HAMP

hepcidin antimicrobial peptide

Basic information

Region (hg38): 19:35280716-35285143

Links

ENSG00000105697 ∙ NCBI:57817 ∙ OMIM:606464 ∙ HGNC:15598 ∙ Uniprot:P81172 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemochromatosis type 2B (Strong), mode of inheritance: AR
• hemochromatosis type 2B (Strong), mode of inheritance: AR
• hemochromatosis type 2 (Supportive), mode of inheritance: AR
• hemochromatosis type 2B (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hemochromatosis, type 2B	AR	Biochemical; Gastrointestinal; Hematologic	Patients may benefit from surveillance related to iron overload, and from interventions such as venesection; Certain agents should be avoided (eg, alcohol consumption; iron-containing compounds; uncooked seafood); Hormone therapy may be beneficial in order to prevent osteoporosis	Biochemical; Cardiovascular; Endocrine; Gastrointestinal; Hematologic	10205270; 12490283; 12915468; 12469120; 15099344; 15345104; 14670915; 15024747; 15198949; 16204153; 19214511; 20301349; 22297252; 22924847
Digenic inheritance (with HFE) has been reported; HAMP variants may contribute to severity/manifestations of hemochromatosis associated with variants in other genes

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HAMP gene.

• Hereditary hemochromatosis (1 variants)
• Hemochromatosis type 2B (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HAMP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				28		28
missense			10	1		11
nonsense		1	2			3
start loss		1				1
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	3		4
non coding	1		1	16	4	22
Total	1	2	14	45	4

Highest pathogenic variant AF is 0.0000131

Variants in HAMP

This is a list of pathogenic ClinVar variants found in the HAMP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
19-35281996-A-G		Hereditary hemochromatosis	Benign (Jan 18, 2024)
19-35282425-C-T		Hereditary hemochromatosis • Hemochromatosis type 2B	Conflicting classifications of pathogenicity (Aug 17, 2023)
19-35282506-C-T		Hereditary hemochromatosis • Hemochromatosis type 2B	Benign (Aug 04, 2023)
19-35282511-G-C		Juvenile hemochromatosis	Uncertain significance (Jun 14, 2016)
19-35282553-G-A		Hemochromatosis type 2B • Hereditary hemochromatosis	Pathogenic (Oct 04, 2023)
19-35282577-G-A		Hemochromatosis type 2B	Uncertain significance (Jan 13, 2018)
19-35282579-T-C			Likely pathogenic (Aug 15, 2023)
19-35282586-G-A		Hereditary hemochromatosis	Likely benign (May 17, 2023)
19-35282598-C-A		Hereditary hemochromatosis	Likely benign (Apr 28, 2023)
19-35282598-C-T		Hereditary hemochromatosis	Likely benign (Sep 28, 2021)
19-35282604-C-G		Hereditary hemochromatosis	Likely benign (Jan 10, 2024)
19-35282604-C-T		Hereditary hemochromatosis	Likely benign (Jul 17, 2023)
19-35282613-C-A		Hereditary hemochromatosis	Likely benign (Feb 20, 2023)
19-35282616-GCTCCTC-G		Hereditary hemochromatosis	Uncertain significance (Aug 24, 2021)
19-35282619-C-G		Hereditary hemochromatosis	Likely benign (Dec 20, 2023)
19-35282622-C-G		Hereditary hemochromatosis	Likely benign (Feb 18, 2023)
19-35282622-C-T			Likely benign (Apr 30, 2018)
19-35282625-C-T		Hereditary hemochromatosis	Likely benign (Jan 31, 2024)
19-35282631-C-G		Hereditary hemochromatosis	Likely benign (Sep 21, 2023)
19-35282631-C-T		Hereditary hemochromatosis	Likely benign (Nov 10, 2023)
19-35282638-C-T		Hereditary hemochromatosis	Likely benign (Jan 09, 2024)
19-35282640-G-C		Hereditary hemochromatosis	Likely benign (Nov 19, 2023)
19-35282642-C-T		Hereditary hemochromatosis • Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
19-35282643-C-T		Hereditary hemochromatosis	Likely benign (Oct 14, 2023)
19-35282649-C-T		Hereditary hemochromatosis	Likely benign (Jan 16, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HAMP	protein_coding	protein_coding	ENST00000598398	3	4428

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00818	0.578	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.151	43	45.9	0.937	0.00000259	542
Missense in Polyphen		7	13.171	0.53146		147
Synonymous	-1.90	29	18.6	1.56	0.00000114	162
Loss of Function	0.198	3	3.39	0.884	1.50e-7	32

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000617	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000381	0.000381
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma. Controls the major flows of iron into plasma: absorption of dietary iron in the intestine, recycling of iron by macrophages, which phagocytose old erythrocytes and other cells, and mobilization of stored iron from hepatocytes (PubMed:22306005). {ECO:0000269|PubMed:22306005}.
• Disease: DISEASE: Hemochromatosis 2B (HFE2B) [MIM:613313]: A juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy. {ECO:0000269|PubMed:12915468, ECO:0000269|PubMed:14630809, ECO:0000269|PubMed:14633868, ECO:0000269|PubMed:14670915, ECO:0000269|PubMed:15099344}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Iron metabolism in placenta;Hfe effect on hepcidin production (Consensus)

Recessive Scores

• pRec: 0.542

Intolerance Scores

• loftool: 0.438
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.16

Haploinsufficiency Scores

• pHI: 0.314
• hipred: N
• hipred_score: 0.261

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hamp
• Phenotype: immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; liver/biliary system phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: hamp
• Affected structure: vertebra
• Phenotype tag: abnormal
• Phenotype quality: decreased occurrence

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cellular iron ion homeostasis;acute-phase response;immune response;aging;response to iron ion;response to zinc ion;regulation of signaling receptor activity;killing of cells of other organism;response to vitamin A;negative regulation of iron ion transmembrane transport;response to erythropoietin;defense response to bacterium;response to ethanol;defense response to fungus;multicellular organismal iron ion homeostasis;positive regulation of cell growth involved in cardiac muscle cell development;cellular response to lipopolysaccharide;cellular response to interleukin-6;cellular response to tumor necrosis factor;cellular response to X-ray;liver regeneration;cellular response to bile acid;negative regulation of intestinal absorption;response to iron ion starvation
• Cellular component: extracellular region;extracellular space;intercalated disc;apical cortex
• Molecular function: hormone activity