MCID: HMC035
MIFTS: 40

Hemochromatosis, Type 4

Categories: Genetic diseases, Rare diseases, Liver diseases, Metabolic diseases

Aliases & Classifications for Hemochromatosis, Type 4

MalaCards integrated aliases for Hemochromatosis, Type 4:

Name: Hemochromatosis, Type 4 57 13 44 40 73
Hemochromatosis Type 4 12 76 53 59 29 6
Hemochromatosis Due to Defect in Ferroportin 57 12 53 59 75
Hfe4 57 12 53 75
Autosomal Dominant Hereditary Hemochromatosis 12 53 59
Hemochromatosis, Autosomal Dominant 57 53 55
Ferroportin Disease 12 53 59
Hemochromatosis Autosomal Dominant 75
Hemochromatosis 4 75

Characteristics:

Orphanet epidemiological data:

59
hemochromatosis type 4
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hemochromatosis, type 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 606069
Disease Ontology 12 DOID:0111028
ICD10 33 E83.1
Orphanet 59 ORPHA139491
UMLS via Orphanet 74 C1853733
MESH via Orphanet 45 C537249
ICD10 via Orphanet 34 E83.1
MedGen 42 C1853733
UMLS 73 C1853733

Summaries for Hemochromatosis, Type 4

NIH Rare Diseases : 53 Hemochromatosis type 4 (also called ferroportin disease) is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas. Hemochromatosis type 4 can be further divided into two subtypes:Hemochromatosis type 4A Hemochromatosis type 4B People with hemochromatosis type 4A might not have any symptoms of the disease. Other individuals may develop liver disease as they get older. Hemochromatosis type 4B can be associated with fatigue, weakness, and joint pain. Other symptoms may include abdominal pain, loss of sex drive, liver disease, diabetes, heart problems, difficulty breathing, and skin discoloration. Symptoms of hemochromatosis type 4B can begin anytime from childhood to adulthood. Hemochromatosis type 4 is most common in people of southern European ancestry. Hemochromatosis type 4 is caused by genetic changes (mutations or pathogenic variants) to the SLC40A1 gene. The disease is inherited in an autosomal dominant manner. A diagnosis of hemochromatosis type 4 is suspected when a doctor observes signs and symptoms of the disease. A doctor may decide to order laboratory tests including a liver biopsy, MRI, or blood test. The diagnosis can be confirmed with genetic testing. Treatment of hemochromatosis type 4B usually involves reducing iron levels by removing blood (phlebotomy) or iron chelation. These treatments can prevent additional organ damage but typically do not reverse existing damage. People with hemochromatosis type 4A may not be recommended to have phlebotomy because it can increase the risk for complications such as anemia. To learn more about other types of hemochromatosis click on the disease names below:Hemochromatosis type 1 Hemochromatosis type 2 Hemochromatosis type 3 Hemochromatosis type 5 Neonatal hemochromatosis

MalaCards based summary : Hemochromatosis, Type 4, also known as hemochromatosis type 4, is related to hemochromatosis type 2 and hemochromatosis, type 1, and has symptoms including arthralgia and fatigue. An important gene associated with Hemochromatosis, Type 4 is SLC40A1 (Solute Carrier Family 40 Member 1), and among its related pathways/superpathways is Iron metabolism in placenta. The drugs Iron and Anti-Infective Agents have been mentioned in the context of this disorder. Affiliated tissues include liver, testes and skin, and related phenotypes are joint dislocation and limitation of joint mobility

Disease Ontology : 12 A hemochromatosis that has material basis in heterozygous mutation in the SLC40A1 gene on chromosome 2q32.

UniProtKB/Swiss-Prot : 75 Hemochromatosis 4: A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.

Wikipedia : 76 Hemochromatosis type 4, also known as ferroportin disease, is a hereditary iron overload disorder that... more...

