Mitochondrial disorder with complex I deficiency

Gene: NDUFB7

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 11 Dec 2025, 10:58 a.m. | Last Modified: 11 Dec 2025, 10:58 a.m.

Panel Version: 3.17

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Although only two unrelated cases have been reported to date (PMID: 33502047, 40025060) there is strong functional data and an animal model that support the association. The existence of a therapeutic strategy further supports timely inclusion of this gene on a diagnostic panel.

Created: 18 Mar 2025, 11:13 a.m. | Last Modified: 18 Mar 2025, 11:13 a.m.

Panel Version: 3.11

PMID: 40025060 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 18 Mar 2025, 11:11 a.m. | Last Modified: 18 Mar 2025, 11:11 a.m.

Panel Version: 3.10

PMID: 40025060 (2025) - another patient with compound heterozygous variants (c.133_135del; p.Glu45del and c.311G>C; p.Arg104Pro) in NDUFB7 presented with features of mitochondrial disease including pons abnormality, lactic acidosis, prematurity, prenatal and postnatal growth deficiency, ventral hernia, and pseudo-obstruction. Unlike the previously reported patient who died 55 days after birth, this patient was stable at 20 years old at the time of reporting, following multiple surgeries and ongoing treatment with CoenzymeQ and vitamin B complex.

The patient’s skin fibroblasts were deficient in Complex I assembly and reduced supercomplex formation. A knockdown Ndufb7 zebrafish model exhibited brain ventricle and neuronal defects, elevated lactic acid levels, and reduced oxygen consumption, indicating defective mitochondrial respiration. These phenotypes were rescued by ectopic expression of ndufb7.

Created: 18 Mar 2025, 11:10 a.m. | Last Modified: 18 Mar 2025, 11:10 a.m.

Panel Version: 3.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135

Publications

• 40025060

Comment on phenotypes: No OMIM or MONDO phenotype (21/4/2021)

Created: 21 Apr 2021, 12:58 p.m. | Last Modified: 21 Apr 2021, 12:58 p.m.

Panel Version: 1.13

Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371).

Created: 21 Apr 2021, 12:54 p.m. | Last Modified: 21 Apr 2021, 12:54 p.m.

Panel Version: 1.10

I don't know

Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: no reports of human disease; complex I subunit

Created: 10 May 2019, 9:50 a.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Publications

• none found

Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter.

Created: 10 May 2019, 10:16 a.m.

Comment on list classification: This gene has been demoted to Amber until further evidence is provided. This gene is currently Red on the Mitochondrial disorders panel (code 112, Version 1.131) - further evidence needs to be submitted to support promoting this gene family member to Green.

Created: 29 Mar 2019, 11:04 a.m.

Green List (high evidence)

Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group. Gene Symbol submitted: NDUFB7; Suggested intial gene rating: Green.

Created: 1 Feb 2019, 4:29 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

I don't know

no mutation reports in literature; good candidate gene for complex I deficiency (encodes a subunit of the enzyme)

Created: 4 Feb 2016, 8:26 p.m.