FOXRED1

FAD dependent oxidoreductase domain containing 1, the group of Mitochondrial respiratory chain complex assembly factors

Basic information

Region (hg38): 11:126269023-126278131

Links

ENSG00000110074 ∙ NCBI:55572 ∙ OMIM:613622 ∙ HGNC:26927 ∙ Uniprot:Q96CU9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency, nuclear type 1 (Definitive), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency, nuclear type 1 (Strong), mode of inheritance: AR
• Leigh syndrome (Moderate), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 19	AR	Biochemical	Medical treatment (eg, riboflavin, uniquinol) may be beneficial	Biochemical; Cardiovascular; Musculoskeletal; Neurologic; Ophthalmologic	11743516; 20818383; 20858599

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXRED1 gene.

• not provided (266 variants)
• Mitochondrial complex I deficiency, nuclear type 1 (50 variants)
• not specified (29 variants)
• Inborn genetic diseases (22 variants)
• Mitochondrial complex 1 deficiency, nuclear type 19 (22 variants)
• Leigh syndrome (9 variants)
• Mitochondrial complex I deficiency (4 variants)
• Leigh syndrome;Mitochondrial complex I deficiency, nuclear type 1 (2 variants)
• FOXRED1-related condition (1 variants)
• Mitochondrial encephalopathy (1 variants)
• Seizure (1 variants)
• Developmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXRED1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	78		80
missense	1	5	78	3	3	90
nonsense	5	4	2			11
start loss			1			1
frameshift	5					5
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	5	1			8
splice region			5	8		13
non coding			9	54	13	76
Total	13	14	94	135	16

Highest pathogenic variant AF is 0.0000329

Variants in FOXRED1

This is a list of pathogenic ClinVar variants found in the FOXRED1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-126269044-G-C		Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Aug 22, 2020)
11-126269056-C-A		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
11-126269114-C-G			Likely benign (Jul 15, 2018)
11-126269172-G-A			Uncertain significance (Oct 09, 2014)
11-126269176-A-G		not specified • Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Jan 13, 2018)
11-126269177-G-A		not specified	Likely benign (Aug 31, 2017)
11-126269192-G-A		not specified	Likely benign (Feb 10, 2017)
11-126269205-T-C		Mitochondrial complex I deficiency, nuclear type 1 • Mitochondrial complex 1 deficiency, nuclear type 19	Benign (Aug 10, 2021)
11-126269207-A-G			Uncertain significance (Apr 04, 2022)
11-126269213-C-T		not specified	Uncertain significance (Dec 14, 2023)
11-126269215-G-A		not specified • Mitochondrial complex I deficiency, nuclear type 1	Conflicting classifications of pathogenicity (Jan 30, 2024)
11-126269215-G-C			Likely benign (Jan 12, 2024)
11-126269216-A-C			Likely benign (Nov 20, 2023)
11-126269216-A-G		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Feb 18, 2022)
11-126269217-G-T			Uncertain significance (Dec 02, 2021)
11-126269222-C-T			Likely benign (Jan 22, 2024)
11-126269226-C-T		Leigh syndrome	Uncertain significance (Jul 22, 2022)
11-126269227-G-T			Likely benign (Sep 19, 2023)
11-126269228-C-T			Uncertain significance (Aug 19, 2022)
11-126269231-G-C		not specified	Conflicting classifications of pathogenicity (Aug 23, 2022)
11-126269232-G-A		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
11-126269233-C-T			Uncertain significance (Aug 10, 2023)
11-126269240-CG-C			Pathogenic (Jun 01, 2023)
11-126269241-G-C		Mitochondrial complex I deficiency, nuclear type 1	Uncertain significance (Jan 13, 2018)
11-126269245-C-A			Likely benign (May 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXRED1	protein_coding	protein_coding	ENST00000263578	11	9077

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.99e-16	0.0144	125609	0	139	125748	0.000553

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.402	291	272	1.07	0.0000175	3115
Missense in Polyphen		81	83.238	0.97311		933
Synonymous	-1.60	135	113	1.19	0.00000770	1010
Loss of Function	0.261	25	26.4	0.945	0.00000162	276

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000648	0.000647
Ashkenazi Jewish	0.000995	0.000993
East Asian	0.000109	0.000109
Finnish	0.000378	0.000370
European (Non-Finnish)	0.000706	0.000703
Middle Eastern	0.000109	0.000109
South Asian	0.000523	0.000523
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, PubMed:25678554). Involved in mid-late stages of complex I assembly (PubMed:25678554). {ECO:0000269|PubMed:20858599, ECO:0000269|PubMed:25678554}.
• Disease: DISEASE: Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. {ECO:0000269|PubMed:20818383, ECO:0000269|PubMed:20858599, ECO:0000269|PubMed:25678554}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0857

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.85

Haploinsufficiency Scores

• pHI: 0.0267
• hipred: N
• hipred_score: 0.144
• ghis: 0.539

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.115

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Foxred1

Gene ontology

• Biological process: mitochondrial respiratory chain complex I assembly;oxidation-reduction process
• Cellular component: cytoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex I;integral component of membrane
• Molecular function: oxidoreductase activity