SPH4
MCID: SPH016
MIFTS: 43

Spherocytosis, Type 4 (SPH4)

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

Aliases & Classifications for Spherocytosis, Type 4

MalaCards integrated aliases for Spherocytosis, Type 4:

Name: Spherocytosis, Type 4 56 13 39 71
Hereditary Spherocytosis Type 4 12 73 15
Sph4 56 12 73
Hs4 56 12 73
Spherocytosis Type 4 29 6
Spherocytosis, Hereditary, 4; Hs4 56
Spherocytosis, Hereditary, 4 56
Hereditary Spherocytosis 4 12
Spherocytosis 4 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
increased risk of post-splenectomy thrombotic complications (in some patients)


HPO:

31
spherocytosis, type 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110919
OMIM 56 612653
MedGen 41 C2675212
UMLS 71 C2675212

Summaries for Spherocytosis, Type 4

UniProtKB/Swiss-Prot : 73 Spherocytosis 4: Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.

MalaCards based summary : Spherocytosis, Type 4, also known as hereditary spherocytosis type 4, is related to thalassemia and erythroleukemia, familial, and has symptoms including icterus An important gene associated with Spherocytosis, Type 4 is SLC4A1 (Solute Carrier Family 4 Member 1 (Diego Blood Group)), and among its related pathways/superpathways are Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S and Hematopoietic Stem Cell Differentiation. Affiliated tissues include b cells, bone marrow and bone, and related phenotypes are splenomegaly and hemolytic anemia

Disease Ontology : 12 A hereditary spherocytosis that has material basis in an autosomal dominant mutation of SLC4A1 on chromosome 17q21.31.

More information from OMIM: 612653

Related Diseases for Spherocytosis, Type 4

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 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 thalassemia 30.7 SLC4A1 KLF1 GATA1
2 erythroleukemia, familial 30.5 NFE2 KLF1 GATA1
3 mental retardation, autosomal dominant 21 10.4 CTCFL CTCF
4 retinitis pigmentosa 24 10.4 IGHV4-38-2 H2AC18 CTCF
5 composite lymphoma 10.4 PAX5 IGHV4-38-2
6 blood protein disease 10.3 KLF1 IGHV4-38-2 H2AC18
7 tracheal lymphoma 10.3 PAX5 IGHV4-38-2
8 spinal cord lymphoma 10.3 PAX5 IGHV4-38-2
9 mediastinal malignant lymphoma 10.3 POU2AF1 PAX5
10 mediastinal gray zone lymphoma 10.3 POU2AF1 PAX5
11 mental retardation, autosomal dominant 33 10.3 PAX5 IGHV4-38-2
12 retinitis pigmentosa 23 10.3 RPS3A IGHV4-38-2 H2AC18 CTCF
13 gray zone lymphoma 10.3 POU2AF1 PAX5
14 hodgkin's lymphoma, mixed cellularity 10.3 POU2AF1 PAX5
15 lymphatic system cancer 10.3 PAX5 IGHV4-38-2 H2AC18
16 bone marrow cancer 10.3 IGHV4-38-2 H2AC18 GATA1
17 intraocular lymphoma 10.2 PAX5 IGHV4-38-2
18 mature b-cell neoplasm 10.2 PAX5 IGHV4-38-2 H2AC18
19 appendix lymphoma 10.2 POU2AF1 PAX5 IGHV4-38-2
20 silver-russell syndrome 10.2 H2AC18 CTCFL CTCF
21 hodgkin's lymphoma, lymphocytic depletion 10.2 POU2AF1 PAX5 IGHV4-38-2
22 schuurs-hoeijmakers syndrome 10.1 IGHV4-38-2 H2AC18
23 autosomal dominant non-syndromic intellectual disability 10.1 RPS3A PAX5 IGHV4-38-2 H2AC18
24 leukemia, chronic lymphocytic 10.1
25 beta-thalassemia 10.1
26 diffuse large b-cell lymphoma 10.1
27 lymphoma 10.1
28 lymphocytic leukemia 10.1
29 hemoglobinopathy 10.1
30 severe acute respiratory syndrome 10.1
31 iga glomerulonephritis 10.1
32 embryonal carcinoma 10.1
33 hemolytic anemia 10.1
34 b-cell lymphoma 10.1
35 cornelia de lange syndrome 10.1 H2AC18 CTCFL CTCF
36 diamond-blackfan anemia 10.0 RPS3A RPS21 RPS15 KLF1 GATA1
37 spherocytosis, type 2 10.0 OR51V1 NFE2 KLF1 GATA1
38 deficiency anemia 9.9 SLC4A1 NFE2 KLF1 H2AC18 GATA1
39 leukemia, acute myeloid 9.9 RPS3A PAX5 IGHV4-38-2 H2AC18 GATA1 CTCF
40 myeloma, multiple 9.6 RPS3A PAX5 IGHV4-38-2 H2AC18
41 hypotrichosis 2 9.6 OR51V1 OR51M1 NFE2 KLF1 H2AC18 GATA1
42 spherocytosis, type 3 9.0 VPS41 TMEM121 RPS23 RPS21 RPS15 NFE2
43 hereditary spherocytosis 7.5 VPS41 VEZF1 USF1 TMEM121 SLC4A1 RPS3A

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



Diseases related to Spherocytosis, Type 4

Symptoms & Phenotypes for Spherocytosis, Type 4

Human phenotypes related to Spherocytosis, Type 4:

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

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Abdomen Liver:
jaundice

Skin Nails Hair Skin:
jaundice, neonatal or in early childhood

Hematology:
hemolytic anemia
spherocytosis
increased red cell osmotic fragility
increased reticulocyte count
increased red cell membrane cation permeability at cold temperatures (in some patients)

Laboratory Abnormalities:
hyperbilirubinemia
pseudohyperkalemia (in some patients)

Clinical features from OMIM:

612653

UMLS symptoms related to Spherocytosis, Type 4:


icterus

GenomeRNAi Phenotypes related to Spherocytosis, Type 4 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00106-A-0 9.77 RPS15 RPS3A
2 Decreased viability GR00240-S-1 9.77 GATA1 RPS15 RPS21 RPS23 RPS3A
3 Decreased viability GR00381-A-1 9.77 RPS3A
4 Decreased viability GR00402-S-2 9.77 GATA1 RPS15 RPS21 RPS23 RPS3A
5 Nucleoplasmic pre-40S maturation defects GR00209-A-1 8.8 RPS15 RPS21 RPS3A

Drugs & Therapeutics for Spherocytosis, Type 4

Search Clinical Trials , NIH Clinical Center for Spherocytosis, Type 4

Genetic Tests for Spherocytosis, Type 4

Genetic tests related to Spherocytosis, Type 4:

# Genetic test Affiliating Genes
1 Spherocytosis Type 4 29 SLC4A1

Anatomical Context for Spherocytosis, Type 4

MalaCards organs/tissues related to Spherocytosis, Type 4:

40
B Cells, Bone Marrow, Bone, Spinal Cord, Myeloid, Appendix

Publications for Spherocytosis, Type 4

Articles related to Spherocytosis, Type 4:

(show all 19)
# Title Authors PMID Year
1
Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1. 56 6
16227998 2005
2
Homozygous missense mutation (band 3 Fukuoka: G130R): a mild form of hereditary spherocytosis with near-normal band 3 content and minimal changes of membrane ultrastructure despite moderate protein 4.2 deficiency. 56 6
9734643 1998
3
Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis. 56 6
9973643 1998
4
Hereditary spherocytosis with band 3 deficiency. Association with a nonsense mutation of the band 3 gene (allele Lyon), and aggravation by a low-expression allele occurring in trans (allele Genas). 56 6
8704215 1996
5
Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis and substitution in a highly conserved position of transmembrane segment 11. 56 6
8547122 1995
6
Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis. 56 6
7530501 1995
7
Duplication of 10 nucleotides in the erythroid band 3 (AE1) gene in a kindred with hereditary spherocytosis and band 3 protein deficiency (band 3PRAGUE). 56 6
8282779 1994
8
Human erythrocyte protein 4.2 deficiency associated with hemolytic anemia and a homozygous 40glutamic acid-->lysine substitution in the cytoplasmic domain of band 3 (band 3Montefiore). 56 6
8471774 1993
9
Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III. 6
11380459 2001
10
Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3. 6
10942416 2000
11
Modulation of clinical expression and band 3 deficiency in hereditary spherocytosis. 6
9207478 1997
12
Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects. 56
9233560 1997
13
Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. 56
8640229 1996
14
A nonsense mutation in the erythrocyte band 3 gene associated with decreased mRNA accumulation in a kindred with dominant hereditary spherocytosis. 6
8567957 1996
15
Hereditary spherocytosis associated with protein band 3 defect in a Swiss kindred. 6
8011524 1994
16
Band 3 Tuscaloosa: Pro327----Arg327 substitution in the cytoplasmic domain of erythrocyte band 3 protein associated with spherocytic hemolytic anemia and partial deficiency of protein 4.2. 6
1378323 1992
17
Structural analysis of the Leptospiral sphingomyelinases: in silico and experimental evaluation of Sph2 as an Mg-dependent sphingomyelinase. 61
22441407 2012
18
Evaluation of the expression and protective potential of Leptospiral sphingomyelinases. 61
19826861 2010
19
Immunobiochemical evidence for the loss of sperm specific histones during male pronucleus formation in monospermic zygotes of sea urchins. 61
1939362 1991

