Human Disease Model Report: Koolen-De Vries syndrome

General Information

Name

Koolen-De Vries syndrome

FlyBase ID

FBhh0000145

Disease Ontology Term

Koolen de Vries syndrome

Parent Disease

intellectual disability, autosomal dominant

OMIM

KOOLEN-DE VRIES SYNDROME; KDVS

Overview

This report describes Koolen-De Vries syndrome (KDVS), which is one of the series of diseases classified as intellectual disability, autosomal dominant. The human gene implicated in this disease is KANSL1 (KAT8 regulatory NSL complex, subunit 1), which is a component of histone acetylase complexes. There is a second similar gene in humans, KANSL1L. There is a single Drosophila ortholog, Dmel\nsl1, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human KANSL1 gene has not been introduced into flies.

Homozygous loss-of-function mutations of Dmel\nsl1 are lethal. Expression in the brain of an RNAi construct targeting nsl1 results in a learning defective phenotype. Physical interactions of the nsl1 protein product have been described; see below and in the FlyBase gene report for Dmel\nsl1.

[updated Jan. 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: intellectual disability, autosomal dominant

Symptoms and phenotype

Intellectual disability is characterized by impairments in intellectual functioning and adaptive behavior; symptoms must be present before a child becomes 18 years old (http://medical-dictionary.thefreedictionary.com/mental+retardation; 2016.01.19).

(FlyBase Curators, 2013-)

Intellectual disability can be subdivided into syndromic forms, characterized by cognitive impairment accompanied by dysmorphic features, malformations or neurological abnormalities, and nonsyndromic forms, characterized by cognitive impairment without additional features (Basel-Vanagaite, 2008; DOI: 10.1002/9780470015902.a0021454).

(FlyBase Curators, 2013-)

Specific Disease Summary: Koolen-De Vries syndrome

OMIM report

[KOOLEN-DE VRIES SYNDROME; KDVS](https://omim.org/entry/610443)

Human gene(s) implicated

[KAT8 REGULATORY NSL COMPLEX, SUBUNIT 1; KANSL1](https://omim.org/entry/612452)

Symptoms and phenotype

Koolen-De Vries syndrome (KDVS) is characterized by moderate to severe intellectual disability, hypotonia, friendly demeanor, and highly distinctive facial features. More variable features include cardiac or genitourinary anomalies and seizures (summary by Koolen et al., 2012; pubmed:22544363). [from MIM:610443; 2016.01.25]

(OMIM, 2013-)

Genetics

Koolen-De Vries syndrome can be caused either by heterozygous mutation in the KANSL1 (KAT8 regulatory NSL complex, subunit 1) gene or by a larger deletion of several genes, including KANSL1.

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The KANSL1 gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. [Gene Cards, KANSL1; 2016.01.25]

(FlyBase Curators, 2013-)

Histone acetylation/deacetylation plays a role in epigenetic transcription regulation.

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): KANSL1
Gene Cards: KANSL1
GeneReviews, NCBI Bookshelf: KANSL1-Related Intellectual Disability Syndrome
MedlinePlus (condition): Koolen-de Vries syndrome
MedlinePlus (gene): KANSL1
MARRVEL (human gene): KANSL1
NCBI MedGen: Koolen-de Vries syndrome (KDVS)
NCBI (Entrez) gene: KANSL1; KAT8 regulatory NSL complex subunit 1

Disease synonyms

chromosome 17q21.31 deletion syndrome

KDVS

microdeletion 17q21.31 syndrome

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Intellectual developmental disorder, autosomal dominant

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[CSS1](https://omim.org/entry/135900)

[ARID1B](https://omim.org/entry/614556)

Coffin-Siris syndrome 1

[CSS2](https://omim.org/entry/614607)

[ARID1A](https://omim.org/entry/603024)

Coffin-Siris syndrome 2

[CSS3](https://omim.org/entry/614608)

[SMARCB1](https://omim.org/entry/601607)

Coffin-Siris syndrome 3

[CSS4](https://omim.org/entry/614609)

[SMARCA4](https://omim.org/entry/603254)

Coffin-Siris syndrome 4

[CSS8](https://omim.org/entry/618362)

[SMARCC2](https://omim.org/entry/601734)

Coffin-Siris syndrome 8

[CSS11](https://omim.org/entry/618779)

[SMARCD1](https://omim.org/entry/601735)

Coffin-Siris syndrome 11

[CSS12](https://omim.org/entry/619325)

[BICRA](https://omim.org/entry/605690)

Coffin-Siris syndrome 12

[GAND](https://omim.org/entry/615074)

[GATAD2B](https://omim.org/entry/614998)

GAND syndrome

[KDVS](https://omim.org/entry/610443)

