MCID: SPH016
MIFTS: 37

Spherocytosis, Type 4

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

Aliases & Classifications for Spherocytosis, Type 4

MalaCards integrated aliases for Spherocytosis, Type 4:

Name: Spherocytosis, Type 4 57 13 40 73
Hereditary Spherocytosis Type 4 12 75 15
Sph4 57 12 75
Hs4 57 12 75
Spherocytosis Type 4 29 6
Spherocytosis, Hereditary, 4; Hs4 57
Spherocytosis, Hereditary, 4 57
Hereditary Spherocytosis 4 12
Spherocytosis 4 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
spherocytosis, type 4:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 612653
Disease Ontology 12 DOID:0110919
MedGen 42 C2675212
UMLS 73 C2675212

Summaries for Spherocytosis, Type 4

UniProtKB/Swiss-Prot : 75 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 spherocytosis, type 5 and thalassemia, 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. Related phenotypes are jaundice and splenomegaly

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

Description 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:

# Related Disease Score Top Affiliating Genes
1 spherocytosis, type 5 10.2 CTCF GATA1
2 thalassemia 10.1
3 acute erythroid leukemia 10.0 GATA1 KLF1
4 spherocytosis, type 3 9.8 F13B GATA1 KLF1
5 spherocytosis, type 1 9.5 GATA1 RPS23 RPS3A
6 spherocytosis, type 2 9.4 F13B GATA1 KLF1 RPS23
7 diamond-blackfan anemia 9.1 GATA1 KLF1 RPS3A
8 hereditary spherocytosis 7.8 CTCF GATA1 KLF1 NFE2 RPS23 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

Symptoms via clinical synopsis from OMIM:

57
Abdomen Liver:
jaundice

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

Laboratory Abnormalities:
hyperbilirubinemia
pseudohyperkalemia (in some patients)

AbdomenSpleen:
splenomegaly

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


Clinical features from OMIM:

612653

Human phenotypes related to Spherocytosis, Type 4:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 jaundice 32 HP:0000952
2 splenomegaly 32 HP:0001744
3 hemolytic anemia 32 HP:0001878
4 reticulocytosis 32 HP:0001923
5 hyperbilirubinemia 32 HP:0002904
6 spherocytosis 32 HP:0004444
7 increased red cell osmotic fragility 32 HP:0005502

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 9.61 RPS25 RPS3A PAX5
2 Decreased viability GR00240-S-1 9.61 RPS3A
3 Decreased viability GR00381-A-1 9.61 RPS25 RPS3A
4 Decreased viability GR00402-S-2 9.61 RPS25 RPS3A PAX5
5 Decreased Hepatitis C virus replication GR00180-A-1 9.33 RPS23 RPS25 RPS3A
6 Increased viability GR00386-A-1 9.23 CTCF F13B HMGXB4 PAX5 RPS23 RPS25

Drugs & Therapeutics for Spherocytosis, Type 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Relevance of Biomarkers in the Process of Weaning Unknown status NCT01341561
2 Young Consumers' Attitudes and Behaviour Towards Sustainable and Healthy Eating Completed NCT02776410 Not Applicable

Search 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

Publications for Spherocytosis, Type 4

Variations for Spherocytosis, Type 4

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

75 (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
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
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

ClinVar genetic disease variations for Spherocytosis, Type 4:

6
(show all 35)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC4A1 NM_000342.3(SLC4A1): c.-62G> A single nucleotide variant Pathogenic rs387906565 GRCh37 Chromosome 17, 42340296: 42340296
2 SLC4A1 NM_000342.3(SLC4A1): c.-62G> A single nucleotide variant Pathogenic rs387906565 GRCh38 Chromosome 17, 44262928: 44262928
3 SLC4A1 NM_000342.3(SLC4A1): c.980C> G (p.Pro327Arg) single nucleotide variant Pathogenic rs28931583 GRCh37 Chromosome 17, 42335888: 42335888
4 SLC4A1 NM_000342.3(SLC4A1): c.980C> G (p.Pro327Arg) single nucleotide variant Pathogenic rs28931583 GRCh38 Chromosome 17, 44258520: 44258520
5 SLC4A1 NM_000342.3(SLC4A1): c.2464_2465insCACCCAGATG (p.Val822Alafs) insertion Pathogenic rs387906566 GRCh37 Chromosome 17, 42328803: 42328804
6 SLC4A1 NM_000342.3(SLC4A1): c.2464_2465insCACCCAGATG (p.Val822Alafs) insertion Pathogenic rs387906566 GRCh38 Chromosome 17, 44251435: 44251436
7 SLC4A1 NM_000342.3(SLC4A1): c.2312G> A (p.Gly771Asp) single nucleotide variant Pathogenic rs121912741 GRCh37 Chromosome 17, 42328956: 42328956
8 SLC4A1 NM_000342.3(SLC4A1): c.2312G> A (p.Gly771Asp) single nucleotide variant Pathogenic rs121912741 GRCh38 Chromosome 17, 44251588: 44251588
9 SLC4A1 NM_000342.3(SLC4A1): c.988C> T (p.Gln330Ter) single nucleotide variant Pathogenic rs121912742 GRCh37 Chromosome 17, 42335880: 42335880
10 SLC4A1 NM_000342.3(SLC4A1): c.988C> T (p.Gln330Ter) single nucleotide variant Pathogenic rs121912742 GRCh38 Chromosome 17, 44258512: 44258512
11 SLC4A1 NM_000342.3(SLC4A1): c.448C> T (p.Arg150Ter) single nucleotide variant Pathogenic rs56361140 GRCh37 Chromosome 17, 42337809: 42337809
12 SLC4A1 NM_000342.3(SLC4A1): c.448C> T (p.Arg150Ter) single nucleotide variant Pathogenic rs56361140 GRCh38 Chromosome 17, 44260441: 44260441
13 SLC4A1 NM_000342.3(SLC4A1): c.388G> A (p.Gly130Arg) single nucleotide variant Pathogenic rs121912749 GRCh37 Chromosome 17, 42337869: 42337869
14 SLC4A1 NM_000342.3(SLC4A1): c.388G> A (p.Gly130Arg) single nucleotide variant Pathogenic rs121912749 GRCh38 Chromosome 17, 44260501: 44260501
15 SLC4A1 NM_000342.3(SLC4A1): c.2509A> G (p.Thr837Ala) single nucleotide variant Pathogenic rs121912750 GRCh37 Chromosome 17, 42328673: 42328673
16 SLC4A1 NM_000342.3(SLC4A1): c.2509A> G (p.Thr837Ala) single nucleotide variant Pathogenic rs121912750 GRCh38 Chromosome 17, 44251305: 44251305
17 SLC4A1 NM_000342.3(SLC4A1): c.1462G> A (p.Val488Met) single nucleotide variant Pathogenic rs28931584 GRCh37 Chromosome 17, 42334882: 42334882
18 SLC4A1 NM_000342.3(SLC4A1): c.1462G> A (p.Val488Met) single nucleotide variant Pathogenic rs28931584 GRCh38 Chromosome 17, 44257514: 44257514
19 SLC4A1 NM_000342.3(SLC4A1): c.268G> A (p.Glu90Lys) single nucleotide variant Pathogenic rs28929480 GRCh37 Chromosome 17, 42338084: 42338084
20 SLC4A1 NM_000342.3(SLC4A1): c.268G> A (p.Glu90Lys) single nucleotide variant Pathogenic rs28929480 GRCh38 Chromosome 17, 44260716: 44260716
21 SLC4A1 NM_000342.3(SLC4A1): c.2608C> T (p.Arg870Trp) single nucleotide variant Pathogenic rs28931585 GRCh37 Chromosome 17, 42328574: 42328574
22 SLC4A1 NM_000342.3(SLC4A1): c.2608C> T (p.Arg870Trp) single nucleotide variant Pathogenic rs28931585 GRCh38 Chromosome 17, 44251206: 44251206
23 SLC4A1 NM_000342.3(SLC4A1): c.2279G> A (p.Arg760Gln) single nucleotide variant Pathogenic rs121912755 GRCh37 Chromosome 17, 42330518: 42330518
24 SLC4A1 NM_000342.3(SLC4A1): c.2279G> A (p.Arg760Gln) single nucleotide variant Pathogenic rs121912755 GRCh38 Chromosome 17, 44253150: 44253150
25 SLC4A1 NM_000342.3(SLC4A1): c.(1094_1375)_(2057+11_2058-41)del deletion Pathogenic
26 SLC4A1 NM_000342.3(SLC4A1): c.2423G> A (p.Arg808His) single nucleotide variant Likely pathogenic rs866727908 GRCh37 Chromosome 17, 42328845: 42328845
27 SLC4A1 NM_000342.3(SLC4A1): c.2423G> A (p.Arg808His) single nucleotide variant Likely pathogenic rs866727908 GRCh38 Chromosome 17, 44251477: 44251477
28 SLC4A1 NM_000342.3(SLC4A1): c.1458C> G (p.Tyr486Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 17, 42334886: 42334886
29 SLC4A1 NM_000342.3(SLC4A1): c.1458C> G (p.Tyr486Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 17, 44257518: 44257518
30 SLC4A1 NM_000342.3(SLC4A1): c.1322T> G (p.Leu441Arg) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 44257768: 44257768
31 SLC4A1 NM_000342.3(SLC4A1): c.1322T> G (p.Leu441Arg) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 42335136: 42335136
32 SLC4A1 NM_000342.3(SLC4A1): c.695-3C> A single nucleotide variant Likely pathogenic rs772264078 GRCh37 Chromosome 17, 42336715: 42336715
33 SLC4A1 NM_000342.3(SLC4A1): c.695-3C> A single nucleotide variant Likely pathogenic rs772264078 GRCh38 Chromosome 17, 44259347: 44259347
34 SLC4A1 NM_000342.3(SLC4A1): c.486-2A> G single nucleotide variant Pathogenic GRCh38 Chromosome 17, 44259934: 44259934
35 SLC4A1 NM_000342.3(SLC4A1): c.486-2A> G single nucleotide variant Pathogenic GRCh37 Chromosome 17, 42337302: 42337302

