Human Disease Model Report: cancer, multiple, NEK2-RAS-CSK(SRC)-related

General Information

Name

cancer, multiple, NEK2-RAS-CSK(SRC)-related

FlyBase ID

FBhh0001099

Disease Ontology Term

cancer

Parent Disease

OMIM

Overview

This report describes a Drosophila model of cancer that combines overexpression of the Dmel\Nek2 gene (orthologous to human NEK2) with a multi-component fly RAS-SRC cancer model. NEK2 encodes a protein kinase involved in the control of centrosome separation and bipolar spindle formation. Overexpression of human NEK2 is observed in multiple different cancers and is thought to contribute to dysregulation of the centrosome cycle and aneuploidy. Addressed in this model is the possibility that the initial impact of NEK2 overexpression occurs at an earlier stage, and is not confined to increasing chromosomal instability.

The human NEK2 gene has not been introduced into flies.

A previously developed Drosophila model of cancer uses an activated mutation in the fly RAS protein Ras85D (Ras85D^V12) combined with a loss-of-function mutation in the fly gene orthologous to the human CSK kinase gene, Dmel\Csk. Phosphorylation by CSK suppresses the activity of multiple genes, including the SRC proto-oncogene. See the human disease model report 'cancer, multiple, RAS-CSK(SRC)-related' (FBhh0000664). Assessed using somatic clones in larval eye discs, RAS(activated)-CSK mutant clones exhibit limited tissue overgrowth. Addition of Dmel\Nek2 overexpression results in increased overgrowth and appearance of secondary tumors in other parts of the body. The overgrowth phenotype is reduced and the metastatic phenotype completely suppressed by feeding of a drug known to inhibit the activity of the PI3K/AKT pathway.

[updated Jul. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: cancer, multiple, NEK2-RAS-CSK(SRC)-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

NEK2 encodes a protein kinase involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. The protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. [Gene Cards, NEK2; 2019.07.23]

(FlyBase Curators, 2013-)

External links

COSMIC gene: NEK2
Gene2Function (human gene): NEK2
Gene Cards: NEK2
MedlinePlus (gene): NEK2
KEGG Disease Pathways: Pathways in Cancer
MARRVEL (human gene): NEK2
NCBI (Entrez) gene: NEK2; NIMA related kinase 2

Disease synonyms

Related Diseases

Related human health report(s)

cancer, multiple, NEK2-RET-related

cancer, multiple, RAS-CSK(SRC)-related

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

NEK2; NIMA related kinase 2

D. melanogaster ortholog (based on DIOPT)

Dmel\Nek2

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila; additional more distantly related gene(s) in both species.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (3)

Dmel\Csk

Gene Snapshot

C-terminal Src kinase (Csk) encodes a cytoplasmic tyrosine kinase that acts as a tumor suppressor through Src pathway inibition as well as a mediator of the activity of the product of Egfr. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human CSK; moderate-scoring ortholog of human MATK (1 Drosophila to 2 human); Dmel\Csk shares 62% identity and 75% similarity with the human CSK gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Nek2

Gene Snapshot

Nek2 (Nek2) encodes a Ser/Thr kinase belonging to the NIMA family of kinases. It regulates centrosome disjunction, bipolar spindle formation, and kinetochore microtubule dynamics during mitosis. It also participates in meiosis by regulating chromatin condensation events. [Date last reviewed: 2018-10-11]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate- to high-scoring ortholog of human NEK2 (1 Drosophila to 1 human); additional more distantly related gene(s) in both species. Dmel\Nek2 shares 36% identity and 52% similarity with the human gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Dmel\Ras85D

Gene Snapshot

Ras oncogene at 85D (Ras85D) encodes a protein that acts downstream of several cell signals, most notably from Receptor Tyrosine Kinases, to regulate tissue growth and development. When abnormally activated it can direct developmental defects and tissue hyperplasia, mimicking aspects of human disease including Rasopathies and cancer, respectively. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human genes KRAS, HRAS, and NRAS (many to many; multiple paralogs and orthologs in both species). Dmel\Ras85D shares 78-86% identity and 86-92% similarity with KRAS, HRAS, and NRAS; for these three human genes, Ras85D is the highest-scoring ortholog in Drosophila.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (48 groups)

Csk

protein-protein

Interacting group

Assay

References

Csk - ASPP

anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot

(Langton et al., 2007)

Csk - Gli

proximity ligation assay, fluorescence microscopy

(Samarasekera and Auld, 2018)

Csk - Src42A

enzymatic study, western blot, autoradiography

(Pedraza et al., 2004, Stewart et al., 2003)

Csk - Src64B

enzymatic study, autoradiography

(Pedraza et al., 2004)

