IMD31A
MCID: IMM182
MIFTS: 28

Immunodeficiency 31a (IMD31A)

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

Aliases & Classifications for Immunodeficiency 31a

MalaCards integrated aliases for Immunodeficiency 31a:

Name: Immunodeficiency 31a 57 12 72 29 6 70
Imd31a 57 12 72
Mendelian Susceptibility to Mycobacterial Diseases Due to Partial Signal Transducer and Activator of Transcription 1 Deficiency 12 58
Mendelian Susceptibility to Mycobacterial Diseases Due to Partial Stat1 Deficiency 12 58
Msmd Due to Partial Signal Transducer and Activator of Transcription 1 Deficiency 12 58
Immunodeficiency 31a, Mycobacteriosis, Autosomal Dominant 57 72
Stat1 Deficiency, Autosomal Dominant 57 72
Msmd Due to Partial Stat1 Deficiency 12 58
Immunodeficiency, Type 31a, Mycobacteriosis, Autosomal Dominant 39
Autosomal Dominant Immunodeficiency 31a, Mycobacteriosis 12

Characteristics:

Orphanet epidemiological data:

58
mendelian susceptibility to mycobacterial diseases due to partial stat1 deficiency
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
incomplete penetrance
onset in early childhood
infections may be triggered by bcg vaccination

Inheritance:
autosomal dominant


HPO:

31
immunodeficiency 31a:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0111945
OMIM® 57 614892
OMIM Phenotypic Series 57 PS300755
ICD10 via Orphanet 33 D84.8
Orphanet 58 ORPHA319595
SNOMED-CT via HPO 68 234532001 263681008 428638009
UMLS 70 C4013950

Summaries for Immunodeficiency 31a

UniProtKB/Swiss-Prot : 72 Immunodeficiency 31A: A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. IMD31A has low penetrance, and affected individuals have relatively mild disease and good prognosis. IMD31A confers a predisposition to mycobacterial infections only, with no increased susceptibility to viral infections.

MalaCards based summary : Immunodeficiency 31a, is also known as imd31a. An important gene associated with Immunodeficiency 31a is STAT1 (Signal Transducer And Activator Of Transcription 1). Related phenotypes are immunodeficiency and herpes simplex encephalitis

Disease Ontology : 12 A primary immunodeficiency disease characterized by impaired response to IFNG but not to INFA or IFNB resulting in increased susceptibility to mycobacterial infection that has material basis in heterozygous mutation in STAT1 on chromosome 2q32.2.

OMIM® : 57 IMD31A results from autosomal dominant (AD) STAT1 deficiency. STAT1 is crucial for cellular responses to IFNA (147660)/IFNB (147640) (type I interferon) and IFNG (147570) (type III interferon). AD STAT1 deficiency selectively affects the IFNG pathway, but not the IFNA/IFNB pathway, and confers a predisposition to mycobacterial infections. Pathogens reported in IMD31A patients include bacillus Calmette-Guerin (BCG) and Mycobacterium avium complex, as well as Mycobacterium tuberculosis. IMD31A has low penetrance and a mild clinical phenotype with good prognosis for recovery (review by Al-Muhsen and Casanova, 2008). Two patients with heterozygous STAT1 mutations have been reported with increased susceptibility to adult-onset herpes simplex encephalitis (HSE) without a history of other significant infections (Mork et al., 2015). (614892) (Updated 05-Apr-2021)

Related Diseases for Immunodeficiency 31a

Symptoms & Phenotypes for Immunodeficiency 31a

Human phenotypes related to Immunodeficiency 31a:

31
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 31 HP:0002721
2 herpes simplex encephalitis 31 HP:0012302

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
herpes simplex encephalitis

Laboratory Abnormalities:
poor immunologic response to gamma-interferon

Immunology:
increased susceptibility to disseminated mycobacterial infections
increased susceptibility to herpes simplex encephalitis

