Human Disease Model Report: alcohol, response to, insulin signaling pathway

General Information

Name

alcohol, response to, insulin signaling pathway

FlyBase ID

FBhh0000692

Disease Ontology Term

alcohol use disorder

Parent Disease

alcohol use disorder, susceptibility to (fly models overview)

OMIM

Overview

This report includes general characterization of the fly response to alcohol using Drosophila genes within the insulin signaling pathway; links to additional reports for specific genes are provided.

Genetic manipulations in Drosophila that impair the function of insulin-producing cells result in increased sensitivity to ethanol sedation.

Animals heterozygous for loss-of-function mutations in InR (insulin-like receptor; see FBhh0000693) or chico (an insulin receptor substrate) exhibit increased sensitivity to ethanol sedation.

Pan-neuronal expression of constitutively active mutations of InR or S6k (ribosomal S6 kinase) result in reduced sensitivity to ethanol-induced sedation. An acute, sedating dose of ethanol causes loss of S6k activity.

Animals homozygous for loss-of-function mutations of Arf51F (a small GTPase that regulates membrane trafficking) are extremely sensitive to ethanol sedation (see FBhh0000690). It is postulated that the Arf51F protein is a downstream mediator of InR signaling in this response, and that S6k acts downstream of Arf51F.

[updated Jan. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)

Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

(FlyBase Curators, 2013-)

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

(FlyBase Curators, 2013-)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

(FlyBase Curators, 2013-)

Alcoholism is a multifactorial, genetically influenced disorder. [from MIM:103780; 2017.12.19]

(OMIM, 2013-)

Specific Disease Summary: alcohol, response to, insulin signaling pathway

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

KEGG Disease Pathways: insulin signaling pathway

Disease synonyms

AUD susceptibility, insulin signaling pathway

Search term: alcohol use disorder

Related Diseases

Related human health report(s)

alcohol, response to, ARF6-related

alcohol, response to, INSR-related

alcohol, response to, RPS6KB-related

alcohol use disorder, susceptibility to (fly models overview)

Related Specific Diseases

OMIM phenotypic series

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

Ortholog Information

Human gene(s) in FlyBase

Other mammalian ortholog(s) used

D. melanogaster Gene Information (4)

Dmel\InR

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

INS-C
RTK

Comments on ortholog(s)

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\chico

Gene Snapshot

chico (chico) encodes a substrate of the product of InR. As a key component of the Insulin pathway, the chico product plays an essential role in the control of cell size and growth. [Date last reviewed: 2019-06-13]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

INS-C

Comments on ortholog(s)

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\S6k

Gene Snapshot

Ribosomal protein S6 kinase (S6k) encodes an important component of the target of rapamycin pathway. It is involved in the control of synapse development, autophagy and cell size. [Date last reviewed: 2019-09-12]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

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\Arf6

Gene Snapshot

ADP ribosylation factor 6 (Arf6) belongs to the Arf family, which are members of the Ras superfamily of small GTPases. Arf proteins are involved in the regulation of vesicular trafficking mediating processes such as cargo-sorting, vesicle assembly and membrane fusion. Arf proteins regulate cell shape changes and cell movements in multiple organs. [Date last reviewed: 2019-03-07]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

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 (143 groups)

InR

protein-protein

Interacting group

Assay

References

InR

molecular sieving, molecular weight estimation by staining, enzymatic study

(Cai et al., 2025, Krishnan et al., 2024)

InR - 14-3-3ζ

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - Cdc37

bimolecular fluorescence complementation, fluorescence microscopy, proximity ligation assay

(Huang and Wang, 2018)

InR - CG10916

anti tag coimmunoprecipitation, peptide massfingerprinting, anti tag western blot

(Friedman et al., 2011, Friedman et al., 2011)

InR - CG30122

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - cher

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - chico

fluorescent resonance energy transfer, anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Almudi et al., 2013, Friedman et al., 2011, Glatter et al., 2011, Pflieger et al., 2008, Kulansky Poltilove et al., 2000)

InR - CNBP

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - ctp

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Vinayagam et al., 2016, Friedman et al., 2011)

