IMD54
MCID: IMM177
MIFTS: 44

Immunodeficiency 54 (IMD54)

Categories: Blood diseases, Cancer diseases, Endocrine diseases, Genetic diseases, Immune diseases, Infectious diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Immunodeficiency 54

MalaCards integrated aliases for Immunodeficiency 54:

Name: Immunodeficiency 54 57 12 72 15
Natural Killer Cell and Glucocorticoid Deficiency with Dna Repair Defect 57 72 29 13 6 39
Natural Killer Cell Deficiency, Familial Isolated 57 44 70
Imd54 57 12 72
Nkcd 57 12 72
Primary Immunodeficiency with Natural-Killer Cell Deficiency and Adrenal Insufficiency 12 58
Familial Isolated Natural Killer Cell Deficiency 12 72
Primary Immunodeficiency Due to Mcm4 Deficiency 12 58
Nkgcd 57 72
Natural Killer Cell and Glucocorticoid Deficiency with Dna Repair Defect; Nkgcd 57
Natural Killer Cell Deficiency, Familial Isolated; Nkcd 57

Characteristics:

Orphanet epidemiological data:

58
primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

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

Miscellaneous:
growth retardation onset in utero
glucocorticoid deficiency occurs in mid-childhood
founder effect in irish traveler population


HPO:

31
immunodeficiency 54:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0111967
OMIM® 57 609981
OMIM Phenotypic Series 57 PS300755
NCIt 50 C123729
ICD10 via Orphanet 33 D84.8
Orphanet 58 ORPHA75391
MedGen 41 C1864947
UMLS 70 C1864947

Summaries for Immunodeficiency 54

OMIM® : 57 Immunodeficiency-54 is an autosomal recessive primary immunodeficiency characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer (NK) cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer. Laboratory studies of patient cells showed a DNA repair defect (summary by Gineau et al., 2012). (609981) (Updated 05-Apr-2021)

MalaCards based summary : Immunodeficiency 54, also known as natural killer cell and glucocorticoid deficiency with dna repair defect, is related to esophageal neuroendocrine tumor and ovarian large-cell neuroendocrine carcinoma. An important gene associated with Immunodeficiency 54 is MCM4 (Minichromosome Maintenance Complex Component 4), and among its related pathways/superpathways are Innate Immune System and Allograft rejection. Affiliated tissues include nk cells and lung, and related phenotypes are respiratory failure and global developmental delay

Disease Ontology : 12 An NK cell deficiency characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of CD56(dim) natural killer cells, adrenal insufficiency, and recurrent viral infections that has material basis in homozygous or compound heterozygous mutation in MCM4 on chromosome 8q11.21.

UniProtKB/Swiss-Prot : 72 Immunodeficiency 54: An autosomal recessive disorder characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer.

Related Diseases for Immunodeficiency 54

Graphical network of the top 20 diseases related to Immunodeficiency 54:



Diseases related to Immunodeficiency 54

Symptoms & Phenotypes for Immunodeficiency 54

Human phenotypes related to Immunodeficiency 54:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 respiratory failure 31 occasional (7.5%) HP:0002878
2 global developmental delay 31 HP:0001263
3 splenomegaly 31 HP:0001744
4 hepatomegaly 31 HP:0002240
5 recurrent respiratory infections 31 HP:0002205
6 microcephaly 31 HP:0000252
7 intrauterine growth retardation 31 HP:0001511
8 postnatal growth retardation 31 HP:0008897
9 lymphadenopathy 31 HP:0002716
10 adrenal insufficiency 31 HP:0000846
11 recurrent viral infections 31 HP:0004429
12 lymphoproliferative disorder 31 HP:0005523

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen Spleen:
splenomegaly

Respiratory:
recurrent respiratory infections
respiratory failure (in some patients)

Growth Other:
intrauterine growth retardation
postnatal growth retardation
poor overall growth

Endocrine Features:
adrenal insufficiency
corticosteroid deficiency

Laboratory Abnormalities:
increased acth
cell studies show increased dna breakage

Neurologic Central Nervous System:
delayed cognitive development, mild (reported in 1 family)

Abdomen Liver:
hepatomegaly

Head And Neck Head:
microcephaly

Immunology:
lymphadenopathy
recurrent viral infections
decreased numbers of circulating nk cells (less than 5%)

Skin Nails Hair Skin:
hyperpigmentation

Respiratory Lung:
lung fibrosis

Neoplasia:
increased susceptibility to cancer
lymphoproliferative disorders

Clinical features from OMIM®:

609981 (Updated 05-Apr-2021)

GenomeRNAi Phenotypes related to Immunodeficiency 54 according to GeneCards Suite gene sharing:

