SPH2
MCID: SPH014
MIFTS: 38

Spherocytosis, Type 2 (SPH2)

Categories: Blood diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Spherocytosis, Type 2

MalaCards integrated aliases for Spherocytosis, Type 2:

Name: Spherocytosis, Type 2 57 39
Hereditary Spherocytosis Type 2 12 72 15
Spherocytosis, Hereditary, 2 57 72 70
Sph2 57 12 72
Hs2 57 12 72
Spherocytosis Type 2 29 6
Spherocytosis, Type 2, Autosomal Dominant 72
Spherocytosis, Hereditary, 2; Hs2 57
Hereditary Spherocytosis 2 12
Spherocytosis 2 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant


HPO:

31
spherocytosis, type 2:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110917
OMIM® 57 616649
MeSH 44 D013103
UMLS 70 C2674219

Summaries for Spherocytosis, Type 2

OMIM® : 57 Hereditary spherocytosis refers to a group of heterogeneous disorders that are characterized by the presence of spherical-shaped erythrocytes (spherocytes) on the peripheral blood smear. The disorders are characterized clinically by anemia, jaundice, and splenomegaly, with variable severity. Common complications include cholelithiasis, hemolytic episodes, and aplastic crises (review by Perrotta et al., 2008). For a general description and a discussion of genetic heterogeneity of hereditary spherocytosis, see 182900. (616649) (Updated 05-Apr-2021)

MalaCards based summary : Spherocytosis, Type 2, also known as hereditary spherocytosis type 2, is related to acute erythroid leukemia and thalassemia, and has symptoms including icterus An important gene associated with Spherocytosis, Type 2 is SPTB (Spectrin Beta, Erythrocytic), and among its related pathways/superpathways is Factors involved in megakaryocyte development and platelet production. Related phenotypes are splenomegaly and jaundice

Disease Ontology : 12 A hereditary spherocytosis that has material basis in an autosomal dominant mutation of SPTB on chromosome 14q23.3.

UniProtKB/Swiss-Prot : 72 Spherocytosis 2: An autosomal dominant form of hereditary spherocytosis, a group of hematologic disorders characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Clinical manifestations include chronic hemolytic anemia, jaundice, and splenomegaly, with variable severity.

Related Diseases for Spherocytosis, Type 2

Diseases in the Hereditary Spherocytosis family:

Spherocytosis, Type 1 Spherocytosis, Type 3
Spherocytosis, Type 4 Spherocytosis, Type 5
Spherocytosis, Type 2 Epb42-Related Hereditary Spherocytosis

Diseases related to Spherocytosis, Type 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 acute erythroid leukemia 30.1 KLF1 HBG1 HBB GATA1
2 thalassemia 30.1 HBG1 HBB GATA1
3 spherocytosis, type 1 29.9 RPS3A PRSS54 PGLYRP1 EXOSC1
4 sickle cell anemia 29.8 HBG2 HBG1 HBB
5 deficiency anemia 29.4 SPTB SPTA1 KLF1 HBG2 HBG1 HBB
6 spherocytosis, type 3 28.9 SPTA1 RPS3A LDB2 LDB1 KLF1 HBB
7 spherocytosis, type 4 28.8 RPS3A OR51V1 LDB2 LDB1 KLF1 HBG2
8 pyropoikilocytosis, hereditary 10.3 SPTB SPTA1
9 anemia, congenital dyserythropoietic, type iii 10.2 KLF1 GATA1
10 anemia, congenital dyserythropoietic, type ib 10.2 KLF1 GATA1
11 developmental and epileptic encephalopathy 5 10.2 SPTB SPTA1
12 pontocerebellar hypoplasia, type 1b 10.2 EXOSC9 EXOSC1
13 x-linked nephrolithiasis type i 10.2 EXOSC9 EXOSC1
14 hereditary elliptocytosis 10.2 SPTB SPTA1 HBB
15 cutaneous porphyria 10.2 KLF1 GATA1
16 anemia, congenital dyserythropoietic, type iv 10.1 KLF1 GATA1
17 sickle cell disease 10.1 HBG2 HBG1 HBB
18 fetal hemoglobin quantitative trait locus 1 10.1 HBG2 HBG1 HBB
19 thalassemia minor 10.1 KLF1 HBB GATA1
20 blood protein disease 10.1 HBG2 HBG1 HBB
21 hemoglobin e disease 10.1 KLF1 HBB
22 hereditary persistence of fetal hemoglobin-beta-thalassemia syndrome 10.1 KLF1 HBG2 HBG1 HBB
23 leptospirosis 10.1
24 hemoglobin h disease 10.0 KLF1 HBG2 HBG1 HBB
25 hereditary persistence of fetal hemoglobin-sickle cell disease syndrome 10.0 KLF1 HBG2 HBG1 HBB
26 thrombocytopenia with beta-thalassemia, x-linked 10.0 KLF1 HBG2 HBG1 GATA1
27 fetal hemoglobin quantitative trait locus 6 9.9
28 hyperoxaluria, primary, type iii 9.9 EXOSC9 EXOSC1
29 hemoglobinopathy 9.9 KLF1 HBG2 HBG1 HBB GATA1
30 hemolytic anemia 9.9 SPTB SPTA1 KLF1 HBG2 HBG1 HBB
31 alpha-thalassemia 9.9 KLF1 HBG2 HBG1 HBB GATA1
32 beta-thalassemia 9.7 SPTB SPTA1 KLF1 HBG2 HBG1 HBB
33 hypotrichosis 2 9.6 OR51V1 LDB2 LDB1 KLF1 GATA1
34 congenital hemolytic anemia 9.6 SPTB SPTA1 RPS3A KLF1 HBG2 HBG1
35 hereditary spherocytosis 8.6 SPTB SPTA1 RPS3A PGLYRP1 OR51V1 LDB2

