FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: mitochondrial complex I deficiency, nuclear type 18
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General Information
Name
mitochondrial complex I deficiency, nuclear type 18
FlyBase ID
FBhh0001389
Disease Ontology Term
Parent Disease
OMIM
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 18; MC1DN18
Overview

This report describes mitochondrial complex I deficiency, nuclear type 18 (MC1DN18); MC1DN18 exhibits autosomal recessive inheritance. The human gene implicated in this disease is NDUFAF3, an essential protein for assembly of mitochondrial complex I, the first enzyme complex in the mitochondrial respiratory electron transport chain. There is a single orthologous gene in Drosophila, CG5569, for which multiple genetic reagents have been generated including RNAi-targeting constructs, a targeted CRISPR knockout construct, and a targeted CRISPR activation construct.

The human NDUFAF3 gene has not been introduced into flies.

RNAi-mediated knockdown of CG5569 in all muscles is lethal. Knockdown restricted to thoracic muscles allows survival to adulthood and has been used in this disease model. The impact upon complex I assembly has been characterized. Animals with reduced levels of CG5569 in adult thoracic muscles exhibit reduced locomotor activity. Overexpression of the Drosophila ortholog of NDUFAF4 (CG11722) reverses the locomotor phenotype and, in fact, increases adult locomotor activity relative to wild-type.

[updated Sep. 2021 by FlyBase; FBrf0222196]

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

Mitochondrial complex I deficiency causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, and liver disease. [from MIM:252010; 2016.08.12]

(OMIM, 2013-)
Specific Disease Summary: mitochondrial complex I deficiency, nuclear type 18
OMIM report

[MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 18; MC1DN18](https://omim.org/entry/618240)

Human gene(s) implicated

[NADH DEHYDROGENASE (UBIQUINONE) COMPLEX I, ASSEMBLY FACTOR 3; NDUFAF3](https://omim.org/entry/612911)

Symptoms and phenotype

MC1DN18 is a fatal neonatal disorder of the oxidative phosphorylation system. [Gene Cards, NDUFAF3; 21.09.16]

(FlyBase Curators, 2013-)
Genetics

Mitochondrial complex I deficiency nuclear type 18 (MC1DN18) is caused by homozygous or compound heterozygous mutation in the NDUFAF3 gene. [from MIM:618240; 2021.09.16]

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

NDUFAF3 encodes an essential mitochondrial complex I assembly protein that interacts with complex I subunits. [Gene Cards, NDUFAF3; 21.09.16]

(FlyBase Curators, 2013-)
External links
Disease synonyms
MC1DN18
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    NDUFAF3; NADH:ubiquinone oxidoreductase complex assembly factor 3
    D. melanogaster ortholog (based on DIOPT)
    Dmel\NdufAF3
    (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\NdufAF3
      Gene Snapshot
      Contributions welcome
      Molecular function (GO)
        Cellular component (GO)
        Gene Groups / Pathways
        Comments on ortholog(s)

        High-scoring ortholog of human NDUFAF3 (1 Drosophila to 1 human). Dmel\CG5569 shares 36% identity and 56% 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 (0 groups)
          Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
          NdufAF3
          Models Based on Experimental Evidence ( 2 )
          Modifiers Based on Experimental Evidence ( 2 )
          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
          NdufAF3GD10552
          P{GD10552}
          w1118; P{GD10552}v21569
          NdufAF3KK102896
          P{KK102896}
          P{KK102896}VIE-260B
          NdufAF3NIG.5569R
          P{NIG.5569R}
          P{NIG.5569R}2
          NdufAF3HMC03468
          P{TRiP.HMC03468}
          y1 v1; P{TRiP.HMC03468}attP40
          Selected Drosophila classical alleles
          Allele
          Allele class
          Mutagen
          Publicly Available Stocks
          References (4)