JAGN1

Chr 3AR

jagunal vesicle mediated transporter 1

Also known as: GL009, SCN6

NCBI Gene: 84522ENSG00000171135UniProt: Q8N5M9

The protein encoded by this gene is a transmembrane protein. It functions in the early secretory pathway and is necessary for neutrophil differentiation and survival. Mutations in this gene result in severe congenital neutropenia. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Neutropenia, severe congenital, 6, autosomal recessiveMIM #616022
AR
235
ClinVar variants
50
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— JAGN1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 109 VUS of 235 total submissions
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.35LOEUF
pLI 0.007
Z-score 0.97
OE 0.60 (0.29–1.35)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.06Z-score
OE missense 0.98 (0.84–1.16)
103 obs / 104.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.60 (0.29–1.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.84–1.16)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 4 / 6.7Missense obs/exp: 103 / 104.7Syn Z: -0.84

ClinVar Variant Classifications

235 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic5
VUS109
Likely Benign57
Benign11
Conflicting8
45
Pathogenic
5
Likely Pathogenic
109
VUS
57
Likely Benign
11
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
44
0
45
Likely Pathogenic
1
0
4
0
5
VUS
6
75
28
0
109
Likely Benign
0
3
13
41
57
Benign
0
0
8
3
11
Conflicting
—8
Total7799744235

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

View in ClinVar →

Protein Context — Lollipop Plot

JAGN1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

JAGN1-related severe congenital neutropenia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
JAGUNAL HOMOLOG 1; JAGN1
MIM #616012 · *

Neutropenia, severe congenital, 6, autosomal recessive

MIM #616022

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Phenotypic Variability Associated with Jagunal Homolog 1 (JAGN1) Deficiency Caused by the c.63G>T Variant.
Pantea CL et al.·Int J Mol Sci
2026
Macrophage-derived exosome miR-146a-5p modulates PNKP/DDOST/JAGN1 complex to regulate NETs formation in atherosclerosis.
Liu Z et al.·Cell Signal
2025
A case of JAGN1 mutation presenting with atypical diabetes and immunodeficiency.
De Cuyper C et al.·J Pediatr Endocrinol Metab
2025
Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients: a multicenter study by ESID and EBMT IEWP.
Fekadu-Siebald J et al.·Blood Adv
2025🔓 Open AccessCohort
Case report: Granulocyte-macrophage colony-stimulating factor sargramostim did not rescue the neutrophil phenotype in two patients with JAGN1-mutant severe congenital neutropenia.
Farmand S et al.·Front Immunol
2024🔓 Open AccessCohort
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools