Human Disease Model Report: Meier-Gorlin syndrome 3

General Information

Name

Meier-Gorlin syndrome 3

FlyBase ID

FBhh0000900

Disease Ontology Term

Meier-Gorlin syndrome 3

Parent Disease

Meier-Gorlin syndrome

OMIM

MEIER-GORLIN SYNDROME 3; MGORS3

Overview

This report describes Meier-Gorlin syndrome 3 (MGORS3), which is a subtype of Meier-Gorlin syndrome; MGORS3 exhibits autosomal recessive inheritance. The human gene implicated in this disease is ORC6, which encodes the smallest subunit of the human origin recognition complex (ORC); the ORC is required for initiation of DNA replication. There is a single orthologous gene in Drosophila, Dmel\Orc6, for which an amorphic mutation, RNAi targeting constructs, and an allele caused by insertional mutagenesis have been generated.

A UAS construct with a tagged wild-type human Hsap\ORC6 gene has been introduced into flies. Partial heterologous rescue (functional complementation) has been demonstrated.

Animals homozygous for an amorphic mutation of Dmel\Orc6 die at the third instar larval stage with abnormal chromosomes and DNA replication defects. The function and physical interactions of the C-terminal portion of the Orc6 protein has been investigated in flies. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): Y225S in the fly Orc6 gene (corresponds to Y232S in the human ORC6 gene); additional mutations and double mutations in the C terminal portion of the protein have been characterized.

[updated Sep. 2018 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: Meier-Gorlin syndrome

Symptoms and phenotype

The Meier-Gorlin syndrome is a rare disorder characterized by severe intrauterine and postnatal growth retardation, microcephaly, bilateral microtia, and aplasia or hypoplasia of the patellae (summary by Shalev and Hall, 2003; pubmed:14564153). While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal (Bicknell et al., 2011; pubmed:21358632). [from MIM:224690; 2018.09.26]

(OMIM, 2013-)

Specific Disease Summary: Meier-Gorlin syndrome 3

OMIM report

[MEIER-GORLIN SYNDROME 3; MGORS3](https://omim.org/entry/613803)

Human gene(s) implicated

[ORIGIN RECOGNITION COMPLEX, SUBUNIT 6; ORC6](https://omim.org/entry/607213)

Symptoms and phenotype

Genetics

Meier-Gorlin syndrome-3 (MGORS3) is caused by homozygous or compound heterozygous mutation in the ORC6 gene. [from MIM:613803; 2018.09.27]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The origin recognition complex (ORC) comprises a highly conserved set of proteins which are bound to origins of DNA replication and mediate the initiation of DNA replication. The ORC6 gene encodes the smallest subunit of human ORC. During mitosis, ORC6 localizes to kinetochores and to a reticular-like structure around the cell periphery. It has been implicated in coordinating chromosome replication and segregation with cytokinesis (Prasanth et al., 2002; pubmed:12169736). [from MIM:607213; 2018.09.27]

(OMIM, 2013-)

External links

Gene2Function (human gene): ORC6
Gene Cards: ORC6
MedlinePlus (gene): ORC6
MARRVEL (human gene): ORC6
NCBI MedGen: Meier-Gorlin syndrome 3 (MGORS3)
NCBI (Entrez) gene: ORC6; origin recognition complex subunit 6

Disease synonyms

MGORS3

Related Diseases

Related human health report(s)

microcephalic primordial dwarfism

Related Specific Diseases

OMIM phenotypic series

Meier-Gorlin syndrome

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[MGORS1](https://omim.org/entry/224690)

[ORC1](https://omim.org/entry/601902)

[MGORS2](https://omim.org/entry/613800)

[ORC4](https://omim.org/entry/603056)

Meier-Gorlin syndrome 2

[MGORS3](https://omim.org/entry/613803)

[ORC6](https://omim.org/entry/607213)

Meier-Gorlin syndrome 3

[MGORS4](https://omim.org/entry/613804)

[CDT1](https://omim.org/entry/605525)

[MGORS5](https://omim.org/entry/613805)

[CDC6](https://omim.org/entry/602627)

[MGORS6](https://omim.org/entry/616835)

[GMNN](https://omim.org/entry/602842)

[MGORS7](https://omim.org/entry/617063)

[CDC45](https://omim.org/entry/603465)