Variations for Spherocytosis, Type 4

ClinVar genetic disease variations for Spherocytosis, Type 4:

6 (show all 24) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC4A1 NM_000342.3(SLC4A1):c.2464_2465insCACCCAGATG (p.Val822Alafs)duplication Pathogenic 17758 rs387906566 17:42328803-42328804 17:44251435-44251436
2 SLC4A1 NM_000342.3(SLC4A1):c.2312G>A (p.Gly771Asp)SNV Pathogenic 17760 rs121912741 17:42328956-42328956 17:44251588-44251588
3 SLC4A1 NM_000342.3(SLC4A1):c.988C>T (p.Gln330Ter)SNV Pathogenic 17761 rs121912742 17:42335880-42335880 17:44258512-44258512
4 SLC4A1 NM_000342.3(SLC4A1):c.448C>T (p.Arg150Ter)SNV Pathogenic 17762 rs56361140 17:42337809-42337809 17:44260441-44260441
5 SLC4A1 NM_000342.4(SLC4A1):c.1765C>T (p.Arg589Cys)SNV Pathogenic 17764 rs121912745 17:42333076-42333076 17:44255708-44255708
6 SLC4A1 NM_000342.3(SLC4A1):c.388G>A (p.Gly130Arg)SNV Pathogenic 17769 rs121912749 17:42337869-42337869 17:44260501-44260501
7 SLC4A1 NM_000342.3(SLC4A1):c.2509A>G (p.Thr837Ala)SNV Pathogenic 17770 rs121912750 17:42328673-42328673 17:44251305-44251305
8 SLC4A1 NM_000342.3(SLC4A1):c.1462G>A (p.Val488Met)SNV Pathogenic 17773 rs28931584 17:42334882-42334882 17:44257514-44257514
9 SLC4A1 NM_000342.3(SLC4A1):c.268G>A (p.Glu90Lys)SNV Pathogenic 17775 rs28929480 17:42338084-42338084 17:44260716-44260716
10 SLC4A1 NM_000342.3(SLC4A1):c.2608C>T (p.Arg870Trp)SNV Pathogenic 17776 rs28931585 17:42328574-42328574 17:44251206-44251206
11 SLC4A1 NM_000342.3(SLC4A1):c.2279G>A (p.Arg760Gln)SNV Pathogenic 17780 rs121912755 17:42330518-42330518 17:44253150-44253150
12 SLC4A1 NM_000342.3(SLC4A1):c.-62G>ASNV Pathogenic 17754 rs387906565 17:42340296-42340296 17:44262928-44262928
13 SLC4A1 NM_000342.3(SLC4A1):c.980C>G (p.Pro327Arg)SNV Pathogenic 17755 rs28931583 17:42335888-42335888 17:44258520-44258520
14 SLC4A1 NM_000342.3(SLC4A1):c.(1094_1375)_(2057+11_2058-41)deldeletion Pathogenic 520435
15 SLC4A1 NM_000342.4(SLC4A1):c.1458C>G (p.Tyr486Ter)SNV Pathogenic 544805 rs1555596072 17:42334886-42334886 17:44257518-44257518
16 SLC4A1 NM_000342.4(SLC4A1):c.486-2A>GSNV Pathogenic 544806 rs1555596757 17:42337302-42337302 17:44259934-44259934
17 SLC4A1 NM_000342.4(SLC4A1):c.2278C>T (p.Arg760Trp)SNV Pathogenic 803425 17:42330519-42330519 17:44253151-44253151
18 SLC4A1 NM_000342.4(SLC4A1):c.1322T>G (p.Leu441Arg)SNV Likely pathogenic 544807 rs1555596165 17:42335136-42335136 17:44257768-44257768
19 SLC4A1 NM_000342.4(SLC4A1):c.695-3C>ASNV Likely pathogenic 544808 rs772264078 17:42336715-42336715 17:44259347-44259347
20 SLC4A1 NM_000342.4(SLC4A1):c.2423G>A (p.Arg808His)SNV Likely pathogenic 544809 rs866727908 17:42328845-42328845 17:44251477-44251477
21 SLC4A1 NM_000342.3(SLC4A1):c.118G>A (p.Glu40Lys)SNV Conflicting interpretations of pathogenicity 17756 rs45562031 17:42338993-42338993 17:44261625-44261625
22 SLC4A1 NM_000342.4(SLC4A1):c.539G>A (p.Arg180His)SNV Conflicting interpretations of pathogenicity 255914 rs147390654 17:42337247-42337247 17:44259879-44259879
23 SLC4A1 NM_000342.4(SLC4A1):c.2561C>T (p.Pro854Leu)SNV Benign/Likely benign 17768 rs2285644 17:42328621-42328621 17:44251253-44251253
24 SLC4A1 NM_000342.4(SLC4A1):c.166A>G (p.Lys56Glu)SNV Benign/Likely benign 17752 rs5036 17:42338945-42338945 17:44261577-44261577