Clinical features from OMIM®:

614892 (Updated 05-Apr-2021)

Drugs & Therapeutics for Immunodeficiency 31a

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 31a

Genetic Tests for Immunodeficiency 31a

Genetic tests related to Immunodeficiency 31a:

# Genetic test Affiliating Genes
1 Immunodeficiency 31a 29 STAT1

Anatomical Context for Immunodeficiency 31a

Publications for Immunodeficiency 31a

Articles related to Immunodeficiency 31a:

(show all 33)
# Title Authors PMID Year
1
Mutations in the TLR3 signaling pathway and beyond in adult patients with herpes simplex encephalitis. 57 6
26513235 2015
2
Dominant-negative STAT1 SH2 domain mutations in unrelated patients with Mendelian susceptibility to mycobacterial disease. 57 6
22573496 2012
3
Impairment of mycobacterial but not viral immunity by a germline human STAT1 mutation. 57 6
11452125 2001
4
Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations. 6
29111217 2018
5
Oesophageal candidiasis and squamous cell cancer in patients with gain-of-function STAT1 gene mutation. 6
28815025 2017
6
A gain-of-function mutation of STAT1: A novel genetic factor contributing to chronic mucocutaneous candidiasis. 6
28597685 2017
7
Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis. 6
28427548 2017
8
Gain-of-function STAT1 mutations are associated with intracranial aneurysms. 6
28161409 2017
9
Molecular mechanism and structural basis of gain-of-function of STAT1 caused by pathogenic R274Q mutation. 6
28258222 2017
10
New and recurrent STAT1 mutations in seven Chinese patients with chronic mucocutaneous candidiasis. 6
27808400 2017
11
Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1. 6
27379765 2016
12
Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. 6
27114460 2016
13
Progressive Multifocal Leukoencephalopathy in Primary Immune Deficiencies: Stat1 Gain of Function and Review of the Literature. 6
26743090 2016
14
Extrapulmonary tuberculosis mimicking Mendelian susceptibility to mycobacterial disease in a patient with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation. 6
26242301 2016
15
The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1. 6
26604104 2016
16
A STAT1-gain-of-function mutation causing Th17 deficiency with chronic mucocutaneous candidiasis, psoriasiform hyperkeratosis and dermatophytosis. 6
26494717 2015
17
Gain-of-function STAT1 mutations impair STAT3 activity in patients with chronic mucocutaneous candidiasis (CMC). 6
26255980 2015
18
Orf Infection in a Patient with Stat1 Gain-of-Function. 6
25367169 2015
19
Clinical exome sequencing for genetic identification of rare Mendelian disorders. 6
25326637 2014
20
Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding. 6
25042743 2014
21
Simple diagnosis of STAT1 gain-of-function alleles in patients with chronic mucocutaneous candidiasis. 6
24343863 2014
22
Penicillium marneffei infection and impaired IFN-γ immunity in humans with autosomal-dominant gain-of-phosphorylation STAT1 mutations. 6
24188975 2014
23
Fatal combined immunodeficiency associated with heterozygous mutation in STAT1. 6
24239102 2014
24
New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe. 6
23709754 2013
25
Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. 6
23534974 2013
26
Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis. 6
23541320 2013
27
Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism. 6
22847544 2012
28
Chronic mucocutaneous candidiasis caused by a gain-of-function mutation in the STAT1 DNA-binding domain. 6
22730530 2012
29
Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. 6
21727188 2011
30
STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. 6
21714643 2011
31
STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis. 6
22195034 2011
32
The genetic heterogeneity of mendelian susceptibility to mycobacterial diseases. 57
19084105 2008
33
Novel STAT1 alleles in otherwise healthy patients with mycobacterial disease. 6
16934001 2006

Variations for Immunodeficiency 31a

ClinVar genetic disease variations for Immunodeficiency 31a:

6 (show top 50) (show all 203)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 STAT1 NM_007315.3(STAT1):c.2117T>C (p.Leu706Ser) SNV Pathogenic 9043 rs137852677 GRCh37: 2:191840556-191840556
GRCh38: 2:190975830-190975830
2 STAT1 NM_007315.3(STAT1):c.1389G>T (p.Gln463His) SNV Pathogenic 9046 rs137852679 GRCh37: 2:191848425-191848425
GRCh38: 2:190983699-190983699
3 STAT1 NM_007315.3(STAT1):c.958G>C (p.Glu320Gln) SNV Pathogenic 9047 rs137852680 GRCh37: 2:191856033-191856033
GRCh38: 2:190991307-190991307
4 STAT1 NM_007315.3(STAT1):c.2018A>G (p.Lys673Arg) SNV Pathogenic 155907 rs587777704 GRCh37: 2:191841607-191841607
GRCh38: 2:190976881-190976881
5 STAT1 NM_007315.3(STAT1):c.1909A>G (p.Lys637Glu) SNV Pathogenic 155908 rs587777705 GRCh37: 2:191841716-191841716
GRCh38: 2:190976990-190976990
6 STAT1 NM_007315.3(STAT1):c.866A>G (p.Tyr289Cys) SNV Pathogenic 541825 rs1553496850 GRCh37: 2:191859865-191859865
GRCh38: 2:190995139-190995139
7 STAT1 NM_007315.4(STAT1):c.1011_1012del (p.Val339fs) Deletion Pathogenic 961842 GRCh37: 2:191855979-191855980
GRCh38: 2:190991253-190991254
8 STAT1 NM_007315.3(STAT1):c.820C>T (p.Arg274Trp) SNV Pathogenic 30083 rs387906758 GRCh37: 2:191859911-191859911
GRCh38: 2:190995185-190995185
9 STAT1 NM_007315.3(STAT1):c.821G>A (p.Arg274Gln) SNV Pathogenic 30085 rs387906760 GRCh37: 2:191859910-191859910
GRCh38: 2:190995184-190995184
10 STAT1 NM_007315.3(STAT1):c.800C>T (p.Ala267Val) SNV Pathogenic 30084 rs387906759 GRCh37: 2:191859931-191859931
GRCh38: 2:190995205-190995205
11 STAT1 NM_007315.3(STAT1):c.1154C>T (p.Thr385Met) SNV Pathogenic 144006 rs587777630 GRCh37: 2:191851647-191851647
GRCh38: 2:190986921-190986921
12 STAT1 NM_007315.3(STAT1):c.800C>T (p.Ala267Val) SNV Pathogenic 30084 rs387906759 GRCh37: 2:191859931-191859931
GRCh38: 2:190995205-190995205
13 STAT1 NM_007315.4(STAT1):c.851A>G (p.Glu284Gly) SNV Likely pathogenic 965491 GRCh37: 2:191859880-191859880
GRCh38: 2:190995154-190995154
14 STAT1 NM_007315.4(STAT1):c.1166T>G (p.Val389Gly) SNV Likely pathogenic 860546 GRCh37: 2:191851635-191851635
GRCh38: 2:190986909-190986909
15 STAT1 NM_007315.3(STAT1):c.876C>A (p.Asp292Glu) SNV Likely pathogenic 426484 rs1085307649 GRCh37: 2:191859855-191859855
GRCh38: 2:190995129-190995129
16 STAT1 NM_007315.4(STAT1):c.856A>C (p.Lys286Gln) SNV Likely pathogenic 848283 GRCh37: 2:191859875-191859875
GRCh38: 2:190995149-190995149
17 STAT1 NM_007315.4(STAT1):c.863C>T (p.Thr288Ile) SNV Likely pathogenic 848760 GRCh37: 2:191859868-191859868
GRCh38: 2:190995142-190995142
18 STAT1 NM_007315.4(STAT1):c.1310C>T (p.Thr437Ile) SNV Likely pathogenic 852805 GRCh37: 2:191849073-191849073
GRCh38: 2:190984347-190984347
19 STAT1 NM_007315.3(STAT1):c.1162A>C (p.Lys388Gln) SNV Likely pathogenic 578600 rs1559011859 GRCh37: 2:191851639-191851639
GRCh38: 2:190986913-190986913
20 STAT1 NM_007315.3(STAT1):c.820C>G (p.Arg274Gly) SNV Likely pathogenic 160354 rs387906758 GRCh37: 2:191859911-191859911
GRCh38: 2:190995185-190995185
21 STAT1 NM_007315.3(STAT1):c.970T>C (p.Cys324Arg) SNV Likely pathogenic 643417 rs1574653439 GRCh37: 2:191856021-191856021
GRCh38: 2:190991295-190991295
22 STAT1 NM_007315.3(STAT1):c.1222-5T>C SNV Conflicting interpretations of pathogenicity 252674 rs191364028 GRCh37: 2:191850391-191850391
GRCh38: 2:190985665-190985665
23 STAT1 NM_007315.3(STAT1):c.1727+13G>A SNV Conflicting interpretations of pathogenicity 333267 rs377146580 GRCh37: 2:191844485-191844485
GRCh38: 2:190979759-190979759
24 STAT1 NM_007315.3(STAT1):c.633+6T>A SNV Conflicting interpretations of pathogenicity 333289 rs45459703 GRCh37: 2:191862937-191862937
GRCh38: 2:190998211-190998211
25 STAT1 NM_007315.3(STAT1):c.796G>A (p.Val266Ile) SNV Conflicting interpretations of pathogenicity 333285 rs41473544 GRCh37: 2:191859935-191859935
GRCh38: 2:190995209-190995209
26 STAT1 NM_007315.4(STAT1):c.850G>A (p.Glu284Lys) SNV Uncertain significance 827741 rs1574657750 GRCh37: 2:191859881-191859881
GRCh38: 2:190995155-190995155
27 STAT1 NM_007315.3(STAT1):c.478A>C (p.Ile160Leu) SNV Uncertain significance 648892 rs371548986 GRCh37: 2:191864415-191864415
GRCh38: 2:190999689-190999689
28 STAT1 NM_007315.4(STAT1):c.541+6G>C SNV Uncertain significance 998635 GRCh37: 2:191864346-191864346
GRCh38: 2:190999620-190999620
29 STAT1 NM_007315.4(STAT1):c.167G>A (p.Arg56His) SNV Uncertain significance 1029155 GRCh37: 2:191873795-191873795
GRCh38: 2:191009069-191009069
30 STAT1 NM_007315.3(STAT1):c.478A>C (p.Ile160Leu) SNV Uncertain significance 648892 rs371548986 GRCh37: 2:191864415-191864415
GRCh38: 2:190999689-190999689
31 STAT1 NM_007315.3(STAT1):c.1632+6G>A SNV Uncertain significance 333271 rs185216067 GRCh37: 2:191845340-191845340
GRCh38: 2:190980614-190980614
32 STAT1 NM_007315.3(STAT1):c.1757G>A (p.Arg586Gln) SNV Uncertain significance 580685 rs144788879 GRCh37: 2:191843698-191843698
GRCh38: 2:190978972-190978972
33 STAT1 NM_007315.3(STAT1):c.722G>A (p.Arg241Gln) SNV Uncertain significance 333286 rs146273341 GRCh37: 2:191862645-191862645
GRCh38: 2:190997919-190997919
34 STAT1 NM_007315.4(STAT1):c.596T>C (p.Leu199Pro) SNV Uncertain significance 842244 GRCh37: 2:191862980-191862980
GRCh38: 2:190998254-190998254
35 STAT1 NM_007315.4(STAT1):c.1886A>T (p.His629Leu) SNV Uncertain significance 843006 GRCh37: 2:191841739-191841739
GRCh38: 2:190977013-190977013
36 STAT1 NM_007315.4(STAT1):c.389T>C (p.Ile130Thr) SNV Uncertain significance 937753 GRCh37: 2:191865873-191865873
