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
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; Multiple mitochondrial dysfunctions syndrome 9B	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; Neurologic; Ophthalmologic	28965846; 29040572; 30250212; 33348459; 36317462; 37046037; 37107710; 37481223

ClinVar

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

Inborn_genetic_diseases (82 variants)
not_provided (59 variants)
FDXR-related_disorder (29 variants)
Auditory_neuropathy-optic_atrophy_syndrome (26 variants)
Multiple_mitochondrial_dysfunctions_syndrome_9b (8 variants)
not_specified (4 variants)
Retinal_dystrophy (2 variants)
Optic_atrophy (1 variants)
Optic_atrophy-ataxia-peripheral_neuropathy-global_developmental_delay_syndrome (1 variants)
Auditory_neuropathy (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. These statistics are base on transcript: NM_000024417.5. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	12 clinvar	4 clinvar	17
missense	2 clinvar	12 clinvar	86 clinvar	12 clinvar	2 clinvar	114
nonsense	1 clinvar	1 clinvar	2 clinvar			4
start loss		2				2
frameshift	1 clinvar	4 clinvar				5
splice donor/acceptor (+/-2bp)		3 clinvar				3
Total	4	22	89	24	6

Highest pathogenic variant AF is 0.00004105785

Loading clinvar variants...

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