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

73 (show all 26)
# Symbol AA change Variation ID SNP ID
1 SLC4A1 p.Pro327Arg VAR_000800 rs28931583
2 SLC4A1 p.Arg518Cys VAR_000802 rs868742796
3 SLC4A1 p.Glu90Lys VAR_013784 rs28929480
4 SLC4A1 p.Gly130Arg VAR_013785 rs121912749
5 SLC4A1 p.Pro147Ser VAR_013786
6 SLC4A1 p.Ala285Asp VAR_013787
7 SLC4A1 p.Gly455Glu VAR_013789
8 SLC4A1 p.Val488Met VAR_013791 rs28931584
9 SLC4A1 p.Arg490Cys VAR_013792 rs139847704
10 SLC4A1 p.Leu707Pro VAR_013804
11 SLC4A1 p.Gly714Arg VAR_013805
12 SLC4A1 p.Arg760Gln VAR_013806 rs121912755
13 SLC4A1 p.Arg760Trp VAR_013807 rs373916826
14 SLC4A1 p.Gly771Asp VAR_013808 rs121912741
15 SLC4A1 p.Ile783Asn VAR_013809
16 SLC4A1 p.Arg808Cys VAR_013810 rs116781474
17 SLC4A1 p.Arg808His VAR_013811 rs866727908
18 SLC4A1 p.His834Pro VAR_013812
19 SLC4A1 p.Thr837Ala VAR_013813 rs121912750
20 SLC4A1 p.Thr837Met VAR_013814
21 SLC4A1 p.Arg870Trp VAR_013816 rs28931585
22 SLC4A1 p.Asp705Tyr VAR_039294
23 SLC4A1 p.Gly455Arg VAR_058038
24 SLC4A1 p.Arg490His VAR_058039
25 SLC4A1 p.Met663Lys VAR_058042
26 SLC4A1 p.Thr837Arg VAR_058043

Expression for Spherocytosis, Type 4

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

Pathways for Spherocytosis, Type 4

GO Terms for Spherocytosis, Type 4

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

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.93 VEZF1 USF1 RPS3A RPS23 RPS21 RPS15
2 nuclear chromatin GO:0000790 9.8 USF1 PAX5 NFE2 KLF1 H2AC18 GATA1
3 ribosome GO:0005840 9.56 RPS3A RPS23 RPS21 RPS15
4 small ribosomal subunit GO:0015935 9.13 RPS23 RPS21 RPS15
5 cytosolic small ribosomal subunit GO:0022627 8.92 RPS3A RPS23 RPS21 RPS15

Biological processes related to Spherocytosis, 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 9.95 VEZF1 USF1 POU2AF1 PAX5 GATA1 CTCFL
2 positive regulation of transcription, DNA-templated GO:0045893 9.85 USF1 NFE2 KLF1 GATA1 CTCFL CTCF
3 translation GO:0006412 9.76 RPS3A RPS23 RPS21 RPS15
4 translational initiation GO:0006413 9.62 RPS3A RPS23 RPS21 RPS15
5 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:0000184 9.56 RPS3A RPS23 RPS21 RPS15
6 transcription by RNA polymerase II GO:0006366 9.55 VEZF1 USF1 POU2AF1 PAX5 GATA1
7 erythrocyte development GO:0048821 9.48 SLC4A1 GATA1
8 regulation of gene expression by genetic imprinting GO:0006349 9.43 CTCFL CTCF
9 viral transcription GO:0019083 9.26 RPS3A RPS23 RPS21 RPS15
10 SRP-dependent cotranslational protein targeting to membrane GO:0006614 8.92 RPS3A RPS23 RPS21 RPS15

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

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity GO:0003700 9.8 USF1 PAX5 NFE2 KLF1 GATA1 CTCF
2 sequence-specific DNA binding GO:0043565 9.77 USF1 NFE2 GATA1 CTCFL CTCF
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.65 POU2AF1 PAX5 GATA1 CTCFL CTCF
4 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.5 USF1 PAX5 NFE2 KLF1 GATA1 CTCFL
5 structural constituent of ribosome GO:0003735 9.46 RPS3A RPS23 RPS21 RPS15
6 DNA binding GO:0003677 9.36 VEZF1 USF1 RPS15 POU2AF1 PAX5 NFE2

Sources for Spherocytosis, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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