Description from OMIM: 606069

Related Diseases for Hemochromatosis, Type 4

Graphical network of the top 20 diseases related to Hemochromatosis, Type 4:



Diseases related to Hemochromatosis, Type 4

Symptoms & Phenotypes for Hemochromatosis, Type 4

Symptoms via clinical synopsis from OMIM:

57
Skeletal:
osteoarthritis
joint pains

Neurologic Behavioral Psychiatric Manifestations:
fatigue

Genitourinary External Genitalia Male:
impotence

Skin Nails Hair Skin:
hyperpigmentation

Abdomen Liver:
fibrosis
iron overload involving parenchymal and mesenchymal cells
iron deposition in kupffer cells and portal macrophages

Head And Neck Eyes:
cataract

Cardiovascular Heart:
arrhythmia
cardiomyopathy

Laboratory Abnormalities:
increased serum ferritin
increased transferrin saturation

Endocrine Features:
impaired glucose tolerance
endocrine disorders

Hematology:
anemia, microcytic


Clinical features from OMIM:

606069

Human phenotypes related to Hemochromatosis, Type 4:

59 32 (show all 17)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint dislocation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001373
2 limitation of joint mobility 59 32 hallmark (90%) Very frequent (99-80%) HP:0001376
3 joint swelling 59 32 hallmark (90%) Very frequent (99-80%) HP:0001386
4 cirrhosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001394
5 hepatic steatosis 59 32 frequent (33%) Frequent (79-30%) HP:0001397
6 abdominal pain 59 32 frequent (33%) Frequent (79-30%) HP:0002027
7 congenital hepatic fibrosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002612
8 arthralgia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002829
9 increased serum ferritin 59 32 hallmark (90%) Very frequent (99-80%) HP:0003281
10 generalized hyperpigmentation 59 32 hallmark (90%) Very frequent (99-80%) HP:0007440
11 cataract 32 HP:0000518
12 impotence 32 HP:0000802
13 glucose intolerance 32 HP:0000833
14 cardiomyopathy 32 HP:0001638
15 osteoarthritis 32 HP:0002758
16 arrhythmia 32 HP:0011675
17 fatigue 32 HP:0012378

UMLS symptoms related to Hemochromatosis, Type 4:


arthralgia, fatigue

Drugs & Therapeutics for Hemochromatosis, Type 4

Drugs for Hemochromatosis, Type 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved Phase 2 7439-89-6 23925
2 Anti-Infective Agents Phase 2
3 Hepcidins Phase 2
4 Micronutrients Phase 2
5 Trace Elements Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Analysis of the Modulation of Serum Hepcidin Level in Response to Iron Oral Intake: Potential Interest for the Differential Diagnosis Between Ferroportin Disease and Dysmetabolic Hepatosiderosis. Recruiting NCT01949467 Phase 2 iron fumarate

Search NIH Clinical Center for Hemochromatosis, Type 4

Cochrane evidence based reviews: hemochromatosis, type 4

Genetic Tests for Hemochromatosis, Type 4

Genetic tests related to Hemochromatosis, Type 4:

# Genetic test Affiliating Genes
1 Hemochromatosis Type 4 29 SLC40A1

Anatomical Context for Hemochromatosis, Type 4

MalaCards organs/tissues related to Hemochromatosis, Type 4:

41
Liver, Testes, Skin, Pancreas, Heart

Publications for Hemochromatosis, Type 4

Articles related to Hemochromatosis, Type 4:

# Title Authors Year
1
Deciphering the molecular basis of ferroportin resistance to hepcidin: Structure/function analysis of rare SLC40A1 missense mutations found in suspected hemochromatosis type 4 patients. ( 28826751 )
2017
2
A Novel Phenotype of a Hereditary Hemochromatosis Type 4 with Ferroportin-1 Mutation, Presenting with Juvenile Cataracts. ( 27629970 )
2016
3
Comprehensive functional annotation of 18 missense mutations found in suspected hemochromatosis type 4 patients. ( 24714983 )
2014
4
Structure-function analysis of the human ferroportin iron exporter (SLC40A1): effect of hemochromatosis type 4 disease mutations and identification of critical residues. ( 23784628 )
2013

