FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: mitochondrial complex III deficiency, nuclear type 1
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General Information
Name
mitochondrial complex III deficiency, nuclear type 1
FlyBase ID
FBhh0001393
Disease Ontology Term
Parent Disease
OMIM
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1
Overview

This report describes mitochondrial complex III deficiency, nuclear type 1 (MC3DN1); MC3DN1 exhibits autosomal recessive inheritance. The gene implicated in this disease is BCS1L, which encodes a protein required for assembly of mitochondrial respiratory chain complex III. There is a single orthologous gene in Drosophila, CG4908, for which a number of genetic reagents have been generated including RNAi-targeting constructs, overexpression constructs, and a targeted CRISPR knockout construct.

The human BCS1L gene has not been introduced into flies.

Partial ubiquitous knockdown of CG4908, effected by RNAi, results in developmental arrest between the third larval and the pupal stages and failure to reach the adult stage; a significant increase in total body lactate in larvae is observed. Partial knockdown in the CNS or mesodermal derivatives also result in lethality prior to adult stage. Knockdown in the fat body has milder effects, allowing survival to adulthood, with a reduction in adult lifespan.

[updated Sep. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: mitochondrial complex III deficiency, nuclear type
Symptoms and phenotype

Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001, pubmed:11528392; De Meirleir et al., 2003, oubmed:12910490 ). [from MIM:124000; 2021.09.26]

(OMIM, 2013-)
Specific Disease Summary: mitochondrial complex III deficiency, nuclear type 1
OMIM report

[MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1](https://omim.org/entry/124000)

Human gene(s) implicated

[BCS1 UBIQUINOL-CYTOCHROME C REDUCTASE COMPLEX CHAPERONE; BCS1L](https://omim.org/entry/603647)

Symptoms and phenotype
Genetics

Mitochondrial complex III deficiency nuclear type 1 (MC3DN1) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded BCS1L gene. [from MIM:124000; 2021.09.26]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

BCS1L encodes a chaperone necessary for the assembly of mitochondrial respiratory chain complex III.

(FlyBase Curators, 2013-)
External links
Disease synonyms
BCS1L-related mitochondrial disease
MC3DN1
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    BCS1L; BCS1 ubiquinol-cytochrome c reductase complex chaperone
    D. melanogaster ortholog (based on DIOPT)
    Dmel\Bcs1
    (DIOPT, 2013-)
    Comments on ortholog(s)

    One to one: 1 human gene to 1 Drosophila gene.

    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (1)
      Dmel\Bcs1
      Gene Snapshot
      Contributions welcome
      Molecular function (GO)
      Cellular component (GO)
      Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human BCS1L (1 Drosophila to 1 human). Dmel\CG4908 shares 60% identity and 78% 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 (14 groups)
        Bcs1
        protein-protein
        Interacting group
        Assay
        References
        Bcs1 - AIF
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - Ask1
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - az2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - cert
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - CG1513
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - CG9205
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - CG10494
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - CG33523
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - cliff
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - GAPcenA
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - l(2)k01209
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - RanGAP
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - rdgB
        experimental knowledge based
        (Guruharsha et al., 2011)
        Bcs1 - Sk2
        experimental knowledge based
        (Guruharsha et al., 2011)
        Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
        Bcs1
        Models Based on Experimental Evidence ( 2 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        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
        Related mammalian, viral, bacterial, or synthetic transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Bcs1GD1055
        P{GD1055}
        w1118; P{GD1055}v44845/TM3
        Bcs1JF01525
        P{TRiP.JF01525}
        y1 v1; P{TRiP.JF01525}attP2
        Bcs1JF01526
        P{TRiP.JF01526}
        y1 v1; P{TRiP.JF01526}attP2
        Bcs1NIG.4908R
        P{NIG.4908R}
        P{NIG.4908R}2
        Bcs1HMC03437
        P{TRiP.HMC03437}
        y1 v1; P{TRiP.HMC03437}attP40
        Bcs1KK102306
        P{KK102306}
        P{KK102306}VIE-260B
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        References (4)