Human Disease Model Report: alcohol, response to, circadian genes

General Information

Name

alcohol, response to, circadian genes

FlyBase ID

FBhh0001625

Disease Ontology Term

alcohol use disorder

Parent Disease

alcohol use disorder, susceptibility to (fly models overview)

OMIM

Overview

A subset of the genes involved in regulating circadian behavior affect acquisition of ethanol tolerance (but not initial ethanol sensitivity). These include per, tim, and cyc. A mutation in the Clk gene does not appear to have any affect on the capacity to acquire tolerance.

Subjecting wild-type flies to constant light, which produces behavioral arrhythmicity, also disrupts the capacity to acquire ethanol tolerance.

[updated Mar. 2025 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, circadian genes

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

External links

Disease synonyms

Related Diseases

Related human health report(s)

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 (3)

Dmel\per

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human PER1, PER2, and PER3 (1 Drosophila to 3 human).

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\tim

Gene Snapshot

timeless (tim) encodes a key component of the tim-per complex, required for the production of circadian rhythms. It is involved in mating behavior, DNA replication and larval phototaxis. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Low-scoring ortholog of human TIMELESS; the Drosophila gene timeout is more closely related to human TIMELESS.

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\cyc

Gene Snapshot

cycle (cyc) is a circadian clock gene. It encodes a transcription factor of the BHLH-PAS family and activates transcription of key clock genes as well as downstream clock-regulated genes. [Date last reviewed: 2018-09-20]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

BHLH

Comments on ortholog(s)

High-scoring ortholog of human BMAL1 and ARNTL2 (1 Drosophila to 2 human).

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 (61 groups)

per

protein-protein

Interacting group

Assay

References

per

molecular sieving, molecular weight, anti tag coimmunoprecipitation, western blot, x-ray crystallography, molecular weight estimation by staining, cosedimentation

(Giesecke et al., 2023, King et al., 2011, Hennig et al., 2009, Landskron et al., 2009)

per - CkIα

anti tag coimmunoprecipitation, anti tag western blot

(Lam et al., 2018)

per - CkIIα

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Top et al., 2016, Szabó et al., 2013)

per - CkIIβ

anti tag coimmunoprecipitation, western blot

(Szabó et al., 2013)

per - Clk

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

(Li et al., 2019, Agrawal et al., 2017, Fu et al., 2016, Lee et al., 2016, Lee et al., 2014, Kaasik et al., 2013, Menet et al., 2010, Sun et al., 2010, Kim et al., 2007, Lee et al., 1999)

per - cry

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

(Schlichting et al., 2018, Kumar et al., 2014, Ozturk et al., 2013, Hemsley et al., 2007, Busza et al., 2004, Rosato et al., 2001, Ceriani et al., 1999)

per - cyc

anti tag coimmunoprecipitation, autoradiography

(Lee et al., 1999)

per - D

two hybrid

(Ma et al., 2000)

per - dco

pull down, western blot, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, autoradiography, enzymatic study, protein kinase assay, Identification by mass spectrometry

(Lam et al., 2018, Fu et al., 2016, Fan et al., 2015, Syed et al., 2011, Sun et al., 2010, Fan et al., 2009, Yu et al., 2009, Kivimäe et al., 2008, Kim et al., 2007, Muskus et al., 2007, Preuss et al., 2004, Kloss et al., 2001)

per - dod

anti bait coimmunoprecipitation, western blot

(Kang et al., 2015)

per - Eip75B

anti bait coimmunoprecipitation, anti tag western blot

(Kumar et al., 2014)

per - Kap-α1

anti tag coimmunoprecipitation, western blot, anti tag western blot

(Jang et al., 2015)

per - nmo

protein kinase assay, western blot

(Chiu et al., 2011)

per - p38b

enzymatic study, electrophoretic mobility-based method, autoradiography

(Dusik et al., 2014)

per - pont

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Liao et al., 2025)

per - Pp1-87B

anti bait coimmunoprecipitation, anti tag western blot

(Xue et al., 2019)

per - PRL-1

anti tag coimmunoprecipitation, anti tag western blot

(Kula-Eversole et al., 2021)

per - rept

anti tag coimmunoprecipitation, anti tag western blot, Identification by mass spectrometry

(Liao et al., 2025)

per - sgg

anti tag coimmunoprecipitation, anti tag western blot

(Top et al., 2016)

per - slmb

pull down, anti tag western blot

(Chiu et al., 2008)

per - Sur-8

anti bait coimmunoprecipitation, anti tag western blot, anti tag coimmunoprecipitation, western blot

(Xue et al., 2019)

per - sxc

anti bait coimmunoprecipitation, anti tag western blot

(Kim et al., 2012)

per - tim

two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry, anti tag western blot, autoradiography

(Liao et al., 2025, Giesecke et al., 2023, Martin Anduaga et al., 2019, Top et al., 2016, Yildirim et al., 2015, Li and Rosbash, 2013, Ozturk et al., 2013, Hara et al., 2011, Saez et al., 2011, Menet et al., 2010, Sun et al., 2010, Hennig et al., 2009, Landskron et al., 2009, Kim et al., 2007, Kloss et al., 2001, Rosato et al., 2001, Ceriani et al., 1999, Lee et al., 1999)