[KANSL1](https://omim.org/entry/612452)

Koolen-De Vries syndrome

[KLEFS1](https://omim.org/entry/610253)

[EHMT1](https://omim.org/entry/607001)

Kleefstra syndrome 1

[MRD21](https://omim.org/entry/615502)

[CTCF](https://omim.org/entry/604167)

intellectual disability, autosomal dominant 21

[MRD48](https://omim.org/entry/617751)

[RAC1](https://omim.org/entry/602048)

intellectual disability, autosomal dominant 48

[MRD53](https://omim.org/entry/617798)

[CAMK2A](https://omim.org/entry/114078)

intellectual disability, autosomal dominant 53

[MRD54](https://omim.org/entry/617799)

[CAMK2B](https://omim.org/entry/607707)

intellectual disability, autosomal dominant 54

[MRD55](https://omim.org/entry/617831)

[NUS1](https://omim.org/entry/610463)

intellectual disability, autosomal dominant 55, with seizures

[MRD75](https://omim.org/entry/620988)

[DHX9](https://omim.org/entry/603115)

intellectual disability, autosomal dominant 75

[NEDHSF](https://omim.org/entry/616351)

[CERT1](https://omim.org/entry/604677)

neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies

[NESCAVS](https://omim.org/entry/614255)

[KIF1A](https://omim.org/entry/601255)

NESCAV syndrome

[WHSUS](https://omim.org/entry/616364)

[POGZ](https://omim.org/entry/614787)

White-Sutton syndrome

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

KANSL1; KAT8 regulatory NSL complex subunit 1

D. melanogaster ortholog (based on DIOPT)

Dmel\nsl1

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila. The human genes KANSL1 and KANSL1L are orthologous to the fly gene Dmel\nsl1.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\nsl1

Gene Snapshot

non-specific lethal 1 (nsl1) encodes a non-catalytic subunit of the NSL histone H4 acetyltransferase complex, and is involved in muscle development, oogenesis and regulation of endocytosis. [Date last reviewed: 2020-11-05]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human genes KANSL1 and KANSL1L (1 Drosophila to 2 human). Dmel\nsl1 shares 18-21% identity and 29-32% similarity with two human genes.

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 (16 groups)

nsl1

protein-protein

Interacting group

Assay

References

nsl1 - Caf1-55

anti bait coimmunoprecipitation, western blot

(Lam et al., 2019)

nsl1 - CG5381

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Raja et al., 2010)

nsl1 - Chro

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

(Raja et al., 2010, Mendjan et al., 2006)

nsl1 - cindr

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Raja et al., 2010)

nsl1 - dgt1

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Lam et al., 2019, Dias et al., 2014, Raja et al., 2010)

nsl1 - E(bx)

anti bait coimmunoprecipitation, western blot

(Lam et al., 2019)

nsl1 - hang

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

(Lenz et al., 2025)

nsl1 - Iswi

pull down, western blot, anti bait coimmunoprecipitation

(Lam et al., 2019)

nsl1 - MBD-R2

coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation, molecular sieving, pull down, molecular weight estimation by staining, Identification by mass spectrometry

(Lenz et al., 2025, Lam et al., 2019, Dias et al., 2014, Kadlec et al., 2011, Raja et al., 2010, Mendjan et al., 2006)

nsl1 - mof

molecular sieving, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, molecular weight estimation by staining

(Lenz et al., 2025, Lam et al., 2019, Dias et al., 2014, Kadlec et al., 2011, Raja et al., 2010, Mendjan et al., 2006)

nsl1 - Nurf-38

anti bait coimmunoprecipitation, western blot

(Lam et al., 2019)

nsl1 - pzg

anti tag coimmunoprecipitation, Identification by mass spectrometry, western blot

(Raja et al., 2010)

nsl1 - Rcd1

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, pull down, molecular weight estimation by staining

(Lam et al., 2019, Meunier et al., 2015, Dias et al., 2014, Kadlec et al., 2011, Raja et al., 2010)

nsl1 - Rcd5

pull down, molecular weight estimation by staining, anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, molecular sieving

(Lenz et al., 2025, Lam et al., 2019, Dias et al., 2014, Raja et al., 2010)

nsl1 - Spindly

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Raja et al., 2010)

nsl1 - wds

x-ray crystallography, anti tag coimmunoprecipitation, Identification by mass spectrometry, pull down, molecular weight estimation by staining, western blot, anti bait coimmunoprecipitation

(Dias et al., 2014, Raja et al., 2010, Mendjan et al., 2006)

Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)

nsl1

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

nsl1^NIG.4699R

model of intellectual disability

CEA

(Koolen et al., 2012)