InR - dock

anti tag coimmunoprecipitation, western blot, two hybrid, anti bait coimmunoprecipitation

(Li et al., 2014, Wu et al., 2011, Song et al., 2003)

InR - Droj2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - Elp6

anti bait coimmunoprecipitation, peptide massfingerprinting

(Bolukbasi et al., 2012)

InR - glo

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - Gp93

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - Hrb98DE

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - Hsp83

bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, peptide massfingerprinting, proximity ligation assay

(Huang and Wang, 2018, Friedman et al., 2011)

InR - Ilp1

electron microscopy

(Cai et al., 2025)

InR - Ilp2

electron microscopy

(Cai et al., 2025)

InR - Ilp5

electron microscopy, competition binding

(Cai et al., 2025, Viola et al., 2023, Sajid et al., 2011)

InR - Ilp8

pull down, Identification by mass spectrometry

(Garelli et al., 2015)

InR - Lar

surface plasmon resonance, enzymatic study, anti bait coimmunoprecipitation, western blot

(Kaur et al., 2019, Madan et al., 2011)

InR - Lnk

fluorescent resonance energy transfer

(Almudi et al., 2013)

InR - M7BP

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - Pi3K21B

anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting

(Vinayagam et al., 2016, Friedman et al., 2011, Glatter et al., 2011)

InR - Pi3K92E

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Vinayagam et al., 2016, Friedman et al., 2011)

InR - Ptp61F

pull down, western blot

(Wu et al., 2011)

InR - Ptp99A

surface plasmon resonance, enzymatic study

(Madan et al., 2011)

InR - RpL6

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - RpL10

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - RpL15

anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting

(Vinayagam et al., 2016, Friedman et al., 2011)

InR - RpL30

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - RpL36

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - RpLP1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - RpS7

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - RpS13

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - RpS23

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - RpS28b

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - SF2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

InR - sta

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

InR - STUB1

enzymatic study, western blot

(Tawo et al., 2017)

InR - UQCR-C2

anti tag coimmunoprecipitation, peptide massfingerprinting

(Friedman et al., 2011)

RNA-protein

Interacting group

Assay

References

InR - DENR

anti bait coimmunoprecipitation, quantitative reverse transcription pcr

(Schleich et al., 2014)

InR - Imp

anti tag coimmunoprecipitation, quantitative reverse transcription pcr

(Sreejith et al., 2022)

InR - lin-28

anti tag coimmunoprecipitation, primer specific pcr, quantitative reverse transcription pcr

(Sreejith et al., 2022, Chen et al., 2015)

RNA-RNA

Interacting group

Assay

References

InR - mir-276a

luminiscence technology

(Lee et al., 2023)

chico

protein-protein

Interacting group

Assay

References

chico - 14-3-3ε

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011, Pflieger et al., 2008)

chico - 14-3-3ζ

anti tag coimmunoprecipitation, Identification by mass spectrometry, peptide massfingerprinting

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011, Pflieger et al., 2008)

chico - CG7668

experimental knowledge based

(Guruharsha et al., 2011)

chico - cmb

experimental knowledge based

(Guruharsha et al., 2011)

chico - dos

experimental knowledge based

(Guruharsha et al., 2011)

chico - Flo1

experimental knowledge based

(Guruharsha et al., 2011)

chico - Flo2

experimental knowledge based

(Guruharsha et al., 2011)

chico - Hsc70-3

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - InR

fluorescent resonance energy transfer, anti tag coimmunoprecipitation, peptide massfingerprinting, two hybrid, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Almudi et al., 2013, Friedman et al., 2011, Glatter et al., 2011, Pflieger et al., 2008, Kulansky Poltilove et al., 2000)

chico - Ist1

experimental knowledge based

(Guruharsha et al., 2011)

chico - Lnk

anti tag coimmunoprecipitation, western blot, fluorescent resonance energy transfer

