HFE4
MCID: HMC035
MIFTS: 52

Hemochromatosis, Type 4 (HFE4)

Categories: Cardiovascular diseases, Endocrine diseases, Genetic diseases, Liver diseases, Metabolic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hemochromatosis, Type 4

MalaCards integrated aliases for Hemochromatosis, Type 4:

Name: Hemochromatosis, Type 4 57 13 44 39 70
Hemochromatosis Type 4 12 73 20 58 29 6 15
Hemochromatosis Due to Defect in Ferroportin 57 12 20 58 72
Hfe4 57 12 20 72
Autosomal Dominant Hereditary Hemochromatosis 12 20 58
Hemochromatosis, Autosomal Dominant 57 20 54
Ferroportin Disease 12 20 58
Hemochromatosis Autosomal Dominant 72
Hemochromatosis 4 72

Characteristics:

Orphanet epidemiological data:

58
hemochromatosis type 4
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant


HPO:

31
hemochromatosis, type 4:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111028
OMIM® 57 606069
OMIM Phenotypic Series 57 PS235200
SNOMED-CT 67 719975002
MESH via Orphanet 45 C537249
ICD10 via Orphanet 33 E83.1
UMLS via Orphanet 71 C1853733
Orphanet 58 ORPHA139491
MedGen 41 C1853733
UMLS 70 C1853733

Summaries for Hemochromatosis, Type 4

GARD : 20 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 5 and hemochromatosis, type 3, and has symptoms including fatigue and arthralgia. An important gene associated with Hemochromatosis, Type 4 is SLC40A1 (Solute Carrier Family 40 Member 1), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Insulin receptor recycling. The drugs Iron and Hepcidins have been mentioned in the context of this disorder. Affiliated tissues include liver, heart and pancreas, and related phenotypes are arthralgia and joint swelling

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

OMIM® : 57 Hemochromatosis type 4 (HFE4) is a dominantly inherited iron overload disorder with heterogeneous phenotypic manifestations that can be classified into 2 groups. One group is characterized by an early rise in ferritin (see 134790) levels with low to normal transferrin (190000) saturation and iron accumulation predominantly in macrophages. The other group is similar to classical hemochromatosis, with high transferrin saturation and prominent parenchymal iron loading (summary by De Domenico et al., 2005). For general background information and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200. (606069) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 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 : 73 Hemochromatosis type 4, is a hereditary iron overload disorder that affects ferroportin, an iron... more...

Related Diseases for Hemochromatosis, Type 4

Diseases in the Rare Hereditary Hemochromatosis family:

Hemochromatosis, Type 1 Hemochromatosis, Type 2a
Hemochromatosis, Type 3 Hemochromatosis, Type 4
Hemochromatosis, Type 2b Hemochromatosis, Type 5
Hemochromatosis Type 2 Tfr2-Related Hereditary Hemochromatosis

