Human Disease Model Report: microcephaly 5, primary, autosomal recessive

General Information

Name

microcephaly 5, primary, autosomal recessive

FlyBase ID

FBhh0000328

Disease Ontology Term

primary autosomal recessive microcephaly 5

Parent Disease

microcephaly, primary

OMIM

MICROCEPHALY 5, PRIMARY, AUTOSOMAL RECESSIVE; MCPH5

Overview

This report describes microcephaly 5, primary, autosomal recessive (MCPH5), which is a subtype of primary microcephaly. The human gene implicated in this disease is Abnormal Spindle Microtubule Assembly (ASPM), which is affects mitotic spindle function or regulation. There is a single fly ortholog, asp, for which for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.

The human ASPM gene has not been introduced into flies.

Animals that are homozygous or hemizygous for an amorphic allele of Dmel\asp are viable but sterile, with small heads; abnormal mitoses are observed in third instar larval central neuroblasts. A small number of physical interactions and a large number of genetic interactions for Dmel\asp have been described; see below and in the gene report for asp.

[updated June 2016 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: microcephaly, primary

Symptoms and phenotype

Primary microcephaly (MCPH) refers to the clinical finding of a head circumference less than 3 standard deviations below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation; additional clinical features may include short stature or mild seizures (review by Woods et al., 2005; pubmed:15806441). [from MIM:251200; 2016.06.16]

(OMIM, 2013-)

Specific Disease Summary: microcephaly 5, primary, autosomal recessive

OMIM report

[MICROCEPHALY 5, PRIMARY, AUTOSOMAL RECESSIVE; MCPH5](https://omim.org/entry/608716)

Human gene(s) implicated

[ABNORMAL SPINDLE-LIKE, MICROCEPHALY-ASSOCIATED; ASPM](https://omim.org/entry/605481)

Symptoms and phenotype

See general description of primary microcephaly, above.

(OMIM, 2013-)

Genetics

MCPH5 is caused by homozygous or compound heterozygous mutation in the ASPM gene. [from MIM:608716; 2016.06.16]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The ASPM gene plays a role in mitotic spindle function or regulation; it may play a role in the regulation of neurogenesis. [from Gene Cards, ASPM; 2016.06.20]

(FlyBase Curators, 2013-)

External links

Gene2Function (human gene): ASPM
Gene Cards: ASPM
MedlinePlus (gene): ASPM
MARRVEL (human gene): ASPM
NCBI MedGen: Primary autosomal recessive microcephaly 5 (MCPH5)
NCBI (Entrez) gene: ASPM; assembly factor for spindle microtubules

Disease synonyms

MCPH5

primary microcephaly 5

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Microcephaly, primary autosomal recessive

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[MCPH1](https://omim.org/entry/251200)

[MCPH1](https://omim.org/entry/607117)

microcephaly 1, primary, autosomal recessive

[MCPH2](https://omim.org/entry/604317)

[WDR62](https://omim.org/entry/613583)

microcephaly 2, primary, autosomal recessive

[MCPH3](https://omim.org/entry/604804)

[CDK5RAP2](https://omim.org/entry/608201)

microcephaly 3, primary, autosomal recessive

[MCPH4](https://omim.org/entry/604321)

[KNL1](https://omim.org/entry/609173)

[MCPH5](https://omim.org/entry/608716)

[ASPM](https://omim.org/entry/605481)

microcephaly 5, primary, autosomal recessive

[MCPH6](https://omim.org/entry/608393)

[CENPJ](https://omim.org/entry/609279)

microcephaly 6, primary, autosomal recessive

[MCPH7](https://omim.org/entry/612703)

[STIL](https://omim.org/entry/181590)

[MCPH8](https://omim.org/entry/614673)

[CEP135](https://omim.org/entry/611423)

[MCPH9](https://omim.org/entry/614852)

[CEP152](https://omim.org/entry/613529)

[MCPH10](https://omim.org/entry/615095)

[ZNF335](https://omim.org/entry/610827)

[MCPH11](https://omim.org/entry/615414)

[PHC1](https://omim.org/entry/602978)

[MCPH12](https://omim.org/entry/616080)

[CDK6](https://omim.org/entry/603368)

[MCPH13](https://omim.org/entry/616051)

[CENPE](https://omim.org/entry/117143)

[MCPH14](https://omim.org/entry/616402)

[SASS6](https://omim.org/entry/609321)

[MCPH16](https://omim.org/entry/616681)

[ANKLE2](https://omim.org/entry/616062)

microcephaly 16, primary, autosomal recessive

[MCPH17](https://omim.org/entry/617090)

[CIT](https://omim.org/entry/605629)

microcephaly 17, primary, autosomal recessive

[MCPH18](https://omim.org/entry/617520)

[WDFY3](https://omim.org/entry/617485)

microcephaly 18, primary, autosomal dominant

[MCPH19](https://omim.org/entry/617800)

