Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel

Hepcidin

Hepcidin wird vom HAMP-Gen kodiert. Es ist ein wichtiger Regulator im Eisenstoffwechsel und reguliert sowohl die Speicherung in den Makrophagen wie auch die Eisen-Aufnahme im Darm. Mutationen führen zur juvenilen Hämochromatose (Typ 2B). Oft liegt eine digenische Erkrankung vor, bei welcher eine heterozygote Mutation zusammen mit einer zweiten HFE1-Mutation auftritt.

Pathologie

G cluster_a Erythroblast cluster_b Hepatozyt cluster_c Makrophagen/duodenale Enterozyten epo EPO r0 EPO EPOR Erythropoetin-Rezeptor epo->r0 + t1 Transcription r0->t1 + erfe FAM132B t1->erfe + r4 FAM132B ERFER Erythroferron-Rezeptor erfe->r4 + l1 Ferritin-(Eisen) r1 FTH1+FTL TFR2 HFE Ferritin-Rezeptor l1->r1 + l2 Transferrin-Eisen r2 BMP6 HJV TMPRSS6 BMP-Rezeptor l2->r2 + r3 TF TFR2 Transferrin-Rezeptor l2->r3 + r1->r2 + t2 Transcription r1->t2 + r2->t2 + r3->r2 + r3->t2 + r4->t2 - hep HAMP t2->hep + fp1 SLC40A1 Ferroportin-Funktion fp2 SLC40A1 Ferroportin-Abbau hep->fp1 - hep->fp2 +
Hepcidin-Regulation des Eisenstoffwechsels

Gentests:

Klinisch Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25 Tage
Probentyp genomische DNS

Verknüpfte Erkrankungen:

Hämochromatose 2b
HAMP

Referenzen:

1.

Roetto A et al. (2003) Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis.

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2.

Nicolas G et al. (2003) Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis.

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3.

Muckenthaler M et al. (2003) Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis.

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4.

Merryweather-Clarke AT et al. (2003) Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis.

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5.

Nemeth E et al. (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.

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6.

Nemeth E et al. (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization.

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7.

Krause A et al. (2000) LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity.

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8.

Park CH et al. (2001) Hepcidin, a urinary antimicrobial peptide synthesized in the liver.

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9.

Pigeon C et al. (2001) A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload.

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10.

Nicolas G et al. (2001) Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

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11.

Nicolas G et al. (2002) Severe iron deficiency anemia in transgenic mice expressing liver hepcidin.

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12.

Lou DQ et al. (2004) Functional differences between hepcidin 1 and 2 in transgenic mice.

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13.

Matthes T et al. (2004) Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene.

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14.

Robson KJ et al. (2004) Recent advances in understanding haemochromatosis: a transition state.

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15.

Lee P et al. (2005) Regulation of hepcidin transcription by interleukin-1 and interleukin-6.

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16.

Babitt JL et al. (2006) Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression.

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17.

Weizer-Stern O et al. (2007) Hepcidin, a key regulator of iron metabolism, is transcriptionally activated by p53.

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18.

Babitt JL et al. (2007) Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance.

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19.

Tanno T et al. (2007) High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin.

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20.

Du X et al. (2008) The serine protease TMPRSS6 is required to sense iron deficiency.

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21.

Kautz L et al. (2008) Iron regulates phosphorylation of Smad1/5/8 and gene expression of Bmp6, Smad7, Id1, and Atoh8 in the mouse liver.

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22.

Andriopoulos B et al. (2009) BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism.

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23.

Peslova G et al. (2009) Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood.

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24.

Vecchi C et al. (2009) ER stress controls iron metabolism through induction of hepcidin.

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25.

Smith CL et al. (2013) IL-22 regulates iron availability in vivo through the induction of hepcidin.

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26.

Orphanet article

Orphanet ID 122364 [^]
27.

NCBI article

NCBI 57817 [^]
28.

OMIM.ORG article

Omim 606464 [^]
29.

Wikipedia Artikel

Wikipedia DE (Hepcidin) [^]
Update: 29. April 2019