Diseases related to Hemochromatosis, Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 hemochromatosis, type 5 31.8 TFR2 HJV HFE
2 hemochromatosis, type 3 30.4 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
3 rare hereditary hemochromatosis 30.1 TFR2 SLC40A1 HJV HFE HAMP
4 hemosiderosis 29.8 TFR2 SLC40A1 SLC11A2 HJV HFE HAMP
5 hemochromatosis type 2 29.8 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
6 siderosis 29.6 TFRC SLC40A1 HFE HAMP
7 hyperferritinemia with or without cataract 29.4 TFR2 SLC40A1 SLC11A2 HJV HFE HAMP
8 hemochromatosis, type 1 29.2 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
9 deficiency anemia 27.3 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
10 hemochromatosis, type 2a 10.1 HJV HAMP
11 sideroblastic anemia 10.1 TFR2 SLC40A1 HAMP
12 folic acid deficiency anemia 10.1 TFRC HAMP
13 autosomal recessive disease 10.0
14 retinitis pigmentosa 50 10.0 HEPH CYBRD1
15 iron-refractory iron deficiency anemia 10.0 TMPRSS6 HJV
16 arthropathy 10.0 HJV HFE HAMP
17 erythrocytosis, familial, 2 10.0 SLC11A2 HAMP CYBRD1
18 inherited metabolic disorder 9.9 TFR2 HJV HFE HAMP
19 anemia, congenital dyserythropoietic, type ia 9.9 TFRC HJV HAMP
20 mitochondrial dna depletion syndrome 3 9.9 SLC40A1 HJV
21 liver cirrhosis 9.9
22 cataract 9.9
23 lung disease 9.9
24 congenital dyserythropoietic anemia 9.9 TFRC HFE HAMP
25 tfr2-related hereditary hemochromatosis 9.9
26 hypochromic microcytic anemia with iron overload 9.9 STEAP3 SLC11A2
27 cutaneous porphyria 9.8 STEAP3 HFE HAMP
28 restless legs syndrome 9.7 TFRC SLC11A2 HAMP
29 alpha-thalassemia 9.7 TFRC HFE HAMP
30 iron overload in africa 9.7 TFR2 SLC40A1 HJV HFE HEPH HAMP
31 nutritional deficiency disease 9.7 TMPRSS6 TFRC HJV HAMP
32 hemoglobinopathy 9.7 TFRC TFR2 HJV HFE HAMP
33 beta-thalassemia 9.4 TMPRSS6 TFRC TFR2 HJV HFE HAMP
34 porphyria cutanea tarda 9.4 TFRC TFR2 SLC40A1 HJV HFE HAMP
35 porphyria 9.4 TFRC TFR2 SLC40A1 HJV HFE HAMP
36 neurodegeneration with brain iron accumulation 9.3 TFRC TFR2 SLC40A1 SLC11A2 HFE HEPH
37 hypochromic microcytic anemia 9.1 TMPRSS6 TFRC STEAP3 SLC11A2 HJV HAMP
38 iron deficiency anemia 8.9 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
39 atransferrinemia 8.9 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
40 metal metabolism disorder 8.7 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
41 iron metabolism disease 8.7 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV
42 microcytic anemia 8.7 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
43 anemia, sideroblastic, 1 8.6 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
44 aceruloplasminemia 8.3 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2

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



Diseases related to Hemochromatosis, Type 4

Symptoms & Phenotypes for Hemochromatosis, Type 4

Human phenotypes related to Hemochromatosis, Type 4:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
2 joint swelling 58 31 hallmark (90%) Very frequent (99-80%) HP:0001386
3 joint dislocation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001373
4 generalized hyperpigmentation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007440
5 limitation of joint mobility 58 31 hallmark (90%) Very frequent (99-80%) HP:0001376
6 increased circulating ferritin concentration 31 hallmark (90%) HP:0003281
7 hepatic steatosis 58 31 frequent (33%) Frequent (79-30%) HP:0001397
8 abdominal pain 58 31 frequent (33%) Frequent (79-30%) HP:0002027
9 cirrhosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001394
10 congenital hepatic fibrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002612
11 cataract 31 HP:0000518
12 fatigue 31 HP:0012378
13 anemia 31 HP:0001903
14 glucose intolerance 31 HP:0001952
15 arrhythmia 31 HP:0011675
16 osteoarthritis 31 HP:0002758
17 impotence 31 HP:0000802
18 cardiomyopathy 31 HP:0001638
19 increased serum ferritin 58 Very frequent (99-80%)
20 impaired glucose tolerance 31 HP:0040270

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
cataract

Cardiovascular Heart:
arrhythmia
cardiomyopathy

Genitourinary External Genitalia Male:
impotence

Endocrine Features:
impaired glucose tolerance
endocrine disorders

Skin Nails Hair Skin:
hyperpigmentation

Neurologic Behavioral Psychiatric Manifestations:
fatigue

Skeletal:
osteoarthritis
joint pains

Laboratory Abnormalities:
increased serum ferritin
increased transferrin saturation

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

Hematology:
anemia, microcytic

Clinical features from OMIM®:

606069 (Updated 20-May-2021)

UMLS symptoms related to Hemochromatosis, Type 4:


fatigue; arthralgia

MGI Mouse Phenotypes related to Hemochromatosis, Type 4:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.86 CYBRD1 HEPH HJV SLC11A2 SLC40A1 STEAP3
2 hematopoietic system MP:0005397 9.81 HEPH HFE HJV SLC11A2 SLC40A1 STEAP3
3 immune system MP:0005387 9.61 HEPH HFE HJV SLC11A2 SLC40A1 STEAP3
4 liver/biliary system MP:0005370 9.32 CYBRD1 HEPH HFE HJV SLC11A2 SLC40A1