Csk - wts

enzymatic study, western blot

(Stewart et al., 2003)

Nek2

protein-protein

Interacting group

Assay

References

Nek2

two hybrid

(Galletta et al., 2016)

Nek2 - ana1

two hybrid

(Galletta et al., 2016)

Nek2 - ana2

two hybrid

(Galletta et al., 2016)

Nek2 - asl

two hybrid

(Galletta et al., 2016)

Nek2 - aurA

two hybrid

(Galletta et al., 2016)

Nek2 - Cep135

two hybrid

(Galletta et al., 2016)

Nek2 - cnn

two hybrid

(Galletta et al., 2016)

Nek2 - Cp110

two hybrid

(Galletta et al., 2016)

Nek2 - dsh

enzymatic study, autoradiography, anti tag coimmunoprecipitation, peptide massfingerprinting, western blot

(Schertel et al., 2013)

Nek2 - Lk6

two hybrid

(Galletta et al., 2016)

Nek2 - Plp

two hybrid

(Galletta et al., 2016)

Nek2 - Sas-4

two hybrid

(Galletta et al., 2016)

Nek2 - spd-2

two hybrid

(Galletta et al., 2016)

Nek2 - tacc

two hybrid

(Galletta et al., 2016)

Ras85D

protein-protein

Interacting group

Assay

References

Ras85D - alt

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Arc1

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - ave

pull down, anti tag western blot

(Maisonneuve et al., 2024)

Ras85D - CG31550

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - cindr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - cno

two hybrid, anti tag coimmunoprecipitation, autoradiography

(Boettner and Van Aelst, 2007, Carmena et al., 2006)

Ras85D - Droj2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - eIF3i

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - glo

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Gyc76C

anti tag coimmunoprecipitation, anti tag western blot

(Iwashita et al., 2020)

Ras85D - lark

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - mod(mdg4)

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Nf1

gtpase assay, autoradiography

(Walker et al., 2006)

Ras85D - Nop60B

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Pi3K92E

two hybrid, pull down, western blot

(Orme et al., 2006)

Ras85D - pico

two hybrid

(Lyulcheva et al., 2008)

Ras85D - Pyk

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - Raf

two hybrid, anti tag coimmunoprecipitation, anti tag western blot, pull down

(Yang and Terman, 2012, Ding et al., 2010, Mishra et al., 2005)

Ras85D - rau

pull down, anti tag western blot

(Sieglitz et al., 2013)

Ras85D - Rgl

two hybrid

(Mirey et al., 2003)

Ras85D - RpL6

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL15

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL21

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL23A

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpL24

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpS2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - RpS27

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

Ras85D - spri

anti tag coimmunoprecipitation, anti tag western blot

(Jekely et al., 2005)

Ras85D - Sumo

anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, covalent binding, western blot

(Nie et al., 2009)

Alleles Reported to Model Human Disease (Disease Ontology) (31 alleles)

Csk

Models Based on Experimental Evidence ( 2 )

Allele

Disease

Evidence

References

Csk^unspecified

model of cancer

CEA with Nek2^UAS.GFP

(Das et al., 2013)

Csk^Q156Stop

model of cancer

CEA with Ras85D^V12.UAS

(Hirabayashi et al., 2013)

model of carcinoma

CEA with Ras85D^V12.UAS

(Hirabayashi and Cagan, 2015)

CEA with InR^A1325D.UAS, Ras85D^V12.UAS

(Hirabayashi and Cagan, 2015)

Modifiers Based on Experimental Evidence ( 4 )

Allele

Disease

Interaction

References

Csk^unspecified

model of cancer

is exacerbated by Nek2^UAS.GFP

(Das et al., 2013)

Csk^j1D8

exacerbates multiple endocrine neoplasia type 2B

modeled by Ret^MEN2B.GMR

(Read et al., 2005)

Csk^Q156Stop

exacerbates cancer

modeled by Ras85D^V12.UAS

(Hirabayashi et al., 2013)

Csk^c04256

exacerbates viral infectious disease

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates infectious mononucleosis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates Epstein-Barr virus hepatitis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

Nek2

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

Nek2^UAS.GFP

model of cancer

CEA

(Das et al., 2013)

CEA with Ret^MEN2B.UAS

(Das et al., 2013)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

Nek2^UAS.GFP

exacerbates cancer

modeled by Csk^unspecified

(Das et al., 2013)

modeled by Ras85D^V12.UAS

(Das et al., 2013)

Ras85D

Models Based on Experimental Evidence ( 17 )

Allele

Disease

Evidence

References

Ras85D^HMS01294

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^G12V.UAS

model of cancer

CEA with RhoGEF2^RE.UAS

(Khoo et al., 2013)

