MCID: HMC021
MIFTS: 40

Hemochromatosis, Type 2a

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

Aliases & Classifications for Hemochromatosis, Type 2a

MalaCards integrated aliases for Hemochromatosis, Type 2a:

Name: Hemochromatosis, Type 2a 57 13 73
Hemochromatosis Type 2a 12 29 6
Hfe2a 57 12 75
Juvenile Hemochromatosis 75 73
Hemochromatosis Type 2 75
Hemochromatosis 2a 75
Hefe2 75
Jh 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset is usually before age 30


HPO:

32
hemochromatosis, type 2a:
Onset and clinical course young adult onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hemochromatosis, Type 2a

OMIM : 57 Juvenile, or type 2, hemochromatosis is an autosomal recessive inborn error of iron metabolism that leads to severe iron loading and organ failure before 30 years of age. The common complications of iron overload, including liver cirrhosis, cardiac disease, endocrine failure, diabetes, arthropathy, and skin pigmentation, are similar to those of adult-onset hereditary hemochromatosis, but hypogonadism and cardiomyopathy are the most common symptoms at presentation. Heart failure and/or major arrhythmias are usually the cause of death in the absence of treatment. Early detection of the disorder is important because iron depletion by phlebotomy can prevent organ damage and all disease manifestations (summary by Roetto et al., 1999). (602390)

MalaCards based summary : Hemochromatosis, Type 2a, also known as hemochromatosis type 2a, is related to hemochromatosis type 2 and hemochromatosis, type 1, and has symptoms including lethargy and weakness. An important gene associated with Hemochromatosis, Type 2a is HJV (Hemojuvelin BMP Co-Receptor), and among its related pathways/superpathways is Hfe effect on hepcidin production. Affiliated tissues include skin, heart and liver, and related phenotypes are azoospermia and hypogonadotrophic hypogonadism

Disease Ontology : 12 A hemochromatosis type 2 that has material basis in homozygous or compound heterozygous mutation in the HJV gene on chromosome 1q21.

UniProtKB/Swiss-Prot : 75 Hemochromatosis 2A: 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.

Related Diseases for Hemochromatosis, Type 2a

Diseases in the Juvenile 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 2a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
# Related Disease Score Top Affiliating Genes
1 hemochromatosis type 2 33.1 HAMP HJV
2 hemochromatosis, type 1 30.3 HAMP HJV
3 cleft lip/palate with abnormal thumbs and microcephaly 11.2
4 hemochromatosis, type 2b 11.0
5 juvenile hereditary hemochromatosis 11.0
6 hemochromatosis, neonatal 11.0
7 hemochromatosis, type 3 11.0
8 hemochromatosis, type 4 11.0
9 hemochromatosis, type 5 11.0
10 lymphoma 10.0
11 leukemia 9.9
12 combined immunodeficiency, x-linked 9.8
13 severe combined immunodeficiency 9.8
14 hypermobility syndrome 9.8
15 leukemia, chronic lymphocytic 2 9.7
16 ehlers-danlos syndrome, hypermobility type 9.7
17 leukemia, chronic lymphocytic 9.7
18 pneumothorax, primary spontaneous 9.7
19 myeloma, multiple 9.7
20 severe combined immunodeficiency, x-linked 9.7
21 persistent polyclonal b-cell lymphocytosis 9.7
22 leukemia, acute lymphoblastic 9.7
23 b-cell expansion with nfkb and t-cell anergy 9.7
24 b-cell lymphomas 9.7
25 diffuse large b-cell lymphoma 9.7
26 follicular lymphoma 9.7
27 mantle cell lymphoma 9.7
28 heavy chain disease 9.7
29 lymphoblastic leukemia 9.7
30 ehlers-danlos syndrome 9.7
31 pneumothorax 9.7
32 richter's syndrome 9.7
33 thyroid cancer 9.7
34 mutism 9.7
35 thyroiditis 9.7
36 macroglobulinemia 9.7
37 hypermobile ehlers-danlos syndrome 9.7
38 leukemia, b-cell, chronic 9.7
39 differentiated thyroid carcinoma 9.7
40 alpha-heavy chain disease 9.7
41 metal metabolism disorder 9.6 HAMP HJV
42 atransferrinemia 9.6 HAMP HJV
43 nutritional deficiency disease 9.5 HAMP HJV
44 iron deficiency anemia 9.5 HAMP HJV
45 inherited metabolic disorder 9.4 HAMP HJV
46 aceruloplasminemia 9.3 HAMP HJV
47 deficiency anemia 9.0 HAMP HJV