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 29936
2 Hepcidins Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prospective, Comparative (5 Groups), Non-randomized, Multicenter, Physiopathological Study, Evaluating Pharmacokinetic Characteristics of Serum Hepcidin Level in Response to Iron Oral Intake in Order to Evaluate Their Interest to Discriminate Patients With Dysmetabolic Hepatosiderosis or Ferroportin Disease. Completed 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:

40
Liver, Heart, Pancreas, Brain, Lung, Bone

Publications for Hemochromatosis, Type 4

Articles related to Hemochromatosis, Type 4:

(show all 50)
# Title Authors PMID Year
1
A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. 57 6 54
11431687 2001
2
Genetic and clinical heterogeneity of ferroportin disease. 6 57
16351644 2005
3
Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. 57 6
11518736 2001
4
The SLC40A1 R178Q mutation is a recurrent cause of hemochromatosis and is associated with a novel pathogenic mechanism. 6 61
30002125 2018
5
Ferroportin disease: A novel SLC40A1 mutation. 6
32360131 2020
6
Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in Chinese patients affected by hereditary hemochromatosis. 6
27896572 2017
7
Identification of hereditary hemochromatosis pedigrees and a novel SLC40A1 mutation in Chinese population. 6
28110135 2017
8
Ferroportin diseases: functional studies, a link between genetic and clinical phenotype. 6
23943237 2013
9
Mild iron overload in an African American man with SLC40A1 D270V. 6
22584997 2012
10
Identification of mutations in SLC40A1 that affect ferroportin function and phenotype of human ferroportin iron overload. 6
21396368 2011
11
Sex and acquired cofactors determine phenotypes of ferroportin disease. 6
21199650 2011
12
Hereditary hemochromatosis: mutations in genes involved in iron homeostasis in Brazilian patients. 6
21411349 2011
13
Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV. 6
17997113 2008
14
Global sequencing approach for characterizing the molecular background of hereditary iron disorders. 6
17951290 2007
15
Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. 6
17276706 2007
16
Ferroportin (SLC40A1) gene in thalassemic patients of Indian descent. 6
16813613 2006
17
Ferroportin (Q248H) mutations in African families with dietary iron overload. 6
16336444 2005
18
The molecular basis of ferroportin-linked hemochromatosis. 57
15956209 2005
19
Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations. 6
12730114 2003
20
Genetic hyperferritinaemia and reticuloendothelial iron overload associated with a three base pair deletion in the coding region of the ferroportin gene (SLC11A3). 6
12406098 2002
21
A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4. 6
12123233 2002
22
Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). 6
12091367 2002
23
Novel mutation in ferroportin1 is associated with autosomal dominant hemochromatosis. 6
12091366 2002
24
Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. 57
10471458 1999
25
Current approach to hemochromatosis. 61 54
18430498 2008
26
Splicing analysis of SLC40A1 missense variations and contribution to hemochromatosis type 4 phenotypes. 61
33341511 2021
27
Juvenile Hemochromatosis: Rheumatic Manifestations of 2 Sisters Responding to Deferasirox Treatment. A Case Series and Literature Review. 61
33488128 2021
28
Reduced iron export associated with hepcidin resistance can explain the iron overload spectrum in ferroportin disease. 61
32450003 2020
29
Disruption of the hepcidin/ferroportin regulatory circuitry causes low axial bone mass in mice. 61
32380257 2020
30
Mild Attenuation of the Pulmonary Inflammatory Response in a Mouse Model of Hereditary Hemochromatosis Type 4. 61
33519502 2020
31
Inherited iron overload disorders. 61
32258529 2020
32
Air-blood barrier thickening and alterations of alveolar epithelial type 2 cells in mouse lungs with disrupted hepcidin/ferroportin regulatory system. 61
30280242 2019
33
Ferroportin disease mutations influence manganese accumulation and cytotoxicity. 61
30247984 2019
34
Deciphering the molecular basis of ferroportin resistance to hepcidin: Structure/function analysis of rare SLC40A1 missense mutations found in suspected hemochromatosis type 4 patients. 61
28826751 2017
35
Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease. 61
28499927 2017
36
A Novel Phenotype of a Hereditary Hemochromatosis Type 4 with Ferroportin-1 Mutation, Presenting with Juvenile Cataracts. 61
27629970 2016
37
Comprehensive functional annotation of 18 missense mutations found in suspected hemochromatosis type 4 patients. 61
24714983 2014
38
[Family with marked hyperferritinemia as a result of hemochromatosis type 4 (ferroportin disease)]. 61
25198087 2014
39
Resistance of ferroportin to hepcidin binding causes exocrine pancreatic failure and fatal iron overload. 61
25100063 2014
40
Structure-function analysis of the human ferroportin iron exporter (SLC40A1): effect of hemochromatosis type 4 disease mutations and identification of critical residues. 61
23784628 2013
41
Effect of ferroportin polymorphism on iron homeostasis and infection. 61
23178444 2013
42
Hemizygous deletion of COL3A1, COL5A2, and MSTN causes a complex phenotype with aortic dissection: a lesson for and from true haploinsufficiency. 61
20648054 2010
43
Clinical presentation and molecular pathophysiology of autosomal dominant hemochromatosis caused by a novel ferroportin mutation. 54
19937651 2010
44
[Non-HFE-related hereditary iron overload]. 61
17540536 2007
45
SLC40A1 c.1402G-->a results in aberrant splicing, ferroportin truncation after glycine 330, and an autosomal dominant hemochromatosis phenotype. 54
18160816 2007
46
A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis. 54
16111902 2005
47
Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease. 61
15986403 2005
48
Hepcidin in iron overload disorders. 61
15671438 2005
49
[Genetics of hereditary iron overload]. 61
15506716 2004
50
Rare causes of hereditary iron overload. 61
12382200 2002

