PDIA3

protein-coding

protein disulfide isomerase family A member 3, the group of Protein disulfide isomerases

Gene summary

This gene encodes a protein of the endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. The protein was once thought to be a phospholipase; however, it has been demonstrated that the protein actually has protein disulfide isomerase activity. It is thought that complexes of lectins and this protein mediate protein folding by promoting formation of disulfide bonds in their glycoprotein substrates. This protein also functions as a molecular chaperone that prevents the formation of protein aggregates. [provided by RefSeq, Dec 2016]

Previous symbols:

GRP58

MANE transcript

NM_005313.5

Inheritance

—

ClinVar variants

P:1U:68B:6

Top phenotype

PDIA3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr15:43,746,394-43,773,279

External References & Databases

Ensembl (ENSG00000167004)

Transcript & Mutation Effects

hg38 • Region Span ~26.9 kb

Loading mutation effect viewer...

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 PDIA3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 6

PDIA3-related disorderTotal: 6

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005313.5. 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	2 clinvar	4
missense		1 clinvar	61 clinvar	1 clinvar	1 clinvar	64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	1	68	3	3	75

Highest pathogenic variant AF is 6.8578544e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005313.5	RefSeq	NP_005304.3	13	MANE Select
ENST00000300289.10	Ensembl	ENSP00000300289.5	13	MANE Select
ENST00000434494.5	Ensembl	ENSP00000398005.1	2	Standard
ENST00000446523.5	Ensembl	ENSP00000391111.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Protein processing in endoplasmic reticulum - Homo sapiens (human)
Prion disease pathway
Calnexin/calreticulin cycle
Post-translational protein modification

Biological Process

antigen processing and presentation of peptide antigen via MHC class I
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
protein folding
proteolysis
protein folding in endoplasmic reticulum

Molecular Function

RNA binding
protein disulfide isomerase activity
cysteine-type endopeptidase activity
phospholipase C activity
protein binding

Cellular Component

extracellular space
nucleus
endoplasmic reticulum
endoplasmic reticulum lumen
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000300289
Coding exons: 13
Length: 26888
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.684	245	277	0.884	0.0000133	3356
Missense (PolyPhen)		45	95.171	0.47283		1167
Synonymous	0.264	97	100	0.966	0.00000490	917
Loss of Function	4.28	2	25.2	0.0794	0.00000124	327

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.444

Intolerance Scores

LoFtool: 0.514
RVIS EVS: -0.51
RVIS percentile EVS: 21.41

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.840

Gene Damage Prediction

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