Graphical network of the top 20 diseases related to Hemochromatosis, Type 2a:



Diseases related to Hemochromatosis, Type 2a

Symptoms & Phenotypes for Hemochromatosis, Type 2a

Symptoms via clinical synopsis from OMIM:

57
Skeletal:
arthritis

Abdomen Liver:
hepatomegaly
cirrhosis
fibrosis

Genitourinary External Genitalia Male:
hypogonadism

GenitourinaryInternal GenitaliaMale:
azoospermia
infertility

Laboratory Abnormalities:
increased serum ferritin
increased serum iron
increased transferrin saturation
increased transaminase values

Skin Nails Hair Skin:
hyperpigmentation

AbdomenSpleen:
splenomegaly

Cardiovascular Heart:
arrhythmia
heart failure
cardiomyopathy, dilated

Genitourinary External Genitalia Female:
hypogonadism

Neurologic Behavioral Psychiatric Manifestations:
lethargy

Genitourinary Internal Genitalia Female:
amenorrhea

Muscle Soft Tissue:
weakness


Clinical features from OMIM:

602390

Human phenotypes related to Hemochromatosis, Type 2a:

32 (show all 16)
# Description HPO Frequency HPO Source Accession
1 azoospermia 32 HP:0000027
2 hypogonadotrophic hypogonadism 32 very rare (1%) HP:0000044
3 amenorrhea 32 HP:0000141
4 infertility 32 HP:0000789
5 hyperpigmentation of the skin 32 HP:0000953
6 lethargy 32 HP:0001254
7 arthritis 32 HP:0001369
8 cirrhosis 32 very rare (1%) HP:0001394
9 congestive heart failure 32 HP:0001635
10 cardiomyopathy 32 very rare (1%) HP:0001638
11 dilated cardiomyopathy 32 HP:0001644
12 splenomegaly 32 HP:0001744
13 hepatomegaly 32 very rare (1%) HP:0002240
14 increased serum ferritin 32 very rare (1%) HP:0003281
15 increased serum iron 32 very rare (1%) HP:0003452
16 arrhythmia 32 HP:0011675

UMLS symptoms related to Hemochromatosis, Type 2a:


lethargy, weakness

Drugs & Therapeutics for Hemochromatosis, Type 2a

Search Clinical Trials , NIH Clinical Center for Hemochromatosis, Type 2a

Genetic Tests for Hemochromatosis, Type 2a

Genetic tests related to Hemochromatosis, Type 2a:

# Genetic test Affiliating Genes
1 Hemochromatosis Type 2a 29 HJV

Anatomical Context for Hemochromatosis, Type 2a

MalaCards organs/tissues related to Hemochromatosis, Type 2a:

41
Skin, Heart, Liver

Publications for Hemochromatosis, Type 2a

Articles related to Hemochromatosis, Type 2a:

(show all 33)
# Title Authors Year
1
Iron Overload in the Liver of 2 Children: Nonalcoholic Steatohepatitis and Juvenile Hemochromatosis. ( 28067690 )
2017
2
Juvenile hemochromatosis and hepatocellular carcinoma in a patient with a novel mutation in the HJV gene. ( 28363629 )
2017
3
HAMP Gene Mutation Associated with Juvenile Hemochromatosis in Brazilian Patients. ( 27007796 )
2016
4
Increased Retinal Expression of the Pro-Angiogenic Receptor GPR91 via BMP6 in a Mouse Model of Juvenile Hemochromatosis. ( 27046124 )
2016
5
TFR2 mutations in patients with juvenile hemochromatosis phenotype. ( 26408288 )
2015
6
Juvenile hemochromatosis associated with heterozygosity for novel hemojuvelin mutations and with unknown cofactors. ( 25152992 )
2014
7
A late presentation of a fatal disease: juvenile hemochromatosis. ( 24106505 )
2013
8
Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis. ( 22297252 )
2012
9
Juvenile hemochromatosis due to homozygosity for the G320V mutation in the HJV gene with fatal outcome. ( 19796184 )
2009
10
Deferasirox reduces iron overload in a murine model of juvenile hemochromatosis. ( 19234060 )
2009
11
Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis. ( 17264300 )
2007
12
Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis. ( 17229647 )
2007
13
Juvenile hemochromatosis caused by a novel combination of hemojuvelin G320V/R176C mutations in a 5-year old girl. ( 17339196 )
2007
14
Glucose metabolism, insulin secretion and insulin sensitivity in juvenile hemochromatosis. A case report and review of the literature. ( 17427110 )
2007
15
A juvenile hemochromatosis patient homozygous for a novel deletion of cDNA nucleotide 81 of hemojuvelin. ( 16424663 )
2006
16
Juvenile hemochromatosis associated with pathogenic mutations of adult hemochromatosis genes. ( 15685557 )
2005
17
HJV gene mutations in European patients with juvenile hemochromatosis. ( 15811010 )
2005
18
A mouse model of juvenile hemochromatosis. ( 16075059 )
2005
19
Juvenile hemochromatosis due to G320V/Q116X compound heterozygosity of hemojuvelin in an Irish patient. ( 15967692 )
2005
20
Homozygosity for a novel nonsense mutation (G66X) of the HJV gene causes severe juvenile hemochromatosis with fatal cardiomyopathy. ( 15611318 )
2005
21
Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin. ( 14982867 )
2004
22
A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis. ( 15099344 )
2004
23
Prevalence of the G320V mutation of the HJV gene, associated with juvenile hemochromatosis, in Greece. ( 15194541 )
2004
24
Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70R). ( 14630809 )
2004
25
Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. ( 14647275 )
2004
26
Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis. ( 14982873 )
2004
27
Juvenile hemochromatosis HJV-related revealed by cardiogenic shock. ( 15315789 )
2004
28
Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. ( 12469120 )
2003
29
Juvenile hemochromatosis in a Spanish family. ( 12064925 )
2002
30
Juvenile hemochromatosis. ( 12382199 )
2002
31
Linkage to chromosome 1q in Greek families with juvenile hemochromatosis. ( 11778658 )
2001
32
Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, canada). ( 10772871 )
2000
33
Juvenile hemochromatosis locus maps to chromosome 1q. ( 10205270 )
1999

Variations for Hemochromatosis, Type 2a

UniProtKB/Swiss-Prot genetic disease variations for Hemochromatosis, Type 2a:

75 (show all 14)
# Symbol AA change Variation ID SNP ID
1 HJV p.Cys80Arg VAR_019617 rs28940586
2 HJV p.Ser85Pro VAR_019618
3 HJV p.Gly99Arg VAR_019619
4 HJV p.Leu101Pro VAR_019620 rs74315327
5 HJV p.Ala168Asp VAR_019621 rs782125244
6 HJV p.Phe170Ser VAR_019622
7 HJV p.Asp172Glu VAR_019623 rs782708481
8 HJV p.Trp191Cys VAR_019624
9 HJV p.Ser205Arg VAR_019625
10 HJV p.Ile222Asn VAR_019626 rs74315325
11 HJV p.Gly250Val VAR_019627 rs863224819
12 HJV p.Arg288Trp VAR_019628
13 HJV p.Gly320Val VAR_019629 rs74315323
14 HJV p.Cys321Trp VAR_019927 rs121434374

ClinVar genetic disease variations for Hemochromatosis, Type 2a:

6
(show all 42)
# Gene Variation Type Significance SNP ID Assembly Location
1 HJV NM_213653.3(HJV): c.959G> T (p.Gly320Val) single nucleotide variant Pathogenic rs74315323 GRCh37 Chromosome 1, 145416614: 145416614
2 HJV NM_213653.3(HJV): c.959G> T (p.Gly320Val) single nucleotide variant Pathogenic rs74315323 GRCh38 Chromosome 1, 146018399: 146018399
3 HJV NM_213653.3(HJV): c.976C> T (p.Arg326Ter) single nucleotide variant Pathogenic rs74315324 GRCh37 Chromosome 1, 145416631: 145416631
4 HJV NM_213653.3(HJV): c.976C> T (p.Arg326Ter) single nucleotide variant Pathogenic rs74315324 GRCh38 Chromosome 1, 146018382: 146018382
5 HJV NM_213653.3(HJV): c.665T> A (p.Ile222Asn) single nucleotide variant Pathogenic rs74315325 GRCh37 Chromosome 1, 145416320: 145416320
6 HJV NM_213653.3(HJV): c.665T> A (p.Ile222Asn) single nucleotide variant Pathogenic rs74315325 GRCh38 Chromosome 1, 146018693: 146018693
7 HJV NM_213653.3(HJV): c.842T> C (p.Ile281Thr) single nucleotide variant Pathogenic rs74315326 GRCh37 Chromosome 1, 145416497: 145416497
8 HJV NM_213653.3(HJV): c.842T> C (p.Ile281Thr) single nucleotide variant Pathogenic rs74315326 GRCh38 Chromosome 1, 146018516: 146018516
9 HJV NM_213653.3(HJV): c.238T> C (p.Cys80Arg) single nucleotide variant Pathogenic rs28940586 GRCh37 Chromosome 1, 145415419: 145415419
10 HJV NM_213653.3(HJV): c.238T> C (p.Cys80Arg) single nucleotide variant Pathogenic rs28940586 GRCh38 Chromosome 1, 146019594: 146019594
11 HJV NM_213653.3(HJV): c.302T> C (p.Leu101Pro) single nucleotide variant Pathogenic rs74315327 GRCh37 Chromosome 1, 145415483: 145415483
12 HJV NM_213653.3(HJV): c.302T> C (p.Leu101Pro) single nucleotide variant Pathogenic rs74315327 GRCh38 Chromosome 1, 146019530: 146019530
13 HJV NM_213653.3(HJV): c.963C> A (p.Cys321Ter) single nucleotide variant Pathogenic rs121434374 GRCh37 Chromosome 1, 145416618: 145416618
14 HJV NM_213653.3(HJV): c.963C> A (p.Cys321Ter) single nucleotide variant Pathogenic rs121434374 GRCh38 Chromosome 1, 146018395: 146018395
15 HJV NM_213653.3(HJV): c.982_985delTCTC (p.Ser328Aspfs) deletion Pathogenic rs786205063 GRCh37 Chromosome 1, 145416637: 145416640
16 HJV NM_213653.3(HJV): c.982_985delTCTC (p.Ser328Aspfs) deletion Pathogenic rs786205063 GRCh38 Chromosome 1, 146018373: 146018376
17 HJV NM_213653.3(HJV): c.160A> T (p.Arg54Ter) single nucleotide variant Pathogenic rs121434375 GRCh37 Chromosome 1, 145415341: 145415341
18 HJV NM_213653.3(HJV): c.160A> T (p.Arg54Ter) single nucleotide variant Pathogenic rs121434375 GRCh38 Chromosome 1, 146019672: 146019672
19 HJV NM_213653.3(HJV): c.1264T> C (p.Trp422Arg) single nucleotide variant Uncertain significance rs863224818 GRCh38 Chromosome 1, 146018094: 146018094
20 HJV NM_213653.3(HJV): c.1264T> C (p.Trp422Arg) single nucleotide variant Uncertain significance rs863224818 GRCh37 Chromosome 1, 145416919: 145416919
21 HJV NM_213653.3(HJV): c.749G> T (p.Gly250Val) single nucleotide variant Uncertain significance rs863224819 GRCh37 Chromosome 1, 145416404: 145416404
22 HJV NM_213653.3(HJV): c.749G> T (p.Gly250Val) single nucleotide variant Uncertain significance rs863224819 GRCh38 Chromosome 1, 146018609: 146018609
23 HJV NM_213653.3(HJV): c.238T> G (p.Cys80Gly) single nucleotide variant Likely pathogenic rs28940586 GRCh38 Chromosome 1, 146019594: 146019594
