IMD40
MCID: IMM120
MIFTS: 43

Immunodeficiency 40 (IMD40)

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

Aliases & Classifications for Immunodeficiency 40

MalaCards integrated aliases for Immunodeficiency 40:

Name: Immunodeficiency 40 57 12 72 29 6 15
Dock2 Deficiency 12 20 58
Imd40 57 12 72
Immunodeficiency, Type 40 39

Characteristics:

Orphanet epidemiological data:

58
dock2 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,late childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
death in childhood occurs without bone marrow transplantation


HPO:

31
immunodeficiency 40:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0111951
OMIM® 57 616433
OMIM Phenotypic Series 57 PS300755
MeSH 44 D016511
ICD10 via Orphanet 33 D81.8
Orphanet 58 ORPHA447737
SNOMED-CT via HPO 68 234532001 258211005 48813009
UMLS 70 C4225328

Summaries for Immunodeficiency 40

OMIM® : 57 Immunodeficiency-40 is an autosomal recessive primary form of combined immunodeficiency mainly affecting T-cell number and function, with other more variable defects in B-cell and NK-cell function. Patients have onset of severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (summary by Dobbs et al., 2015). (616433) (Updated 05-Apr-2021)

MalaCards based summary : Immunodeficiency 40, also known as dock2 deficiency, is related to lymphopenia and omenn syndrome. An important gene associated with Immunodeficiency 40 is DOCK2 (Dedicator Of Cytokinesis 2), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Cytoskeletal Signaling. Affiliated tissues include bone marrow and bone, and related phenotypes are immunodeficiency and lymphopenia

Disease Ontology : 12 A combined T cell and B cell immunodeficiency characterized by reduced T-cell number and function, with variable defects in B-cell and NK-cell function resulting in onset in early childhood of invasive bacterial and viral infections that has material basis in homozygous or compound heterozygous mutation in DOCK2 on chromosome 5q35.1.

UniProtKB/Swiss-Prot : 72 Immunodeficiency 40: A form of combined immunodeficiency characterized by lymphopenia, and defective T-cell, B-cell, and NK-cell responses. Patients suffer from severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation.

Related Diseases for Immunodeficiency 40

Diseases related to Immunodeficiency 40 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 lymphopenia 29.8 RAC2 DOCK2 CORO1A
2 omenn syndrome 29.6 WAS DOCK8 CORO1A
3 combined immunodeficiency 29.2 WAS RAC2 DOCK8 DOCK2 CORO1A
4 malignant syringoma 10.2 DOCK8 DHX8
5 developmental and epileptic encephalopathy 23 10.2 DHX8 DHX37
6 immunodeficiency 19 10.2 DOCK2 CORO1A
7 external ear disease 10.2 DOCK8 DHX37
8 otitis externa 10.2 DOCK8 DHX37
9 mastoiditis 10.1 DOCK8 DHX37
10 coronin-1a deficiency 10.1 DOCK8 DOCK2 CORO1A
11 immunodeficiency, x-linked, with magnesium defect, epstein-barr virus infection, and neoplasia 10.0 DOCK8 CORO1A
12 body mass index quantitative trait locus 11 9.9
13 body mass index quantitative trait locus 9 9.9
14 body mass index quantitative trait locus 8 9.9
15 body mass index quantitative trait locus 4 9.9
16 body mass index quantitative trait locus 10 9.9
17 body mass index quantitative trait locus 7 9.9
18 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 9.9
19 body mass index quantitative trait locus 12 9.9
20 body mass index quantitative trait locus 14 9.9
21 body mass index quantitative trait locus 18 9.9
22 body mass index quantitative trait locus 19 9.9
23 severe combined immunodeficiency 9.9
24 phagocyte bactericidal dysfunction 9.9 RAC2 DOCK8
25 t cell deficiency 9.9 DOCK8 CORO1A
26 leukocyte adhesion deficiency, type i 9.7 WAS RAC2 DOCK8

Graphical network of the top 20 diseases related to Immunodeficiency 40:



Diseases related to Immunodeficiency 40

Symptoms & Phenotypes for Immunodeficiency 40

Human phenotypes related to Immunodeficiency 40:

31
# Description HPO Frequency HPO Source Accession
1 immunodeficiency 31 HP:0002721
2 lymphopenia 31 HP:0001888

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Immunology:
immunodeficiency
invasive bacterial, viral, and mycobacterial infections
t-cell lymphopenia
defective t-cell proliferative responses
b-cell lymphopenia (in some patients)
more

Clinical features from OMIM®:

616433 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Immunodeficiency 40:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hematopoietic system MP:0005397 9.65 CORO1A DHX8 DOCK1 DOCK10 DOCK2 DOCK8
2 immune system MP:0005387 9.28 CORO1A DHX8 DOCK1 DOCK10 DOCK2 DOCK8

Drugs & Therapeutics for Immunodeficiency 40

Search Clinical Trials , NIH Clinical Center for Immunodeficiency 40

Genetic Tests for Immunodeficiency 40

Genetic tests related to Immunodeficiency 40:

# Genetic test Affiliating Genes
1 Immunodeficiency 40 29 DOCK2

Anatomical Context for Immunodeficiency 40

MalaCards organs/tissues related to Immunodeficiency 40:

40
Bone Marrow, Bone

Publications for Immunodeficiency 40

Articles related to Immunodeficiency 40:

# Title Authors PMID Year
1
Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections. 6 57
26083206 2015
2
[Studies on relationship between immunodeficiency in HIV-infected people and condition of upper gastrointestinal tract mucosa, prevalence of mycosis and Helicobacter pylori infection]. 61
16786759 2005
3
High prevalence of a variant of SENV in intravenous drug user HIV-infected patients. 61
12210426 2002
4
Effects of plasmapheresis in a rabbit model of cancer cachexia. 61
9834615 1998

Variations for Immunodeficiency 40

ClinVar genetic disease variations for Immunodeficiency 40:

