HAMP
hepcidin antimicrobial peptide
Basic information
Region (hg38): 19:35280716-35285143
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- Hereditary_hemochromatosis (68 variants)
- Hemochromatosis_type_2B (16 variants)
- not_provided (6 variants)
- Inborn_genetic_diseases (6 variants)
- not_specified (5 variants)
- HAMP-related_disorder (2 variants)
- Hemochromatosis,_juvenile,_digenic (1 variants)
- Hemochromatosis_type_1 (1 variants)
- Hemochromatosis,_type_2a,_modifier_of (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. These statistics are base on transcript: NM_000021175.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 31 | 31 | ||||
| missense | 14 | 18 | ||||
| nonsense | 4 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 4 | 4 | 16 | 33 | 0 |
Highest pathogenic variant AF is 0.000018591
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- ghis
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