Human Disease Model Report: neurodevelopmental disorder, neural stem cell dedifferentiation

General Information

Name

neurodevelopmental disorder, neural stem cell dedifferentiation

FlyBase ID

FBhh0001140

Disease Ontology Term

central nervous system disease

Parent Disease

OMIM

Overview

In Drosophila, it has been found that the integrator complex is required to prevent dedifferentiation of type II neural stem cells. These experiments involved clonal knockout of various components of the integrator complex in the larval brain, including IntS5 (omd), IntS8, IntS1, and IntS2. The integrator complex mediates transcription and 3-prime end processing of small nuclear RNAs U1 and U2. Several recently described neurodevelopmental diseases in human are associated with genes of the integrator complex (MIM:618571, INTS1; MIM:618572, INTS8).

See also the disease model report 'cancer, neural stem cell dedifferentiation' (FBhh0001139).

[updated Nov. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: neurodevelopmental disorder, neural stem cell dedifferentiation

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

INTS1, INTS2, INTS5, INTS8 are components of the integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit and mediates transcription and 3-prime end processing of small nuclear RNAs U1 and U2. [Gene Cards, INTS1, INTS2, INTS5, INTS8; 2019.11.08]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): INTS1
Gene2Function (human gene): INTS8
Gene Cards: INTS1
Gene Cards: INTS8
MedlinePlus (gene): INTS1
MedlinePlus (gene): INTS8
MARRVEL (human gene): INTS8
MARRVEL (human gene): INTS1
NCBI MedGen: NEURODEVELOPMENTAL DISORDER WITH CATARACTS, POOR GROWTH, AND DYSMORPHIC FACIES (NDCAGF)
NCBI MedGen: NEURODEVELOPMENTAL DISORDER WITH CEREBELLAR HYPOPLASIA AND SPASTICITY (NEDCHS)
NCBI (Entrez) gene: INTS1; integrator complex subunit 1
NCBI (Entrez) gene: INTS8; integrator complex subunit 8

Disease synonyms

Related Diseases

Related human health report(s)

cancer, neural stem cell dedifferentiation

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

INTS8; integrator complex subunit 8

D. melanogaster ortholog (based on DIOPT)

Dmel\IntS8

(DIOPT, 2013-)

Dmel\IntS8

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Human gene (HGNC)

Symbol / Name

INTS1; integrator complex subunit 1

D. melanogaster ortholog (based on DIOPT)

Dmel\IntS1

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (4)

Dmel\IntS1

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

INT
INTAC

Comments on ortholog(s)

High-scoring ortholog of human INTS1.

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\IntS2

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

INT
INTAC

Comments on ortholog(s)

High-scoring ortholog of human INTS2.

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\omd

Gene Snapshot

Contributions welcome

Molecular function (GO)

DNA binding

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human INTS5.

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\IntS8

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of human INTS8.

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 (38 groups)

IntS1

protein-protein

Interacting group

Assay

References

IntS1 - asun

anti tag coimmunoprecipitation, western blot

(Chen et al., 2012)

IntS1 - Cdk8

anti tag coimmunoprecipitation, western blot

(Chen et al., 2012)

IntS1 - CycC

anti tag coimmunoprecipitation, western blot

(Chen et al., 2012)

IntS1 - defl

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024, Huang et al., 2020)

IntS1 - IntS4

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Huang et al., 2020)

IntS1 - IntS6

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024)

IntS1 - IntS8

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020)

IntS1 - IntS9

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

(Lin et al., 2024, Lin et al., 2022, Huang et al., 2020, Tatomer et al., 2019)

IntS1 - IntS11

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

(Lin et al., 2024, Lin et al., 2022, Huang et al., 2020, Tatomer et al., 2019)

IntS1 - IntS12

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

(Lin et al., 2024, Huang et al., 2020, Chen et al., 2013)

IntS1 - IntS14

anti tag coimmunoprecipitation, western blot

(Chen et al., 2012)

IntS1 - mts

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Huang et al., 2020)

IntS1 - omd

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020, Tatomer et al., 2019)

IntS1 - Pp2A-29B

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Huang et al., 2020)

IntS1 - Rrp40

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Tatomer et al., 2019)

omd

protein-protein

Interacting group

Assay

References

omd - Dad

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2023)

omd - defl

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024, Huang et al., 2020)

omd - IntS1

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020, Tatomer et al., 2019)

omd - IntS4

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Huang et al., 2020)

omd - IntS6

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024)

omd - IntS8

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

(Lin et al., 2024, Huang et al., 2020)

omd - IntS9

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020, Tatomer et al., 2019)

omd - IntS11

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024, Huang et al., 2020, Tatomer et al., 2019)

omd - IntS12

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020)

omd - mts

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Huang et al., 2020)

omd - Pp2A-29B

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Huang et al., 2020)

omd - Rrp40

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Tatomer et al., 2019)

omd - Smurf

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2023)

omd - tkv

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2023)

IntS8

protein-protein

Interacting group

Assay

References

IntS8 - Dad

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2023)

IntS8 - defl

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Huang et al., 2020)

IntS8 - IntS1

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020)

IntS8 - IntS4

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lin et al., 2024, Huang et al., 2020)

IntS8 - IntS9

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

(Lin et al., 2024, Lin et al., 2022, Huang et al., 2020)

IntS8 - IntS11

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

(Lin et al., 2024, Lin et al., 2022, Huang et al., 2020)

IntS8 - IntS12

anti tag coimmunoprecipitation, western blot, Identification by mass spectrometry

(Lin et al., 2024, Huang et al., 2020)

IntS8 - mts

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Huang et al., 2020)

IntS8 - omd

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

(Lin et al., 2024, Huang et al., 2020)

IntS8 - Pp2A-29B

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

(Huang et al., 2020)

IntS8 - Smurf

anti tag coimmunoprecipitation, anti tag western blot

(Liu et al., 2023)

IntS8 - tkv

anti tag coimmunoprecipitation, western blot, anti tag western blot

(Liu et al., 2023)

Alleles Reported to Model Human Disease (Disease Ontology) (0 alleles)

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

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

IntS1^HMJ23919

P{TRiP.HMJ23919}

y¹ v¹; P{TRiP.HMJ23919}attP40/CyO

IntS1^GD10348

P{GD10348}

w¹¹¹⁸; P{GD10348}v25825/TM3

w¹¹¹⁸; P{GD13846}v24239

y¹ v¹; P{TRiP.HMJ22652}attP40/CyO

omd^GD14262

P{GD14262}

w¹¹¹⁸; P{GD14262}v44696

w¹¹¹⁸; P{GD11789}v45678/CyO

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00721}attP2

w¹¹¹⁸; P{GD11789}v45678/CyO

y¹ sc^* v¹ sev²¹; P{TRiP.HMS00721}attP2

IntS8^RNAi.UAS

P{UAS-IntS8.RNAi}

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

References (3)

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