26 (show all 25)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.72 KLRC2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-116 9.72 KLRC2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.72 KLRK1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-123 9.72 KLRK1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.72 KLRK1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-132 9.72 NCR1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-145 9.72 KLRC2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-146 9.72 KLRC2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.72 KLRK1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-158 9.72 NCR1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-163 9.72 KLRC2
12 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.72 KLRK1
13 Increased shRNA abundance (Z-score > 2) GR00366-A-17 9.72 KLRK1
14 Increased shRNA abundance (Z-score > 2) GR00366-A-171 9.72 KLRK1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-175 9.72 KLRK1
16 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.72 KLRC2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-179 9.72 KLRK1
18 Increased shRNA abundance (Z-score > 2) GR00366-A-191 9.72 KLRC2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-204 9.72 KLRC2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.72 KLRK1
21 Increased shRNA abundance (Z-score > 2) GR00366-A-208 9.72 KLRC2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.72 KLRK1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-23 9.72 KLRC2
24 Increased shRNA abundance (Z-score > 2) GR00366-A-66 9.72 NCR1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-98 9.72 NCR1

Drugs & Therapeutics for Immunodeficiency 54

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Natural Killer Cells Regulatory Role Against Hepatic Fibrosis Following Bariatric Surgery Unknown status NCT02732535

Search NIH Clinical Center for Immunodeficiency 54

Cochrane evidence based reviews: natural killer cell deficiency, familial isolated

Genetic Tests for Immunodeficiency 54

Genetic tests related to Immunodeficiency 54:

# Genetic test Affiliating Genes
1 Natural Killer Cell and Glucocorticoid Deficiency with Dna Repair Defect 29 MCM4

Anatomical Context for Immunodeficiency 54

MalaCards organs/tissues related to Immunodeficiency 54:

40
Nk Cells, Lung

Publications for Immunodeficiency 54

Articles related to Immunodeficiency 54:

# Title Authors PMID Year
1
Recessive mutations in MCM4/PRKDC cause a novel syndrome involving a primary immunodeficiency and a disorder of DNA repair. 57 6
22499342 2012
2
Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency. 57 6
22354167 2012
3
MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. 57 6
22354170 2012
4
A novel primary immunodeficiency with specific natural-killer cell deficiency maps to the centromeric region of chromosome 8. 6 57
16532402 2006
5
A novel variant of familial glucocorticoid deficiency prevalent among the Irish Traveler population. 57
18430777 2008
6
Health-related quality of life in primary immune deficient patients. 61
17242500 2006

Variations for Immunodeficiency 54

ClinVar genetic disease variations for Immunodeficiency 54:

6 (show top 50) (show all 127)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MCM4 NM_182746.3(MCM4):c.71-2A>G SNV Pathogenic 37234 rs1563829725 GRCh37: 8:48874074-48874074
GRCh38: 8:47961514-47961514
2 MCM4 NM_182746.3(MCM4):c.832+2T>C SNV Pathogenic 505469 rs1408879284 GRCh37: 8:48877274-48877274
GRCh38: 8:47964714-47964714
3 MCM4 NM_182746.3(MCM4):c.1054-1G>A SNV Pathogenic 1033041 GRCh37: 8:48879924-48879924
GRCh38: 8:47967364-47967364
4 MCM4 NM_182746.3(MCM4):c.220C>T (p.Gln74Ter) SNV Likely pathogenic 930225 GRCh37: 8:48874225-48874225
GRCh38: 8:47961665-47961665
5 MCM4 NM_182746.3(MCM4):c.1406G>C (p.Ser469Thr) SNV Conflicting interpretations of pathogenicity 718626 rs117063344 GRCh37: 8:48882589-48882589
GRCh38: 8:47970029-47970029
6 MCM4 NM_182746.3(MCM4):c.311G>A (p.Arg104Lys) SNV Uncertain significance 1028961 GRCh37: 8:48874688-48874688
GRCh38: 8:47962128-47962128
7 MCM4 NM_182746.3(MCM4):c.2020G>A (p.Glu674Lys) SNV Uncertain significance 992551 GRCh37: 8:48885508-48885508
GRCh38: 8:47972948-47972948
8 MCM4 NM_182746.3(MCM4):c.2102G>A (p.Arg701Gln) SNV Uncertain significance 910776 GRCh37: 8:48885590-48885590
GRCh38: 8:47973030-47973030
9 MCM4 NM_182746.3(MCM4):c.2257G>C (p.Val753Leu) SNV Uncertain significance 911991 GRCh37: 8:48887414-48887414
GRCh38: 8:47974854-47974854
10 MCM4 NM_182746.3(MCM4):c.487A>G (p.Lys163Glu) SNV Uncertain significance 363218 rs34206069 GRCh37: 8:48874952-48874952
GRCh38: 8:47962392-47962392
11 MCM4 NM_182746.3(MCM4):c.1661G>A (p.Arg554Lys) SNV Uncertain significance 1033042 GRCh37: 8:48883297-48883297
GRCh38: 8:47970737-47970737
12 MCM4 NM_182746.3(MCM4):c.2101C>T (p.Arg701Trp) SNV Uncertain significance 1033043 GRCh37: 8:48885589-48885589
GRCh38: 8:47973029-47973029
13 MCM4 NM_182746.3(MCM4):c.31C>G (p.Arg11Gly) SNV Uncertain significance 626134 rs369039102 GRCh37: 8:48873735-48873735
GRCh38: 8:47961175-47961175
14 MCM4 NM_182746.3(MCM4):c.1175-7C>T SNV Uncertain significance 363229 rs372261482 GRCh37: 8:48882351-48882351
GRCh38: 8:47969791-47969791
15 MCM4 NM_182746.3(MCM4):c.1578C>T (p.Leu526=) SNV Uncertain significance 773909 rs34157149 GRCh37: 8:48883214-48883214
GRCh38: 8:47970654-47970654
16 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-701C>A SNV Uncertain significance 363193 rs886062968 GRCh37: 8:48873004-48873004
GRCh38: 8:47960444-47960444
17 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-479A>G SNV Uncertain significance 363196 rs571102789 GRCh37: 8:48873226-48873226
GRCh38: 8:47960666-47960666
18 MCM4 NM_005914.4(MCM4):c.-347C>A SNV Uncertain significance 363202 rs886062970 GRCh37: 8:48873358-48873358
GRCh38: 8:47960798-47960798
19 MCM4 NM_005914.4(MCM4):c.-205C>T SNV Uncertain significance 363205 rs17287526 GRCh37: 8:48873500-48873500
GRCh38: 8:47960940-47960940
20 MCM4 , LOC106903146 NM_005914.3(MCM4):c.-646delG Deletion Uncertain significance 363194 rs376290735 GRCh37: 8:48873054-48873054
GRCh38: 8:47960494-47960494
21 MCM4 , LOC106903146 NM_005914.3(MCM4):c.-745_-744delAA Deletion Uncertain significance 363191 rs530578769 GRCh37: 8:48872960-48872961
GRCh38: 8:47960400-47960401
22 MCM4 NM_182746.3(MCM4):c.*842G>A SNV Uncertain significance 910828 GRCh37: 8:48890180-48890180
GRCh38: 8:47977620-47977620
23 MCM4 NM_182746.3(MCM4):c.*850T>A SNV Uncertain significance 910829 GRCh37: 8:48890188-48890188
GRCh38: 8:47977628-47977628
24 MCM4 NM_182746.3(MCM4):c.-77G>A SNV Uncertain significance 911893 GRCh37: 8:48873512-48873512
GRCh38: 8:47960952-47960952
25 MCM4 NM_182746.3(MCM4):c.-33A>G SNV Uncertain significance 911894 GRCh37: 8:48873556-48873556
GRCh38: 8:47960996-47960996
26 MCM4 NM_182746.3(MCM4):c.-15+55C>T SNV Uncertain significance 911895 GRCh37: 8:48873629-48873629
GRCh38: 8:47961069-47961069
27 MCM4 NM_182746.3(MCM4):c.899A>G (p.Gln300Arg) SNV Uncertain significance 911936 GRCh37: 8:48878813-48878813
GRCh38: 8:47966253-47966253
28 MCM4 NM_182746.3(MCM4):c.2296C>T (p.Arg766Trp) SNV Uncertain significance 911992 GRCh37: 8:48887453-48887453
GRCh38: 8:47974893-47974893
29 MCM4 NM_182746.3(MCM4):c.2341G>A (p.Val781Met) SNV Uncertain significance 911993 GRCh37: 8:48887498-48887498
GRCh38: 8:47974938-47974938
30 MCM4 NM_182746.3(MCM4):c.2531T>C (p.Leu844Pro) SNV Uncertain significance 911994 GRCh37: 8:48889277-48889277
GRCh38: 8:47976717-47976717
31 MCM4 NM_182746.3(MCM4):c.*37C>T SNV Uncertain significance 911995 GRCh37: 8:48889375-48889375
GRCh38: 8:47976815-47976815
32 MCM4 NM_182746.3(MCM4):c.*1140G>A SNV Uncertain significance 912048 GRCh37: 8:48890478-48890478
GRCh38: 8:47977918-47977918
33 MCM4 NM_182746.3(MCM4):c.*1234T>C SNV Uncertain significance 912049 GRCh37: 8:48890572-48890572
GRCh38: 8:47978012-47978012
34 MCM4 NM_182746.3(MCM4):c.*1266G>A SNV Uncertain significance 912050 GRCh37: 8:48890604-48890604
GRCh38: 8:47978044-47978044
35 MCM4 NM_182746.3(MCM4):c.686dup (p.Tyr229Ter) Duplication Uncertain significance 632521 rs1563831163 GRCh37: 8:48875592-48875593
GRCh38: 8:47963032-47963033
36 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-407G>A SNV Uncertain significance 363200 rs546045069 GRCh37: 8:48873298-48873298
GRCh38: 8:47960738-47960738
37 MCM4 NM_005914.4(MCM4):c.-320dup Duplication Uncertain significance 363203 rs532945813 GRCh37: 8:48873378-48873379
GRCh38: 8:47960818-47960819
38 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-473G>A SNV Uncertain significance 363197 rs537563295 GRCh37: 8:48873232-48873232
GRCh38: 8:47960672-47960672
39 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-453T>C SNV Uncertain significance 363198 rs539732672 GRCh37: 8:48873252-48873252
GRCh38: 8:47960692-47960692
40 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-721dup Duplication Uncertain significance 363192 rs886062967 GRCh37: 8:48872983-48872984
GRCh38: 8:47960423-47960424
41 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-501A>G SNV Uncertain significance 363195 rs570195176 GRCh37: 8:48873204-48873204
GRCh38: 8:47960644-47960644
42 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-372G>A SNV Uncertain significance 363201 rs17334298 GRCh37: 8:48873333-48873333
GRCh38: 8:47960773-47960773
43 MCM4 NM_005914.4(MCM4):c.-253C>T SNV Uncertain significance 363204 rs17334305 GRCh37: 8:48873452-48873452
GRCh38: 8:47960892-47960892
44 MCM4 , LOC106903146 NM_005914.4(MCM4):c.-754G>A SNV Uncertain significance 363190 rs180692385 GRCh37: 8:48872951-48872951
GRCh38: 8:47960391-47960391
45 MCM4 NM_182746.3(MCM4):c.*484del Deletion Uncertain significance 363247 rs886062982 GRCh37: 8:48889822-48889822
GRCh38: 8:47977262-47977262
46 MCM4 NM_182746.3(MCM4):c.604G>A (p.Val202Ile) SNV Uncertain significance 626138 rs748499898 GRCh37: 8:48875511-48875511
GRCh38: 8:47962951-47962951
47 MCM4 NM_182746.3(MCM4):c.440G>A (p.Gly147Asp) SNV Uncertain significance 363217 rs886062976 GRCh37: 8:48874905-48874905
GRCh38: 8:47962345-47962345
48 MCM4 NM_182746.3(MCM4):c.*125A>G SNV Uncertain significance 363240 rs886062979 GRCh37: 8:48889463-48889463
GRCh38: 8:47976903-47976903
49 MCM4 NM_182746.3(MCM4):c.*255A>G SNV Uncertain significance 363243 rs544019622 GRCh37: 8:48889593-48889593
GRCh38: 8:47977033-47977033
50 MCM4 NM_182746.3(MCM4):c.*438A>G SNV Uncertain significance 363246 rs886062981 GRCh37: 8:48889776-48889776
GRCh38: 8:47977216-47977216