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



Diseases related to Spherocytosis, Type 2

Symptoms & Phenotypes for Spherocytosis, Type 2

Human phenotypes related to Spherocytosis, Type 2:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 very rare (1%) HP:0001744
2 jaundice 31 very rare (1%) HP:0000952
3 hemolytic anemia 31 very rare (1%) HP:0001878
4 acanthocytosis 31 very rare (1%) HP:0001927
5 reticulocytosis 31 very rare (1%) HP:0001923
6 hyperbilirubinemia 31 very rare (1%) HP:0002904
7 spherocytosis 31 very rare (1%) HP:0004444
8 increased red cell osmotic fragility 31 very rare (1%) HP:0005502

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Spleen:
splenomegaly

Hematology:
hemolytic anemia
reticulocytosis
spherocytosis

Abdomen Liver:
jaundice

Laboratory Abnormalities:
hyperbilirubinemia
increased reticulocyte count
increased osmotic fragility
reduction of beta-spectrin to protein 4.1 binding

Clinical features from OMIM®:

616649 (Updated 05-Apr-2021)

UMLS symptoms related to Spherocytosis, Type 2:


icterus

Drugs & Therapeutics for Spherocytosis, Type 2

Search Clinical Trials , NIH Clinical Center for Spherocytosis, Type 2

Genetic Tests for Spherocytosis, Type 2

Genetic tests related to Spherocytosis, Type 2:

# Genetic test Affiliating Genes
1 Spherocytosis Type 2 29 SPTB

Anatomical Context for Spherocytosis, Type 2

Publications for Spherocytosis, Type 2

Articles related to Spherocytosis, Type 2:

(show top 50) (show all 56)
# Title Authors PMID Year
1
Novel beta-spectrin mutations in hereditary spherocytosis associated with decreased levels of mRNA. 6 57
19538529 2009
2
beta-Spectrin S(ta) Bárbara: a novel frameshift mutation in hereditary spherocytosis associated with detectable levels of mRNA and a germ cell line mosaicism. 6 57
11703334 2001
3
Beta spectrin kissimmee: a spectrin variant associated with autosomal dominant hereditary spherocytosis and defective binding to protein 4.1. 57 6
8102379 1993
4
A genetic defect in the binding of protein 4.1 to spectrin in a kindred with hereditary spherocytosis. 6 57
6215583 1982
5
Hereditary spherocytosis. 57
18940465 2008
6
Hereditary spherocytosis with spectrin deficiency related to null mutations of the beta-spectrin gene. 6
9714702 1998
7
Beta-spectrin Promiss-ao: a translation initiation codon mutation of the beta-spectrin gene (ATG --> GTG) associated with hereditary spherocytosis and spectrin deficiency in a Brazilian family. 6
9414314 1998
8
Spectrin mutations in hereditary elliptocytosis and hereditary spherocytosis. 6
8844207 1996
9
Recurrent fatal hydrops fetalis associated with a nucleotide substitution in the erythrocyte beta-spectrin gene. 6
7883966 1995
10
Asynchronous synthesis of membrane skeletal proteins during terminal maturation of murine erythroblasts. 6
1385736 1992
11
Synthesis and assembly of membrane skeletal proteins in mammalian red cell precursors. 6
3654760 1987
12
Abnormal oxidant sensitivity and beta-chain structure of spectrin in hereditary spherocytosis associated with defective spectrin-protein 4.1 binding. 57
3611357 1987
13
Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis. 57
7104494 1982
14
Bioactive Metabolites from the Endophytic Fungus Aspergillus sp. SPH2. 61
33540793 2021
15
Hemolymph protease-5 links the melanization and Toll immune pathways in the tobacco hornworm, Manduca sexta. 61
32900946 2020
16
Haemolysin Sph2 of Leptospira interrogans induces cell apoptosis via intracellular reactive oxygen species elevation and mitochondrial membrane injury. 61
30278102 2019
17
cis-Acting Determinant Limiting Expression of Sphingomyelinase Gene sph2 in Leptospira interrogans, Identified with a gfp Reporter Plasmid. 61
30266732 2018
18
Manduca sexta hemolymph protease-2 (HP2) activated by HP14 generates prophenoloxidase-activating protease-2 (PAP2) in wandering larvae and pupae. 61
30098411 2018
19
Vasopressin versus norepinephrine in septic shock: a propensity score matched efficiency retrospective cohort study in the VASST coordinating center hospital. 61
30473792 2018
20
Effects of synthetic iron and aluminium oxide surface charge and hydrophobicity on the formation of bacterial biofilm. 61
28352865 2017
21
Prophenoloxidase activation and antimicrobial peptide expression induced by the recombinant microbe binding protein of Manduca sexta. 61
27989837 2017
22
Temperature and Oxidative Stress as Triggers for Virulence Gene Expression in Pathogenic Leptospira spp. 61
28536558 2017
23
Methylovulum psychrotolerans sp. nov., a cold-adapted methanotroph from low-temperature terrestrial environments, and emended description of the genus Methylovulum. 61
27031985 2016
24
The mechanism of acetylcholine receptor in binding MuSK in myasthenia gravis and the role of HSP90 molecular chaperone. 61
27186300 2016
25
Synthesis, Structure, and Reactivities of Iminosulfane- and Phosphane-Stabilized Carbones Exhibiting Four-Electron Donor Ability. 61
26471447 2015
26
Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans. 61
26274394 2015
27
A well-defined (POCOP)Rh catalyst for the coupling of aryl halides with thiols. 61
25260114 2014
28
Syntheses, structures, and reactivities of two chalcogen-stabilized carbones. 61
25044145 2014
29
Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs. 61
24768974 2014
30
A putative regulatory genetic locus modulates virulence in the pathogen Leptospira interrogans. 61
24686063 2014
31
Factors functioning in nodule melanization of insects and their mechanisms of accumulation in nodules. 61
24262307 2014
32
Biohydrogen production by dark fermentation of glycerol using Enterobacter and Citrobacter Sp. 61
23074037 2013
33
Identification of small molecule inhibitors of cytokinesis and single cell wound repair. 61
23125193 2012
34
Leptospiral outer membrane protein microarray, a novel approach to identification of host ligand-binding proteins. 61
22961849 2012
35
Parenchymal hematoma and total lesion volume in combined IV/IA revascularization stroke therapy. 61
21990518 2012
36
Structural analysis of the Leptospiral sphingomyelinases: in silico and experimental evaluation of Sph2 as an Mg-dependent sphingomyelinase. 61
22441407 2012
37
Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-κB signaling pathways. 61
22870312 2012
38
A unique genotype of Leptospira interrogans serovar Pomona type kennewicki is associated with equine abortion. 61
21450416 2011
39
Identification and application of a different glucose uptake system that functions as an alternative to the phosphotransferase system in Corynebacterium glutamicum. 61
21452034 2011
40
Development of transcriptional fusions to assess Leptospira interrogans promoter activity. 61
21445252 2011
41
Peptidoglycan activation of the proPO-system without a peptidoglycan receptor protein (PGRP)? 61
20713082 2011
42
Egf1.5 is a second phenoloxidase cascade inhibitor encoded by Microplitis demolitor bracovirus. 61
20417280 2010
43
The role of lysozyme in the prophenoloxidase activation system of Manduca sexta: an in vitro approach. 61
19835909 2010
44
Evaluation of the expression and protective potential of Leptospiral sphingomyelinases. 61
19826861 2010
45
A positive feedback mechanism in the Manduca sexta prophenoloxidase activation system. 61
18625399 2008
46
The viral protein Egf1.0 is a dual activity inhibitor of prophenoloxidase-activating proteinases 1 and 3 from Manduca sexta. 61
18519564 2008
47
Cytotoxic activity and probable apoptotic effect of Sph2, a sphigomyelinase hemolysin from Leptospira interrogans strain Lai. 61
18315947 2008
48
Osmotic regulation of expression of two extracellular matrix-binding proteins and a haemolysin of Leptospira interrogans: differential effects on LigA and Sph2 extracellular release. 61
17906138 2007
49
Host-inducible immunogenic sphingomyelinase-like protein, Lk73.5, of Leptospira interrogans. 61
14742516 2004
50
Platinum(IV)-mediated nitrile-sulfimide coupling: a route to heterodiazadienes. 61
12693210 2003

