Mitochondrial disorder with complex III deficiency

Gene: UQCC1

I don't know

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, 8:41 a.m. | Last Modified: 20 Aug 2026, 8:42 a.m.

Panel Version: 2.14

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

Created: 20 Aug 2026, 8:40 a.m. | Last Modified: 20 Aug 2026, 8:40 a.m.

Panel Version: 2.12

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, 8:34 a.m. | Last Modified: 20 Aug 2026, 8:38 a.m.

Panel Version: 2.9

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
mitochondrial respiratory chain complex deficiency, MONDO:0000066

Publications

• 39504961

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, 10:29 a.m. | Last Modified: 12 Aug 2026, 10:29 a.m.

Panel Version: 2.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
lactic acidosis

Publications

• 39504961

Comment on list classification: Demoting to Red as there is no evidence for Mendelian gene-disease association at this time

Created: 29 Jul 2022, 1:02 p.m. | Last Modified: 29 Jul 2022, 1:02 p.m.

Panel Version: 1.5

Comment when marking as ready: 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, 10:53 a.m.

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 III assembly factor

Created: 10 May 2019, 10:51 a.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype

Publications

• none found

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: UGCC1; Suggested intial gene rating: Green.

Created: 1 Feb 2019, 4:33 p.m.

Mode of inheritance
Unknown

Phenotypes
No OMIM phenotype