MCID: SPH013
MIFTS: 46

Spherocytosis, Type 1

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

Aliases & Classifications for Spherocytosis, Type 1

MalaCards integrated aliases for Spherocytosis, Type 1:

Name: Spherocytosis, Type 1 57 13 40 73
Hereditary Spherocytosis Type 1 12 75 15
Sph1 57 12 75
Hs1 57 12 75
Spherocytosis Type 1 29 6
Spherocytosis, Hereditary, 1; Hs1 57
Spherocytosis, Hereditary, 1 57
Hereditary Spherocytosis 1 12
Spherocytosis 1 75
Sph; Hs 57
Sph 57
Hs 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
autosomal recessive inheritance can occur
patients with homozygous mutations have a more severe disorder


HPO:

32
spherocytosis, type 1:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 182900
Disease Ontology 12 DOID:0110916
MeSH 44 D013103
UMLS 73 C2674218

Summaries for Spherocytosis, Type 1

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). Elgsaeter et al. (1986) gave an extensive review of the molecular basis of erythrocyte shape with a discussion of the role of spectrin and other proteins such as ankyrin, actin (102630), band 4.1 (130500), and band 3 (109270), all of which is relevant to the understanding of spherocytosis and elliptocytosis (see 611904). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders. (182900)

MalaCards based summary : Spherocytosis, Type 1, also known as hereditary spherocytosis type 1, is related to hereditary spherocytosis and hidradenitis suppurativa, and has symptoms including icterus An important gene associated with Spherocytosis, Type 1 is ANK1 (Ankyrin 1), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Downstream signaling events of B Cell Receptor (BCR). The drugs Lidocaine and Adjuvants, Anesthesia have been mentioned in the context of this disorder. Affiliated tissues include testes, and related phenotypes are jaundice and cholelithiasis

UniProtKB/Swiss-Prot : 75 Spherocytosis 1: A form of spherocytosis, a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH1 is characterized by severe hemolytic anemia. Inheritance can be autosomal dominant or autosomal recessive. Patients with homozygous mutations have a more severe disorder.

Disease Ontology : 12 A hereditary spherocytosis that has material basis in an autosomal dominant mutation of ANK1 on chromosome 8p11.21.

Related Diseases for Spherocytosis, Type 1

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

(show all 13)
# Related Disease Score Top Affiliating Genes
1 hereditary spherocytosis 27.6 ANK1 CTTN GATA1 HAX1 HCLS1 LYN
2 hidradenitis suppurativa 11.7
3 leukemia, chronic lymphocytic 2 10.2
4 leukemia, chronic lymphocytic 10.2
5 leukemia, b-cell, chronic 10.2
6 leukemia 10.1
7 systemic lupus erythematosus 10.0
8 beta-thalassemia 10.0
9 thalassemia 10.0
10 lupus erythematosus 10.0
11 lymphoma 9.8
12 hantavirus pulmonary syndrome 9.7 LYN SYK
13 spherocytosis, type 4 9.1 GATA1 RPS23 RPS3A

Graphical network of the top 20 diseases related to Spherocytosis, Type 1:



Diseases related to Spherocytosis, Type 1

Symptoms & Phenotypes for Spherocytosis, Type 1

Symptoms via clinical synopsis from OMIM:

57
Abdomen Liver:
jaundice

AbdomenSpleen:
splenomegaly

Laboratory Abnormalities:
increased reticulocyte count
hyperbilirubinemia
increased osmotic fragility
negative direct antiglobulin (coombs) test
elevated mchc

Abdomen Biliary Tract:
gallstones

Hematology:
spherocytosis
hemolytic anemia
reticulocytosis


Clinical features from OMIM:

182900

Human phenotypes related to Spherocytosis, Type 1:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 jaundice 32 HP:0000952
2 cholelithiasis 32 HP:0001081
3 splenomegaly 32 HP:0001744
4 hemolytic anemia 32 HP:0001878
5 reticulocytosis 32 HP:0001923
6 hyperbilirubinemia 32 HP:0002904
7 spherocytosis 32 HP:0004444

UMLS symptoms related to Spherocytosis, Type 1:


icterus

GenomeRNAi Phenotypes related to Spherocytosis, Type 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability in HMC1.1 cells GR00105-A-0 8.62 LYN SRC

MGI Mouse Phenotypes related to Spherocytosis, Type 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.65 ANK1 CTTN FGR GATA1 HAX1 HCLS1
2 immune system MP:0005387 9.32 ANK1 CTTN FGR GATA1 HAX1 HCLS1

