hemochromatosis type 2B

Summary

hemochromatosis type 2B (MONDO:0013220) is a disease caused by HAMP (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: HAMP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hemochromatosis type 2B
Mondo ID	MONDO:0013220
MeSH	C566557
OMIM	613313
DOID	DOID:0111032
UMLS	C1865616
MedGen	356040
GARD	0015647
Is cancer (heuristic)	no

Also known as: HAMP hemochromatosis type 2 · hemochromatosis type 2 caused by mutation in HAMP · hemochromatosis, type 2B · HFE2B

Data availability: 19 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › iron metabolism disease › hemosiderosis › hereditary hemochromatosis › hemochromatosis type 2 › hemochromatosis type 2B

Related subtypes (1): hemochromatosis type 2A

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

19 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 conflicting classifications of pathogenicity, 3 pathogenic, 2 likely pathogenic, 1 benign, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4283	NM_021175.4(HAMP):c.95del (p.Gly32fs)	HAMP	Pathogenic	no assertion criteria provided
4284	NM_021175.4(HAMP):c.166C>T (p.Arg56Ter)	HAMP	Pathogenic	no assertion criteria provided
4287	NM_021175.4(HAMP):c.-25G>A	HAMP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
917401	NM_021175.4(HAMP):c.176G>C (p.Arg59Pro)	HAMP	Pathogenic	no assertion criteria provided
1350113	NM_021175.4(HAMP):c.223C>T (p.Arg75Ter)	HAMP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4075845	NM_021175.4(HAMP):c.185A>G (p.His62Arg)	HAMP	Likely pathogenic	criteria provided, single submitter
216876	NM_021175.4(HAMP):c.92C>T (p.Thr31Met)	HAMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
219770	NM_021175.4(HAMP):c.252G>A (p.Thr84=)	HAMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
414002	NM_021175.4(HAMP):c.150+7G>A	HAMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
871232	NC_000019.10:g.35282425C>T	HAMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891879	NM_021175.4(HAMP):c.189C>T (p.Phe63=)	HAMP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
241375	NM_021175.4(HAMP):c.175C>G (p.Arg59Gly)	HAMP	Uncertain significance	criteria provided, multiple submitters, no conflicts
328836	NM_021175.4(HAMP):c.-1G>A	HAMP	Uncertain significance	criteria provided, single submitter
3382949	NM_021175.4(HAMP):c.40CTC[2] (p.Leu16_Leu18del)	HAMP	Uncertain significance	criteria provided, single submitter
3382950	NM_021175.4(HAMP):c.176G>A (p.Arg59Gln)	HAMP	Uncertain significance	criteria provided, single submitter
891878	NM_021175.4(HAMP):c.167G>A (p.Arg56Gln)	HAMP	Uncertain significance	criteria provided, multiple submitters, no conflicts
891880	NM_021175.4(HAMP):c.223C>G (p.Arg75Gly)	HAMP	Uncertain significance	criteria provided, single submitter
1165507	NC_000019.10:g.35282506C>T	HAMP	Benign	criteria provided, multiple submitters, no conflicts
4286	NM_021175.4(HAMP):c.212G>A (p.Gly71Asp)	HAMP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HAMP	Definitive	Autosomal recessive	hemochromatosis type 2B	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HAMP	Orphanet:648581	Digenic hemochromatosis
HAMP	Orphanet:79230	HJV or HAMP-related hemochromatosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HAMP	HGNC:15598	ENSG00000105697	P81172	Hepcidin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HAMP	Hepcidin	Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HAMP	Other/Unknown	no		Hepcidin

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac atrium	1
right atrium auricular region	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HAMP	223	broad	marker	right lobe of liver, right atrium auricular region, cardiac atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HAMP	1,580

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HAMP	P81172	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of iron ion transmembrane transport	1	16852.0×	2e-04	HAMP
negative regulation of iron export across plasma membrane	1	16852.0×	2e-04	HAMP
negative regulation of intestinal absorption	1	16852.0×	2e-04	HAMP
response to iron ion	1	936.2×	0.003	HAMP
multicellular organismal-level iron ion homeostasis	1	581.1×	0.004	HAMP
defense response to fungus	1	443.5×	0.005	HAMP
killing of cells of another organism	1	271.8×	0.006	HAMP
intracellular iron ion homeostasis	1	244.2×	0.006	HAMP
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	1	210.7×	0.006	HAMP
defense response to bacterium	1	108.0×	0.011	HAMP
immune response	1	47.1×	0.023	HAMP
negative regulation of transcription by RNA polymerase II	1	17.7×	0.056	HAMP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HAMP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HAMP	9	Binding:9

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HAMP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
HAMP	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.