(Almudi et al., 2013, Song et al., 2010)

chico - mib2

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Glatter et al., 2011, Guruharsha et al., 2011)

chico - Pgam5

anti tag coimmunoprecipitation, peptide massfingerprinting

(Glatter et al., 2011)

chico - Pi3K21B

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016, Glatter et al., 2011)

chico - Pi3K92E

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Breitkopf et al., 2016, Vinayagam et al., 2016)

chico - Pp2A-29B

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RanBPM

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL4

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL7A

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL14

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL17

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL18

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpL30

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpS15Aa

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - RpS26

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - tws

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

chico - Vps4

experimental knowledge based

(Guruharsha et al., 2011)

chico - Vps60

experimental knowledge based

(Guruharsha et al., 2011)

S6k

protein-protein

Interacting group

Assay

References

S6k - 14-3-3ζ

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Act5C

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Aldh

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - αCOP

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - ana2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Arc42

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Arf1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - AsnRS

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - β'COP

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - βTub56D

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - βTub60D

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - βTub97EF

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - bif

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - cathD

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - CCT1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - CCT4

anti bait coimmunoprecipitation, western blot, pull down

(Kim and Choi, 2019)

S6k - CCT5

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Cdc37

anti tag coimmunoprecipitation, peptide massfingerprinting, Identification by mass spectrometry

(Vinayagam et al., 2016, Glatter et al., 2011)

S6k - CG1316

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - CG4972

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - CG5504

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Chc

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Chd64

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - cpa

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Dp1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Dref

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Droj2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - eEF1α1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - eIF4A

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - fax

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Fib

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Gale

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - galla2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Gtpbp1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Hel25E

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - His2B

enzymatic study, autoradiography

(Montagne et al., 2010)

S6k - Hsc70-3

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Ipo9

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Kap-α3

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Kcmf1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - kuk

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - l(1)G0320

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Ldh

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - levy

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - lic

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Mcad

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Mcm7

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Mec2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - msn

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - mt:CoII

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Nfs1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Pcb

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Pef

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Pp1-87B

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Pyk

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Rab27

proximity ligation assay, fluorescence microscopy, anti tag coimmunoprecipitation, western blot

(Lien et al., 2020)

S6k - raptor

anti tag coimmunoprecipitation, peptide massfingerprinting

(Glatter et al., 2011)

S6k - RPA1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - RpS5a

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - Scsα1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - ScsβA

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - sqd

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - sqh

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - SsRβ

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - tws

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - UQCR-C2

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

S6k - wrd

anti tag coimmunoprecipitation, anti tag western blot

(Hahn et al., 2010)

Arf6

protein-protein

Interacting group

Assay

References

Arf6 - Arfip

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Chang et al., 2013, Peru Y Colón de Portugal et al., 2012)

Arf6 - hh

anti bait coimmunoprecipitation, western blot

(Chabu et al., 2017)

Arf6 - Iqsec

enzymatic study, autoradiography

(Chen et al., 2003)

Arf6 - pav

two hybrid, pull down, western blot

(Dyer et al., 2007)

Alleles Reported to Model Human Disease (Disease Ontology) (44 alleles)

InR

Models Based on Experimental Evidence ( 13 )

Allele

Disease

Evidence

References

InR⁰⁵⁵⁴⁵

model of diabetes mellitus

CEA

(Banzai and Nishimura, 2023)

CEC with InR^Y902C

(Banzai and Nishimura, 2023)

model of type 2 diabetes mellitus

CEA with InR^3T5

(Murillo-Maldonado et al., 2011)

InR^93Dj-4

model of diabetic neuropathy

CEA with InR^E19

(Wang et al., 2023)

InR^A1325D.UAS

model of glucose metabolism disease

CEA

(Musselman et al., 2018)

model of carcinoma

CEA with Csk^Q156Stop, Ras85D^V12.UAS

(Hirabayashi and Cagan, 2015)

InR^E19

model of diabetic neuropathy

CEA with InR^93Dj-4

(Wang et al., 2023)

model of type 2 diabetes mellitus

CEA with InR^3T5

(Murillo-Maldonado et al., 2011)

model of glucose metabolism disease

CEA with InR^3T5

(Álvarez-Rendón and Riesgo-Escovar, 2023, Álvarez-Rendón and Riesgo-Escovar, 2020)

InR^K1409A.UAS

model of sleep disorder

CEA

(Metaxakis et al., 2014)

model of type 2 diabetes mellitus

CEA

(Cao et al., 2022)

InR^UAS.Exel

model of cancer

CEA

(Khaket et al., 2024)

InR^GD104

model of glucose metabolism disease

CEA

(Musselman et al., 2018)

InR^JF01482

model of diabetic neuropathy

CEA

(Wang et al., 2023)

InR^3T5

model of type 2 diabetes mellitus

CEA with InR^E19

(Murillo-Maldonado et al., 2011)

CEA with InR⁰⁵⁵⁴⁵

(Murillo-Maldonado et al., 2011)

model of glucose metabolism disease

CEA with InR^E19

(Álvarez-Rendón and Riesgo-Escovar, 2023, Álvarez-Rendón and Riesgo-Escovar, 2020)

InR^UAS.cUa

model of cervical cancer

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

(Padash Barmchi et al., 2016)

model of high grade glioma

CEA

(Witte et al., 2009)

InR^CA.UAS.cUa

model of alcohol dependence

CEA

(Acevedo et al., 2015)

InR^{lexAop.HMS03166}

model of type 2 diabetes mellitus

CEA

(Tsao et al., 2023)

InR^Y902C

model of diabetes mellitus

CEA

(Banzai and Nishimura, 2023)

CEC with InR⁰⁵⁵⁴⁵

(Banzai and Nishimura, 2023)

Modifiers Based on Experimental Evidence ( 16 )

Allele

Disease

Interaction

References

InR⁰⁵⁵⁴⁵

ameliorates fragile X syndrome

modeled by Fmr1³

(Monyak et al., 2017)

InR³³⁹

ameliorates germ cell cancer

modeled by bam^Δ86

(Zhao et al., 2018)

InR^A1325D.UAS

exacerbates central nervous system cancer

modeled by N^ΔE.UAS

(Voutyraki et al., 2023)

ameliorates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-GR^PO-100.UAS

(Atilano et al., 2021)

modeled by Zzzz\poly-GA^400.UAS

(Morón-Oset et al., 2023)

exacerbates cancer

modeled by Csk^Q156Stop, Ras85D^V12.UAS

(Hirabayashi et al., 2013)

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Pragati and Sarkar, 2024)

ameliorates cancer

modeled by Ras85D^V12.QUAS.cLa, scrib^{QUAS.HMS01490}

(Bakopoulos et al., 2023)

InR^E19

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)

InR^K1409A.UAS

ameliorates central nervous system cancer

modeled by N^ΔE.UAS

(Voutyraki et al., 2023)

ameliorates cancer

modeled by Ras85D^V12.GMR

(Okada et al., 2023)

modeled by scrib¹

(Sanaki et al., 2020)

ameliorates colorectal cancer

modeled by SH3PX1^JF02730

(Zhang et al., 2019)

exacerbates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-GR^PO-100.UAS

(Atilano et al., 2021)

modeled by Zzzz\GGGGCC^36.UAS

(Atilano et al., 2021)

ameliorates Huntington's disease

modeled by Hsap\HTT^{N548.Q128.UAS}

(Martin et al., 2021)

ameliorates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Pragati and Sarkar, 2025, Pragati and Sarkar, 2024)

InR^K414P.UAS

ameliorates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Pragati and Sarkar, 2025, Pragati and Sarkar, 2024)

InR^UAS.Exel

ameliorates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Tandon and Sarkar, 2021, Raj and Sarkar, 2019)

ameliorates Huntington's disease

modeled by Hsap\HTT^Q93.ex1.UAS

(Raj and Sarkar, 2019)

modeled by Hsap\HTT^{Q138.UAS.mRFP1}

(Tandon and Sarkar, 2021, Raj and Sarkar, 2019)

ameliorates syndrome

modeled by NSD^EY01950

(Quintero-Rivera et al., 2021)

exacerbates cancer

modeled by scrib¹

(Sanaki et al., 2020)

model of cancer

is ameliorated by SARS-CoV-2\nsp1^UAS.cZa

(Khaket et al., 2024)

InR^del.UAS

ameliorates fragile X syndrome

modeled by Fmr1^Δ50M

(Vita et al., 2021)

InR^JF01183

ameliorates cancer

modeled by Ras85D^V12.GMR

(Okada et al., 2023)

InR^JF01482

ameliorates cancer

modeled by Ras85D^V12.GMR

(Okada et al., 2023)

exacerbates Parkinson's disease 1

modeled by Hsap\SNCA^H50Q.UAS

(Rai and Kumar, 2025)

InR^GL00139

ameliorates cancer

modeled by Ras85D^V12.GMR

(Okada et al., 2023)

InR^NIG.18402R

exacerbates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.E693G.UAS.VTR}

(Sharma et al., 2025)

InR^UAS.cUa

ameliorates Parkinson's disease 1

modeled by Hsap\SNCA^H50Q.UAS

(Rai and Kumar, 2025)

ameliorates Alzheimer's disease 1

modeled by Hsap\APP^{Aβ42.E693G.UAS.VTR}

(Sharma et al., 2025)

InR^UAS.ECFP

ameliorates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Raj and Sarkar, 2019)

InR^HMS03166

ameliorates lung adenocarcinoma

modeled by Hsap\KIF5B::Hsap\RET^UAS.cDa

(Das and Cagan, 2017)

ameliorates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Pragati and Sarkar, 2025, Pragati and Sarkar, 2024)

modeled by Hsap\MAPT^V337M.UAS

(Pragati and Sarkar, 2024)

modeled by Hsap\MAPT^R406W.UAS

(Pragati and Sarkar, 2024)

InR^RNAi.UAS.cUa

exacerbates Machado-Joseph disease

modeled by Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}

(Raj and Sarkar, 2019)

chico

Models Based on Experimental Evidence ( 4 )

Allele

Disease

Evidence

References

chico¹

model of type 2 diabetes mellitus

CEA

(Murillo-Maldonado et al., 2011)

model of intellectual disability

CEA

(Naganos et al., 2016)

model of glucose metabolism disease

CEA

(Naganos et al., 2012)

CEA with chico^flp147E

(Naganos et al., 2012)

model of amnestic disorder

CEA

(Naganos et al., 2012)

CEA with chico^flp147E

(Naganos et al., 2012)

chico^flp147E

model of glucose metabolism disease

CEA with chico¹

(Naganos et al., 2012)

model of amnestic disorder

CEA with chico¹

(Naganos et al., 2012)

chico^HMS01553

model of type 2 diabetes mellitus

CEA

(Tsao et al., 2023)

chico^{lexAop.HMS01553}

model of type 2 diabetes mellitus

CEA

(Tsao et al., 2023)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

chico¹

ameliorates Parkinson's disease

modeled by Hsap\SNCA^UAS.cFa

(Knight et al., 2014)

model of intellectual disability

is ameliorated by Adcy1^UAS.cUa

(Naganos et al., 2016)

exacerbates cancer

modeled by scrib¹

(Sanaki et al., 2020)

chico^KG00032

ameliorates viral infectious disease

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates infectious mononucleosis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

ameliorates Epstein-Barr virus hepatitis

modeled by EBV\BRLF1^GMR.PA

(Adamson and Lajeunesse, 2012)

chico^KK107581

exacerbates C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis

modeled by Zzzz\poly-GR^50.UAS.EGFP

(Lee et al., 2016)

ameliorates cancer

modeled by Pten^KK109278

(Parniewska and Stocker, 2020)

exacerbates cancer

modeled by scrib¹

(Sanaki et al., 2020)

chico^UAS.cNa

ameliorates type 2 diabetes mellitus

modeled by Uch^KO

(Lee et al., 2024)

chico^UAS.cCa

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Chatterjee et al., 2019)

S6k

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

S6k⁰⁷⁰⁸⁴

model of type 2 diabetes mellitus

CEA with S6k^l-1

(Murillo-Maldonado et al., 2011)

model of glucose metabolism disease

CEA with S6k^l-1

(Álvarez-Rendón and Riesgo-Escovar, 2023, Álvarez-Rendón and Riesgo-Escovar, 2020)

S6k^l-1

model of type 2 diabetes mellitus

CEA with S6k⁰⁷⁰⁸⁴

(Murillo-Maldonado et al., 2011)

model of glucose metabolism disease

CEA with S6k⁰⁷⁰⁸⁴

(Álvarez-Rendón and Riesgo-Escovar, 2023, Álvarez-Rendón and Riesgo-Escovar, 2020)

