ERP44

protein-coding

endoplasmic reticulum protein 44, the group of Thioredoxin domain containing |Protein disulfide isomerases

Gene summary

This gene encodes a member of the protein disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins. It has an inferred N-terminal signal peptide, a catalytically active thioredoxin (TRX) domain, two TRX-like domains and a C-terminal ER-retention sequence. This protein functions as a pH-regulated chaperone of the secretory pathway and likely plays a role in protein quality control at the endoplasmic reticulum - Golgi interface. [provided by RefSeq, Dec 2016]

Previous symbols:

TXNDC4

MANE transcript

NM_015051.3

Inheritance

—

ClinVar variants

U:43B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr9:99,979,185-100,099,052

External References & Databases

Ensembl (ENSG00000023318)

Transcript & Mutation Effects

hg38 • Region Span ~119.9 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 ERP44 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 39

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015051.3. 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						0
missense			40 clinvar	1 clinvar		41
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	43	1	0	44

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015051.3	RefSeq	NP_055866.1	12	MANE Select
ENST00000262455.7	Ensembl	ENSP00000262455.6	12	MANE Select
ENST00000684842.1	Ensembl	ENSP00000509528.1	5	Standard
ENST00000686275.1	Ensembl	ENSP00000510307.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
erp44	Danio rerio	Structure: endocardial cushion Quality: lacks parts or has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

erp44

Danio rerio

Structure: endocardial cushion

Quality: lacks parts or has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

protein folding
response to unfolded protein
glycoprotein metabolic process
response to endoplasmic reticulum stress
neutrophil degranulation

Molecular Function

protein disulfide isomerase activity
protein binding

Cellular Component

extracellular region
endoplasmic reticulum lumen
endoplasmic reticulum membrane
endoplasmic reticulum-Golgi intermediate compartment
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262455
Coding exons: 12
Length: 119862
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125721
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.29	120	214	0.561	0.0000108	2716
Missense (PolyPhen)		11	56.806	0.19364		750
Synonymous	-0.109	75	73.8	1.02	0.00000391	714
Loss of Function	4.05	2	23.0	0.0871	0.00000124	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif. Inhibits the calcium channel activity of ITPR1. May have a role in the control of oxidative protein folding in the endoplasmic reticulum. Required to retain ERO1A and ERO1B in the endoplasmic reticulum. {ECO:0000269|PubMed:11847130, ECO:0000269|PubMed:14517240}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

LoFtool: 0.416
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.955

Gene Damage Prediction

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