CEA with Rok^CAT.UAS

(Khoo et al., 2013)

CEA with sqh^{E20E21.UAS.cCa}

(Khoo et al., 2013)

Ras85D^G13Q.UAS

model of cancer

CEA

(Xu et al., 2023)

CEA with Pten^HMS00044, Rbf^HMS03004

(Parkhitko et al., 2021)

Ras85D^N17.UAS

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^Q13.UAS

model of cancer

CEA

(Tamamouna et al., 2021)

Ras85D^V12.GMR

model of cancer

CEA

(Okada et al., 2023)

Ras85D^V12.S35.UAS

model of cardiomyopathy

CEA

(Yu et al., 2013)

model of carcinoma

CEC

(Karim and Rubin, 1998)

Ras85D^V12.UAS

model of carcinoma

CEA

(Martínez-Abarca Millán and Martín-Bermudo, 2023, Ito and Igaki, 2021, Kong et al., 2021, Rackley et al., 2021, Soler Beatty et al., 2021, Wei et al., 2021, Wu et al., 2021, Murcia et al., 2019, Zoranovic et al., 2018, Pérez et al., 2015, Igaki et al., 2006)

CEA with dlg1^GD4689

(Santabárbara-Ruiz and Léopold, 2021)

CEA with scrib⁶⁷³

(Amcheslavsky et al., 2018, Pérez et al., 2015)

CEC

(Rosen et al., 2019, Karim and Rubin, 1998)

CEC with scrib¹

(Rosen et al., 2019)

CEA with l(2)gl⁴

(Ding et al., 2022, Singh et al., 2022, Ito and Igaki, 2021, Wu et al., 2021, Mishra-Gorur et al., 2019, Zhang et al., 2019, Srivastava et al., 2007, Igaki et al., 2006)

CEA with Lkb1^4A4-2

(Rackley et al., 2021)

CEA with scrib¹

(Kong et al., 2021, Mishra-Gorur et al., 2019, Srivastava et al., 2007, Igaki et al., 2006, Uhlirova and Bohmann, 2006)

CEA with dlg1¹⁴

(Ito and Igaki, 2021, Igaki et al., 2006)

CEA with shg^k03401

(Igaki et al., 2006)

CEA with msn³²⁰⁸

(Kong et al., 2021)

CEA with sna^UAS.cAa

(Wu et al., 2021)

CEA with scrib^KK101128

(Murcia et al., 2019)

CEA with scrib^HMJ21977

(Snigdha et al., 2021)

CEA with Csk^Q156Stop

(Hirabayashi and Cagan, 2015)

CEA with Csk^Q156Stop, InR^A1325D.UAS

(Hirabayashi and Cagan, 2015)

model of cancer

CEA with fmt¹

(Ma et al., 2017)

CEA with PpV^Δ1

(Ma et al., 2017)

CEA with l(2)gl⁴

(Guo et al., 2020, Ma et al., 2017, Ma et al., 2013, Pagliarini and Xu, 2003)

CEA with PpV^GD7532

(Ma et al., 2017)

CEA

(Khalili et al., 2023, Martínez-Abarca Millán et al., 2023, Enomoto et al., 2021, Santabárbara-Ruiz and Léopold, 2021, Tamamouna et al., 2021, Ma et al., 2020, Jung et al., 2019, Rives-Quinto et al., 2017, Chabu and Xu, 2014, Hirabayashi et al., 2013, Ma et al., 2013)

CEA with scrib⁶⁷³

(Katheder et al., 2017, Pérez et al., 2017)

CEA with scrib¹

(Kakemura and Igaki, 2024, Cong et al., 2021, Hodgson et al., 2021, Katheder et al., 2017, Figueroa-Clarevega and Bilder, 2015, Külshammer et al., 2015, Stickel and Su, 2014, Willoughby et al., 2013, Wu et al., 2010, Pagliarini and Xu, 2003)

CEA with dlg1^GD4689

(Katheder et al., 2017, Muzzopappa et al., 2017, Figueroa-Clarevega and Bilder, 2015, Willecke et al., 2011)

CEA with scrib^j7B3

(Waghmare et al., 2024, Pagliarini and Xu, 2003)

CEA with Src64B^UAS.cCa

(Enomoto et al., 2021)

CEA with dlg1¹⁴

(Kakemura and Igaki, 2024, Pagliarini and Xu, 2003)

CEA with baz⁴

(Pagliarini and Xu, 2003)

CEA with sdt^XN

(Pagliarini and Xu, 2003)

CEA with Cdc42¹

(Pagliarini and Xu, 2003)

CEA with dor^C107

(Chi et al., 2010)