RNA-protein

Interacting group

Assay

References

per - Atx2

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

(Lee et al., 2017, Lim and Allada, 2013, Zhang et al., 2013)

per - B52

clip, quantitative reverse transcription pcr

(Zhang et al., 2018)

per - tyf

anti tag coimmunoprecipitation, primer specific pcr

(Lim and Allada, 2013, Lim et al., 2011)

tim

RNA-protein

Interacting group

Assay

References

tim - Atx2

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

(Lee et al., 2017, Lim and Allada, 2013, Zhang et al., 2013)

tim - tyf

anti tag coimmunoprecipitation, primer specific pcr

(Lim and Allada, 2013, Lim et al., 2011)

RNA-RNA

Interacting group

Assay

References

tim - mir-276a

luminiscence technology, western blot

(Zhang et al., 2021, Chen and Rosbash, 2016)

tim - mir-276b

luminiscence technology

(Zhang et al., 2021)

protein-protein

Interacting group

Assay

References

tim - brm

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Kwok et al., 2015)

tim - Cam

pull down, tag visualisation by enzyme assay

(Tataroglu et al., 2015)

tim - CkIIα

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot

(Top et al., 2016, Szabó et al., 2013)

tim - CkIIβ

anti tag coimmunoprecipitation, western blot

(Szabó et al., 2013)

tim - Clk

anti tag coimmunoprecipitation, autoradiography, anti bait coimmunoprecipitation, anti tag western blot, western blot

(Lee et al., 2016, Menet et al., 2010, Sun et al., 2010, Lee et al., 1999)

tim - cry

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag western blot, two hybrid, pull down, fluorescence technology, cross-linking study, molecular sieving, Identification by mass spectrometry, electron microscopy, tag visualisation by fluorescence, molecular weight estimation by staining

(DeOliveira et al., 2024, Ozcelik et al., 2024, Lin et al., 2023, Lin et al., 2022, Chandrasekaran et al., 2021, Agrawal et al., 2017, Ozturk et al., 2013, Vaidya et al., 2013, Peschel et al., 2009, Hemsley et al., 2007, Busza et al., 2004, Rosato et al., 2001, Ceriani et al., 1999)

tim - Cul3

coimmunoprecipitation, western blot

(Grima et al., 2012)

tim - cyc

anti tag coimmunoprecipitation, autoradiography

(Lee et al., 1999)

tim - dco

anti bait coimmunoprecipitation, western blot

(Yu et al., 2009, Kloss et al., 2001)

tim - emb

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

(Cai et al., 2021)

tim - eya

anti tag coimmunoprecipitation, anti tag western blot

(Abrieux et al., 2020)

tim - flw

anti tag coimmunoprecipitation, anti tag western blot

(Fang et al., 2007)

tim - jet

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Peschel et al., 2009, Koh et al., 2006)

tim - Kap-α1

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Jang et al., 2015)

tim - Nup153

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

(Jang et al., 2015)

tim - per

two hybrid, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, Identification by mass spectrometry, anti tag western blot, autoradiography

tim - Pp1-13C

anti tag coimmunoprecipitation, anti tag western blot

(Fang et al., 2007)

tim - Pp1-87B

anti tag coimmunoprecipitation, anti tag western blot

(Fang et al., 2007)

tim - Pp1α-96A

anti tag coimmunoprecipitation, anti tag western blot

(Fang et al., 2007)

tim - PRL-1

anti tag coimmunoprecipitation, anti tag western blot

(Kula-Eversole et al., 2021)

tim - Ran

pull down, western blot

(Jang et al., 2015)

tim - Rpn10

anti tag coimmunoprecipitation, western blot

(Szabó et al., 2018)

tim - sgg

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Top et al., 2016)

tim - Ubqn

anti tag coimmunoprecipitation, western blot

(Szabó et al., 2018)

cyc

RNA-protein

Interacting group

Assay

References

cyc - Atx2

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

(Lee et al., 2017, Lim and Allada, 2013)

protein-protein

Interacting group

Assay

References

cyc - CG18011

two hybrid array

(Shokri et al., 2019)

cyc - Clk

anti tag coimmunoprecipitation, anti tag western blot, autoradiography, anti bait coimmunoprecipitation, pull down, tag visualisation, two hybrid

(Wang et al., 2025, Liu et al., 2017, Lee et al., 2016, Lee et al., 2014, Cheng et al., 2013, Kazemian et al., 2013, Maurer et al., 2009, Hung et al., 2007, Ceriani et al., 1999, Lee et al., 1999, Darlington et al., 1998)

cyc - Eip78C

two hybrid array

(Shokri et al., 2019)

cyc - foxo

two hybrid array

(Shokri et al., 2019)

cyc - Hr78

two hybrid array

(Shokri et al., 2019)

cyc - hyd

anti tag coimmunoprecipitation, anti tag western blot

(Duan et al., 2024)