FDX2

ferredoxin 2, the group of Mitochondrial respiratory chain complex assembly factors|Ferredoxin family

Basic information

Region (hg38): 19:10309915-10316015

Previous symbols: [ "FDX1L" ]

Links

ENSG00000267673 ∙ NCBI:112812 ∙ OMIM:614585 ∙ HGNC:30546 ∙ Uniprot:Q6P4F2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy (Moderate), mode of inheritance: AR
• mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy	AR	Musculoskeletal; Renal	Among other features, the condition can include rhabdomyolysis, and awareness may allow medical management	Biochemical; Musculoskeletal; Neurologic; Renal	24281368;30010796

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FDX2 gene.

• not provided (109 variants)
• not specified (10 variants)
• Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy (2 variants)
• Inborn mitochondrial myopathy (2 variants)
• Mitochondrial myopathy, episodic, without optic atrophy and reversible leukoencephalopathy (1 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 FDX2 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			1	25	4	30
missense		1	29		3	33
nonsense			1			1
start loss		1	1			2
frameshift			1			1
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1	1	4
non coding			4	20	13	37
Total	0	2	39	45	20

Highest pathogenic variant AF is 0.00000657

Variants in FDX2

This is a list of pathogenic ClinVar variants found in the FDX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-10310306-G-C			Benign (Jun 14, 2018)
19-10310499-G-C			Uncertain significance (Jun 30, 2022)
19-10310515-C-T			Uncertain significance (Aug 16, 2022)
19-10310517-T-A			Uncertain significance (Feb 10, 2022)
19-10310519-G-C			Uncertain significance (Dec 02, 2021)
19-10310540-C-A		not specified	Benign (Jan 29, 2024)
19-10310542-G-A			Likely benign (Sep 13, 2022)
19-10310546-G-A			Likely benign (Jan 12, 2024)
19-10310552-C-T			Likely benign (Mar 28, 2022)
19-10310567-C-T			Likely benign (Nov 19, 2023)
19-10310568-G-A			Uncertain significance (Sep 23, 2021)
19-10310573-C-G			Likely benign (Apr 09, 2022)
19-10310576-C-T			Likely benign (Jan 17, 2022)
19-10310578-C-T			Uncertain significance (Aug 19, 2022)
19-10310582-C-A			Uncertain significance (Mar 02, 2022)
19-10310591-C-G			Likely benign (Dec 12, 2023)
19-10310595-C-T			Uncertain significance (Jul 25, 2022)
19-10310596-G-A			Uncertain significance (Feb 24, 2023)
19-10310597-C-T		not specified	Benign/Likely benign (Jan 26, 2024)
19-10310616-G-A		Inborn mitochondrial myopathy	Likely pathogenic (Jul 19, 2019)
19-10310618-G-A			Likely benign (Sep 14, 2022)
19-10310622-A-G			Uncertain significance (Feb 18, 2022)
19-10310633-G-A			Likely benign (May 22, 2022)
19-10310635-C-T			Uncertain significance (Aug 19, 2022)
19-10310636-G-A			Likely benign (Mar 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FDX2	protein_coding	protein_coding	ENST00000393708	5	10589

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00165	0.716	125632	0	22	125654	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.529	91	106	0.856	0.00000535	1151
Missense in Polyphen		20	33.665	0.59409		342
Synonymous	-1.64	61	46.8	1.30	0.00000256	387
Loss of Function	0.807	5	7.36	0.679	3.12e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000160	0.000157
Ashkenazi Jewish	0.00	0.00
East Asian	0.000333	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.0000952	0.0000880
Middle Eastern	0.000333	0.000326
South Asian	0.000105	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for heme A and Fe/S protein biosynthesis. {ECO:0000269|PubMed:20547883}.
• 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;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• pHI: 0.116
• hipred: N
• hipred_score: 0.162

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Fdx1l

Gene ontology

• Biological process: C21-steroid hormone biosynthetic process;sterol metabolic process;electron transport chain;small molecule metabolic process
• Cellular component: mitochondrial matrix
• Molecular function: protein binding;electron transfer activity;metal ion binding;2 iron, 2 sulfur cluster binding