CEA with dor⁸

(Chi et al., 2010)

CEA with dor^D185

(Chi et al., 2010)

CEA with car^RNAi.UAS

(Chi et al., 2010)

CEA with Vps16A^RNAi.UAS.WIZ

(Chi et al., 2010)

CEA with upd1^UAS.cUa

(Wu et al., 2010)

CEA with upd2^UAS.cUa

(Wu et al., 2010)

CEA with upd1^UAS.cUa, upd2^UAS.cUa, upd3^UAS.cUa

(Wu et al., 2010)

CEA with l(2)gl^unspecified

(Xu et al., 2023, Wu et al., 2010)

CEA with pnut^GD1512

(Gerlach et al., 2018)

CEC with l(2)gl⁴

(Ma et al., 2014)

CEA with Hsap\S100A4^wt.UAS

(Ismail et al., 2017)

CEA with scrib^RNAi.UAS.cUa

(Hodgson et al., 2021)

CEA with Csk^Q156Stop

(Hirabayashi et al., 2013)

CEA with scrib^KK101128

(Muzzopappa et al., 2017)

CEA with mud^JF02911

(Muzzopappa et al., 2017)

CEA with mud^HMS01458

(Muzzopappa et al., 2017)

CEA with N^RNAi.P.UAS

(Tamamouna et al., 2021)

CEA with N^DN.UAS.cUa

(Xu et al., 2023)

CEA with emei^GD3587

(Ma et al., 2020)

CEA with Rox8^GD11645

(Guo et al., 2020)

CEA with BacA\p35^UAS.cHa

(Khalili et al., 2023)

CEA with dlg1^RNAi.UAS.cUa

(Bakopoulos et al., 2023)

model of intestinal cancer

CEA

(Cabrera et al., 2023, Nászai et al., 2021)

CEA with Apc2^N175K, Apc^Q8

(Martorell et al., 2014, Martorell et al., 2014)

model of colorectal cancer

CEA

(Bangi et al., 2012)

model of leukemia

CEA

(Arefin et al., 2017)

CEA with l(2)gl^KK100777

(Arefin et al., 2017)

CEA with scrib^KK101128

(Arefin et al., 2017)

model of benign neoplasm

CEA with Alg9^c02021

(de Vreede et al., 2018)

DOES NOT model cancer

CEA with Hsap\S100A4^Δ2.UAS

(Ismail et al., 2017)

model of heart disease

CEA

(Karekar et al., 2021)

model of prostate cancer

CEA

(Rambur et al., 2020)

model of high grade glioma

CEA

(Kumar et al., 2024)

CEA with Pten^RNAi.UAS.cUa

(Cheng et al., 2016)

model of kidney cancer

CEA

(Zeng et al., 2010)

model of ovarian carcinoma

CEA with aPKC^ΔN.UAS

(Hsi et al., 2023)

model of hypertrophic cardiomyopathy

CEA

(Petersen et al., 2022)

Ras85D^V12.ey

model of carcinoma

CEC

(Karim and Rubin, 1998)

Ras85D^V12.cUa.UAS

model of cervical cancer

CEA

(Padash Barmchi et al., 2016)

CEA with Hsap\UBE3A^UAS.cRa, HPV18\E6^UAS.Tag:MYC

(Padash Barmchi et al., 2016)

CEA with Hsap\UBE3A^UAS.cRa, HPV18\E6^{V158A.UAS.Tag:MYC}

(Padash Barmchi et al., 2016)

model of cancer

CEA with l(2)gl⁴

(Fangninou et al., 2023, Liu et al., 2022, Yang et al., 2022)

CEA with Ptp61F^Δ

(Liu et al., 2022)

CEA with Syx7³¹¹⁹

(Liu et al., 2022)

CEA with Rabex-5³⁶⁷²

(Liu et al., 2022)

CEA with Vps36²⁵⁸⁶

(Liu et al., 2022)

CEA with TSG101^P26

(Liu et al., 2022)

CEA with N^DN.UAS.cUa

(Lee et al., 2021)

CEA with dlg1^RNAi.UAS.cUa

(Lodge et al., 2021)

CEA

(Yang et al., 2022, Dong et al., 2021, Yeom et al., 2021, Dunn et al., 2018, Vicente et al., 2018)

CEA with scrib¹

(Yang et al., 2022, Khezri et al., 2021)

CEA with baz⁴

(Yang et al., 2022)

CEA with fmt¹

(Yang et al., 2022)

CEA with dlg1^GD4689

(Yang et al., 2022)

CEA with Ptip³⁸⁰⁴

(Dong et al., 2021)

model of colorectal cancer

CEA

(Zipper et al., 2022)