Variations for Hemochromatosis, Type 4

UniProtKB/Swiss-Prot genetic disease variations for Hemochromatosis, Type 4:

75 (show all 12)
# Symbol AA change Variation ID SNP ID
1 SLC40A1 p.Ala77Asp VAR_022594 rs28939076
2 SLC40A1 p.Asn144His VAR_022595 rs104893662
3 SLC40A1 p.Asp157Gly VAR_022596 rs104893663
4 SLC40A1 p.Gln182His VAR_022598 rs104893670
5 SLC40A1 p.Gly323Val VAR_022599 rs104893671
6 SLC40A1 p.Tyr64Asn VAR_030057
7 SLC40A1 p.Gly80Val VAR_030059 rs104893673
8 SLC40A1 p.Asn144Asp VAR_030060
9 SLC40A1 p.Asn144Thr VAR_030061
10 SLC40A1 p.Asp181Val VAR_030063 rs104893672
11 SLC40A1 p.Gly267Asp VAR_030064 rs104893664
12 SLC40A1 p.Asp270Val VAR_030065 rs368420430

ClinVar genetic disease variations for Hemochromatosis, Type 4:

6
(show top 50) (show all 62)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC40A1 NM_014585.5(SLC40A1): c.430A> C (p.Asn144His) single nucleotide variant Pathogenic rs104893662 GRCh37 Chromosome 2, 190436525: 190436525
2 SLC40A1 NM_014585.5(SLC40A1): c.430A> C (p.Asn144His) single nucleotide variant Pathogenic rs104893662 GRCh38 Chromosome 2, 189571799: 189571799
3 SLC40A1 NM_014585.5(SLC40A1): c.230C> A (p.Ala77Asp) single nucleotide variant Pathogenic rs28939076 GRCh37 Chromosome 2, 190439928: 190439928
4 SLC40A1 NM_014585.5(SLC40A1): c.230C> A (p.Ala77Asp) single nucleotide variant Pathogenic rs28939076 GRCh38 Chromosome 2, 189575202: 189575202
5 SLC40A1 NM_014585.5(SLC40A1): c.470A> G (p.Asp157Gly) single nucleotide variant Pathogenic rs104893663 GRCh37 Chromosome 2, 190436485: 190436485
6 SLC40A1 NM_014585.5(SLC40A1): c.470A> G (p.Asp157Gly) single nucleotide variant Pathogenic rs104893663 GRCh38 Chromosome 2, 189571759: 189571759
7 SLC40A1 NM_014585.5(SLC40A1): c.546G> T (p.Gln182His) single nucleotide variant Pathogenic rs104893670 GRCh37 Chromosome 2, 190430294: 190430294
8 SLC40A1 NM_014585.5(SLC40A1): c.546G> T (p.Gln182His) single nucleotide variant Pathogenic rs104893670 GRCh38 Chromosome 2, 189565568: 189565568
9 SLC40A1 SLC40A1, 3-BP DEL, VAL162DEL deletion Pathogenic
10 SLC40A1 NM_014585.5(SLC40A1): c.968G> T (p.Gly323Val) single nucleotide variant Pathogenic rs104893671 GRCh37 Chromosome 2, 190428744: 190428744
11 SLC40A1 NM_014585.5(SLC40A1): c.968G> T (p.Gly323Val) single nucleotide variant Pathogenic rs104893671 GRCh38 Chromosome 2, 189564018: 189564018
12 SLC40A1 NM_014585.5(SLC40A1): c.542A> T (p.Asp181Val) single nucleotide variant Pathogenic rs104893672 GRCh37 Chromosome 2, 190430298: 190430298
13 SLC40A1 NM_014585.5(SLC40A1): c.542A> T (p.Asp181Val) single nucleotide variant Pathogenic rs104893672 GRCh38 Chromosome 2, 189565572: 189565572
14 SLC40A1 NM_014585.5(SLC40A1): c.239G> T (p.Gly80Val) single nucleotide variant Pathogenic rs104893673 GRCh37 Chromosome 2, 190439919: 190439919
15 SLC40A1 NM_014585.5(SLC40A1): c.239G> T (p.Gly80Val) single nucleotide variant Pathogenic rs104893673 GRCh38 Chromosome 2, 189575193: 189575193