GRCh38: 2:191001147-191001147
37 STAT1 NM_007315.4(STAT1):c.955G>A (p.Val319Met) SNV Uncertain significance 944892 GRCh37: 2:191856036-191856036
GRCh38: 2:190991310-190991310
38 STAT1 NM_007315.4(STAT1):c.68A>T (p.Asp23Val) SNV Uncertain significance 965789 GRCh37: 2:191874662-191874662
GRCh38: 2:191009936-191009936
39 STAT1 NM_007315.4(STAT1):c.1276G>A (p.Val426Ile) SNV Uncertain significance 1013684 GRCh37: 2:191849107-191849107
GRCh38: 2:190984381-190984381
40 STAT1 NM_007315.4(STAT1):c.1202C>A (p.Ala401Glu) SNV Uncertain significance 1017833 GRCh37: 2:191851599-191851599
GRCh38: 2:190986873-190986873
41 STAT1 NM_007315.4(STAT1):c.877_891del (p.Pro293_Asn297del) Deletion Uncertain significance 1017838 GRCh37: 2:191859840-191859854
GRCh38: 2:190995114-190995128
42 STAT1 NM_007315.4(STAT1):c.1632+5G>A SNV Uncertain significance 1019127 GRCh37: 2:191845341-191845341
GRCh38: 2:190980615-190980615
43 STAT1 NM_007315.4(STAT1):c.976C>T (p.Pro326Ser) SNV Uncertain significance 1019308 GRCh37: 2:191856015-191856015
GRCh38: 2:190991289-190991289
44 STAT1 NM_007315.3(STAT1):c.1341C>A (p.Asp447Glu) SNV Uncertain significance 333273 rs140351189 GRCh37: 2:191849042-191849042
GRCh38: 2:190984316-190984316
45 STAT1 NM_007315.4(STAT1):c.1221+6G>T SNV Uncertain significance 1023104 GRCh37: 2:191851574-191851574
GRCh38: 2:190986848-190986848
46 STAT1 NC_000002.11:g.(?_191835409)_(191835463_?)dup Duplication Uncertain significance 1023507 GRCh37: 2:191835409-191835463
GRCh38:
47 STAT1 NM_007315.4(STAT1):c.246C>A (p.Asn82Lys) SNV Uncertain significance 842864 GRCh37: 2:191873716-191873716
GRCh38: 2:191008990-191008990
48 STAT1 NM_007315.4(STAT1):c.1349C>T (p.Thr450Met) SNV Uncertain significance 854394 GRCh37: 2:191848465-191848465
GRCh38: 2:190983739-190983739
49 STAT1 NM_007315.4(STAT1):c.1038-3C>T SNV Uncertain significance 856748 GRCh37: 2:191854403-191854403
GRCh38: 2:190989677-190989677
50 STAT1 NM_007315.4(STAT1):c.1038A>C (p.Arg346Ser) SNV Uncertain significance 857689 GRCh37: 2:191854400-191854400
GRCh38: 2:190989674-190989674

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 31a:

72
# Symbol AA change Variation ID SNP ID
1 STAT1 p.Leu706Ser VAR_018266 rs137852677
2 STAT1 p.Glu320Gln VAR_065816 rs137852680
3 STAT1 p.Gln463His VAR_065817 rs137852679
4 STAT1 p.Lys637Glu VAR_068713 rs587777705
5 STAT1 p.Lys673Arg VAR_068714 rs587777704

Expression for Immunodeficiency 31a

Search GEO for disease gene expression data for Immunodeficiency 31a.

Pathways for Immunodeficiency 31a

GO Terms for Immunodeficiency 31a

Sources for Immunodeficiency 31a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....