HAMP

Chr 19AR

hepcidin antimicrobial peptide

Also known as: HEPC, HFE2B, LEAP1, PLTR

NCBI Gene: 57817 ENSG00000105697 UniProt: P81172 OMIM: 606464

HAMP encodes hepcidin, a liver-produced hormone that regulates iron homeostasis by controlling iron absorption in the intestine and iron distribution across tissues. Mutations cause autosomal recessive hemochromatosis type 2B (juvenile hemochromatosis), characterized by severe iron overload leading to cardiomyopathy, cirrhosis, and endocrine failure with early onset. The gene shows low constraint to loss-of-function variants (pLI 0.008, LOEUF 1.81), consistent with its recessive inheritance pattern.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.811 OMIM phenotype

Clinical Summary— HAMP

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Gene-Disease Validity (ClinGen)

hemochromatosis type 2B · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 21 VUS of 95 total submissions

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Clinical Trials

8 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — HAMP

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.15Z-score

OE missense 0.94 (0.73–1.21)

43 obs / 45.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.88 (0.39–1.81)

0≤0.351.4

Missense OE?0.94 (0.73–1.21)

0≤0.61.4

Synonymous OE?1.56

0≤1.21.6

LoF obs/exp: 3 / 3.4Missense obs/exp: 43 / 45.9Syn Z: -1.90

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveHAMP-related haemochromatosis, juvenileLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.75top 25%

GOF

0.4085th %ile

LOF

0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4

Likely Pathogenic4

VUS21

Likely Benign50

Benign6

Conflicting6

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	1	0	0	4
Likely Pathogenic	1	2	1	0	4
VUS	2	17	2	0	21
Likely Benign	0	1	20	29	50
Benign	0	0	6	0	6
Conflicting	—				6
Total	6	21	29	29	91

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap HAMP — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →