FDXR

ferredoxin reductase, the group of Mitochondrial respiratory chain complex assembly factors|Mitochondrial iron-sulfur assembly components

Basic information

Region (hg38): 17:74862497-74873031

Previous symbols: [ "ADXR" ]

Links

ENSG00000161513 ∙ NCBI:2232 ∙ OMIM:103270 ∙ HGNC:3642 ∙ Uniprot:P22570 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• auditory neuropathy-optic atrophy syndrome (Strong), mode of inheritance: AR
• auditory neuropathy-optic atrophy syndrome (Supportive), mode of inheritance: AR
• optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome (Supportive), mode of inheritance: AR
• auditory neuropathy-optic atrophy syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Auditory neuropathy and optic atrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Ophthalmologic	28965846

ClinVar

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

• Auditory neuropathy-optic atrophy syndrome (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FDXR 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				8	5	13
missense	1	7	55	5	4	72
nonsense		1	1			2
start loss		2				2
frameshift	1	2				3
inframe indel	1					1
splice donor/acceptor (+/-2bp)		2				2
splice region			1		1	2
non coding			2	4	19	25
Total	3	14	58	17	28

Variants in FDXR

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

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

Position	Type	Phenotype	Significance	ClinVar
17-74862587-G-A			Benign (May 12, 2021)
17-74862678-G-T			Benign (May 12, 2021)
17-74862819-A-G			Uncertain significance (Jun 13, 2022)
17-74862834-G-A		Auditory neuropathy-optic atrophy syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 01, 2022)
17-74862839-A-G		Auditory neuropathy-optic atrophy syndrome	Uncertain significance (Mar 22, 2022)
17-74862864-C-T		Auditory neuropathy-optic atrophy syndrome	Uncertain significance (May 11, 2023)
17-74862879-T-C		FDXR-related disorder	Benign/Likely benign (Nov 01, 2023)
17-74862926-G-C		Inborn genetic diseases	Uncertain significance (Mar 19, 2021)
17-74862937-T-C		FDXR-related disorder	Benign (Dec 31, 2019)
17-74862945-C-T		Inborn genetic diseases	Uncertain significance (May 23, 2024)
17-74862956-G-G			Benign (Jan 07, 2021)
17-74863078-C-T			Uncertain significance (Apr 01, 2017)
17-74863093-G-T			Uncertain significance (Jan 21, 2023)
17-74863112-C-T		Inborn genetic diseases • Auditory neuropathy-optic atrophy syndrome	Uncertain significance (May 26, 2016)
17-74863137-C-T		FDXR-related disorder	Likely benign (Jan 06, 2020)
17-74863142-C-A		FDXR-related disorder	Conflicting classifications of pathogenicity (Jan 01, 2023)
17-74863166-G-A		Auditory neuropathy-optic atrophy syndrome	Pathogenic (Oct 12, 2017)
17-74863169-C-T		not specified	Uncertain significance (May 04, 2022)
17-74863211-T-C		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
17-74863213-G-A			Likely pathogenic (Aug 08, 2024)
17-74863219-C-T		FDXR-related disorder	Uncertain significance (Nov 01, 2018)
17-74863227-C-A			Uncertain significance (Apr 06, 2022)
17-74863914-G-A		Inborn genetic diseases • Auditory neuropathy-optic atrophy syndrome • FDXR-related disorder • Multiple mitochondrial dysfunctions syndrome 9b	Pathogenic/Likely pathogenic (Dec 13, 2023)
17-74863920-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (May 01, 2023)
17-74863956-G-A			Uncertain significance (Oct 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FDXR	protein_coding	protein_coding	ENST00000442102	12	10538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000115	0.988	125687	0	41	125728	0.000163

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.906	294	341	0.862	0.0000216	3369
Missense in Polyphen		82	101.55	0.80752		907
Synonymous	0.740	133	144	0.922	0.00000925	1174
Loss of Function	2.28	14	26.7	0.523	0.00000142	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000183	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000207	0.000202
Middle Eastern	0.000111	0.000109
South Asian	0.000393	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver. {ECO:0000250|UniProtKB:P08165}.
• Disease: DISEASE: Auditory neuropathy and optic atrophy (ANOA) [MIM:617717]: An autosomal recessive disease characterized by hearing loss, visual impairment and optic atrophy, with onset in the first or second decades of life. Optic atrophy is caused by degeneration of nerve fibers which arise in the retina and converge to form the optic disk, optic nerve, optic chiasm and optic tracts. {ECO:0000269|PubMed:28965846}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Phase I - Functionalization of compounds;Electron transport from NADPH to Ferredoxin;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Mitochondrial iron-sulfur cluster biogenesis;Metabolism;Pregnenolone biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Validated transcriptional targets of TAp63 isoforms;Direct p53 effectors;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.383

Intolerance Scores

• loftool: 0.495
• rvis_EVS: 0.54
• rvis_percentile_EVS: 81.07

Haploinsufficiency Scores

• pHI: 0.111
• hipred: Y
• hipred_score: 0.715
• ghis: 0.427

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.826

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fdxr
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: generation of precursor metabolites and energy;steroid biosynthetic process;C21-steroid hormone biosynthetic process;ubiquinone biosynthetic process;cholesterol metabolic process;sterol metabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix
• Molecular function: ferredoxin-NADP+ reductase activity;NADPH-adrenodoxin reductase activity;oxidoreductase activity