HJV

Chr 1AR

hemojuvelin BMP co-receptor

Also known as: HFE2, HFE2A, JH, RGMC

NCBI Gene: 148738ENSG00000168509UniProt: Q6ZVN8

The product of this gene is involved in iron metabolism. It may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression. It could also represent the cellular receptor for hepcidin. Two uORFs in the 5' UTR negatively regulate the expression and activity of the encoded protein. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Defects in this gene are the cause of hemochromatosis type 2A, also called juvenile hemochromatosis (JH). JH is an early-onset autosomal recessive disorder due to severe iron overload resulting in hypogonadotrophic hypogonadism, hepatic fibrosis or cirrhosis and cardiomyopathy, occurring typically before age of 30. [provided by RefSeq, Oct 2015]

Primary Disease Associations & Inheritance

Hemochromatosis, type 2AMIM #602390
AR
UniProtHemochromatosis 2A
668
ClinVar variants
132
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— HJV
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
132 Pathogenic / Likely Pathogenic· 136 VUS of 668 total submissions

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.
0.88LOEUF
pLI 0.004
Z-score 1.89
OE 0.44 (0.24–0.88)
Tolerant

Typical tolerance to LoF variation

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.
-0.15Z-score
OE missense 1.03 (0.93–1.14)
247 obs / 240.3 exp
Tolerant

Tolerant to missense variation

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.0.44 (0.24–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.93–1.14)
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.0.94
0≤1.21.6
LoF obs/exp: 6 / 13.5Missense obs/exp: 247 / 240.3Syn Z: 0.43

ClinVar Variant Classifications

668 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic101
Likely Pathogenic31
VUS136
Likely Benign206
Benign8
Conflicting15
101
Pathogenic
31
Likely Pathogenic
136
VUS
206
Likely Benign
8
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
1
78
0
101
Likely Pathogenic
8
5
18
0
31
VUS
1
66
66
3
136
Likely Benign
0
3
26
177
206
Benign
0
1
5
2
8
Conflicting
—15
Total3176193182497

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

View in ClinVar →

Protein Context — Lollipop Plot

HJV · protein map & ClinVar variants

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

Gene2Phenotype Curations

HJV-related haemochromatosis, juvenile

definitive
ARLoss Of FunctionAbsent Gene Product
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hemochromatosis, type 2A

MIM #602390

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Haemochromatosis.
Brissot P et al.·Nat Rev Dis Primers
2018Review
Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment.
Pietrangelo A·Gastroenterology
2010Review
Juvenile haemochromatosis.
Griffiths WJH et al.·Lancet Child Adolesc Health
2021Review
Hepcidin in hepatocellular carcinoma.
Joachim JH et al.·Br J Cancer
2022Review
Non-HFE hemochromatosis.
Pietrangelo A·Semin Liver Dis
2005Review
Bone morphogenic proteins in iron homeostasis.
Xiao X et al.·Bone
2020Review
Non-HFE hepatic iron overload.
Pietrangelo A et al.·Semin Liver Dis
2011Review
HJV and HFE Play Distinct Roles in Regulating Hepcidin.
Wu Q et al.·Antioxid Redox Signal
2015
Ferroportin disease: pathogenesis, diagnosis and treatment.
Pietrangelo A·Haematologica
2017Review
Hemojuvelin deficiency promotes liver mitochondrial dysfunction and predisposes mice to hepatocellular carcinoma.
Allameh A et al.·Commun Biol
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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