S6k^CA.UAS.cUa

model of alcohol dependence

CEA

(Acevedo et al., 2015)

Modifiers Based on Experimental Evidence ( 10 )

Allele

Disease

Interaction

References

S6k⁰⁷⁰⁸⁴

ameliorates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN8OS^CTG112.UAS

(Mutsuddi et al., 2004)

S6k^KQ.UAS

ameliorates amyotrophic lateral sclerosis

modeled by Vap33^P58S.cRa.UAS

(Deivasigamani et al., 2014)

ameliorates congenital muscular dystrophy due to LMNA mutation

modeled by LamC^G489V.UAS

(Chandran et al., 2019)

S6k^STDE.UAS

exacerbates Parkinson's disease 6

modeled by Pink1^RNAi.UAS.cYa

(Liu and Lu, 2010)

S6k^STDETE.UAS

exacerbates Parkinson's disease 6

modeled by Pink1^RNAi.UAS.cYa

(Liu and Lu, 2010)

exacerbates amyotrophic lateral sclerosis type 10

modeled by TBPH^UAS.cLa

(Cheng et al., 2015)

S6k^TE.UAS

exacerbates Parkinson's disease 6

modeled by Pink1^RNAi.UAS.cYa

(Liu and Lu, 2010)

modeled by Pink1^B9

(Liu and Lu, 2010)

S6k^l-1

ameliorates Parkinson's disease

modeled by Hsap\LRRK2^UAS.cVa

(Penney et al., 2016)

modeled by Lrrk^UAS.cIa

(Penney et al., 2016)

S6k^GD6646

ameliorates brain glioma

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

(Read et al., 2009)

S6k^KK107986

ameliorates cancer

modeled by Pten^KK109278

(Parniewska and Stocker, 2020)

S6k^UAS.cUa

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Bakhoum et al., 2014)

exacerbates Parkinson's disease 6

modeled by Pink1^RNAi.UAS.cYa

(Liu and Lu, 2010)

S6k^RNAi.UAS.cUa

ameliorates brain cancer

modeled by brat^RNAi.UAS.cUa

(Mukherjee et al., 2018)

ameliorates Parkinson's disease 6

modeled by Pink1^RNAi.UAS.cYa

(Liu and Lu, 2010)

Arf6

Models Based on Experimental Evidence ( 3 )

Allele

Disease

Evidence

References

Arf6^EP2612

model of alcohol use disorder

CEA

(Gonzalez et al., 2018)

CEA with Arf6^NP5226

(Gonzalez et al., 2018)

Arf6^KK108126

model of candidiasis

CEA

(Glittenberg et al., 2022)

Arf6^NP5226

model of alcohol use disorder

CEA with Arf6^EP2612

(Gonzalez et al., 2018)

Modifiers Based on Experimental Evidence ( 0 )

Allele

Disease

Interaction

References

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

chico^UAS.cCa

P{UAS-chico.C}

w¹¹¹⁸; P{UAS-chico.C}3/TM3, Sb¹

w¹¹¹⁸; P{UAS-S6k.TE}2

S6k^STDETE.UAS

P{UAS-S6k.STDETE}

w¹¹¹⁸; P{UAS-S6k.STDETE}2

S6k^STDE.UAS

P{UAS-S6k.STDE}

w¹¹¹⁸; P{UAS-S6k.STDE}3

S6k^KQ.UAS

P{UAS-S6k.KQ}

w¹¹¹⁸; P{UAS-S6k.KQ}2

y¹ w¹¹¹⁸; P{UAS-InR.del}2

InR^UAS.Exel

P{UAS-InR.Exel}

y¹ w¹¹¹⁸; P{UAS-InR.Exel}2

InR^K414P.UAS

P{UAS-InR.K414P}

y¹ w¹¹¹⁸; P{UAS-InR.K414P}2

InR^K1409A.UAS

P{UAS-InR.K1409A}

P{UAS-InR.K1409A}1, y¹ w¹¹¹⁸

InR^A1325D.UAS

P{UAS-InR.A1325D}

y¹ w¹¹¹⁸; P{UAS-InR.A1325D}2

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

chico^RNAi.UAS.cUa

P{UAS-chico.RNAi.U}

chico^{lexAop.HMS01553}

P{lexAop-HMS01553}

chico^GD1402

P{GD1402}

w¹¹¹⁸; P{GD1402}v7776

y¹ sc^* v¹ sev²¹; P{TRiP.GL00525}attP40

chico^HMS01553

P{TRiP.HMS01553}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS01553}attP2/TM3, Sb¹

