtubule stability (vertebrate, fly, worm), spindle orientation (vertebrate, fly), chromosome segregation, tumor suppressor (vertebrate) (Yamashita et al., 2003; Mizumoto and Sawa, 2007; McCartney and Näthke, 2008; Bahmanyar et al., 2009) Familial adenomatous polyposis (FAP), gastrointestinal tumors (Minde et al., 2011) Armadillo repeats, oligomerization domain, CRM1, β-catenin, microtubule-binding domains, 
vegf pvf1, pvf2, pvf3 pvf-1 Cell migration (vertebrate, fly), growth factor, oncogene, spindle orientation, angiogenesis (vertebrate) (Duchek et al., 2001; Tarsitano et al., 2006; Beck et al., 2011; Sitohy et al., 2012) Epithelia skin cancer (Beck et al., 2011) PDGF domain 
vhl vhl vhl-1 HIF1α regulation (vertebrate, fly, worm), microtubule stability, endocytosis, cell migration (vertebrate, fly), tumor suppressor, spindle orientation, genome integrity (vertebrate) (Thoma et al., 2009; Hsu, 2012) Renal cell carcinoma (Kaelin, 2008) Cullin E3 ubiquitin ligase 
pten pten daf-18 PI3K signaling (vertebrate, fly, worm), tumor suppressor, spindle orientation, genome integrity, cell growth (vertebrate), cell growth, actin cytoskeleton organization, (fly) (Ogg and Ruvkun, 1998; Stocker and Hafen, 2000; von Stein et al., 2005; Toyoshima et al., 2007; Hollander et al., 2011) PTEN hamartoma tumor syndromes (PHTS) (Hollander et al., 2011) Protein and lipid phosphatase 
mcph1/microcephalin/brit1 mcph1 – DNA damage response, centrosome integrity, chromosome segregation (vertebrate, fly), spindle orientation (vertebrate) (Thornton and Woods, 2009; Gruber et al., 2011) Microcephaly (Jackson et al., 2002) BRCA1 C-terminal (BRCT) domains 
mcph2/wdr62 – – Centrosome integrity, spindle orientation, chromosome alignment (vertebrate) (Bogoyevitch et al., 2012) Microcephaly, lissencephaly, schizencephaly (Bilgüvar et al., 2010; Nicholas et al., 2010; Yu et al., 2010) WD40 repeats 
mcph3/cdk5rap2/cep215 cnn – Centrosome assembly, spindle orientation, chromosome segregation (vertebrate, fly), DNA damage response (vertebrate) (Siller and Doe, 2008; Megraw et al., 2011) Microcephaly (Bond et al., 2005) Coiled-coil domains, centrosomin motives (CM) 1 and 2 
mcph4/cep152 asl – Centriole formation and duplication (vertebrate, fly), genome integrity (vertebrate) (Kalay et al., 2011; Brito et al., 2012) Microcephaly (Guernsey et al., 2010), Seckel syndrome (Kalay et al., 2011) Coiled-coil domains 
mcph5/aspm/calmbp1 asp aspm-1 Spindle assembly, spindle orientation, cytokinesis (vertebrate, fly), the integrity of spindle poles and the central spindle (fly), meiotic spindle orientation (worm) (Varmark, 2004; van der Voet et al., 2009; Higgins et al., 2010) Microcephaly (Bond et al., 2002), tumorigenesis (Lin et al., 2008) Calponin homology (CH) domains, IQ-repeat motifs 
mcph6/cenpj/cpap sas4 sas-4 Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate), ACD (fly) (Leidel and Gönczy, 2005; Basto et al., 2006; Kitagawa et al., 2011; Brito et al., 2012) Microcephaly (Bond et al., 2005), Seckel syndrome (Al-Dosari et al., 2010) Coiled-coil motives, PN2-3 domain, T-complex protein 10 (TCP) domain 
mcph7/stil/sil ana2 sas-5 Centriole duplication (vertebrate, fly, worm), spindle orientation (vertebrate, fly), ACD (fly) (Leidel and Gönczy, 2005; Wang et al., 2011; Brito et al., 2012) Microcephaly (Kumar et al., 2009), leukemia (Aplan et al., 1991) Coiled-coil domain, STIL/ANA2 (STAN) motif 
cep63 – – Spindle assembly, mitotic entry, genome maintenance, centrosome duplication (vertebrate) (Smith et al., 2009; Löffler et al., 2011) Microcephaly (Sir et al., 2011) Coiled-coil domains 

In many cases genes mutated in these pathologies control spindle orientation at the cellular level. ACD, asymmetric cell division.

a

The function of the genes has not been characterized.

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