Variations for Hemochromatosis, Type 4

ClinVar genetic disease variations for Hemochromatosis, Type 4:

6 (show top 50) (show all 93)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SLC40A1 NM_014585.5(SLC40A1):c.430A>C (p.Asn144His) SNV Pathogenic 5410 rs104893662 GRCh37: 2:190436525-190436525
GRCh38: 2:189571799-189571799
2 SLC40A1 NM_014585.5(SLC40A1):c.230C>A (p.Ala77Asp) SNV Pathogenic 5411 rs28939076 GRCh37: 2:190439928-190439928
GRCh38: 2:189575202-189575202
3 SLC40A1 NM_014585.5(SLC40A1):c.470A>G (p.Asp157Gly) SNV Pathogenic 5412 rs104893663 GRCh37: 2:190436485-190436485
GRCh38: 2:189571759-189571759
4 SLC40A1 NM_014585.5(SLC40A1):c.546G>T (p.Gln182His) SNV Pathogenic 5413 rs104893670 GRCh37: 2:190430294-190430294
GRCh38: 2:189565568-189565568
5 SLC40A1 NM_014585.5(SLC40A1):c.476_478TTG[3] (p.Val162del) Microsatellite Pathogenic 5414 rs878854984 GRCh37: 2:190436468-190436470
GRCh38: 2:189571742-189571744
6 SLC40A1 NM_014585.5(SLC40A1):c.968G>T (p.Gly323Val) SNV Pathogenic 5415 rs104893671 GRCh37: 2:190428744-190428744
GRCh38: 2:189564018-189564018
7 SLC40A1 NM_014585.5(SLC40A1):c.542A>T (p.Asp181Val) SNV Pathogenic 5416 rs104893672 GRCh37: 2:190430298-190430298
GRCh38: 2:189565572-189565572
8 SLC40A1 NM_014585.5(SLC40A1):c.239G>T (p.Gly80Val) SNV Pathogenic 5417 rs104893673 GRCh37: 2:190439919-190439919
GRCh38: 2:189575193-189575193
9 SLC40A1 NM_014585.5(SLC40A1):c.800G>A (p.Gly267Asp) SNV Pathogenic 5418 rs104893664 GRCh37: 2:190428912-190428912
GRCh38: 2:189564186-189564186
10 SLC40A1 NP_055400.1(SLC40A1):p.Gln248His protein only Pathogenic 208986 GRCh37:
GRCh38:
11 SLC40A1 NM_014585.5(SLC40A1):c.809A>T (p.Asp270Val) SNV Pathogenic 208987 rs368420430 GRCh37: 2:190428903-190428903
GRCh38: 2:189564177-189564177
12 SLC40A1 NM_014585.5(SLC40A1):c.1469G>A (p.Gly490Asp) SNV Pathogenic 406376 rs1060501102 GRCh37: 2:190426851-190426851
GRCh38: 2:189562125-189562125
13 SLC40A1 NM_014585.5(SLC40A1):c.1049C>A (p.Ala350Asp) SNV Pathogenic 488154 rs1553493234 GRCh37: 2:190428663-190428663
GRCh38: 2:189563937-189563937
14 SLC40A1 NM_014585.5(SLC40A1):c.541G>A (p.Asp181Asn) SNV Pathogenic 488152 rs1553493481 GRCh37: 2:190430299-190430299
GRCh38: 2:189565573-189565573
15 SLC40A1 NM_014585.5(SLC40A1):c.544C>G (p.Gln182Glu) SNV Pathogenic 488155 rs1553493479 GRCh37: 2:190430296-190430296
GRCh38: 2:189565570-189565570
16 SLC40A1 NM_014585.5(SLC40A1):c.-205A>C SNV Pathogenic 488156 rs1553495699 GRCh37: 2:190445391-190445391
GRCh38: 2:189580665-189580665