[MGORS8](https://omim.org/entry/617564)

[MCM5](https://omim.org/entry/602696)

Ortholog Information

Human gene(s) in FlyBase

Hsap\ORC6

Human gene (HGNC)

Symbol / Name

ORC6; origin recognition complex subunit 6

D. melanogaster ortholog (based on DIOPT)

Dmel\Orc6

(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\Orc6

Gene Snapshot

Origin recognition complex subunit 6 (Orc6) encodes a subunit of the origin recognition complex (ORC), which is essential for the initiation of DNA replication in eukaryotic cells. Orc6 product has an additional independent function in cytokinesis through the interaction with the septin protein encoded by pnut. [Date last reviewed: 2019-03-21]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Moderate-scoring ortholog of human ORC6 (1 Drosophila to 1 human). Dmel\Orc6 shares 28% identity and 48% 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 (12 groups)

Orc6

protein-protein

Interacting group

Assay

References

Orc6

fluorescence polarization spectroscopy, pull down, molecular weight estimation by staining, fluorescent resonance energy transfer, molecular sieving, western blot

(Akhmetova et al., 2015)

Orc6 - cav

anti bait coimmunoprecipitation, western blot, pull down, autoradiography

(Badugu et al., 2003, Shareef et al., 2001)

Orc6 - Cdc6

pull down, molecular weight estimation by staining, electron microscopy

(Schmidt and Bleichert, 2020, Bleichert et al., 2018)

Orc6 - e(y)2

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

(Maksimenko et al., 2018, Kopytova et al., 2016)

Orc6 - Orc1

fluorescence polarization spectroscopy, predetermined participant, pull down, molecular weight estimation by staining, electron microscopy, x-ray crystallography

(Schmidt and Bleichert, 2020, Bleichert et al., 2018, Bleichert et al., 2015, Bleichert et al., 2013)

Orc6 - Orc2

anti tag coimmunoprecipitation, anti tag western blot, electron microscopy, anti bait coimmunoprecipitation, western blot, x-ray crystallography, pull down, molecular weight estimation by staining, fluorescence polarization spectroscopy, predetermined participant, cross-linking study, Identification by mass spectrometry

(Balasov et al., 2020, Schmidt and Bleichert, 2020, Bleichert et al., 2018, Kopytova et al., 2016, Balasov et al., 2015, Bleichert et al., 2015, Bleichert et al., 2013, Beall et al., 2002, Pak et al., 1997)

Orc6 - Orc3

cross-linking study, anti bait coimmunoprecipitation, western blot, Identification by mass spectrometry, electron microscopy, x-ray crystallography, fluorescence polarization spectroscopy, predetermined participant, pull down, molecular weight estimation by staining, autoradiography

(Balasov et al., 2020, Schmidt and Bleichert, 2020, Bleichert et al., 2018, Kopytova et al., 2016, Bleichert et al., 2015, Bleichert et al., 2013)

Orc6 - Orc4

pull down, molecular weight estimation by staining, fluorescence polarization spectroscopy, predetermined participant, electron microscopy, cross-linking study, Identification by mass spectrometry, autoradiography, x-ray crystallography, anti bait coimmunoprecipitation, western blot

(Schmidt and Bleichert, 2020, Bleichert et al., 2018, Kopytova et al., 2016, Bleichert et al., 2015, Bleichert et al., 2013)

Orc6 - Orc5

pull down, molecular weight estimation by staining, cross-linking study, Identification by mass spectrometry, fluorescence polarization spectroscopy, predetermined participant, anti bait coimmunoprecipitation, western blot, electron microscopy, x-ray crystallography

(Schmidt and Bleichert, 2020, Bleichert et al., 2018, Kopytova et al., 2016, Bleichert et al., 2015, Bleichert et al., 2013)

Orc6 - pnut

transmission electron microscopy, pull down, autoradiography, two hybrid, anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation, western blot

(Akhmetova et al., 2018, Akhmetova et al., 2015, Huijbregts et al., 2009, Chesnokov et al., 2003)

Orc6 - Su(var)205

affinity chromatography technology, western blot, pull down

(Pak et al., 1997)

Orc6 - xmas

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

(Kopytova et al., 2016)

Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)

Orc6

Models Based on Experimental Evidence ( 2 )

Allele

Disease