Mitochondrial disorders

Gene: UQCC1

Comment on list classification: As reviewed by Hannah Robinson, there are now 2 related families reported with a founder UQCC1 missense variant. There are also supportive functional studies. Hence, this gene can be rated Amber. A 'watchlist' tag was added in anticipation of further cases. MOI set to BOTH for the moment, as it is not clear what mode is correct here.

Created: 20 Aug 2026, 8:56 a.m. | Last Modified: 20 Aug 2026, 8:56 a.m.

Panel Version: 10.23

PMID: 39504961 AlAbdi et al., 2025
Study of a large exome/genome dataset - Arab population, 17,592 local exomes and 768 local genomes. A founder variant in UQCC1 (NM_018244.5:c.656T>A;p.(Ile219Asn)) was identified in two Arab families with lactic acidosis and borderline microcephaly. Diagnosed with 'UQCC1-related mitochondrial energy disorder'. 1 individual was homozygous, and 3 heterozygous for the variant (presuming all 4 are affected?). No segregation or functional evidence provided.

Created: 20 Aug 2026, 8:56 a.m. | Last Modified: 20 Aug 2026, 8:56 a.m.

Panel Version: 10.22

Comment on phenotypes: No OMIM phenotype associated as of 20th Aug 2026.

Created: 20 Aug 2026, 8:44 a.m. | Last Modified: 20 Aug 2026, 8:44 a.m.

Panel Version: 10.20

I don't know

Report of an Arab founder variant in UQCC1 (NM_018244.5:c.656T>A;p.(Ile219Asn)) - identified in two families with lactic acidosis and borderline microcephaly. UQCC1 cooperates with UQCC2 for mitochondrial complex III assembly, and pathogenic variants of UQCC2 are an established cause of mitochondrial complex III deficiency in humans (PMID: 24385928).

GeneMatcher cohort of families with biallelic UQCC1 variants, together with functional evidence, is in preparation for publication.
Add as Amber gene with watchlist tag for now.

Created: 12 Aug 2026, 10:30 a.m. | Last Modified: 12 Aug 2026, 10:30 a.m.

Panel Version: 10.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
lactic acidosis

Publications

• 39504961

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

Created: 29 Jul 2022, 1:47 p.m. | Last Modified: 29 Jul 2022, 1:47 p.m.

Panel Version: 2.109

Red List (low evidence)

Cannot find evidence for Mendelian gene-disease association.

Created: 19 Mar 2020, 10:19 a.m. | Last Modified: 19 Mar 2020, 10:19 a.m.

Panel Version: 2.5

I don't know

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.

Created: 23 Jul 2019, 10:13 a.m. | Last Modified: 23 Jul 2019, 10:13 a.m.

Panel Version: 1.412