24 HJV NM_213653.3(HJV): c.238T> G (p.Cys80Gly) single nucleotide variant Likely pathogenic rs28940586 GRCh37 Chromosome 1, 145415419: 145415419
25 HJV NM_213653.3(HJV): c.204_206dupAGG (p.Gly69_Arg70insGly) duplication Likely benign rs864622168 GRCh37 Chromosome 1, 145415385: 145415387
26 HJV NM_213653.3(HJV): c.204_206dupAGG (p.Gly69_Arg70insGly) duplication Likely benign rs864622168 GRCh38 Chromosome 1, 146019626: 146019628
27 HJV NM_213653.3(HJV): c.98-6C> G single nucleotide variant Benign/Likely benign rs56025621 GRCh38 Chromosome 1, 146019740: 146019740
28 HJV NM_213653.3(HJV): c.98-6C> G single nucleotide variant Benign/Likely benign rs56025621 GRCh37 Chromosome 1, 145415273: 145415273
29 HJV NM_213653.3(HJV): c.9G> C (p.Glu3Asp) single nucleotide variant Benign rs12025510 GRCh38 Chromosome 1, 146020223: 146020223
30 HJV NM_213653.3(HJV): c.9G> C (p.Glu3Asp) single nucleotide variant Benign rs12025510 GRCh37 Chromosome 1, 145414790: 145414790
31 HJV NM_213653.3(HJV): c.929C> G (p.Ala310Gly) single nucleotide variant Benign/Likely benign rs7540883 GRCh38 Chromosome 1, 146018429: 146018429
32 HJV NM_213653.3(HJV): c.929C> G (p.Ala310Gly) single nucleotide variant Benign/Likely benign rs7540883 GRCh37 Chromosome 1, 145416584: 145416584
33 HJV NC_000001.10: g.(?_145414693)_(145417545_?)del deletion Pathogenic GRCh37 Chromosome 1, 145414693: 145417545
34 HJV NM_213653.3(HJV): c.305C> T (p.Ala102Val) single nucleotide variant Uncertain significance rs782681137 GRCh38 Chromosome 1, 146019527: 146019527
35 HJV NM_213653.3(HJV): c.305C> T (p.Ala102Val) single nucleotide variant Uncertain significance rs782681137 GRCh37 Chromosome 1, 145415486: 145415486
36 HJV NC_000001.10: g.(?_145414776)_(145416941_?)dup duplication Uncertain significance GRCh37 Chromosome 1, 145414776: 145416941
37 HJV NM_213653.3(HJV): c.792G> C (p.Ser264=) single nucleotide variant Benign rs35710964 GRCh38 Chromosome 1, 146018566: 146018566
38 HJV NM_213653.3(HJV): c.792G> C (p.Ser264=) single nucleotide variant Benign rs35710964 GRCh37 Chromosome 1, 145416447: 145416447
39 HJV NM_213653.3(HJV): c.432C> G (p.Ala144=) single nucleotide variant Likely benign rs139401358 GRCh38 Chromosome 1, 146019400: 146019400
40 HJV NM_213653.3(HJV): c.432C> G (p.Ala144=) single nucleotide variant Likely benign rs139401358 GRCh37 Chromosome 1, 145415613: 145415613
41 HJV NM_213653.3(HJV): c.497A> G (p.His166Arg) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 146019335: 146019335
42 HJV NM_213653.3(HJV): c.497A> G (p.His166Arg) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 145415678: 145415678

Expression for Hemochromatosis, Type 2a

Search GEO for disease gene expression data for Hemochromatosis, Type 2a.

Pathways for Hemochromatosis, Type 2a

Pathways related to Hemochromatosis, Type 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.47 HAMP HJV

GO Terms for Hemochromatosis, Type 2a

Biological processes related to Hemochromatosis, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 8.96 HAMP HJV
2 cellular iron ion homeostasis GO:0006879 8.62 HAMP HJV

Sources for Hemochromatosis, Type 2a

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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