PRDX3

protein-coding

peroxiredoxin 3, the group of Peroxiredoxins

Gene summary

This gene encodes a mitochondrial protein with antioxidant function. The protein is similar to the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase, and it can rescue bacterial resistance to alkylhydroperoxide in E. coli that lack the C22 subunit. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologs suggest that these genes consist of a family that is responsible for the regulation of cellular proliferation, differentiation and antioxidant functions. This family member can protect cells from oxidative stress, and it can promote cell survival in prostate cancer. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1, 3, 13 and 22. [provided by RefSeq, Oct 2014]

Previous symbols:

AOP1

MANE transcript

NM_006793.5

Inheritance

AR, AD

ClinVar variants

P:11U:47B:4

Top phenotype

Corneal dystrophy, punctiform and polychromatic pre-Descemet; Spinocerebellar ataxia, autosomal recessive 32

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr10:119,167,720-119,178,812

External References & Databases

Ensembl (ENSG00000165672)

Transcript & Mutation Effects

hg38 • Region Span ~11.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebellar ataxiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0000437

Submitter: PanelApp Australia

spinocerebellar ataxia, autosomal recessive 32STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859245

Submitter: Labcorp Genetics (formerly Invitae)

spinocerebellar ataxia, autosomal recessive 32MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859245

Submitter: G2P

corneal dystrophy, punctiform and polychromatic pre-descemetSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859248

Submitter: Labcorp Genetics (formerly Invitae)

spinocerebellar ataxia, autosomal recessive 32MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859245

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Corneal dystrophy, punctiform and polychromatic pre-Descemet; Spinocerebellar ataxia, autosomal recessive 32AD/AR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 31782998; 33889951; 34369396; 35792670

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDX3 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 39

Spinocerebellar ataxia, autosomal recessive 32Total: 13

not providedTotal: 11

Corneal dystrophy, punctiform and polychromatic pre-descemetTotal: 2

not specifiedTotal: 1

Autosomal recessive cerebellar ataxiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006793.5. 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			2 clinvar	3 clinvar		5
missense	3 clinvar	1 clinvar	43 clinvar	1 clinvar		48
nonsense	2 clinvar	2 clinvar	1 clinvar			5
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	7	4	47	4	0	62

Highest pathogenic variant AF is 0.00013337535

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006793.5	RefSeq	NP_006784.1	7	MANE Select
ENST00000298510.4	Ensembl	ENSP00000298510.2	7	MANE Select
NM_001302272.2	RefSeq	NP_001289201.1	6	Standard
ENST00000865257.1	Ensembl	ENSP00000535316.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Selenium Micronutrient Network
Detoxification of Reactive Oxygen Species
Cellular responses to stress
Cellular responses to external stimuli
Validated targets of C-MYC transcriptional activation

Biological Process

maternal placenta development
apoptotic process
response to oxidative stress
mitochondrion organization
positive regulation of cell population proliferation

Molecular Function

protein binding
protein C-terminus binding
thioredoxin peroxidase activity
alkyl hydroperoxide reductase activity
kinase binding

Cellular Component

cytoplasm
mitochondrion
mitochondrial matrix
early endosome
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000298510
Coding exons: 7
Length: 11131
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125748
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0584	145	147	0.986	0.00000785	1660
Missense (PolyPhen)		44	52.458	0.83876		649
Synonymous	0.627	52	58.1	0.895	0.00000360	508
Loss of Function	1.89	6	13.5	0.445	8.26e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides (PubMed:7733872, PubMed:17707404). Acts synergistically with MAP3K13 to regulate the activation of NF-kappa-B in the cytosol (PubMed:12492477). {ECO:0000269|PubMed:12492477, ECO:0000269|PubMed:17707404, ECO:0000269|PubMed:7733872}.;

Recessive Scores

pRec: 0.338

Intolerance Scores

LoFtool: 0.844
RVIS EVS: 0.35
RVIS percentile EVS: 74.18

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.886

Gene Damage Prediction

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