CEA with Pten^sgRNA.UAS

(Zipper et al., 2022)

CEA with Med^sgRNA.UAS

(Zipper et al., 2022)

CEA with cic^sgRNA.UAS

(Zipper et al., 2022)

CEA with Apc2^sgRNA.UAS

(Zipper et al., 2022)

CEA with Apc^sgRNA.UAS

(Zipper et al., 2022)

CEA with p53^sgRNA.UAS

(Zipper et al., 2022)

CEA with p53^RNAi.UAS.cUa, Pten^GD13500, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with p53^RNAi.UAS.cUa, Pten^GD13500, Apc^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with p53^RNAi.UAS.cUa, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

CEA with Pten^GD13500, Apc^RNAi.UAS.cUa, Med^RNAi.UAS.cUa

(Bangi et al., 2016)

model of cardiomyopathy

CEA

(Yu et al., 2013)

model of adenocarcinoma

CEA with l(2)gl^GD4047

(Casas-Tintó et al., 2016)

CEA with l(2)gl^GD4047, wupA^JF02172

(Casas-Tintó et al., 2016)

model of carcinoma

CEA

(Guo et al., 2024, Hogan et al., 2009)

CEA with l(2)gl⁴

(Sun et al., 2019)

CEA with dlg1^HMS00172

(Toggweiler et al., 2016)

model of intestinal cancer

CEA with Apc^Q8

(Campbell et al., 2019)

CEA

(Kim et al., 2022, Dai et al., 2020, Singh et al., 2016)

CEA with Apc2^N175K, Apc^Q8

(Parisi et al., 2023)

CEA with Apc^GD1333, p53^GD4483

(Quintero and Bangi, 2023)

CEA with Apc^GD1333, Pten^RNAi.UAS.cUa, p53^GD4483

(Quintero and Bangi, 2023)

CEA with Apc^GD1333, Med^GD1483, p53^GD4483

(Quintero and Bangi, 2023)

model of high grade glioma

CEA with Pten^{RNAi.Exel.UAS}

(Gangwani et al., 2020)

CEA

(Liu et al., 2021)

model of brain cancer

CEA with dlg1^GD4689

(Manzanero-Ortiz et al., 2021)

CEA with l(2)gl^KK100777

(Manzanero-Ortiz et al., 2021)

CEA with wts^KK101055

(Manzanero-Ortiz et al., 2021)

CEA with scrib⁶⁷³

(Manzanero-Ortiz et al., 2021)

Ras85D^V152G.UASp

model of Noonan syndrome 3

CEA

(Cattaneo et al., 2020)

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

CEA

(Washington et al., 2020)

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

CEA

(Washington et al., 2020)

Ras85D^V12.QUAS.cHa

model of cancer

CEA with scrib¹

(Hodgson et al., 2021)

Ras85D^V12.QUAS.cLa

model of cancer

CEA with scrib^{QUAS.HMS01490}

(Bakopoulos et al., 2023, Lodge et al., 2021)

Ras85D^G12D.UAS.cSa

model of pancreatic ductal adenocarcinoma

CEA with CycE^{UAS.Tag:HA.Medsh}, Med^{RNAi.UAS.CycE-HA}, p53^{RNAi.UAS.RasG12D}

(Sekiya et al., 2023)

Ras85D^{G12D.UAS.p53sh}

model of pancreatic ductal adenocarcinoma

CEA with CycE^{UAS.Tag:HA.Medsh}, Med^{RNAi.UAS.CycE-HA}, p53^{RNAi.UAS.RasG12D}

(Sekiya et al., 2023)

Modifiers Based on Experimental Evidence ( 19 )

Allele

Disease

Interaction

References

Ras85D^HMS01294

ameliorates hematologic cancer

modeled by mxc¹

(Kurihara et al., 2020)

Ras85D^ΔC40B

ameliorates multiple endocrine neoplasia type 2B

modeled by Ret^MEN2B.GMR

(Read et al., 2005)

Ras85D⁰⁶⁶⁷⁷

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82Q.UAS

(Park et al., 2013)

ameliorates multiple endocrine neoplasia type 2B

modeled by Ret^MEN2B.GMR

(Read et al., 2005)

ameliorates multiple endocrine neoplasia type 2A

modeled by Ret^MEN2A.GMR

(Read et al., 2005)

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

Ras85D^G13Q.UAS

model of cancer

is exacerbated by ITP^UAS.F

(Xu et al., 2023)

Ras85D^N17.UAS

ameliorates brain glioma

modeled by btl::Egfr^λ.UAS, Pi3K92E^{UAS.Tag:MYC,Tag:PM(hKRAS)}

(Read et al., 2009)