17 SLC40A1 NM_014585.5(SLC40A1):c.1481G>A (p.Gly494Asp) SNV Pathogenic 488153 rs1553492997 GRCh37: 2:190426839-190426839
GRCh38: 2:189562113-189562113
18 SLC40A1 NM_014585.5(SLC40A1):c.479T>C (p.Val160Ala) SNV Pathogenic 488151 rs1553494286 GRCh37: 2:190436476-190436476
GRCh38: 2:189571750-189571750
19 SLC40A1 NM_014585.6(SLC40A1):c.533G>A (p.Arg178Gln) SNV Pathogenic 839124 GRCh37: 2:190430307-190430307
GRCh38: 2:189565581-189565581
20 SLC40A1 NM_014585.6(SLC40A1):c.1592T>C (p.Val531Ala) SNV Pathogenic 917398 GRCh37: 2:190426728-190426728
GRCh38: 2:189562002-189562002
21 SLC40A1 NM_014585.6(SLC40A1):c.626C>T (p.Ser209Leu) SNV Pathogenic 951489 GRCh37: 2:190430214-190430214
GRCh38: 2:189565488-189565488
22 SLC40A1 NM_014585.5(SLC40A1):c.610G>A (p.Gly204Ser) SNV Likely pathogenic 56158 rs387907377 GRCh37: 2:190430230-190430230
GRCh38: 2:189565504-189565504
23 SLC40A1 NM_014585.5(SLC40A1):c.474G>T (p.Trp158Cys) SNV Likely pathogenic 568628 rs1423207026 GRCh37: 2:190436481-190436481
GRCh38: 2:189571755-189571755
24 SLC40A1 NM_014585.5(SLC40A1):c.1570G>A (p.Val524Ile) SNV Conflicting interpretations of pathogenicity 333162 rs142456282 GRCh37: 2:190426750-190426750
GRCh38: 2:189562024-189562024
25 SLC40A1 NM_014585.5(SLC40A1):c.957del (p.Met319fs) Deletion Uncertain significance 631836 rs1559010409 GRCh37: 2:190428755-190428755
GRCh38: 2:189564029-189564029
26 SLC40A1 NM_014585.6(SLC40A1):c.365C>T (p.Thr122Ile) SNV Uncertain significance 843706 GRCh37: 2:190437594-190437594
GRCh38: 2:189572868-189572868
27 SLC40A1 NM_014585.6(SLC40A1):c.271+6T>A SNV Uncertain significance 855912 GRCh37: 2:190439881-190439881
GRCh38: 2:189575155-189575155
28 SLC40A1 NM_014585.6(SLC40A1):c.695C>A (p.Ala232Asp) SNV Uncertain significance 801842 rs760236238 GRCh37: 2:190430145-190430145
GRCh38: 2:189565419-189565419
29 SLC40A1 NM_014585.6(SLC40A1):c.546G>A (p.Gln182=) SNV Uncertain significance 895347 GRCh37: 2:190430294-190430294
GRCh38: 2:189565568-189565568
30 SLC40A1 NM_014585.6(SLC40A1):c.*1187T>G SNV Uncertain significance 896702 GRCh37: 2:190425417-190425417
GRCh38: 2:189560691-189560691
31 SLC40A1 NM_014585.6(SLC40A1):c.*1000A>T SNV Uncertain significance 896703 GRCh37: 2:190425604-190425604
GRCh38: 2:189560878-189560878
32 SLC40A1 NM_014585.6(SLC40A1):c.272-14C>T SNV Uncertain significance 896757 GRCh37: 2:190437701-190437701
GRCh38: 2:189572975-189572975
33 SLC40A1 NM_014585.6(SLC40A1):c.235A>G (p.Ile79Val) SNV Uncertain significance 896758 GRCh37: 2:190439923-190439923
GRCh38: 2:189575197-189575197