6 (show top 50) (show all 260)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 DOCK2 DOCK2, 2-BP INS Insertion Pathogenic 199262 GRCh37:
GRCh38:
2 DOCK2 NM_004946.3(DOCK2):c.3633C>G (p.Tyr1211Ter) SNV Pathogenic 835804 GRCh37: 5:169463527-169463527
GRCh38: 5:170036523-170036523
3 DOCK2 DOCK2, 2-BP INS Insertion Pathogenic 199258 GRCh37:
GRCh38:
4 DOCK2 NM_004946.3(DOCK2):c.3970C>T (p.Gln1324Ter) SNV Pathogenic 199259 rs762909359 GRCh37: 5:169474517-169474517
GRCh38: 5:170047513-170047513
5 DOCK2 NM_004946.3(DOCK2):c.2253G>T (p.Arg751Ser) SNV Pathogenic 199261 rs1581090174 GRCh37: 5:169145781-169145781
GRCh38: 5:169718777-169718777
6 DOCK2 NM_004946.3(DOCK2):c.321+1G>A SNV Likely pathogenic 565766 rs1561585424 GRCh37: 5:169098179-169098179
GRCh38: 5:169671175-169671175
7 DOCK2 NM_004946.3(DOCK2):c.4213+1G>A SNV Likely pathogenic 578786 rs1561898523 GRCh37: 5:169477402-169477402
GRCh38: 5:170050398-170050398
8 DOCK2 NM_004946.3(DOCK2):c.4729-2A>G SNV Likely pathogenic 1028824 GRCh37: 5:169502949-169502949
GRCh38: 5:170075945-170075945
9 DOCK2 NM_004946.3(DOCK2):c.1843+1G>T SNV Likely pathogenic 846770 GRCh37: 5:169141216-169141216
GRCh38: 5:169714212-169714212
10 DOCK2 NM_004946.3(DOCK2):c.3381+2T>C SNV Likely pathogenic 643518 rs1581531492 GRCh37: 5:169446114-169446114
GRCh38: 5:170019110-170019110
11 DOCK2 NM_004946.3(DOCK2):c.1360G>A (p.Ala454Thr) SNV Conflicting interpretations of pathogenicity 475999 rs114888195 GRCh37: 5:169129408-169129408
GRCh38: 5:169702404-169702404
12 DOCK2 NM_004946.3(DOCK2):c.2939T>C (p.Ile980Thr) SNV Conflicting interpretations of pathogenicity 721274 rs148694888 GRCh37: 5:169412872-169412872
GRCh38: 5:169985868-169985868
13 DOCK2 NM_004946.3(DOCK2):c.1384-4T>C SNV Uncertain significance 1028312 GRCh37: 5:169135169-169135169
GRCh38: 5:169708165-169708165
14 DOCK2 NM_004946.3(DOCK2):c.1936G>A (p.Val646Met) SNV Uncertain significance 1028313 GRCh37: 5:169141456-169141456
GRCh38: 5:169714452-169714452
15 DOCK2 NM_004946.3(DOCK2):c.2782C>T (p.Arg928Trp) SNV Uncertain significance 1028822 GRCh37: 5:169267839-169267839
GRCh38: 5:169840835-169840835
16 DOCK2 NM_004946.3(DOCK2):c.4163T>A (p.Met1388Lys) SNV Uncertain significance 1028823 GRCh37: 5:169477351-169477351
GRCh38: 5:170050347-170050347
17 DOCK2 NM_004946.3(DOCK2):c.2051T>A (p.Ile684Asn) SNV Uncertain significance 579098 rs1400969417 GRCh37: 5:169144407-169144407
GRCh38: 5:169717403-169717403
18 DOCK2 NM_004946.3(DOCK2):c.3854T>C (p.Ile1285Thr) SNV Uncertain significance 579521 rs369071999 GRCh37: 5:169469114-169469114
GRCh38: 5:170042110-170042110
19 DOCK2 NM_004946.3(DOCK2):c.4182G>A (p.Pro1394=) SNV Uncertain significance 581259 rs751200591 GRCh37: 5:169477370-169477370
GRCh38: 5:170050366-170050366
20 DOCK2 NM_004946.3(DOCK2):c.3683G>A (p.Arg1228His) SNV Uncertain significance 583294 rs139600790 GRCh37: 5:169468076-169468076
GRCh38: 5:170041072-170041072
21 DOCK2 NM_004946.3(DOCK2):c.4151A>G (p.Asn1384Ser) SNV Uncertain significance 567785 rs375716929 GRCh37: 5:169477339-169477339
GRCh38: 5:170050335-170050335
22 DOCK2 NM_004946.3(DOCK2):c.5221_5226del (p.Ile1741_Pro1742del) Deletion Uncertain significance 571239 rs1561912393 GRCh37: 5:169507219-169507224
GRCh38: 5:170080215-170080220
23 DOCK2 NM_004946.3(DOCK2):c.5083C>G (p.Leu1695Val) SNV Uncertain significance 573372 rs1561911758 GRCh37: 5:169506067-169506067
GRCh38: 5:170079063-170079063
24 DOCK2 NM_004946.3(DOCK2):c.1606A>G (p.Lys536Glu) SNV Uncertain significance 802176 rs1581078478 GRCh37: 5:169139174-169139174
GRCh38: 5:169712170-169712170
25 DOCK2 NM_004946.3(DOCK2):c.3484G>A (p.Ala1162Thr) SNV Uncertain significance 802177 rs1581543762 GRCh37: 5:169461419-169461419
GRCh38: 5:170034415-170034415
