HAMP

Chr 19AR

hepcidin antimicrobial peptide

Also known as: HEPC, HFE2B, LEAP1, PLTR

NCBI Gene: 57817ENSG00000105697UniProt: P81172

The product encoded by this gene is involved in the maintenance of iron homeostasis, and it is necessary for the regulation of iron storage in macrophages, and for intestinal iron absorption. The preproprotein is post-translationally cleaved into mature peptides of 20, 22 and 25 amino acids, and these active peptides are rich in cysteines, which form intramolecular bonds that stabilize their beta-sheet structures. These peptides exhibit antimicrobial activity against bacteria and fungi. Mutations in this gene cause hemochromatosis type 2B, also known as juvenile hemochromatosis, a disease caused by severe iron overload that results in cardiomyopathy, cirrhosis, and endocrine failure. [provided by RefSeq, Oct 2014]

Primary Disease Associations & Inheritance

Hemochromatosis, type 2BMIM #613313
AR
UniProtHemochromatosis 2B
115
ClinVar variants
24
Pathogenic / LP
0.01
pLI score
6
Active trials
Clinical Summary— HAMP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 25 VUS of 115 total submissions
💊
Clinical Trials
6 active or recruiting trials — potential therapeutic options may be available

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.
1.81LOEUF
pLI 0.008
Z-score 0.20
OE 0.88 (0.39–1.81)
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.
0.15Z-score
OE missense 0.94 (0.73–1.21)
43 obs / 45.9 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.0.88 (0.39–1.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.73–1.21)
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.1.56
0≤1.21.6
LoF obs/exp: 3 / 3.4Missense obs/exp: 43 / 45.9Syn Z: -1.90

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic4
VUS25
Likely Benign50
Benign6
Conflicting6
20
Pathogenic
4
Likely Pathogenic
25
VUS
50
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
17
0
20
Likely Pathogenic
0
2
2
0
4
VUS
0
15
10
0
25
Likely Benign
0
1
20
29
50
Benign
0
0
6
0
6
Conflicting
—6
Total2195529111

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

View in ClinVar →

Protein Context — Lollipop Plot

HAMP · protein map & ClinVar variants

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

Gene2Phenotype Curations

HAMP-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 2B

MIM #613313

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Two to tango: regulation of Mammalian iron metabolism.
Hentze MW et al.·Cell
2010Review
Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.
Nemeth E et al.·Science
2004
Hereditary hemochromatosis.
Pietrangelo A·Annu Rev Nutr
2006Review
Molecular characterization of HAMP rs10421768 gene and phenotypic expression of hepcidin; a case-control study among sickle cell anaemia patients in Ghana.
Appiah SK et al.·PLoS One
2024Cohort
Non-HFE hemochromatosis.
Pietrangelo A·Semin Liver Dis
2005Review
Identification of a novel mutation gene signature HAMP for cholangiocarcinoma through comprehensive TCGA and GEO data mining.
Wang Z et al.·Int Immunopharmacol
2021
The Hepatitis C virus NS5A and core proteins exert antagonistic effects on HAMP gene expression: the hidden interplay with the MTF-1/MRE pathway.
Dimitriadis A et al.·FEBS Open Bio
2021
Prognostic biomarker HAMP and associates with immune infiltration in gastric cancer.
Yang J et al.·Int Immunopharmacol
2022
Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene.
Altès A et al.·Ann Hematol
2009Cohort
Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant.
Parajes S et al.·BMC Genet
2010Functional
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
PregnancyIron Deficiency

Efficacy and Adverse Side Effects of Two Forms of Iron in Pregnancy

RECRUITING
NCT06014983Phase NAUniversity of British ColumbiaStarted 2024-04-12
Ferrous fumarateFerrous bisglycinate
Micronutrient Status

Micronutrient Dose Response Study in Bangladesh

ACTIVE NOT RECRUITING
NCT06081114Phase NAJohns Hopkins Bloomberg School of Public HealthStarted 2023-10-22
Micronutrient Supplement
Physiological AdaptationsSport PerformanceAerobic Capacity

Molecular Hydrogen Inhalation: Effects on Health, Exercise Capacity and Inflammatory Response - in Vivo/in Vitro Studies

NOT YET RECRUITING
NCT07130942Phase NAGdansk University of Physical Education and SportStarted 2025-10-01
Inhalation using a molecular hydrogen generator
Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
ObesityObesity, Infant

Maternal Characteristics Associated With Child Growth and Adiposity

RECRUITING
NCT05798676Instituto de Desarrollo e Investigaciones Pediátricas Prof. Dr. Fernando E. ViteriStarted 2019-05-02
overweight/obesity
Heart Failure

Metabolic Response to the Initiation of Heart Failure Therapy

RECRUITING
NCT06283420Vojtech Melenovsky, MD, PhDStarted 2024-08-23

External Resources

Links to major genomics databases and tools