FDX1

protein-coding

ferredoxin 1, the group of Ferredoxin family

Gene summary

This gene encodes a small iron-sulfur protein that transfers electrons from NADPH through ferredoxin reductase to mitochondrial cytochrome P450, involved in steroid, vitamin D, and bile acid metabolism. Pseudogenes of this functional gene are found on chromosomes 20 and 21. [provided by RefSeq, Aug 2011]

Previous symbols:

MANE transcript

NM_004109.5

Inheritance

—

ClinVar variants

U:27B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr11:110,429,948-110,464,884

External References & Databases

Ensembl (ENSG00000137714)

Transcript & Mutation Effects

hg38 • Region Span ~34.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FDX1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004109.5. 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			1 clinvar		1 clinvar	2
missense			26 clinvar	2 clinvar		28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	27	2	1	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004109.5	RefSeq	NP_004100.1	4	MANE Select
ENST00000260270.3	Ensembl	ENSP00000260270.2	4	MANE Select
ENST00000963821.1	Ensembl	ENSP00000633880.1	5	Standard
ENST00000963821.2	Ensembl	ENSP00000633880.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
fdx1	Danio rerio	Structure: epiboly involved in gastrulation with mouth forming second Quality: delayed abnormal

Gene / Model

Organism

Observed Phenotype

fdx1

Danio rerio

Structure: epiboly involved in gastrulation with mouth forming second

Quality: delayed

abnormal

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
cholesterol metabolic process
sterol metabolic process
electron transport chain
hormone biosynthetic process

Molecular Function

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

Cellular Component

mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260270
Coding exons: 4
Length: 34999
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125727
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.448	57	67.4	0.846	0.00000337	1167
Missense (PolyPhen)		26	34.483	0.754		397
Synonymous	-0.256	25	23.4	1.07	0.00000101	405
Loss of Function	1.10	2	4.51	0.443	1.87e-7	81

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential for the synthesis of various steroid hormones (PubMed:20547883, PubMed:21636783). Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis (PubMed:20547883, PubMed:21636783). Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage (PubMed:20547883, PubMed:21636783). Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons (By similarity). {ECO:0000250|UniProtKB:P00257, ECO:0000269|PubMed:20547883, ECO:0000269|PubMed:21636783}.;

Recessive Scores

pRec: 0.307

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.823

Gene Damage Prediction

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