[COPB2](https://omim.org/entry/606990)

[MCPH20](https://omim.org/entry/617914)

[KIF14](https://omim.org/entry/611279)

[MCPH21](https://omim.org/entry/617983)

[NCAPD2](https://omim.org/entry/615638)

[MCPH22](https://omim.org/entry/617984)

[NCAPD3](https://omim.org/entry/609276)

[MCPH23](https://omim.org/entry/617985)

[NCAPH](https://omim.org/entry/602332)

[MCPH24](https://omim.org/entry/618179)

[NUP37](https://omim.org/entry/609264)

[MCPH25](https://omim.org/entry/618351)

[TRAPPC14](https://omim.org/entry/618350)

[NEDMISBA](https://omim.org/entry/616486)

[MFSD2A](https://omim.org/entry/614397)

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

ASPM; assembly factor for spindle microtubules

D. melanogaster ortholog (based on DIOPT)

Dmel\asp

(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\asp

Gene Snapshot

Contributions welcome

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

Ortholog of human ASPM (1 Drosophila to 1 human). Dmel\asp shares 23% identity and 40% similarity with human ASPM.

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 (7 groups)

asp

protein-protein

Interacting group

Assay

References

asp - Cam

two hybrid

(Schoborg et al., 2015)

asp - fzr

anti tag coimmunoprecipitation, peptide massfingerprinting

(Meghini et al., 2016)

asp - Mlc-c

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

(Franke et al., 2006)

asp - p53

pull down, autoradiography

(Lunardi et al., 2010)

asp - wdb

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

(Quiniou et al., 2025)

asp - wrd

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Quiniou et al., 2025)

asp - zip

anti tag coimmunoprecipitation, western blot

(Rujano et al., 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (8 alleles)

asp

Models Based on Experimental Evidence ( 5 )

Allele

Disease

Evidence

References

asp^MB11367

model of microcephaly

CEA with asp^E3

(Rujano et al., 2013)

asp^t25

model of microcephaly

CEA

(Schoborg et al., 2015)

model of primary autosomal recessive microcephaly 5

CEC

(Schoborg et al., 2019)

CEA

(Mannino et al., 2023)

asp¹

model of microcephaly

CEA with asp^E3

(Rujano et al., 2013)

asp^E3

model of microcephaly

CEA

(Rujano et al., 2013)

CEA with asp^L1

(Rujano et al., 2013)

CEA with asp¹

(Rujano et al., 2013)

CEA with asp^MB11367

(Rujano et al., 2013)

model of primary autosomal recessive microcephaly 5

CEC

(Schoborg et al., 2019)

CEA

(Buffin et al., 2007)

asp^L1

model of microcephaly

CEA with asp^E3

(Rujano et al., 2013)

model of primary autosomal recessive microcephaly 5

CEC

(Schoborg et al., 2019)

Modifiers Based on Experimental Evidence ( 5 )

Allele

Disease

Interaction

References

asp^t25

model of primary autosomal recessive microcephaly 5

is exacerbated by Wdr62^Δ3-9

(Schoborg et al., 2019)

is ameliorated by asp^MF.GFP

(Schoborg et al., 2019)

is ameliorated by asp^MF.UAS.GFP

(Mannino et al., 2023)

asp^E3

model of primary autosomal recessive microcephaly 5

is ameliorated by mad2^Δ

(Buffin et al., 2007)

is ameliorated by mad2^G6595

(Buffin et al., 2007)

is ameliorated by rod^unspecified

(Buffin et al., 2007)

asp^UASp.EGFP

exacerbates tauopathy

modeled by Hsap\MAPT^UAS.cWa

(Feuillette et al., 2020)

asp^MF.GFP

ameliorates primary autosomal recessive microcephaly 5

modeled by asp^t25

(Schoborg et al., 2019)

asp^MF.UAS.GFP

ameliorates primary autosomal recessive microcephaly 5

modeled by asp^t25

(Mannino et al., 2023)

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

Primary microcephaly

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

w^*; P{UASp-asp.GFP}attP2

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

asp^GD1375

P{GD1375}

w¹¹¹⁸; P{GD1375}v2911

asp^JF03169

P{TRiP.JF03169}

y¹ v¹; P{TRiP.JF03169}attP2

y¹ sc^* v¹ sev²¹; P{TRiP.GL00108}attP2

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

asp¹

ethyl methanesulfonate

In(3R)Ubx^7LLats^R, asp¹ ats¹ p^p/TM6B, Tb¹ ca¹; y¹/Dp(1;Y)y⁺

asp^L1

X ray

red^* asp^L1/TM6B, Tb¹

asp^E3

X ray

w^*; asp^E3/TM3, P{ActGFP}JMR2, Ser¹

asp^MB11367

w¹¹¹⁸; Mi{ET1}asp^MB11367/TM6C, Sb¹

asp^t25

amorphic allele - molecular evidence

References (19)

Report Sections

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