Ras85D^Q13.UAS

model of cancer

is ameliorated by Cat^UAS.cAa

(Tamamouna et al., 2021)

is ameliorated by Sod1^UAS.cAa

(Tamamouna et al., 2021)

is ameliorated by btl^DN.UAS

(Tamamouna et al., 2021)

Ras85D^V12.GMR

model of cancer

is ameliorated by InR^GL00139

(Okada et al., 2023)

is ameliorated by InR^JF01183

(Okada et al., 2023)

is ameliorated by InR^JF01482

(Okada et al., 2023)

is ameliorated by InR^K1409A.UAS

(Okada et al., 2023)

is ameliorated by NetB^Δ

(Okada et al., 2023)

is ameliorated by NetB^KK103672

(Okada et al., 2023)

is ameliorated by NetB^VSH330183

(Okada et al., 2023)

is ameliorated by unc-5^HMS01099

(Okada et al., 2023)

is ameliorated by unc-5^KK102074

(Okada et al., 2023)

is ameliorated by unc-5^MI04273

(Okada et al., 2023)

Ras85D^V12.UAS

model of carcinoma

is exacerbated by mys^RNAi.UAS.cUa

(Martínez-Abarca Millán and Martín-Bermudo, 2023)

is exacerbated by mys^RNAi.UAS.cUa

(Martínez-Abarca Millán and Martín-Bermudo, 2023)

is ameliorated by Atg1^GD7149

(Pérez et al., 2015)

is ameliorated by HAdV-C\E4orf4^UAS.cPa

(Rosen et al., 2019)

is ameliorated by HAdV-C\E4orf4^UAS.cPb

(Rosen et al., 2019)

is exacerbated by dap^HMS01610

(Ito and Igaki, 2021)

is exacerbated by dap^HMS05362

(Ito and Igaki, 2021)

is ameliorated by pnt^P1.UAS

(Ito and Igaki, 2021)

is exacerbated by hep^Act.UAS

(Uhlirova and Bohmann, 2006)

is exacerbated by egr^UAS.cIa

(Igaki et al., 2006)

is exacerbated by ZnT86D^KK101698

(Wei et al., 2021)

is exacerbated by msn¹⁷²

(Kong et al., 2021)

is exacerbated by msn³²⁰⁸

(Kong et al., 2021)

is exacerbated by l(2)gl⁴

(Wu et al., 2021)

is exacerbated by sna^UAS.cAa

(Wu et al., 2021)

is ameliorated by rl^GD4697

(Murcia et al., 2019)

is exacerbated by Tsp29Fb^GD1018

(Zoranovic et al., 2018)

is ameliorated by Tsp29Fb^UAS.Tag:HA

(Zoranovic et al., 2018)

is ameliorated by Raf^DN.UAS

(Zoranovic et al., 2018)

is ameliorated by Hsap\CDKN1A^UAS.cHa

(Karim and Rubin, 1998)

is ameliorated by Raf^XS-2541

(Karim and Rubin, 1998)

is exacerbated by rl^Sem

(Karim and Rubin, 1998)

is exacerbated by Egfrap^ΔSH2

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^HMJ23378

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^LS

(Soler Beatty et al., 2021)

is exacerbated by Egfrap^L

(Soler Beatty et al., 2021)

is exacerbated by PVRAP^HMJ23233

(Soler Beatty et al., 2021)

model of cancer

is ameliorated by Sec15^KK101708

(Chabu and Xu, 2014)

is ameliorated by Sec6^GD11616

(Chabu and Xu, 2014)

is ameliorated by Sec8^KK101531

(Chabu and Xu, 2014)

is ameliorated by Sec15¹

(Chabu and Xu, 2014)

is ameliorated by Sec15^GD12109

(Chabu and Xu, 2014)

is ameliorated by Src64B^GD12263

(Ma et al., 2013)

is ameliorated by Dronc^NIG.8091R

(Waghmare et al., 2024)

is ameliorated by bsk^DN.UAS

(Waghmare et al., 2024)

is ameliorated by sgg^S9A.UAS

(Waghmare et al., 2024)

is ameliorated by yki^RNAi.C.UAS

(Waghmare et al., 2024)

is ameliorated by yki^RNAi.N.UAS

(Waghmare et al., 2024)

is ameliorated by chinmo¹

(Enomoto et al., 2021)

is exacerbated by PVRAP¹

(Martínez-Abarca Millán et al., 2023)

is exacerbated by PVRAP^HMJ23233

(Martínez-Abarca Millán et al., 2023)

is exacerbated by by^33c

(Martínez-Abarca Millán et al., 2023)

is exacerbated by by^VSH330366

(Martínez-Abarca Millán et al., 2023)