34 SLC40A1 NM_014585.5(SLC40A1):c.524C>A (p.Ala175Asp) SNV Uncertain significance 406375 rs1060501101 GRCh37: 2:190430316-190430316
GRCh38: 2:189565590-189565590
35 SLC40A1 NM_014585.5(SLC40A1):c.-31C>G SNV Uncertain significance 333176 rs753784669 GRCh37: 2:190445217-190445217
GRCh38: 2:189580491-189580491
36 SLC40A1 NM_014585.5(SLC40A1):c.-253C>A SNV Uncertain significance 333178 rs886055363 GRCh37: 2:190445439-190445439
GRCh38: 2:189580713-189580713
37 SLC40A1 NM_014585.5(SLC40A1):c.1483G>A (p.Val495Ile) SNV Uncertain significance 333164 rs763188298 GRCh37: 2:190426837-190426837
GRCh38: 2:189562111-189562111
38 SLC40A1 NM_014585.5(SLC40A1):c.289G>A (p.Val97Met) SNV Uncertain significance 333172 rs886055361 GRCh37: 2:190437670-190437670
GRCh38: 2:189572944-189572944
39 SLC40A1 NM_014585.5(SLC40A1):c.-344C>G SNV Uncertain significance 333182 rs747058400 GRCh37: 2:190445530-190445530
GRCh38: 2:189580804-189580804
40 SLC40A1 NM_014585.5(SLC40A1):c.-201T>G SNV Uncertain significance 333177 rs886055362 GRCh37: 2:190445387-190445387
GRCh38: 2:189580661-189580661
41 SLC40A1 NM_014585.5(SLC40A1):c.*309G>A SNV Uncertain significance 333158 rs886055360 GRCh37: 2:190426295-190426295
GRCh38: 2:189561569-189561569
42 SLC40A1 NM_014585.5(SLC40A1):c.1520A>G (p.His507Arg) SNV Uncertain significance 216680 rs863224768 GRCh37: 2:190426800-190426800
GRCh38: 2:189562074-189562074
43 SLC40A1 NM_014585.5(SLC40A1):c.476_478TTG[5] (p.Val162dup) Microsatellite Uncertain significance 240919 rs878854984 GRCh37: 2:190436467-190436468
GRCh38: 2:189571741-189571742
44 SLC40A1 NM_014585.5(SLC40A1):c.430A>T (p.Asn144Tyr) SNV Uncertain significance 240918 rs104893662 GRCh37: 2:190436525-190436525
GRCh38: 2:189571799-189571799
45 SLC40A1 NM_014585.5(SLC40A1):c.*646C>T SNV Uncertain significance 333156 rs886055359 GRCh37: 2:190425958-190425958
GRCh38: 2:189561232-189561232
46 SLC40A1 NM_014585.6(SLC40A1):c.190T>C (p.Tyr64His) SNV Uncertain significance 956190 GRCh37: 2:190439968-190439968
GRCh38: 2:189575242-189575242
47 SLC40A1 NM_014585.6(SLC40A1):c.1402G>A (p.Gly468Ser) SNV Uncertain significance 1016173 GRCh37: 2:190428310-190428310
GRCh38: 2:189563584-189563584
48 SLC40A1 NM_014585.6(SLC40A1):c.44-2A>G SNV Uncertain significance 1017290 GRCh37: 2:190444608-190444608
GRCh38: 2:189579882-189579882
49 SLC40A1 NM_014585.6(SLC40A1):c.5C>G (p.Thr2Ser) SNV Uncertain significance 1034696 GRCh37: 2:190445182-190445182
GRCh38: 2:189580456-189580456
50 SLC40A1 NM_014585.6(SLC40A1):c.1402+4A>G SNV Uncertain significance 1035851 GRCh37: 2:190428306-190428306
GRCh38: 2:189563580-189563580

