FOXRED1

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

Basic information

Region (hg38): 11:126269024-126278131

Links

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

Phenotypes

GenCC

Source: genCC

• Leigh syndrome (Moderate), mode of inheritance: AR
• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• Leigh syndrome with leukodystrophy (Supportive), 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
• mitochondrial complex I deficiency, nuclear type 19 (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 (407 variants)
• Inborn_genetic_diseases (65 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_1 (35 variants)
• Mitochondrial_complex_I_deficiency,_nuclear_type_19 (33 variants)
• not_specified (30 variants)
• Leigh_syndrome (12 variants)
• FOXRED1-related_disorder (9 variants)
• Mitochondrial_complex_I_deficiency (4 variants)
• Mitochondrial_disease (2 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. These statistics are base on transcript: NM_000017547.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	147		150
missense	1	12	116	19	2	150
nonsense	17	6	1			24
start loss			1			1
frameshift	13	3	1			17
splice donor/acceptor (+/-2bp)	2	16				18
Total	33	37	122	166	2

Highest pathogenic variant AF is 0.000311194

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