is exacerbated by Csk^Q156Stop

(Hirabayashi et al., 2013)

is exacerbated by emei¹

(Ma et al., 2020)

is exacerbated by emei²

(Ma et al., 2020)

is exacerbated by emei³

(Ma et al., 2020)

is ameliorated by Arc1^esm18

(Khalili et al., 2023)

is exacerbated by Nek2^UAS.GFP

(Das et al., 2013)

model of intestinal cancer

is ameliorated by shg^HMS00693

(Cabrera et al., 2023)

is ameliorated by shg^JF02769

(Cabrera et al., 2023)

is ameliorated by Cortactin^HMS00658

(Cabrera et al., 2023)

is ameliorated by Cortactin^KK108594

(Cabrera et al., 2023)

exacerbates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

exacerbates gastrointestinal system cancer

modeled by Apc2^g10, Apc^Q8

(Wang et al., 2013)

model of colorectal cancer

is ameliorated by Jra^NIG.2275R

(Bangi et al., 2012)

is ameliorated by bsk^DN.UAS

(Bangi et al., 2012)

is ameliorated by bsk^HMS00777

(Bangi et al., 2012)

is exacerbated by hep^Act.UAS

(Bangi et al., 2012)

is exacerbated by imd^UAS.cGa

(Bangi et al., 2012)

is ameliorated by Timp^UAS.cPa

(Bangi et al., 2012)

ameliorates cancer

modeled by dlg1^A40.2

(Parisi et al., 2014)

exacerbates carcinoma

modeled by scrib¹

(Brumby and Richardson, 2003)

modeled by arm^UAS.Exel

(Zhang et al., 2019)

model of prostate cancer

is ameliorated by Egfr^GD1654

(Rambur et al., 2020)

is ameliorated by Pi3K92E^HMC05152

(Rambur et al., 2020)

is ameliorated by mTor^GL00156

(Rambur et al., 2020)

is ameliorated by rl^HMS00173

(Rambur et al., 2020)

is ameliorated by spi^HMS01120

(Rambur et al., 2020)

exacerbates intestinal cancer

modeled by Rab11^KK108297

(Nie et al., 2019)

exacerbates cancer

modeled by Hipk^UAS.Tag:HA

(Blaquiere et al., 2018)

model of kidney cancer

is ameliorated by Pka-C1^B3

(Zeng et al., 2010)

is ameliorated by mTor^ΔP

(Zeng et al., 2010)

exacerbates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.UAS.cUa}

(Cheng et al., 2021)

exacerbates hematologic cancer

modeled by mxc¹

(Kurihara et al., 2020)

Ras85D^V12.ey

model of carcinoma

is ameliorated by Raf^XS-2541

(Karim and Rubin, 1998)

Ras85D^e1B

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

exacerbates viral infectious disease

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates infectious mononucleosis

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

exacerbates Epstein-Barr virus hepatitis

modeled by EBV\BZLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates gastrointestinal system cancer

modeled by Apc2^g10, Apc^Q8

(Wang et al., 2013)

exacerbates tuberous sclerosis

modeled by Tsc1^UAS.cTa, gig^UAS.cTa

(Tapon et al., 2001)

ameliorates cancer

modeled by Alk^UAS.cLa

(Wolfstetter et al., 2020)

Ras85D^e2F

ameliorates alveolar rhabdomyosarcoma

modeled by Hsap\FOXO1::Hsap\PAX7^UAS.cGa

(Galindo et al., 2006)

Ras85D^unspecified

ameliorates neurofibromatosis

modeled by Nf1^E2

(Walker et al., 2006)

Ras85D^V12.cUa.UAS

model of cancer

is exacerbated by Ptp61F^Δ

(Liu et al., 2022)

is exacerbated by ex^e1

(Liu et al., 2022)

is exacerbated by Not3^KK102144

(Vicente et al., 2018)

is exacerbated by M6^W186stop

(Dunn et al., 2018)

is ameliorated by Ptip³⁸⁰⁴

(Dong et al., 2021)

is exacerbated by p53^UAS.cUa

(Dong et al., 2021)

is ameliorated by Ilp8^MI00727

(Yeom et al., 2021)

model of intestinal cancer

is ameliorated by Cortactin^HMS00658

(Kim et al., 2022)

is exacerbated by Clbn^1Q

(Dai et al., 2020)

model of high grade glioma

is ameliorated by Nmnat^RNAi.UAS.cUa

(Liu et al., 2021)

is ameliorated by Dcp-1^RNAi.UAS.cUa

(Liu et al., 2021)

is exacerbated by Nmnat^UAS.PC

(Liu et al., 2021)

exacerbates carcinoma

modeled by Nkap^GD11807

(Guo et al., 2024)

model of carcinoma

is exacerbated by Nkap^GD11807

(Guo et al., 2024)