Variations for Spherocytosis, Type 2

ClinVar genetic disease variations for Spherocytosis, Type 2:

6 (show all 21)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SPTB NM_001355436.2(SPTB):c.604T>C (p.Trp202Arg) SNV Pathogenic 12835 rs121918646 GRCh37: 14:65268515-65268515
GRCh38: 14:64801797-64801797
2 SPTB SPTB, EX22-23DEL Deletion Pathogenic 12838 GRCh37:
GRCh38:
3 SPTB NM_001355436.2(SPTB):c.1912del (p.Arg638fs) Deletion Pathogenic 12842 rs863223304 GRCh37: 14:65260469-65260469
GRCh38: 14:64793751-64793751
4 SPTB NM_001355436.2(SPTB):c.5266C>T (p.Arg1756Ter) SNV Pathogenic 12843 rs267607086 GRCh37: 14:65239585-65239585
GRCh38: 14:64772867-64772867
5 SPTB NM_001355436.2(SPTB):c.1331_1338del (p.Leu444fs) Deletion Pathogenic 544810 rs1555370967 GRCh37: 14:65263278-65263285
GRCh38: 14:64796560-64796567
6 SPTB NM_001355436.2(SPTB):c.2863C>T (p.Arg955Ter) SNV Pathogenic 544812 rs1555369657 GRCh37: 14:65253820-65253820
GRCh38: 14:64787102-64787102
7 SPTB NM_001355436.2(SPTB):c.1A>G (p.Met1Val) SNV Pathogenic 12841 rs121918651 GRCh37: 14:65289812-65289812
GRCh38: 14:64823094-64823094
8 SPTB NM_001355436.2(SPTB):c.5623C>T (p.Gln1875Ter) SNV Pathogenic 544817 rs1555367359 GRCh37: 14:65237778-65237778
GRCh38: 14:64771060-64771060
9 SPTB NM_001355436.2(SPTB):c.6119C>T (p.Thr2040Ile) SNV Likely pathogenic 870421 GRCh37: 14:65234481-65234481
GRCh38: 14:64767763-64767763
10 SPTB NM_001355436.2(SPTB):c.3784_3787del (p.Lys1262fs) Deletion Likely pathogenic 800358 rs1594773586 GRCh37: 14:65252323-65252326
GRCh38: 14:64785605-64785608
11 SPTB NM_001355436.2(SPTB):c.6055T>C (p.Ser2019Pro) SNV Likely pathogenic 12837 rs121918648 GRCh37: 14:65234545-65234545
GRCh38: 14:64767827-64767827
12 SPTB NM_001355436.2(SPTB):c.4973+5G>A SNV Likely pathogenic 544813 rs1555367789 GRCh37: 14:65241110-65241110
GRCh38: 14:64774392-64774392
13 SPTB NM_001355436.2(SPTB):c.3916C>T (p.Arg1306Ter) SNV Likely pathogenic 544816 rs150471537 GRCh37: 14:65251051-65251051
GRCh38: 14:64784333-64784333
14 SPTB NM_001355436.2(SPTB):c.647G>A (p.Arg216Gln) SNV Likely pathogenic 544811 rs1555371769 GRCh37: 14:65268472-65268472
GRCh38: 14:64801754-64801754
15 SPTB NM_001355436.2(SPTB):c.1795+1G>A SNV Likely pathogenic 189194 rs786204766 GRCh37: 14:65261184-65261184
GRCh38: 14:64794466-64794466
16 SPTB NM_001355436.2(SPTB):c.5455G>T (p.Glu1819Ter) SNV Likely pathogenic 225481 rs200386310 GRCh37: 14:65239396-65239396
GRCh38: 14:64772678-64772678
17 SPTB NM_001355436.2(SPTB):c.774G>A (p.Thr258=) SNV Uncertain significance 1028698 GRCh37: 14:65267576-65267576
GRCh38: 14:64800858-64800858
18 SPTB NM_001355436.2(SPTB):c.2519G>A (p.Arg840His) SNV Uncertain significance 811593 rs146326769 GRCh37: 14:65259862-65259862
GRCh38: 14:64793144-64793144
19 SPTB NM_001355436.2(SPTB):c.413T>C (p.Ile138Thr) SNV Uncertain significance 982665 GRCh37: 14:65270386-65270386
GRCh38: 14:64803668-64803668
20 SPTB NM_001355436.2(SPTB):c.6074T>G (p.Leu2025Arg) SNV Uncertain significance 12839 rs121918649 GRCh37: 14:65234526-65234526
GRCh38: 14:64767808-64767808
21 SPTA1 NM_003126.4(SPTA1):c.145C>T (p.Leu49Phe) SNV Uncertain significance 12851 rs121918639 GRCh37: 1:158655017-158655017
GRCh38: 1:158685227-158685227

