IMD9
MCID: IMM066
MIFTS: 30

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 56 73
Immune Dysfunction with T-Cell Inactivation Due to Calcium Entry Defect 1 56 52 73 29 13 6 39 71
Imd9 56 73
Severe Combined Immunodeficiency Due to Crac Channel Dysfunction 73
Combined Immunodeficiency Due to Orai1 Deficiency 58
Cid Due to Orai1 Deficiency 58

Characteristics:

Orphanet epidemiological data:

58
combined immunodeficiency due to orai1 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

31
immunodeficiency 9:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Immunodeficiency 9

UniProtKB/Swiss-Prot : 73 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 failure to thrive and muscular hypotonia

OMIM : 56 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:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 31 HP:0001508
2 muscular hypotonia 31 HP:0001252
3 myopathy 31 HP:0003198
4 respiratory insufficiency due to muscle weakness 31 HP:0002747
5 immunodeficiency 31 HP:0002721
6 recurrent infections 31 HP:0002719
7 difficulty walking 31 HP:0002355
8 amelogenesis imperfecta 31 HP:0000705
9 gowers sign 31 HP:0003391
10 recurrent aphthous stomatitis 31 HP:0011107
11 ectodermal dysplasia 31 HP:0000968
12 heat intolerance 31 HP:0002046
13 stomatitis 31 HP:0010280
14 recurrent fever 31 HP:0001954

Symptoms via clinical synopsis from OMIM:

56
Growth Other:
failure to thrive

Respiratory:
respiratory insufficiency due to muscle weakness

Skin Nails Hair Skin:
heat intolerance
ectodermal dysplasia, anhidrotic

Metabolic Features:
intermittent fever

Muscle Soft Tissue:
muscular hypotonia
difficulty walking
proximal muscle weakness
gowers sign
loss of ambulation
more
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:

40
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. 56 6
20004786 2009
2
A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. 56 6
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. 56 6
8814256 1996
4
A primary T-cell immunodeficiency associated with defective transmembrane calcium influx. 56 6
7531512 1995
5
The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. 56 6
7798233 1994
6
Dynamic coupling of the putative coiled-coil domain of ORAI1 with STIM1 mediates ORAI1 channel activation. 6
18187424 2008
7
The duration of nuclear residence of NFAT determines the pattern of cytokine expression in human SCID T cells. 56
10861065 2000
8
Primary severe immunodeficiency due to impaired signal transduction in T cells. 56
8167687 1993
9
Development of a Low-Cost Stem-Loop Real-Time Quantification PCR Technique for EBV miRNA Expression Analysis. 61
27246439 2016
10
Progression of Common Variable Immunodeficiency Interstitial Lung Disease Accompanies Distinct Pulmonary and Laboratory Findings. 61
26372540 2015
11
Inpatient allergy/immunology consultations in a tertiary care setting. 61
20615326 2010
12
Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. 61
18653625 2009
13
Effect of intravenous immunoglobulins on in vitro immunoglobulin formation in patients with antibody immunodeficiency. 61
12076273 2002
14
Primary immunodeficiencies in Switzerland: first report of the national registry in adults and children. 61
3065352 1988

Variations for Immunodeficiency 9

ClinVar genetic disease variations for Immunodeficiency 9:

6 (show all 25) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ORAI1 NM_032790.3(ORAI1):c.261dup (p.Ala88fs)duplication Pathogenic 192286 rs878853261 12:122064911-122064912 12:121627005-121627006
2 ORAI1 NM_032790.3(ORAI1):c.308C>A (p.Ala103Glu)SNV Pathogenic 192287 rs786205890 12:122078951-122078951 12:121641045-121641045
3 ORAI1 NM_032790.3(ORAI1):c.581T>C (p.Leu194Pro)SNV Pathogenic 192288 rs782753385 12:122079224-122079224 12:121641318-121641318
4 ORAI1 NM_032790.3(ORAI1):c.271C>T (p.Arg91Trp)SNV Pathogenic 1283 rs118203993 12:122064924-122064924 12:121627018-121627018
5 ORAI1 NM_032790.3(ORAI1):c.141_142insCCGCCGCCGCAGCGGGGACGGGGAGCCCCCGGGGGCC (p.Ser48fs)insertion Pathogenic 470188 rs1555322558 12:122064794-122064795 12:121626888-121626889
6 ORAI1 NM_032790.3(ORAI1):c.546del (p.Ile182fs)deletion Likely pathogenic 639606 12:122079189-122079189 12:121641283-121641283
7 ORAI1 NM_032790.3(ORAI1):c.100A>C (p.Ser34Arg)SNV Conflicting interpretations of pathogenicity 541941 rs781829024 12:122064747-122064747 12:121626842-121626842
8 ORAI1 NC_000012.12:g.121626879_121626884delACCGCCdeletion Conflicting interpretations of pathogenicity 193469 rs1555322544 12:122064785-122064790 12:121626879-121626884
9 ORAI1 NM_032790.3(ORAI1):c.115C>G (p.Pro39Ala)SNV Uncertain significance 541940 rs782531427 12:122064762-122064762 12:121626857-121626857
10 ORAI1 NM_032790.3(ORAI1):c.212T>G (p.Met71Arg)SNV Uncertain significance 541942 rs1286173837 12:122064865-122064865 12:121626959-121626959
11 ORAI1 NM_032790.3(ORAI1):c.85_99dup (p.Arg29_Arg33dup)duplication Uncertain significance 541943 rs1372064351 12:122064726-122064727 12:121626821-121626822
12 ORAI1 NM_032790.3(ORAI1):c.783G>A (p.Leu261=)SNV Uncertain significance 569389 rs781878981 12:122079426-122079426 12:121641520-121641520
13 ORAI1 NM_032790.3(ORAI1):c.845T>A (p.Leu282Ter)SNV Uncertain significance 565877 rs1566472954 12:122079488-122079488 12:121641582-121641582
14 ORAI1 NM_032790.3(ORAI1):c.6T>G (p.His2Gln)SNV Uncertain significance 644104 12:122064653-122064653 12:121626748-121626748
15 ORAI1 NM_032790.3(ORAI1):c.7C>T (p.Pro3Ser)SNV Uncertain significance 662981 12:122064654-122064654 12:121626749-121626749
16 ORAI1 NM_032790.3(ORAI1):c.37A>T (p.Ser13Cys)SNV Uncertain significance 652118 12:122064684-122064684 12:121626779-121626779
17 ORAI1 NM_032790.3(ORAI1):c.113_121del (p.Glu38_Pro40del)deletion Uncertain significance 650573 12:122064758-122064766 12:121626853-121626861
18 ORAI1 NM_032790.3(ORAI1):c.114G>T (p.Glu38Asp)SNV Uncertain significance 660638 12:122064761-122064761 12:121626856-121626856
19 ORAI1 NM_032790.3(ORAI1):c.700G>A (p.Ala234Thr)SNV Uncertain significance 664256 12:122079343-122079343 12:121641437-121641437
20 ORAI1 NM_032790.3(ORAI1):c.140C>T (p.Pro47Leu)SNV Uncertain significance 430344 rs781855511 12:122064793-122064793 12:121626887-121626887
21 ORAI1 NM_032790.3(ORAI1):c.137_143CGCCGTC[3] (p.Thr51fs)short repeat Uncertain significance 475180 rs1555322554 12:122064788-122064789 12:121626882-121626883
22 ORAI1 NM_032790.3(ORAI1):c.132_137dup (p.Pro46_Pro47dup)duplication Likely benign 475179 rs1555322544 12:122064772-122064773 12:121626873-121626874
23 ORAI1 NM_032790.3(ORAI1):c.786T>C (p.Val262=)SNV Benign 379438 rs3825174 12:122079429-122079429 12:121641523-121641523
24 ORAI1 NM_032790.3(ORAI1):c.652A>G (p.Ser218Gly)SNV Benign 379436 rs3741596 12:122079295-122079295 12:121641389-121641389
25 ORAI1 NM_032790.3(ORAI1):c.705T>C (p.Ala235=)SNV Benign 379437 rs3741597 12:122079348-122079348 12:121641442-121641442

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

73
# 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 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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