Expression for Immunodeficiency 54

Search GEO for disease gene expression data for Immunodeficiency 54.

Pathways for Immunodeficiency 54

GO Terms for Immunodeficiency 54

Cellular components related to Immunodeficiency 54 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 integral component of membrane GO:0016021 9.61 PRF1 NCR1 NCAM1 KLRK1 KLRD1 KLRC2
2 cell surface GO:0009986 9.46 NCAM1 KLRK1 IL15 EGFR
3 receptor complex GO:0043235 8.8 KLRD1 KLRC2 EGFR

Biological processes related to Immunodeficiency 54 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 9.88 NCR1 KLRK1 KLRC2 IL15 EGFR CHL1
2 innate immune response GO:0045087 9.67 KLRK1 KLRD1 KLRC2 IRF1
3 regulation of immune response GO:0050776 9.56 NCR1 KLRK1 KLRD1 IRF1
4 cellular defense response GO:0006968 9.33 PRF1 NCR1 KLRC2
5 natural killer cell activation GO:0030101 9.32 NCR1 KLRK1
6 natural killer cell mediated immunity GO:0002228 8.96 KLRD1 KLRC2
7 positive regulation of natural killer cell mediated cytotoxicity GO:0045954 8.8 KLRK1 KLRD1 KLRC2

Molecular functions related to Immunodeficiency 54 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane signaling receptor activity GO:0004888 9.43 KLRD1 KLRC2 EGFR
2 carbohydrate binding GO:0030246 9.33 KLRK1 KLRD1 KLRC2
3 protein antigen binding GO:1990405 8.96 KLRD1 KLRC2
4 MHC class I protein complex binding GO:0023024 8.62 KLRD1 KLRC2

Sources for Immunodeficiency 54

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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