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

72 (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 rs128565330
7 SLC40A1 p.Gly80Val VAR_030059 rs104893673
8 SLC40A1 p.Asn144Asp VAR_030060
9 SLC40A1 p.Asn144Thr VAR_030061 rs143410165
10 SLC40A1 p.Asp181Val VAR_030063 rs104893672
11 SLC40A1 p.Gly267Asp VAR_030064 rs104893664
12 SLC40A1 p.Asp270Val VAR_030065 rs368420430

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
Show member pathways
13.01 TFRC STEAP3 SLC40A1 SLC11A2 HEPH CYBRD1
2
Show member pathways
12.08 TFRC STEAP3 SLC40A1 SLC11A2 HEPH CYBRD1
3
Show member pathways
11.53 SLC40A1 SLC11A2 HEPH
4 11.39 SLC40A1 SLC11A2 HEPH CYBRD1
5 11.17 TFRC STEAP3 SLC40A1 SLC11A2
6 10.18 TFRC TFR2 STEAP3 SLC40A1 SLC11A2 HAMP
7 10.1 TMPRSS6 HJV HFE HAMP

GO Terms for Hemochromatosis, Type 4

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

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.15 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
2 plasma membrane GO:0005886 10.02 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
3 integral component of membrane GO:0016021 9.73 TMPRSS6 TFRC TFR2 STEAP3 SLC40A1 SLC11A2
4 basolateral plasma membrane GO:0016323 9.58 TFRC SLC40A1 HEPH
5 recycling endosome GO:0055037 9.43 TFRC SLC11A2 HFE
6 basal part of cell GO:0045178 9.16 SLC11A2 HFE
7 HFE-transferrin receptor complex GO:1990712 8.92 TFRC TFR2 HJV HFE

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.92 STEAP3 SLC40A1 SLC11A2 HFE HEPH
2 transferrin transport GO:0033572 9.62 TFRC TFR2 STEAP3 HFE
3 acute-phase response GO:0006953 9.61 TFR2 HFE HAMP
4 iron ion homeostasis GO:0055072 9.61 TMPRSS6 TFR2 STEAP3 SLC40A1 SLC11A2 HJV
5 iron ion transport GO:0006826 9.56 TFRC TFR2 SLC11A2 HEPH
6 liver regeneration GO:0097421 9.55 HFE HAMP
7 response to iron ion GO:0010039 9.55 TFR2 SLC11A2 HFE HAMP CYBRD1
8 copper ion transport GO:0006825 9.54 SLC11A2 HEPH
9 multicellular organismal iron ion homeostasis GO:0060586 9.54 SLC40A1 SLC11A2 HAMP
10 positive regulation of peptide hormone secretion GO:0090277 9.51 TFR2 HFE
11 iron ion transmembrane transport GO:0034755 9.49 SLC40A1 SLC11A2
12 cellular response to iron ion GO:0071281 9.48 TFR2 HFE
13 divalent inorganic cation transport GO:0072511 9.46 SLC40A1 SLC11A2
14 response to iron ion starvation GO:1990641 9.4 HFE HAMP
15 cellular iron ion homeostasis GO:0006879 9.32 TMPRSS6 TFRC TFR2 SLC40A1 SLC11A2 HJV

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

# Name GO ID Score Top Affiliating Genes
1 co-receptor binding GO:0039706 9.32 TFR2 HFE
2 transferrin receptor binding GO:1990459 9.26 HJV HFE
3 iron ion transmembrane transporter activity GO:0005381 9.16 SLC40A1 SLC11A2
4 ferrous iron transmembrane transporter activity GO:0015093 8.96 SLC40A1 SLC11A2
5 transferrin receptor activity GO:0004998 8.62 TFRC TFR2

Sources for Hemochromatosis, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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