AGR2

anterior gradient 2, protein disulphide isomerase family member, the group of Protein disulfide isomerases

Basic information

Region (hg38): 7:16791810-16833433

Links

ENSG00000106541 ∙ NCBI:10551 ∙ OMIM:606358 ∙ HGNC:328 ∙ Uniprot:O95994 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• respiratory infections, recurrent, and failure to thrive with or without diarrhea (Limited), mode of inheritance: AR
• respiratory infections, recurrent, and failure to thrive with or without diarrhea (Strong), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGR2 gene.

• Inborn genetic diseases (8 variants)
• Respiratory infections, recurrent, and failure to thrive with or without diarrhea (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGR2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding						0
Total	0	1	8	0	0

Highest pathogenic variant AF is 0.00000657

Variants in AGR2

This is a list of pathogenic ClinVar variants found in the AGR2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-16794972-G-T		not specified	Uncertain significance (Mar 29, 2023)
7-16794986-C-T		Respiratory infections, recurrent, and failure to thrive with or without diarrhea	Pathogenic (Jan 31, 2023)
7-16795011-G-C		not specified	Uncertain significance (Aug 08, 2023)
7-16795017-G-T		not specified	Uncertain significance (Jul 10, 2023)
7-16797667-G-T		not specified	Uncertain significance (Dec 22, 2023)
7-16797676-G-A		Respiratory infections, recurrent, and failure to thrive with or without diarrhea	Likely pathogenic (Mar 14, 2024)
7-16797693-T-C		Respiratory infections, recurrent, and failure to thrive with or without diarrhea	Uncertain significance (Mar 26, 2024)
7-16797695-C-T		AGR2-related disorder	Uncertain significance (Feb 16, 2024)
7-16799743-C-A		Respiratory infections, recurrent, and failure to thrive with or without diarrhea	Pathogenic (Jan 31, 2023)
7-16799806-C-T		not specified	Uncertain significance (Oct 05, 2021)
7-16801149-A-G		Respiratory infections, recurrent, and failure to thrive with or without diarrhea • AGR2-related disorder	Conflicting classifications of pathogenicity (Feb 16, 2024)
7-16801164-G-C		not specified	Uncertain significance (Jan 26, 2023)
7-16801196-G-T		Respiratory infections, recurrent, and failure to thrive with or without diarrhea	Likely pathogenic (Mar 25, 2024)
7-16801687-C-T		not specified	Likely benign (Feb 06, 2024)
7-16801703-C-G		not specified	Uncertain significance (Sep 12, 2023)
7-16801735-C-A		not specified	Uncertain significance (Feb 27, 2023)
7-16801763-G-A		not specified	Uncertain significance (Aug 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGR2	protein_coding	protein_coding	ENST00000419304	7	41623

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.24e-8	0.177	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.844	67	89.5	0.749	0.00000414	1131
Missense in Polyphen		20	33.73	0.59294		429
Synonymous	0.730	28	33.4	0.839	0.00000162	328
Loss of Function	0.103	11	11.4	0.967	5.45e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000132	0.000132
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells (By similarity). Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth. Promotes cell adhesion (PubMed:23274113). {ECO:0000250, ECO:0000269|PubMed:18199544, ECO:0000269|PubMed:23274113}.

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.625
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.0754
• hipred: Y
• hipred_score: 0.638
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0406

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Agr2
• Phenotype: hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: agr2
• Affected structure: goblet cell
• Phenotype tag: abnormal
• Phenotype quality: immature

Gene ontology

• Biological process: positive regulation of gene expression;positive regulation of cell-substrate adhesion;response to endoplasmic reticulum stress;positive regulation of epidermal growth factor receptor signaling pathway;digestive tract morphogenesis;positive regulation of developmental growth;lung goblet cell differentiation;negative regulation of cell death;mucus secretion;positive regulation of protein localization to plasma membrane;positive regulation of IRE1-mediated unfolded protein response;positive regulation of PERK-mediated unfolded protein response
• Cellular component: extracellular space;endoplasmic reticulum
• Molecular function: dystroglycan binding;epidermal growth factor receptor binding;protein binding;protein homodimerization activity