JAG2

jagged canonical Notch ligand 2, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 14:105140981-105168824

Links

ENSG00000184916 ∙ NCBI:3714 ∙ OMIM:602570 ∙ HGNC:6189 ∙ Uniprot:Q9Y219 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy, limb-girdle, autosomal recessive 27 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy, limb-girdle, autosomal recessive 27	AR	Cardiovascular	The condition can include cardiomyopathy and arrhythmia, and awareness may allow early diagnosis and management	Cardiovascular; Musculoskeletal	33861953

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the JAG2 gene.

• Muscular dystrophy, limb-girdle, autosomal recessive 27 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the JAG2 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				36	11	47
missense		1	107	8	5	121
nonsense		2				2
start loss						0
frameshift	1					1
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region				9	1	10
non coding				4		4
Total	1	3	107	48	17

Variants in JAG2

This is a list of pathogenic ClinVar variants found in the JAG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-105142691-G-A		JAG2-related disorder	Likely benign (Sep 10, 2019)
14-105142706-C-T		JAG2-related disorder	Likely benign (Jan 04, 2024)
14-105142709-C-T		JAG2-related disorder	Benign (Dec 16, 2019)
14-105142723-T-C		not specified	Uncertain significance (Dec 12, 2023)
14-105142759-C-A		not specified	Uncertain significance (Oct 05, 2023)
14-105142773-G-A		JAG2-related disorder	Likely benign (Oct 04, 2021)
14-105142776-C-T		JAG2-related disorder	Likely benign (Apr 11, 2023)
14-105142777-G-A		JAG2-related disorder	Likely benign (Apr 17, 2023)
14-105142792-C-T		not specified	Uncertain significance (Jan 17, 2024)
14-105142807-G-A		not specified	Uncertain significance (Jun 10, 2022)
14-105142821-G-A			Likely benign (Mar 01, 2023)
14-105142851-C-G		not specified	Uncertain significance (Aug 08, 2022)
14-105142871-C-T		not specified	Uncertain significance (Jan 31, 2022)
14-105142874-C-T		not specified	Uncertain significance (Dec 28, 2022)
14-105142875-C-G		not specified	Uncertain significance (Feb 06, 2024)
14-105142892-C-T			Uncertain significance (Feb 22, 2023)
14-105142898-C-A		not specified	Uncertain significance (Aug 29, 2023)
14-105142898-C-T		not specified	Uncertain significance (Sep 16, 2021)
14-105142909-G-A		not specified	Uncertain significance (Sep 01, 2021)
14-105142930-G-A		not specified	Uncertain significance (Nov 09, 2023)
14-105142937-G-A		not specified	Uncertain significance (Jan 31, 2023)
14-105142941-C-T		JAG2-related disorder	Likely benign (May 01, 2022)
14-105142944-C-T		JAG2-related disorder	Likely benign (Jun 02, 2023)
14-105142945-G-A		not specified	Uncertain significance (Nov 17, 2022)
14-105142973-C-T		not specified	Uncertain significance (Feb 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
JAG2	protein_coding	protein_coding	ENST00000331782	26	27844

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.39e-8	125282	0	9	125291	0.0000359

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	626	801	0.782	0.0000589	8019
Missense in Polyphen		207	354.69	0.5836		3584
Synonymous	-2.34	413	357	1.16	0.0000312	2372
Loss of Function	6.95	4	63.9	0.0626	0.00000328	685

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000214
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000477	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Putative Notch ligand involved in the mediation of Notch signaling. Involved in limb development (By similarity). {ECO:0000250}.
• Pathway: Breast cancer - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);NOTCH-Core;Notch Signaling Pathway;NOTCH1 regulation of human endothelial cell calcification;Canonical and Non-canonical Notch signaling;EMT transition in Colorectal Cancer;Notch Signaling Pathway;Notch Signaling Pathway;Notch;Disease;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor;Notch;p73 transcription factor network;Signaling by NOTCH1;Signaling by NOTCH2;NOTCH3 Activation and Transmission of Signal to the Nucleus;Signaling by NOTCH3;Signaling by NOTCH4;Signaling by NOTCH;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;NOTCH2 Activation and Transmission of Signal to the Nucleus;Notch signaling pathway;Constitutive Signaling by NOTCH1 HD Domain Mutants;Signaling by NOTCH1 HD Domain Mutants in Cancer;GPCR signaling-G alpha i;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Diseases of signal transduction;Activated NOTCH1 Transmits Signal to the Nucleus (Consensus)

Recessive Scores

• pRec: 0.354

Intolerance Scores

• loftool: 0.00958
• rvis_EVS: -1.3
• rvis_percentile_EVS: 4.99

Haploinsufficiency Scores

• pHI: 0.802
• hipred: Y
• hipred_score: 0.793
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.921

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Jag2
• Phenotype: hematopoietic 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); reproductive system phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: jag2b
• Affected structure: pronephric tubule
• Phenotype tag: abnormal
• Phenotype quality: has extra parts of type

Gene ontology

• Biological process: skeletal system development;in utero embryonic development;respiratory system process;Notch signaling pathway;spermatogenesis;auditory receptor cell fate commitment;regulation of signaling receptor activity;morphogenesis of embryonic epithelium;cell differentiation;regulation of cell adhesion;T cell differentiation;regulation of cell population proliferation;odontogenesis of dentin-containing tooth;gamma-delta T cell differentiation;thymic T cell selection;positive regulation of Notch signaling pathway;epithelial cell apoptotic process involved in palatal shelf morphogenesis
• Cellular component: plasma membrane;integral component of plasma membrane
• Molecular function: Notch binding;calcium ion binding;protein binding;growth factor activity