JAG2

Chr 14AR

jagged canonical Notch ligand 2

Also known as: HJ2, LGMDR27, SER2

NCBI Gene: 3714 ENSG00000184916 UniProt: Q9Y219 OMIM: 602570

The protein encoded by JAG2 is a Notch signaling ligand that activates Notch receptors and is involved in limb development. Mutations cause limb-girdle muscular dystrophy type 27, inherited in an autosomal recessive pattern. JAG2 is highly constrained against loss-of-function variants, indicating the gene is intolerant to mutation.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The Notch signaling pathway is an intercellular signaling mechanism that is essential for proper embryonic development. Members of the Notch gene family encode transmembrane receptors that are critical for various cell fate decisions. The protein encoded by this gene is one of several ligands that activate Notch and related receptors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.141 OMIM phenotype

Clinical Summary— JAG2

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Gene-Disease Validity (ClinGen)

autosomal recessive limb-girdle muscular dystrophy · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

5 unique Pathogenic / Likely Pathogenic· 253 VUS of 380 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.14LOEUF

pLI 1.000

Z-score 6.95

OE 0.06 (0.03–0.14)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.20Z-score

OE missense 0.78 (0.73–0.83)

626 obs / 801.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.14)

0≤0.351.4

Missense OE?0.78 (0.73–0.83)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 4 / 63.9Missense obs/exp: 626 / 801.0Syn Z: -2.34

ClinVar Variant Classifications

380 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic4

VUS253

Likely Benign75

Benign23

Conflicting6

Pathogenic

Likely Pathogenic

253

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	2	2	0	0	4
VUS	2	250	1	0	253
Likely Benign	0	14	15	46	75
Benign	0	6	2	15	23
Conflicting	—				6
Total	5	272	18	61	362

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

57 pathogenic / likely-pathogenic (of 78) ClinVar copy-number / structural variants overlap JAG2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →