IMD9
MCID: IMM066
MIFTS: 29

Immunodeficiency 9 (IMD9)

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

Aliases & Classifications for Immunodeficiency 9

MalaCards integrated aliases for Immunodeficiency 9:

Name: Immunodeficiency 9 57 74
Immune Dysfunction with T-Cell Inactivation Due to Calcium Entry Defect 1 57 53 74 29 13 6 40 72
Imd9 57 74
Severe Combined Immunodeficiency Due to Crac Channel Dysfunction 74
Combined Immunodeficiency Due to Orai1 Deficiency 59
Cid Due to Orai1 Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
combined immunodeficiency due to orai1 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in the neonatal period
early death may occur without bone marrow transplant


HPO:

32
immunodeficiency 9:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare immunological diseases


External Ids:

MeSH 44 D007153
ICD10 via Orphanet 34 D81.8
Orphanet 59 ORPHA317428
MedGen 42 C2748568
UMLS 72 C2748568

Summaries for Immunodeficiency 9

UniProtKB/Swiss-Prot : 74 Immunodeficiency 9: An immune disorder characterized by recurrent infections, impaired activation and proliferative response of T-cells, decreased T-cell production of cytokines, and normal lymphocytes counts and serum immunoglobulin levels. In surviving patients ectodermal dysplasia with anhidrosis and non-progressive myopathy may be observed.

MalaCards based summary : Immunodeficiency 9, also known as immune dysfunction with t-cell inactivation due to calcium entry defect 1, is related to autoimmune lymphoproliferative syndrome, type iii. An important gene associated with Immunodeficiency 9 is ORAI1 (ORAI Calcium Release-Activated Calcium Modulator 1). Affiliated tissues include t cells, bone and bone marrow, and related phenotypes are muscular hypotonia and failure to thrive

OMIM : 57 Immunodeficiency-9 is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (summary by McCarl et al., 2009). (612782)

Related Diseases for Immunodeficiency 9

Diseases related to Immunodeficiency 9 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autoimmune lymphoproliferative syndrome, type iii 11.2

Symptoms & Phenotypes for Immunodeficiency 9

Human phenotypes related to Immunodeficiency 9:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 muscular hypotonia 32 HP:0001252
2 failure to thrive 32 HP:0001508
3 myopathy 32 HP:0003198
4 respiratory insufficiency due to muscle weakness 32 HP:0002747
5 immunodeficiency 32 HP:0002721
6 recurrent infections 32 HP:0002719
7 difficulty walking 32 HP:0002355
8 amelogenesis imperfecta 32 HP:0000705
9 gowers sign 32 HP:0003391
10 recurrent aphthous stomatitis 32 HP:0011107
11 ectodermal dysplasia 32 HP:0000968
12 heat intolerance 32 HP:0002046
13 stomatitis 32 HP:0010280
14 recurrent fever 32 HP:0001954

Symptoms via clinical synopsis from OMIM:

57
Muscle Soft Tissue:
muscular hypotonia
difficulty walking
proximal muscle weakness
gower sign
loss of ambulation
more
Respiratory:
respiratory insufficiency due to muscle weakness

Skin Nails Hair Skin:
heat intolerance
ectodermal dysplasia, anhidrotic

Metabolic Features:
intermittent fever

Growth Other:
failure to thrive

Immunology:
recurrent infections
impaired t cell activation
impaired t cell proliferative response
normal lymphocyte counts
normal serum immunoglobulin levels
more
Head And Neck Teeth:
dysplastic dental enamel
hypocalcified amelogenesis imperfecta

Head And Neck Mouth:
aphthous stomatitis

Clinical features from OMIM:

612782

Drugs & Therapeutics for Immunodeficiency 9

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effects of Short-chain Fatty Acids, Here Sodium Propionate, a Metabolism Product of the Human Gut-microbiome, on Inflammatory and Metabolic Parameters in Patients on Maintenance Hemodialysis - a Pilot Study Unknown status NCT02976688 Phase 2, Phase 3

Search NIH Clinical Center for Immunodeficiency 9

Genetic Tests for Immunodeficiency 9

Genetic tests related to Immunodeficiency 9:

# Genetic test Affiliating Genes
1 Immune Dysfunction with T-Cell Inactivation Due to Calcium Entry Defect 1 29 ORAI1

Anatomical Context for Immunodeficiency 9

MalaCards organs/tissues related to Immunodeficiency 9:

41
T Cells, Bone, Bone Marrow, Lung

Publications for Immunodeficiency 9

Articles related to Immunodeficiency 9:

(show all 14)
# Title Authors PMID Year
1
ORAI1 deficiency and lack of store-operated Ca2+ entry cause immunodeficiency, myopathy, and ectodermal dysplasia. 8 71
20004786 2009
2
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. 8 71
16582901 2006
3
Severe combined immunodeficiency due to defective binding of the nuclear factor of activated T cells in T lymphocytes of two male siblings. 8 71
8814256 1996
4
A primary T-cell immunodeficiency associated with defective transmembrane calcium influx. 8 71
7531512 1995
5
The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. 8 71
7798233 1994
6
Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. 71
18187424 2008
7
The duration of nuclear residence of NFAT determines the pattern of cytokine expression in human SCID T cells. 8
10861065 2000
8
Primary severe immunodeficiency due to impaired signal transduction in T cells. 8
8167687 1993
9
Development of a Low-Cost Stem-Loop Real-Time Quantification PCR Technique for EBV miRNA Expression Analysis. 38
27246439 2016
10
Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings. 38
26372540 2015
11
Inpatient allergy/immunology consultations in a tertiary care setting. 38
20615326 2010
12
Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. 38
18653625 2009
13
Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiency. 38
12076273 2002
14
Primary immunodeficiencies in Switzerland: first report of the national registry in adults and children. 38
3065352 1988

Variations for Immunodeficiency 9

ClinVar genetic disease variations for Immunodeficiency 9:

6 (show all 27)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ORAI1 NM_032790.3(ORAI1) insertion Pathogenic rs1555322558 12:122064794-122064795 12:121626888-121626889
2 ORAI1 NM_032790.3(ORAI1): c.271C> T (p.Arg91Trp) single nucleotide variant Pathogenic rs118203993 12:122064924-122064924 12:121627018-121627018
3 ORAI1 NM_032790.3(ORAI1): c.261dup (p.Ala88fs) duplication Pathogenic rs878853261 12:122064914-122064914 12:121627008-121627008
4 ORAI1 NM_032790.3(ORAI1): c.308C> A (p.Ala103Glu) single nucleotide variant Pathogenic rs786205890 12:122078951-122078951 12:121641045-121641045
5 ORAI1 NM_032790.3(ORAI1): c.581T> C (p.Leu194Pro) single nucleotide variant Pathogenic rs782753385 12:122079224-122079224 12:121641318-121641318
6 ORAI1 NM_032790.3(ORAI1): c.546del (p.Ile182fs) deletion Likely pathogenic 12:122079189-122079189 12:121641283-121641283
7 ORAI1 NC_000012.12: g.121626879_121626884delACCGCC deletion Conflicting interpretations of pathogenicity rs1555322544 12:122064785-122064790 12:121626879-121626884
8 ORAI1 NM_032790.3(ORAI1): c.783G> A (p.Leu261=) single nucleotide variant Uncertain significance 12:122079426-122079426 12:121641520-121641520
9 ORAI1 NM_032790.3(ORAI1): c.845T> A (p.Leu282Ter) single nucleotide variant Uncertain significance 12:122079488-122079488 12:121641582-121641582
10 ORAI1 NM_032790.3(ORAI1): c.6T> G (p.His2Gln) single nucleotide variant Uncertain significance 12:122064653-122064653 12:121626748-121626748
11 ORAI1 NM_032790.3(ORAI1): c.7C> T (p.Pro3Ser) single nucleotide variant Uncertain significance 12:122064654-122064654 12:121626749-121626749
12 ORAI1 NM_032790.3(ORAI1): c.37A> T (p.Ser13Cys) single nucleotide variant Uncertain significance 12:122064684-122064684 12:121626779-121626779
13 ORAI1 NM_032790.3(ORAI1): c.113_121del (p.Glu38_Pro40del) deletion Uncertain significance 12:122064758-122064766 12:121626855-121626863
14 ORAI1 NM_032790.3(ORAI1): c.114G> T (p.Glu38Asp) single nucleotide variant Uncertain significance 12:122064761-122064761 12:121626856-121626856
15 ORAI1 NM_032790.3(ORAI1): c.100A> C (p.Ser34Arg) single nucleotide variant Uncertain significance rs781829024 12:122064747-122064747 12:121626842-121626842
16 ORAI1 NM_032790.3(ORAI1): c.140C> T (p.Pro47Leu) single nucleotide variant Uncertain significance rs781855511 12:122064793-122064793 12:121626887-121626887
17 ORAI1 NM_032790.3(ORAI1): c.700G> A (p.Ala234Thr) single nucleotide variant Uncertain significance 12:122079343-122079343 12:121641437-121641437
18 ORAI1 NM_032790.3(ORAI1): c.115C> G (p.Pro39Ala) single nucleotide variant Uncertain significance rs782531427 12:122064762-122064762 12:121626857-121626857
19 ORAI1 NM_032790.3(ORAI1): c.212T> G (p.Met71Arg) single nucleotide variant Uncertain significance rs1286173837 12:122064865-122064865 12:121626959-121626959
20 ORAI1 NM_032790.3(ORAI1): c.85_99dup (p.Arg29_Arg33dup) duplication Uncertain significance rs1372064351 12:122064732-122064746 12:121626827-121626841
21 ORAI1 NM_032790.3(ORAI1): c.137_143CGCCGTC[3] (p.Thr51fs) short repeat Uncertain significance rs1555322554 12:122064797-122064803 12:121626891-121626897
22 ORAI1 NM_032790.3(ORAI1): c.132_137dup (p.Pro46_Pro47dup) duplication Likely benign rs1555322544 12:122064772-122064773 12:121626879-121626884
23 ORAI1 NM_032790.3(ORAI1): c.668A> G (p.Asn223Ser) single nucleotide variant Likely benign rs75603737 12:122079311-122079311 12:121641405-121641405
24 ORAI1 NM_032790.3(ORAI1): c.49C> T (p.Pro17Ser) single nucleotide variant Likely benign rs568054544 12:122064696-122064696 12:121626791-121626791
25 ORAI1 NM_032790.3(ORAI1): c.786T> C (p.Val262=) single nucleotide variant Benign rs3825174 12:122079429-122079429 12:121641523-121641523
26 ORAI1 NM_032790.3(ORAI1): c.652A> G (p.Ser218Gly) single nucleotide variant Benign rs3741596 12:122079295-122079295 12:121641389-121641389
27 ORAI1 NM_032790.3(ORAI1): c.705T> C (p.Ala235=) single nucleotide variant Benign rs3741597 12:122079348-122079348 12:121641442-121641442

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 9:

74
# Symbol AA change Variation ID SNP ID
1 ORAI1 p.Arg91Trp VAR_026226 rs118203993

Expression for Immunodeficiency 9

Search GEO for disease gene expression data for Immunodeficiency 9.

Pathways for Immunodeficiency 9

GO Terms for Immunodeficiency 9

Sources for Immunodeficiency 9

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
Content
Loading form....