Drugs & Therapeutics for Spherocytosis, Type 1

Drugs for Spherocytosis, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 20)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Lidocaine Approved, Vet_approved Phase 2 137-58-6 3676
2 Adjuvants, Anesthesia Phase 2
3 Anesthetics Phase 2
4 Anesthetics, Local Phase 2
5 Anti-Arrhythmia Agents Phase 2
6 Anticonvulsants Phase 2
7 Autonomic Agents Phase 2
8 Bromides Phase 2
9 Butylscopolammonium Bromide Phase 2
10 Central Nervous System Depressants Phase 2
11 Cholinergic Agents Phase 2
12 Cholinergic Antagonists Phase 2
13 Diuretics, Potassium Sparing Phase 2
14 Muscarinic Antagonists Phase 2
15 Mydriatics Phase 2
16 Neurotransmitter Agents Phase 2
17 Parasympatholytics Phase 2
18 Peripheral Nervous System Agents Phase 2
19 Scopolamine hydrobromide Phase 2 114-49-8
20 Sodium Channel Blockers Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Time Study for Biometry Measurements With the Lenstar and IntraOcularLens (IOL) Master 500 Completed NCT01550939 Phase 4
2 Oral Hyoscine Butyl Bromide With Cervical Lidocaine Cream in Reducing Pain During Hysterosalpingography Completed NCT02710305 Phase 2 oral hyoscine butyl bromide tablets plus lidocaine cream;oral placebo tablets plus placebo cream
3 Feasibility Study to Evaluate the Safety of Topically Applied Revera in Subjects With Venous Leg Ulcers Completed NCT00823446 Phase 1

Search NIH Clinical Center for Spherocytosis, Type 1

Genetic Tests for Spherocytosis, Type 1

Genetic tests related to Spherocytosis, Type 1:

# Genetic test Affiliating Genes
1 Spherocytosis Type 1 29 ANK1

Anatomical Context for Spherocytosis, Type 1

MalaCards organs/tissues related to Spherocytosis, Type 1:

41
Testes

Publications for Spherocytosis, Type 1

Variations for Spherocytosis, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Spherocytosis, Type 1:

75
# Symbol AA change Variation ID SNP ID
1 ANK1 p.Val463Ile VAR_000596 rs140085544
2 ANK1 p.Leu276Arg VAR_054991
3 ANK1 p.Ile1054Thr VAR_054992

ClinVar genetic disease variations for Spherocytosis, Type 1:

6
(show all 32)
# Gene Variation Type Significance SNP ID Assembly Location
1 ANK1 NM_001142446.1(ANK1): c.5128G> T (p.Glu1710Ter) single nucleotide variant Pathogenic rs137852829 GRCh37 Chromosome 8, 41529963: 41529963
2 ANK1 NM_001142446.1(ANK1): c.5128G> T (p.Glu1710Ter) single nucleotide variant Pathogenic rs137852829 GRCh38 Chromosome 8, 41672445: 41672445
3 ANK1 NM_001142446.1(ANK1): c.5286G> A (p.Trp1762Ter) single nucleotide variant Pathogenic rs137852830 GRCh37 Chromosome 8, 41526016: 41526016
4 ANK1 NM_001142446.1(ANK1): c.5286G> A (p.Trp1762Ter) single nucleotide variant Pathogenic rs137852830 GRCh38 Chromosome 8, 41668498: 41668498
5 ANK1 NM_020476.2(ANK1): c.5497C> T (p.Arg1833Ter) single nucleotide variant Pathogenic rs137852831 GRCh37 Chromosome 8, 41519441: 41519441
6 ANK1 NM_020476.2(ANK1): c.5497C> T (p.Arg1833Ter) single nucleotide variant Pathogenic rs137852831 GRCh38 Chromosome 8, 41661923: 41661923
7 ANK1 NM_001142446.1(ANK1): c.1618dupC (p.Leu540Profs) duplication Pathogenic rs397514029 GRCh37 Chromosome 8, 41573253: 41573253
8 ANK1 NM_001142446.1(ANK1): c.1618dupC (p.Leu540Profs) duplication Pathogenic rs397514029 GRCh38 Chromosome 8, 41715735: 41715735
9 ANK1 NM_020476.2(ANK1): c.1801-17G> A single nucleotide variant Pathogenic rs786205243 GRCh37 Chromosome 8, 41566510: 41566510
10 ANK1 NM_020476.2(ANK1): c.1801-17G> A single nucleotide variant Pathogenic rs786205243 GRCh38 Chromosome 8, 41708992: 41708992
11 ANK1 NM_020476.2(ANK1): c.5479-3T> C single nucleotide variant Benign/Likely benign rs515071 GRCh37 Chromosome 8, 41519462: 41519462
12 ANK1 NM_020476.2(ANK1): c.5479-3T> C single nucleotide variant Benign/Likely benign rs515071 GRCh38 Chromosome 8, 41661944: 41661944
13 ANK1 NM_020476.2(ANK1): c.5265G> A (p.Val1755=) single nucleotide variant Benign/Likely benign rs750625 GRCh37 Chromosome 8, 41525914: 41525914
14 ANK1 NM_020476.2(ANK1): c.5265G> A (p.Val1755=) single nucleotide variant Benign/Likely benign rs750625 GRCh38 Chromosome 8, 41668396: 41668396
15 ANK1 NM_020476.2(ANK1): c.5096+16T> C single nucleotide variant Benign rs508112 GRCh37 Chromosome 8, 41529856: 41529856
16 ANK1 NM_020476.2(ANK1): c.5096+16T> C single nucleotide variant Benign rs508112 GRCh38 Chromosome 8, 41672338: 41672338
17 ANK1 NM_020476.2(ANK1): c.2913G> C (p.Leu971=) single nucleotide variant Benign/Likely benign rs504574 GRCh37 Chromosome 8, 41553928: 41553928
18 ANK1 NM_020476.2(ANK1): c.2913G> C (p.Leu971=) single nucleotide variant Benign/Likely benign rs504574 GRCh38 Chromosome 8, 41696410: 41696410
19 ANK1 NM_020476.2(ANK1): c.2349C> T (p.Thr783=) single nucleotide variant Benign/Likely benign rs2304880 GRCh37 Chromosome 8, 41559609: 41559609
20 ANK1 NM_020476.2(ANK1): c.2349C> T (p.Thr783=) single nucleotide variant Benign/Likely benign rs2304880 GRCh38 Chromosome 8, 41702091: 41702091
21 ANK1 NM_020476.2(ANK1): c.315C> T (p.Asn105=) single nucleotide variant Benign/Likely benign rs2304871 GRCh37 Chromosome 8, 41585438: 41585438
22 ANK1 NM_020476.2(ANK1): c.315C> T (p.Asn105=) single nucleotide variant Benign/Likely benign rs2304871 GRCh38 Chromosome 8, 41727920: 41727920
23 ANK1 NM_020476.2(ANK1): c.5152C> T (p.Gln1718Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 8, 41526027: 41526027
24 ANK1 NM_020476.2(ANK1): c.5152C> T (p.Gln1718Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 8, 41668509: 41668509
25 ANK1 NM_020476.2(ANK1): c.4462C> T (p.Arg1488Ter) single nucleotide variant Pathogenic rs777701149 GRCh37 Chromosome 8, 41542137: 41542137
26 ANK1 NM_020476.2(ANK1): c.4462C> T (p.Arg1488Ter) single nucleotide variant Pathogenic rs777701149 GRCh38 Chromosome 8, 41684619: 41684619
27 ANK1 NM_020476.2(ANK1): c.1702-2A> C single nucleotide variant Pathogenic GRCh37 Chromosome 8, 41571774: 41571774
28 ANK1 NM_020476.2(ANK1): c.1702-2A> C single nucleotide variant Pathogenic GRCh38 Chromosome 8, 41714256: 41714256
29 ANK1 NM_020476.2(ANK1): c.534delC (p.His178Glnfs) deletion Pathogenic GRCh37 Chromosome 8, 41583357: 41583357
30 ANK1 NM_020476.2(ANK1): c.534delC (p.His178Glnfs) deletion Pathogenic GRCh38 Chromosome 8, 41725839: 41725839
31 ANK1 NM_020476.2(ANK1): c.1A> G (p.Met1Val) single nucleotide variant Likely pathogenic GRCh37 Chromosome 8, 41655056: 41655056
32 ANK1 NM_020476.2(ANK1): c.1A> G (p.Met1Val) single nucleotide variant Likely pathogenic GRCh38 Chromosome 8, 41797538: 41797538

Expression for Spherocytosis, Type 1

Search GEO for disease gene expression data for Spherocytosis, Type 1.