Ras85D^GD12553

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

modeled by Src64B^UAS.cCa

(Cordero et al., 2014)

ameliorates neurofibromatosis

modeled by Nf1^JF01866

(Georganta et al., 2021)

Ras85D^KK108029

ameliorates colorectal cancer

modeled by Src42A^CA.UAS

(Cordero et al., 2014)

modeled by Src64B^UAS.cCa

(Cordero et al., 2014)

ameliorates intestinal cancer

modeled by Egfr^UAS.cBa

(Nászai et al., 2021)

Ras85D^JF02478

ameliorates colorectal cancer

modeled by SH3PX1^HMJ21552

(Zhang et al., 2019)

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

is exacerbated by Egfr^2.UAS

(Washington et al., 2020)

is ameliorated by Rabex-5^{DPYT.UAS.Tag:MYC}

(Washington et al., 2020)

is exacerbated by hop^JF01267

(Washington et al., 2020)

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

model of cancer

is exacerbated by Egfr^2.UAS

(Washington et al., 2020)

is ameliorated by Rabex-5^{DPYT.UAS.Tag:MYC}

(Washington et al., 2020)

Ras85D^DN.UAS.cUa

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.UAS.cUa}

(Cheng et al., 2021)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

Ras85D^{G12V.UAS.Tag:FLAG,Tag:polyHis}

P{UAS-FH-Ras85D.G12V}

Ras85D^{Y4F.G12V.UAS.Tag:FLAG,Tag:polyHis}

P{UAS-FH-Ras85D.Y4F.G12V}

Ras85D^V12.QUAS.cHa

P{QUAS-Ras85D.V12.H}

Ras85D^V12.QUAS.cLa

PBac{QUAS-Ras85D.V12.L}

Ras85D^{G12D.UAS.p53sh}

P{UAS-Ras85D(G12D).UAS-p53(shRNA)}

Ras85D^V12.UAS

P{UAS-Ras85D.V12}

w¹¹¹⁸; P{UAS-Ras85D.V12}TL1

Ras85D^N17.UAS

P{UAS-Ras85D.N17}

P{UAS-Ras85D.N17}TL1, w¹¹¹⁸

P{UAS-Ras85D.V12.S35}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

Nek2^GD9324

P{GD9324}

w¹¹¹⁸; P{GD9324}v40052

y¹ v¹; P{TRiP.HM05088}attP2/TM3, Sb¹

Nek2^GL00235

P{TRiP.GL00235}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00235}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS04457}attP40

Nek2^HMC05100

P{TRiP.HMC05100}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC05100}attP2

Ras85D^{TH201501177.S}

w¹¹¹⁸; P{GD12553}v28129

y¹ v¹; P{TRiP.JF02478}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01294}attP2

Ras85D^GL00336

P{TRiP.GL00336}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00336}attP2/TM3, Sb¹

Csk^GD15975

P{GD15975}

w¹¹¹⁸; P{GD15975}v48282

Csk^GD9345

P{GD9345}

w¹¹¹⁸; P{GD9345}v32877

y¹ sc^* v¹ sev²¹; P{TRiP.GL00044}attP2

Csk^HMS02277

P{TRiP.HMS02277}

y¹ v¹; P{TRiP.HMS02277}attP40/CyO

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

Ras85D⁰⁶⁶⁷⁷

P-element activity

P{PZ}Ras85D⁰⁶⁶⁷⁷ ry⁵⁰⁶/TM3, ry^RK Sb¹ Ser¹

Ras85D^e2F

sev¹⁴; Ras85D^e2F/TM3, Sb¹

Ras85D^e1B

ethyl methanesulfonate

sev¹⁴; Ras85D^e1B/TM3, Sb¹

Ras85D^unspecified

Ras85D^ΔC40B

loss of function allele

Ras85D^x7b

loss of function allele

P-element activity

Ras85D^Δ17b

amorphic allele - genetic evidence

Csk^S030003

loss of function allele

Delta2-3 transposase

Csk^S017909

loss of function allele

Delta2-3 transposase

Csk^j1D8

loss of function allele

P-element activity

y^d2 w¹¹¹⁸ P{ey-FLP.N}2 P{5xglBS-lacZ.38-1}TPN1; P{neoFRT}82B P{3'lacW}j1D8/TM6B, P{Car20y}TPN1, Tb¹

Csk^c04256

piggyBac activity

w¹¹¹⁸; PBac{PB}Csk^c04256

Csk^Q156Stop

ethyl methanesulfonate

Csk^unspecified

References (4)

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