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 9.56 CTCF GATA1 KLF1 NFE2 PAX5 RPS23
2 ribosome GO:0005840 9.43 RPS23 RPS25 RPS3A
3 protein-DNA complex GO:0032993 9.32 GATA1 NFE2
4 small ribosomal subunit GO:0015935 9.16 RPS23 RPS25
5 cytosolic small ribosomal subunit GO:0022627 8.8 RPS23 RPS25 RPS3A

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

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.99 CTCF GATA1 HMGXB4 KLF1 NFE2 PAX5
2 translation GO:0006412 9.67 RPS23 RPS25 RPS3A
3 positive regulation of transcription, DNA-templated GO:0045893 9.67 CTCF GATA1 KLF1 NFE2
4 rRNA processing GO:0006364 9.58 RPS23 RPS25 RPS3A
5 regulation of megakaryocyte differentiation GO:0045652 9.52 GATA1 NFE2
6 blood coagulation GO:0007596 9.5 F13B GATA1 NFE2
7 hemostasis GO:0007599 9.48 F13B NFE2
8 cytoplasmic translation GO:0002181 9.46 RPS23 RPS3A
9 erythrocyte differentiation GO:0030218 9.43 GATA1 KLF1
10 translational initiation GO:0006413 9.43 RPS23 RPS25 RPS3A
11 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:0000184 9.33 RPS23 RPS25 RPS3A
12 viral transcription GO:0019083 9.13 RPS23 RPS25 RPS3A
13 SRP-dependent cotranslational protein targeting to membrane GO:0006614 8.8 RPS23 RPS25 RPS3A

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

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.65 CTCF GATA1 KLF1 NFE2 PAX5
2 DNA binding GO:0003677 9.63 CTCF GATA1 HMGXB4 KLF1 NFE2 PAX5
3 DNA binding transcription factor activity GO:0003700 9.35 CTCF GATA1 KLF1 NFE2 PAX5
4 proximal promoter sequence-specific DNA binding GO:0000987 8.62 KLF1 NFE2

Sources for Spherocytosis, 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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