What is NUBPL?

Gene Name: NUBPL, acronym for Nucleotide-binding protein-like

Also Known As:  Iron-sulfur protein required for NADH dehydrogenase or IND1

Location: Chromosome 14q12

Symbols: NUBPL; IND1; huInd1; C14orf127

Genetic Inheritance: Recessive

Gene Function: It is an iron-sulfur (Fe/S) protein that, in humans, is encoded by the NUBPL gene. It that has an early role in the assembly of the mitochondrial complex I assembly pathway.

Mutations in the NUBPL gene may cause a rare form of mitochondrial complex I disorder.

Typical clinical signs and symptoms:

  • Age of onset 1-2 years old
  • Developmental delay: Some patients
  • Delay: Motor; Unable to walk
  • Speech: Abnormal (Dysarthria)
  • Eyes: Strabismus; Nystagmus
  • Ataxia: Trunk & Limbs
  • Contractures
  • Spasticity
  • Cognitive: Normal or Reduced
  • Myopathy
  • Other organs: Normal
  • Course: Progressive, continuous or episodic

Laboratory signs:

  • MRI: Leukoencephalopathy with abnormal:
    • Cerebellar cortex: Progressive
    • Cerebral white matter, deep: May resolve
    • Corpus callosum: May resolve
      *Although these are characteristic MRI findings, there are others including abnormalities in the grey matter of the cerebellum, as is discussed in Hope for Katherine Belle.
  • Lactate: Serum normal or high; CSF normal or high
  • NUBPL protein: Reduced
  • Muscle biopsy
    • Histology: Ragged red fibers; No COX- fibers

Biochemistry: Complex I deficiency

Overview of NUBPL Mutations
GeneDx (USA): c.166G>A (maternal); c.815-27T>A (maternal); and c.693+1G>A (paternal)

Ambry 1 & 2 (USA): c.311T>C (maternal); p.L104P (maternal); and c.815-27T>C (paternal)

Kevelam 1 (Arg.): c.166G>A (unknown); and c.815-27T>C (unknown) (older results)

Kevelam 2 (Ger.): c.166G>A (paternal); c.815-27T>C (paternal); and c.667_668insCCTTGTGCTG (maternal)

Kevelam 3&4 (Can.): c.166G>A (paternal); c.815-27T>C (paternal); and c.313G>T (maternal)

Kevelam 5 (USA): c.166G>A (paternal); c.815-27T>A (paternal); and c.693+1G>A (maternal)

Kevelam 6 (Neth.): c.166G>A (maternal); c.815-27T>C (maternal); and c.579A>C (paternal)

Kevelam 7 (Australia): c.166G>A (paternal); c.815-27T>C (paternal); 240-kb deletion (maternal); and 137-kb duplication (maternal)


Sheftel, A. “Human Ind1, an Iron-Sulfur Cluster Assembly Factor for Respiratory Complex I”. Mcb.asm.org. Retrieved 25 April 2015

Sheftel, A. “Human ind1, an iron-sulfur cluster assembly factor for respiratory complex I”. Mol. Cell. Biol. 29 (22): 6059–6073. PMID 19752196.

Calvo, S. “High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency”. PMID 20818383.

Kevelam, S. “NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern”. Neurology 80 (17): 1577–1583. PMID 23553477


The more we connect with other NUBPL families, the closer we get to finding a cure.  Do you have NUBPL or do you think you may?  Or, are you a researcher who is interested in studying NUBPL?  Please contact us.  We want to hear from you. Although some families are public about their journey, we respect your desire for privacy.



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