16 SLC40A1 NM_014585.5(SLC40A1): c.800G> A (p.Gly267Asp) single nucleotide variant Pathogenic rs104893664 GRCh37 Chromosome 2, 190428912: 190428912
17 SLC40A1 NM_014585.5(SLC40A1): c.800G> A (p.Gly267Asp) single nucleotide variant Pathogenic rs104893664 GRCh38 Chromosome 2, 189564186: 189564186
18 SLC40A1 NM_014585.5(SLC40A1): c.610G> A (p.Gly204Ser) single nucleotide variant Likely pathogenic rs387907377 GRCh37 Chromosome 2, 190430230: 190430230
19 SLC40A1 NM_014585.5(SLC40A1): c.610G> A (p.Gly204Ser) single nucleotide variant Likely pathogenic rs387907377 GRCh38 Chromosome 2, 189565504: 189565504
20 SLC40A1 NM_014585.5(SLC40A1): c.809A> T (p.Asp270Val) single nucleotide variant Pathogenic rs368420430 GRCh37 Chromosome 2, 190428903: 190428903
21 SLC40A1 NM_014585.5(SLC40A1): c.809A> T (p.Asp270Val) single nucleotide variant Pathogenic rs368420430 GRCh38 Chromosome 2, 189564177: 189564177
22 SLC40A1 NP_055400.1(SLC40A1): p.Gln248His protein only Pathogenic
23 SLC40A1 NM_014585.5(SLC40A1): c.1520A> G (p.His507Arg) single nucleotide variant Uncertain significance rs863224768 GRCh38 Chromosome 2, 189562074: 189562074
24 SLC40A1 NM_014585.5(SLC40A1): c.1520A> G (p.His507Arg) single nucleotide variant Uncertain significance rs863224768 GRCh37 Chromosome 2, 190426800: 190426800
25 SLC40A1 NM_014585.5(SLC40A1): c.430A> T (p.Asn144Tyr) single nucleotide variant Uncertain significance rs104893662 GRCh38 Chromosome 2, 189571799: 189571799
26 SLC40A1 NM_014585.5(SLC40A1): c.430A> T (p.Asn144Tyr) single nucleotide variant Uncertain significance rs104893662 GRCh37 Chromosome 2, 190436525: 190436525
27 SLC40A1 NM_014585.5(SLC40A1): c.485_487dupTTG (p.Val162_Ala163insVal) duplication Uncertain significance rs878854984 GRCh37 Chromosome 2, 190436468: 190436470
28 SLC40A1 NM_014585.5(SLC40A1): c.485_487dupTTG (p.Val162_Ala163insVal) duplication Uncertain significance rs878854984 GRCh38 Chromosome 2, 189571742: 189571744
29 SLC40A1 NM_014585.5(SLC40A1): c.744G> T (p.Gln248His) single nucleotide variant Benign/Likely benign rs11568350 GRCh38 Chromosome 2, 189565370: 189565370
30 SLC40A1 NM_014585.5(SLC40A1): c.744G> T (p.Gln248His) single nucleotide variant Benign/Likely benign rs11568350 GRCh37 Chromosome 2, 190430096: 190430096
31 SLC40A1 NM_014585.5(SLC40A1): c.271+10_271+12delGTT deletion Likely benign rs768786843 GRCh38 Chromosome 2, 189575149: 189575151
32 SLC40A1 NM_014585.5(SLC40A1): c.271+10_271+12delGTT deletion Likely benign rs768786843 GRCh37 Chromosome 2, 190439875: 190439877
33 SLC40A1 NM_014585.5(SLC40A1): c.1570G> A (p.Val524Ile) single nucleotide variant Uncertain significance rs142456282 GRCh37 Chromosome 2, 190426750: 190426750
34 SLC40A1 NM_014585.5(SLC40A1): c.1570G> A (p.Val524Ile) single nucleotide variant Uncertain significance rs142456282 GRCh38 Chromosome 2, 189562024: 189562024