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

72
# Symbol AA change Variation ID SNP ID
1 SPTB p.Trp202Arg VAR_001352 rs121918646

Expression for Spherocytosis, Type 2

Search GEO for disease gene expression data for Spherocytosis, Type 2.

Pathways for Spherocytosis, Type 2

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

# Super pathways Score Top Affiliating Genes
1 11.12 HBG2 HBG1 HBB GATA1

GO Terms for Spherocytosis, Type 2

Cellular components related to Spherocytosis, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exosome (RNase complex) GO:0000178 9.4 EXOSC9 EXOSC1
2 nuclear exosome (RNase complex) GO:0000176 9.37 EXOSC9 EXOSC1
3 spectrin GO:0008091 9.32 SPTB SPTA1
4 spectrin-associated cytoskeleton GO:0014731 9.26 SPTB SPTA1
5 intrinsic component of the cytoplasmic side of the plasma membrane GO:0031235 9.16 SPTB SPTA1
6 hemoglobin complex GO:0005833 9.13 HBG2 HBG1 HBB
7 haptoglobin-hemoglobin complex GO:0031838 8.8 HBG2 HBG1 HBB

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

# Name GO ID Score Top Affiliating Genes
1 cellular oxidant detoxification GO:0098869 9.54 HBG2 HBG1 HBB
2 actin filament capping GO:0051693 9.4 SPTB SPTA1
3 blood coagulation GO:0007596 9.35 HBG2 HBG1 HBB GATA1 F13B
4 hydrogen peroxide catabolic process GO:0042744 9.33 HBG2 HBG1 HBB
5 epithelial structure maintenance GO:0010669 9.32 LDB2 LDB1
6 regulation of kinase activity GO:0043549 9.26 LDB2 LDB1
7 oxygen transport GO:0015671 8.8 HBG2 HBG1 HBB

Molecular functions related to Spherocytosis, Type 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.65 HBG2 HBG1 HBB
2 RNA polymerase II activating transcription factor binding GO:0001102 9.58 LDB2 LDB1 EXOSC9
3 peroxidase activity GO:0004601 9.54 HBG2 HBG1 HBB
4 oxygen binding GO:0019825 9.5 HBG2 HBG1 HBB
5 exoribonuclease activity GO:0004532 9.46 EXOSC9 EXOSC1
6 LIM domain binding GO:0030274 9.43 LDB2 LDB1
7 oxygen carrier activity GO:0005344 9.43 HBG2 HBG1 HBB
8 organic acid binding GO:0043177 9.33 HBG2 HBG1 HBB
9 haptoglobin binding GO:0031720 9.13 HBG2 HBG1 HBB
10 hemoglobin alpha binding GO:0031721 8.8 HBG2 HBG1 HBB

Sources for Spherocytosis, Type 2

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 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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