26 DOCK2 NM_004946.3(DOCK2):c.1843+6C>T SNV Uncertain significance 476004 rs374362264 GRCh37: 5:169141221-169141221
GRCh38: 5:169714217-169714217
27 DOCK2 NM_004946.3(DOCK2):c.5483C>T (p.Thr1828Met) SNV Uncertain significance 938465 GRCh37: 5:169509852-169509852
GRCh38: 5:170082848-170082848
28 DOCK2 NM_004946.3(DOCK2):c.679G>C (p.Val227Leu) SNV Uncertain significance 946089 GRCh37: 5:169111272-169111272
GRCh38: 5:169684268-169684268
29 DOCK2 NM_004946.3(DOCK2):c.1427A>G (p.Tyr476Cys) SNV Uncertain significance 947151 GRCh37: 5:169135216-169135216
GRCh38: 5:169708212-169708212
30 DOCK2 NM_004946.3(DOCK2):c.2042T>C (p.Ile681Thr) SNV Uncertain significance 949086 GRCh37: 5:169144398-169144398
GRCh38: 5:169717394-169717394
31 DOCK2 NM_004946.3(DOCK2):c.3311G>A (p.Arg1104Gln) SNV Uncertain significance 950058 GRCh37: 5:169446042-169446042
GRCh38: 5:170019038-170019038
32 DOCK2 NM_004946.3(DOCK2):c.4913G>A (p.Arg1638His) SNV Uncertain significance 951443 GRCh37: 5:169504760-169504760
GRCh38: 5:170077756-170077756
33 DOCK2 NM_004946.3(DOCK2):c.239T>G (p.Ile80Ser) SNV Uncertain significance 955171 GRCh37: 5:169098096-169098096
GRCh38: 5:169671092-169671092
34 DOCK2 NM_004946.3(DOCK2):c.3056C>G (p.Thr1019Arg) SNV Uncertain significance 958609 GRCh37: 5:169423152-169423152
GRCh38: 5:169996148-169996148
35 DOCK2 NM_004946.3(DOCK2):c.2938A>G (p.Ile980Val) SNV Uncertain significance 966256 GRCh37: 5:169412871-169412871
GRCh38: 5:169985867-169985867
36 DOCK2 NM_004946.3(DOCK2):c.5087G>A (p.Arg1696Gln) SNV Uncertain significance 968235 GRCh37: 5:169506071-169506071
GRCh38: 5:170079067-170079067
37 DOCK2 NM_004946.3(DOCK2):c.3496A>G (p.Thr1166Ala) SNV Uncertain significance 969015 GRCh37: 5:169461431-169461431
GRCh38: 5:170034427-170034427
38 DOCK2 NM_004946.3(DOCK2):c.4378G>A (p.Ala1460Thr) SNV Uncertain significance 542608 rs1554128971 GRCh37: 5:169483770-169483770
GRCh38: 5:170056766-170056766
39 DOCK2 NM_004946.3(DOCK2):c.5039A>G (p.Gln1680Arg) SNV Uncertain significance 542609 rs373168304 GRCh37: 5:169506023-169506023
GRCh38: 5:170079019-170079019
40 DOCK2 NM_004946.3(DOCK2):c.3986A>G (p.Tyr1329Cys) SNV Uncertain significance 542614 rs766635884 GRCh37: 5:169474533-169474533
GRCh38: 5:170047529-170047529
41 DOCK2 NM_004946.3(DOCK2):c.4512G>A (p.Thr1504=) SNV Uncertain significance 639285 rs376411478 GRCh37: 5:169494558-169494558
GRCh38: 5:170067554-170067554
42 DOCK2 NM_004946.3(DOCK2):c.1540C>T (p.Arg514Trp) SNV Uncertain significance 641961 rs1169435264 GRCh37: 5:169138996-169138996
GRCh38: 5:169711992-169711992
43 DOCK2 NM_004946.3(DOCK2):c.2525T>C (p.Ile842Thr) SNV Uncertain significance 642484 rs148384873 GRCh37: 5:169188600-169188600
GRCh38: 5:169761596-169761596
44 DOCK2 NM_004946.3(DOCK2):c.2479C>T (p.Pro827Ser) SNV Uncertain significance 643199 rs1581153476 GRCh37: 5:169188554-169188554
GRCh38: 5:169761550-169761550
45 DOCK2 NM_004946.3(DOCK2):c.3310C>T (p.Arg1104Trp) SNV Uncertain significance 199260 rs780318765 GRCh37: 5:169446041-169446041
GRCh38: 5:170019037-170019037
46 DOCK2 NM_004946.3(DOCK2):c.5166G>A (p.Arg1722=) SNV Uncertain significance 1028825 GRCh37: 5:169506150-169506150
GRCh38: 5:170079146-170079146
47 DOCK2 , INSYN2B NM_004946.3(DOCK2):c.2799+42206G>A SNV Uncertain significance 1034135 GRCh37: 5:169310062-169310062
GRCh38: 5:169883058-169883058
48 DOCK2 NM_004946.3(DOCK2):c.3073-8A>G SNV Uncertain significance 1034136 GRCh37: 5:169435493-169435493
GRCh38: 5:170008489-170008489
49 DOCK2 NM_004946.3(DOCK2):c.4463C>T (p.Ser1488Leu) SNV Uncertain significance 1034677 GRCh37: 5:169484666-169484666
GRCh38: 5:170057662-170057662
50 DOCK2 NM_004946.3(DOCK2):c.3358C>G (p.Gln1120Glu) SNV Uncertain significance 1035804 GRCh37: 5:169446089-169446089
GRCh38: 5:170019085-170019085

UniProtKB/Swiss-Prot genetic disease variations for Immunodeficiency 40:

72
# Symbol AA change Variation ID SNP ID
1 DOCK2 p.Arg751Ser VAR_073859
2 DOCK2 p.Arg1104Trp VAR_073860 rs780318765

Expression for Immunodeficiency 40

Search GEO for disease gene expression data for Immunodeficiency 40.

Pathways for Immunodeficiency 40

GO Terms for Immunodeficiency 40

Cellular components related to Immunodeficiency 40 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.44 WAS RAC2 ELMO1 DOCK9 DOCK8 DOCK6
2 guanyl-nucleotide exchange factor complex GO:0032045 9.16 ELMO1 DOCK1
3 actin filament GO:0005884 9.13 WAS RAC2 CORO1A

Biological processes related to Immunodeficiency 40 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 cell migration GO:0016477 9.8 ELMO1 DOCK5 DOCK1 CORO1A
2 blood coagulation GO:0007596 9.73 WAS DOCK9 DOCK8 DOCK6 DOCK11 DOCK1
3 actin cytoskeleton organization GO:0030036 9.71 RAC2 ELMO1 DOCK2 CORO1A
4 positive regulation of GTPase activity GO:0043547 9.7 DOCK9 DOCK8 DOCK5 DOCK2 DOCK11 DOCK10
5 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.69 WAS ELMO1 DOCK1
6 actin filament organization GO:0007015 9.67 WAS RAC2 ELMO1 CORO1A
7 regulation of catalytic activity GO:0050790 9.65 WAS ELMO1 DOCK9 DOCK8 DOCK6 DOCK5
8 phagocytosis GO:0006909 9.61 ELMO1 DOCK1 CORO1A
9 positive regulation of epithelial cell migration GO:0010634 9.56 DOCK5 DOCK1
10 regulation of defense response to virus by virus GO:0050690 9.55 ELMO1 DOCK2
11 Rac protein signal transduction GO:0016601 9.54 RAC2 ELMO1
12 B cell homeostasis GO:0001782 9.52 DOCK11 DOCK10
13 immunological synapse formation GO:0001771 9.5 DOCK8 DOCK2 CORO1A
14 regulation of actin polymerization or depolymerization GO:0008064 9.48 WAS CORO1A
15 marginal zone B cell differentiation GO:0002315 9.46 DOCK11 DOCK10
16 small GTPase mediated signal transduction GO:0007264 9.28 RAC2 DOCK9 DOCK8 DOCK6 DOCK5 DOCK2

Molecular functions related to Immunodeficiency 40 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 guanyl-nucleotide exchange factor activity GO:0005085 9.28 ELMO1 DOCK9 DOCK8 DOCK6 DOCK5 DOCK2
2 SH3 domain binding GO:0017124 9.13 WAS ELMO1 DOCK1

Sources for Immunodeficiency 40

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
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