Human Disease Model Report: Coffin-Siris syndrome (postulated), PHF10-related

General Information

Name

Coffin-Siris syndrome (postulated), PHF10-related

FlyBase ID

FBhh0001095

Disease Ontology Term

Coffin-Siris syndrome

Parent Disease

Coffin-Siris syndrome

OMIM

Overview

This report describes a Drosophila model using the fly gene e(y)3 to model intellectual developmental disorder(s) caused by disruption of SWI/SNF complexes. Multiple genes within the SWI/SNF family have been implicated in a form of syndromic intellectual disability designated Coffin-Siris syndrome (see FBhh0001088). Dmel\e(y)3 encodes a component of some SWI/SNF complexes; these complexes regulate transcription via chromatin remodeling. The e(y)3 protein is not a core member of this family of complexes: it encodes a component of the polybromo-containing SWI/SNF complex (PBAP, analogous to PBAF in human). One classical hypomorphic allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for e(y)3.

Dmel\e(y)3 is orthologous to the human gene PHF10; there are no diseases associated with this gene in OMIM. PHF10 is a component of the Polybromo-associated complex (PBAF in human) and has also been reported to be a component of a specific neural progenitor BAF (npBAF).

Animals homozygous for a loss-of-function mutation of e(y)3 die during the embryonic stage. RNAi-targeted knockdown of e(y)3 in the mushroom body (a brain region associated with learning and memory) causes male flies not to reduce courtship attempts after being rejected by a female, a measure of memory formation in flies. Both short-term and long-term memory impairment are observed. Defects in mushroom body morphology are observed, including defects in pruning of the MBγ neurons during pupal morphogenesis. Physical and genetic interactions of Dmel\e(y)3 have been described; see below and in the e(y)3 gene report.

[updated Jul. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: Coffin-Siris syndrome

Symptoms and phenotype

Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]

(OMIM, 2013-)

Coffin-Siris syndrome is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014; pubmed:25169447). [from MIM:135900; 2019.07.19]

(FlyBase Curators, 2013-)

Specific Disease Summary: Coffin-Siris syndrome (postulated), PHF10-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Genetics

Cellular phenotype and pathology

Molecular information

PHF10 encodes a protein involved in transcription activity regulation by chromatin remodeling. As a component of a neural-progenitors-specific chromatin remodeling complex (npBAF complex), it is required for the proliferation of neural progenitors. [Gene Cards, PHF10; 2019.07.22]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): PHF10
Gene Cards: PHF10
MedlinePlus (gene): PHF10
MARRVEL (human gene): PHF10
NCBI (Entrez) gene: PHF10; PHD finger protein 10

Disease synonyms

SSRIDD

SWI/SNF-related intellectual disability disorder

Related Diseases

Related human health report(s)

Coffin-Siris syndrome

Related Specific Diseases

OMIM phenotypic series

Coffin-Siris syndrome

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

[CSS5](https://omim.org/entry/616938)

[SMARCE1](https://omim.org/entry/603111)

[CSS6](https://omim.org/entry/617808)

[ARID2](https://omim.org/entry/609539)

[CSS7](https://omim.org/entry/618027)

[DPF2](https://omim.org/entry/601671)

[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

[IDDMOH](https://omim.org/entry/615866)

[SOX11](https://omim.org/entry/600898)

[IDDSDF](https://omim.org/entry/618506)

[SOX4](https://omim.org/entry/184430)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

PHF10; PHD finger protein 10

D. melanogaster ortholog (based on DIOPT)

Dmel\e(y)3

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\e(y)3

Gene Snapshot

enhancer of yellow 3 (e(y)3) encodes a nuclear protein required for embryogenesis and oogenesis. It participates in gene activation in euchromatin as a component of both the SWI/SNF chromatin remodeling complex and the TFIID transcription coactivator. It also contributes to gene silencing in pericentric heterochromatin and is also a coactivator in the JAK/STAT pathway. [Date last reviewed: 2019-09-26]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

PBAP

Comments on ortholog(s)

Moderate-scoring ortholog of human PHF10 (1 Drosophila to 1 human). Dmel\e(y)3 shares 28% identity and 44% 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)

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

Summary of Physical Interactions (21 groups)

e(y)3

protein-protein

Interacting group

Assay

References

e(y)3 - Bap60

ion exchange chromatography, molecular sieving, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry

(Vorobyeva et al., 2009)

e(y)3 - Bap111

anti bait coimmunoprecipitation, western blot

(Chalkley et al., 2008)

e(y)3 - Bap170

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

(Vorobyeva et al., 2009, Chalkley et al., 2008)

e(y)3 - Brd7-9

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Barish et al., 2020)

e(y)3 - brm

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

(Tilly et al., 2021, Vorobyeva et al., 2009, Chalkley et al., 2008)

e(y)3 - CG3517

two hybrid

(Hu et al., 2017.6.13)

e(y)3 - CG9133

two hybrid

(Hu et al., 2017.6.13)

e(y)3 - Hr3

molecular sieving, western blot, two hybrid, anti bait coimmunoprecipitation

(Vorobyeva et al., 2011)

e(y)3 - mor

coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, ion exchange chromatography, molecular sieving, Identification by mass spectrometry

(Vorobyeva et al., 2009, Chalkley et al., 2008, Vorobyeva et al., 2008)

e(y)3 - polybromo

ion exchange chromatography, molecular sieving, western blot, anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, Identification by mass spectrometry, coimmunoprecipitation

(Vorobyeva et al., 2009, Chalkley et al., 2008, Vorobyeva et al., 2008)

e(y)3 - Snr1

anti bait coimmunoprecipitation, western blot

(Chalkley et al., 2008)

e(y)3 - Stat92E

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, anti tag western blot, molecular sieving

(Panov et al., 2012)

e(y)3 - Taf1

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, Identification by mass spectrometry, ion exchange chromatography, molecular sieving

(Vorobyeva et al., 2009, Vorobyeva et al., 2008)

e(y)3 - Taf3

anti bait coimmunoprecipitation, western blot

(Vorobyeva et al., 2009, Soshnikova et al., 2008)

e(y)3 - Taf4

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

(Vorobyeva et al., 2009, Vorobyeva et al., 2008)

e(y)3 - Taf5

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

(Vorobyeva et al., 2009)

e(y)3 - Taf8

anti bait coimmunoprecipitation, Identification by mass spectrometry, western blot

(Vorobyeva et al., 2009)

e(y)3 - Taf9

ion exchange chromatography, molecular sieving, western blot, anti tag coimmunoprecipitation, anti bait coimmunoprecipitation, Identification by mass spectrometry

(Vorobyeva et al., 2009, Vorobyeva et al., 2008)

e(y)3 - Taf10

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation

(Vorobyeva et al., 2009, Soshnikova et al., 2008, Vorobyeva et al., 2008)

e(y)3 - Taf13

anti bait coimmunoprecipitation, western blot

(Vorobyeva et al., 2009, Soshnikova et al., 2008)

e(y)3 - Tbp

anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, ion exchange chromatography, molecular sieving

(Vorobyeva et al., 2009, Soshnikova et al., 2008, Vorobyeva et al., 2008)

Alleles Reported to Model Human Disease (Disease Ontology) (3 alleles)

e(y)3