FlyBase Allele Report: Hsap\DNM1L[G350R.UAS]

General Information

Symbol

Hsap\DNM1L^G350R.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0320377

Feature type

allele

Associated gene

Hsap\DNM1L

Associated Insertion(s)

Carried in Construct

PBac{UAS-hDNM1L.G350R}

Key Links

Transgenic product class

missense_variant

(Chao et al., 2016)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Chao et al., 2016)

Mutagen

in vitro construct

(Chao et al., 2016)

Progenitor genotype

Carried in construct

PBac{UAS-hDNM1L.G350R}

Cytology

Description

UASt regulatory sequences drive expression of Hsap\DNM1L carrying the G350R amino acid replacement identified in whole exome sequencing of an individual with infantile encephalopathy.

(Chao et al., 2016)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\DNM1L

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

Expression Data

Reporter Expression

Additional Information

Statement

Reference

Marker for

Reflects expression of

Reporter construct used in assay

Human Disease Associations

Disease Ontology (DO) Annotations

Models Based on Experimental Evidence ( 1 )

Disease

Evidence

References

model of encephalopathy due to defective mitochondrial and peroxisomal fission 1

CEA with Drp1¹

(Chao et al., 2016)

CEA

(Assia Batzir et al., 2019)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Chao et al., 2016)

DNM1L:p.Gly350Arg

(FlyBase curators, 2019-)

Variants Synonym(s)

DNM1L:p.Gly147Arg

DNM1L:p.Gly363Arg

Associated human disease model(s)

encephalopathy due to defective mitochondrial and peroxisomal fission 1

External database links

ClinVar: DNM1L_253267

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

embryonic/larval salivary gland | third instar larval stage, with Scer\GAL4^Act5C.PI

(Chao et al., 2016)

embryonic/larval somatic muscle cell | third instar larval stage, with Scer\GAL4^Mef2.PU

(Chao et al., 2016)

mitochondrion | third instar larval stage, with Scer\GAL4^Mef2.PU

(Chao et al., 2016)

peroxisome | third instar larval stage, with Scer\GAL4^Act5C.PI

(Chao et al., 2016)

Detailed Description

Statement

Reference

Expression of Hsap\DNM1L^{G350R.Scer\UAS} under the control of Scer\GAL4^Act5C.PI results in increased peroxisome size and decreased number of peroxisomes per cell in the salivary glands of third instar larvae compared to controls. Expression under Scer\GAL4^Mef2.PU causes defects in mitochondria morphology in third instar larval muscles compared to wild-type.

(Chao et al., 2016)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Suppressor of

Statement

Reference

Scer\GAL4^da.PU/Hsap\DNM1L^G350R.UAS is a non-suppressor of lethal phenotype of Drp1²/Drp1¹

(Chao et al., 2016)

Other

Statement

Reference

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Toll-6-D42 has abnormal neuroanatomy | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Act5C.PI has lethal phenotype

(Chao et al., 2016)

Phenotype Manifest In

Other

Statement

Reference

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Mef2.PU has embryonic/larval somatic muscle cell | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Mef2.PU has mitochondrion | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Toll-6-D42 has bouton | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Toll-6-D42 has axon | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Toll-6-D42 has larval ventral nerve cord | third instar larval stage phenotype

(Chao et al., 2016)

Drp1¹, Hsap\DNM1L^G350R.UAS, Scer\GAL4^Toll-6-D42 has mitochondrion | third instar larval stage phenotype

(Chao et al., 2016)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

The lethality of Drp1¹/Drp1² transheterozygotes is not rescued by expression of Hsap\DNM1L^{G350R.Scer\UAS} under the control of Scer\GAL4^da.PU in the mutant background.

Expression of Hsap\DNM1L^{G350R.Scer\UAS} under the control of Scer\GAL4^Act5C.PI causes lethality when expressed in sensitised Drp1¹/+ background while expression under the Scer\GAL4^Mef2.PU driver does not.

Expression of Hsap\DNM1L^{G350R.Scer\UAS} under the control of Scer\GAL4^Mef2.PU in sensitised Drp1¹/+ background causes mitochondria morphological defects (large blocks of interconnected mitochondria) as well as defects in their distribution, leading to decreased number of mitochondria per sarcomere or per muscle area in third instar larval muscles. Expression under the control of Scer\GAL4^Toll-6-D42 also leads to mitochondria trafficking defects in the ventral nerve cord, axons and synaptic boutons in third instar larvae. The number of mitochondria per axon area or per bouton is significantly decreased compared to controls.

(Chao et al., 2016)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (3)

Reported As

Symbol Synonym

DNM1L^(G350R)

(Chao et al., 2016)

Hsap\DNM1L^{G350R.Scer\UAS}

Hsap\DNM1L^G350R.UAS

Name Synonyms

Secondary FlyBase IDs

References (3)

Report Sections

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