FDX2

protein-coding

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

Gene summary

This gene encodes a member of the ferredoxin family. The encoded protein contains a 2Fe-2S ferredoxin-type domain and is essential for heme A and Fe/S protein biosynthesis. Mutation in FDX1L gene is associated with mitochondrial muscle myopathy. [provided by RefSeq, Sep 2014]

Previous symbols:

FDX1L

MANE transcript

NM_001397406.1

Inheritance

ClinVar variants

P:5U:39B:53

Top phenotype

Mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr19:10,309,916-10,316,015

External References & Databases

Ensembl (ENSG00000267673)

Transcript & Mutation Effects

hg38 • Region Span ~6.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020714

Submitter: Ambry Genetics

inborn mitochondrial myopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009637

Submitter: PanelApp Australia

mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020714

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathyAR

Manifestation: Biochemical; Musculoskeletal; Neurologic; Renal

Intervention: Musculoskeletal; Renal

Rationale: Among other features, the condition can include rhabdomyolysis, and awareness may allow medical management

Refs: 24281368;30010796

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FDX2 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 124

not specifiedTotal: 22

FDX2-related disorderTotal: 6

Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathyTotal: 5

Inborn mitochondrial myopathyTotal: 2

FDX1L & FDX2-related disordersTotal: 1

Inborn genetic diseasesTotal: 1

Mitochondrial myopathy, episodic, without optic atrophy and reversible leukoencephalopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001397406.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				47 clinvar	1 clinvar	48
missense		1 clinvar	35 clinvar	4 clinvar	1 clinvar	41
nonsense		1 clinvar	2 clinvar			3
start loss		2 clinvar				2
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	5	39	51	2	97

Highest pathogenic variant AF is 0.00006775846

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001397406.1	RefSeq	NP_001384335.1	5	MANE Select
ENST00000393708.3	Ensembl	ENSP00000377311.5	5	MANE Select
ENST00000492239.5	Ensembl	ENSP00000488228.1	1	Standard
ENST00000494368.5	Ensembl	ENSP00000467188.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phase I - Functionalization of compounds
Electron transport from NADPH to Ferredoxin
Metabolism of lipids
Endogenous sterols
Cytochrome P450 - arranged by substrate type

Biological Process

C21-steroid hormone biosynthetic process
sterol metabolic process
electron transport chain
small molecule metabolic process

Molecular Function

protein binding
electron transfer activity
metal ion binding
2 iron, 2 sulfur cluster binding

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000393708
Coding exons: 5
Length: 10589
Individuals with no LoFs: 125632
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125654
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.529	91	106	0.856	0.00000535	1151
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000034	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000095	0.000088	rare
South Asian	0.00010	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for heme A and Fe/S protein biosynthesis. {ECO:0000269|PubMed:20547883}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

RVIS EVS: 0.35
RVIS percentile EVS: 74.18

Essentials

Essential (gene trap): E