35 SLC40A1 NM_014585.5(SLC40A1): c.387C> T (p.Leu129=) single nucleotide variant Benign rs11568344 GRCh38 Chromosome 2, 189572846: 189572846
36 SLC40A1 NM_014585.5(SLC40A1): c.387C> T (p.Leu129=) single nucleotide variant Benign rs11568344 GRCh37 Chromosome 2, 190437572: 190437572
37 SLC40A1 NM_014585.5(SLC40A1): c.327C> T (p.Ile109=) single nucleotide variant Benign rs11568345 GRCh38 Chromosome 2, 189572906: 189572906
38 SLC40A1 NM_014585.5(SLC40A1): c.327C> T (p.Ile109=) single nucleotide variant Benign rs11568345 GRCh37 Chromosome 2, 190437632: 190437632
39 SLC40A1 NM_014585.5(SLC40A1): c.524C> A (p.Ala175Asp) single nucleotide variant Uncertain significance rs1060501101 GRCh37 Chromosome 2, 190430316: 190430316
40 SLC40A1 NM_014585.5(SLC40A1): c.524C> A (p.Ala175Asp) single nucleotide variant Uncertain significance rs1060501101 GRCh38 Chromosome 2, 189565590: 189565590
41 SLC40A1 NM_014585.5(SLC40A1): c.1469G> A (p.Gly490Asp) single nucleotide variant Pathogenic rs1060501102 GRCh37 Chromosome 2, 190426851: 190426851
42 SLC40A1 NM_014585.5(SLC40A1): c.1469G> A (p.Gly490Asp) single nucleotide variant Pathogenic rs1060501102 GRCh38 Chromosome 2, 189562125: 189562125
43 SLC40A1 NM_014585.5(SLC40A1): c.1481G> A (p.Gly494Asp) single nucleotide variant Pathogenic GRCh38 Chromosome 2, 189562113: 189562113
44 SLC40A1 NM_014585.5(SLC40A1): c.1481G> A (p.Gly494Asp) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 190426839: 190426839
45 SLC40A1 NM_014585.5(SLC40A1): c.1049C> A (p.Ala350Asp) single nucleotide variant Pathogenic GRCh38 Chromosome 2, 189563937: 189563937
46 SLC40A1 NM_014585.5(SLC40A1): c.1049C> A (p.Ala350Asp) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 190428663: 190428663
47 SLC40A1 NM_014585.5(SLC40A1): c.544C> G (p.Gln182Glu) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 190430296: 190430296
48 SLC40A1 NM_014585.5(SLC40A1): c.544C> G (p.Gln182Glu) single nucleotide variant Pathogenic GRCh38 Chromosome 2, 189565570: 189565570
49 SLC40A1 NM_014585.5(SLC40A1): c.541G> A (p.Asp181Asn) single nucleotide variant Pathogenic GRCh38 Chromosome 2, 189565573: 189565573
50 SLC40A1 NM_014585.5(SLC40A1): c.541G> A (p.Asp181Asn) single nucleotide variant Pathogenic GRCh37 Chromosome 2, 190430299: 190430299

Expression for Hemochromatosis, Type 4

Search GEO for disease gene expression data for Hemochromatosis, Type 4.

Pathways for Hemochromatosis, Type 4

Pathways related to Hemochromatosis, Type 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.7 SLC40A1 TFR2

GO Terms for Hemochromatosis, Type 4

Biological processes related to Hemochromatosis, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.26 SLC40A1 TFR2
2 cellular iron ion homeostasis GO:0006879 9.16 SLC40A1 TFR2
3 iron ion homeostasis GO:0055072 8.96 SLC40A1 TFR2
4 iron ion transport GO:0006826 8.62 SLC40A1 TFR2

Sources for Hemochromatosis, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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