Arf6^GD13822

P{GD13822}

w¹¹¹⁸; P{GD13822}v24224

y¹ v¹; P{TRiP.JF02549}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.GLC01795}attP2

S6k^HMS06031

P{TRiP.HMS06031}

y¹ v¹; P{TRiP.HMS06031}attP40

S6k^{lexAop.HMS04459}

w¹¹¹⁸ P{GD6646}v18126

y¹ sc^* v¹ sev²¹; P{TRiP.GL01327}attP2

S6k^HMS02267

P{TRiP.HMS02267}

y¹ v¹; P{TRiP.HMS02267}attP2

S6k^HMJ02231

P{TRiP.HMJ02231}

y¹ v¹; P{TRiP.HMJ02231}attP40/CyO

S6k^HMS04459

P{TRiP.HMS04459}

y¹ sc^* v¹ sev²¹; P{TRiP.HMS04459}attP40

S6k^GL00086

P{TRiP.GL00086}

InR^{lexAop.HMS03166}

w¹¹¹⁸; P{GD104}v991/TM3

y¹ v¹; P{TRiP.JF01183}attP2

InR^JF01482

P{TRiP.JF01482}

y¹ v¹; P{TRiP.JF01482}attP2

InR^GL00139

P{TRiP.GL00139}

y¹ sc^* v¹ sev²¹; P{TRiP.GL00139}attP2

y¹ v¹; P{TRiP.HMS03166}attP40/CyO

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

chico¹

amorphic allele - molecular evidence

P-element activity

cn¹ P{ry11}chico¹/CyO; ry⁵⁰⁶

chico^KG00032

P-element activity

y¹ w^67c23; P{SUPor-P}chico^KG00032

chico^flp147E

amorphic allele - molecular evidence

P-element activity

Arf6^EP2612

amorphic allele - genetic evidence

P-element activity

w¹¹¹⁸; P{EP}Arf6^EP2612/CyO

Arf6^KO2

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO3

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO16

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO25

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^KO27

amorphic allele - molecular evidence

ends-out gene targeting

Arf6^NP5226

amorphic allele - genetic evidence

y^* w^*; P{GawB}Arf6^NP5226 / CyO, P{UAS-lacZ.UW14}UW14

Arf6^GX16w-

amorphic allele - molecular evidence

gene targeting by homologous recombination

w^*; TI{TI}Arf6^GX16w-/CyO, P{Wee-P.ph0}Bacc^Wee-P20

Arf6^KO

amorphic allele - molecular evidence

ends-out gene targeting

S6k⁰⁷⁰⁸⁴

P-element activity

P{PZ}S6k⁰⁷⁰⁸⁴ ry⁵⁰⁶/TM3, ry^RK Sb¹ Ser¹

S6k^l-1

Delta2-3 transposase

y¹ w^*; S6k^l-1/TM6B, P{Car20y}TPN1, Tb¹

S6k^UAS.cUa

InR⁰⁵⁵⁴⁵

P-element activity

ry⁵⁰⁶ P{PZ}InR⁰⁵⁵⁴⁵/TM3, ry^RK Sb¹ Ser¹

InR^null(HR)

loss of function allele

ends-out gene targeting

InR^Y902C

spontaneous

InR^93Dj-4

gamma ray

In(3R)GC25, InR^93Dj-4/TM3, Sb¹

InR^E19

ethyl methanesulfonate

InR^E19/TM2

InR³³⁹

w^*; P{neoFRT}82B InR³³⁹/TM3, Sb¹ Ser¹

InR^3T5

References (9)

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