Pathways for Spherocytosis, Type 1

Pathways related to Spherocytosis, Type 1 according to GeneCards Suite gene sharing:

(show all 32)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.19 FGR GATA1 LYN SRC SYK VAV1
2
Show member pathways
12.6 LYN SRC SYK VAV1
3 12.43 GATA1 HCLS1 LYN SYK
4
Show member pathways
12.42 HCLS1 LYN SRC SYK VAV1
5
Show member pathways
12.26 HCLS1 LYN SYK VAV1
6 12.17 ANK1 CTTN HCLS1 SRC
7
Show member pathways
12.03 LYN SRC SYK VAV1
8
Show member pathways
12.02 FGR LYN SRC SYK VAV1
9
Show member pathways
12.01 LYN SYK VAV1
10 11.98 FGR LYN SRC SYK
11
Show member pathways
11.94 LYN SYK VAV1
12 11.91 LYN SRC SYK
13
Show member pathways
11.86 FGR LYN SRC
14
Show member pathways
11.81 LYN SYK VAV1
15 11.73 LYN SYK VAV1
16 11.64 CTTN HCLS1 SRC
17 11.56 CTTN HCLS1 SRC
18 11.55 FGR LYN SRC VAV1
19 11.47 FGR LYN SRC
20 11.42 FGR LYN SRC
21 11.39 FGR LYN SRC
22
Show member pathways
11.31 FGR LYN SRC SYK
23 11.11 FGR LYN SRC SYK
24 11.08 FGR LYN SRC
25 11.06 FGR LYN SRC
26 11.02 FGR LYN SRC
27 10.87 FGR LYN SRC VAV1
28 10.86 CTTN SRC
29 10.84 LYN SYK VAV1
30 10.83 LYN SRC
31 10.75 SRC SYK
32 10.43 FGR LYN SRC SYK

GO Terms for Spherocytosis, Type 1

Cellular components related to Spherocytosis, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial intermembrane space GO:0005758 9.13 FGR HAX1 LYN
2 extrinsic component of cytoplasmic side of plasma membrane GO:0031234 8.92 FGR LYN SRC SYK

Biological processes related to Spherocytosis, Type 1 according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 intracellular signal transduction GO:0035556 9.97 HCLS1 LYN SRC SYK VAV1
2 regulation of cell proliferation GO:0042127 9.9 FGR LYN SRC SYK
3 protein autophosphorylation GO:0046777 9.84 FGR LYN SRC SYK
4 peptidyl-tyrosine phosphorylation GO:0018108 9.83 FGR LYN SRC SYK
5 stimulatory C-type lectin receptor signaling pathway GO:0002223 9.79 LYN SRC SYK
6 T cell costimulation GO:0031295 9.76 LYN SRC VAV1
7 positive regulation of protein kinase B signaling GO:0051897 9.76 HAX1 HCLS1 SRC VAV1
8 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.73 FGR HAX1 HCLS1
9 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.73 FGR LYN SRC SYK
10 erythrocyte differentiation GO:0030218 9.65 GATA1 HCLS1 LYN
11 regulation of ERK1 and ERK2 cascade GO:0070372 9.63 LYN SYK
12 actin filament polymerization GO:0030041 9.63 CTTN HCLS1
13 regulation of autophagy of mitochondrion GO:1903146 9.62 CTTN HAX1
14 platelet activation GO:0030168 9.62 LYN SRC SYK VAV1
15 positive regulation of actin cytoskeleton reorganization GO:2000251 9.61 HAX1 HCLS1
16 dendritic cell differentiation GO:0097028 9.61 GATA1 LYN
17 positive regulation of mast cell degranulation GO:0043306 9.59 FGR SYK
18 regulation of phagocytosis GO:0050764 9.58 FGR SYK
19 positive regulation of phosphatidylinositol 3-kinase activity GO:0043552 9.58 FGR LYN SRC
20 integrin-mediated signaling pathway GO:0007229 9.56 FGR SRC SYK VAV1
21 positive regulation of granulocyte differentiation GO:0030854 9.55 HAX1 HCLS1
22 positive regulation of cytokine secretion GO:0050715 9.54 FGR SRC SYK
23 immune response-regulating cell surface receptor signaling pathway GO:0002768 9.51 FGR LYN
24 regulation of platelet aggregation GO:0090330 9.49 LYN SYK
25 peptidyl-tyrosine autophosphorylation GO:0038083 9.46 FGR LYN SRC SYK
26 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.35 FGR LYN SRC SYK VAV1
27 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.1 GATA1 HAX1 HCLS1 LYN SRC SYK

Molecular functions related to Spherocytosis, Type 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 9.67 FGR LYN SRC SYK
2 integrin binding GO:0005178 9.5 LYN SRC SYK
3 protein tyrosine kinase activity GO:0004713 9.46 FGR LYN SRC SYK
4 obsolete signal transducer, downstream of receptor, with protein tyrosine kinase activity GO:0004716 9.26 LYN SYK
5 phosphotyrosine residue binding GO:0001784 9.13 FGR SYK VAV1
6 non-membrane spanning protein tyrosine kinase activity GO:0004715 8.92 FGR LYN SRC SYK

Sources for Spherocytosis, Type 1

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
Content
Loading form....