RDYS
MCID: RTC002
MIFTS: 56

Reticular Dysgenesis (RDYS)

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

Aliases & Classifications for Reticular Dysgenesis

MalaCards integrated aliases for Reticular Dysgenesis:

Name: Reticular Dysgenesis 56 12 52 58 73 36 29 13 54 6 43 15 39 71
Severe Combined Immunodeficiency with Leukopenia 56 52 58 73
De Vaal Disease 56 12 58 73
Congenital Aleukia 56 52 73
Aleukocytosis 56 12 73
Hematopoietic Hypoplasia, Generalized 56 73
Generalized Hematopoietic Hypoplasia 58
Congenital Aleukocytosis 58
Reticular Dysgenesia 56
Scid with Leukopenia 58
Devaal Disease 52
Ak2 Deficiency 58
Rdys 73
Rd 52

Characteristics:

Orphanet epidemiological data:

58
reticular dysgenesis
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
early death in the first few weeks of life


HPO:

31
reticular dysgenesis:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare immunological diseases


External Ids:

Disease Ontology 12 DOID:0060020
OMIM 56 267500
KEGG 36 H01128
NCIt 49 C27070
SNOMED-CT 67 111584000
MESH via Orphanet 44 C538361
ICD10 via Orphanet 33 D81.0
UMLS via Orphanet 72 C0272167 C1282908
Orphanet 58 ORPHA33355
MedGen 41 C0272167
UMLS 71 C0272167

Summaries for Reticular Dysgenesis

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 33355 Definition Reticular dysgenesis is the most severe form of severe combined immunodeficiency (SCID; see this term) and is characterized by bilateral sensorineural deafness and a lack of innate and adaptive immune functions leading to fatal septicemia within days after birth if not treated. Epidemiology Reticular dysgenesis accounts for less than 2% of all SCID cases. The annual incidence has been estimated at 1/3,000,000-1/5,000,000. Both males and females are affected, and consanguinity has been noted in several families. Clinical description The disease presents earlier than other forms of SCID, at birth or early in the neonatal period, with signs of sepsis, failure to thrive, diarrhea, fever, recurrent infections including upper respiratory tract infections, oral candidiasis, perianal infections and abscesses, and bilateral sensorineural deafness. Despite recurrent infections, no significant lymphoid or tonsillar tissue is evident. Hemoglobin levels are usually within reference ranges at birth, but patients may develop anemia secondary to sepsis and chronic illness. Etiology Reticular dysgenesis is characterized by profound neutropenia and T and natural killer (NK) cell lymphocytopenia, and is caused by mutations in the AK2 gene (1p34). The resulting deficiency in adenylate kinase 2 causes increased apoptosis of myeloid and lymphoid precursors. However, patients without this mutation have been observed implying an alternative cause. An imbalance of growth factor independent-1 transcription repressor (Gfi-1) and/or Gfi-1b has been proposed. Diagnostic methods Diagnosis is based on evidence of sensorineural deafness in combination with evidence of a marked reduction of T and NK cell counts when compared to age-matched healthy controls. Materno-fetal engraftment is usually present. Differential diagnosis Differential diagnosis includes all other forms of SCID. Antenatal diagnosis Prenatal diagnosis can be performed in families where there is a family history and where the genetic mutation has been identified. Genetic counseling Transmission is autosomal recessive . Management and treatment The only curative treatment for this disease is allogenic hematopoietic stem cell transplantation. Prognosis Without treatment, patients die from septicemia within days after birth. Visit the Orphanet disease page for more resources.

MalaCards based summary : Reticular Dysgenesis, also known as severe combined immunodeficiency with leukopenia, is related to severe combined immunodeficiency and lymphopenia. An important gene associated with Reticular Dysgenesis is AK2 (Adenylate Kinase 2), and among its related pathways/superpathways are Purine metabolism and Metabolism of nucleotides. The drug Adenosine has been mentioned in the context of this disorder. Affiliated tissues include myeloid, bone and bone marrow, and related phenotypes are hearing impairment and chronic otitis media

Disease Ontology : 12 A severe combined immunodeficiency that is the most severe form of SCID and has material basis in mutations in the gene encoding mitochondrial adenylate kinase 2. It is characterized by congenital agranulocytosis, lymphopenia, and lymphoid and thymic hypoplasia with absent cellular and humoral immunity functions.

KEGG : 36 Reticular dysgenesis (RD) is a rare congenital immunodeficiency classified within the severe combined immunodeficiencies (SCIDs). It is inherited in an autosomal recessive manner, and is characterized by absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immune functions, leading to fatal septicemia within days after birth. The bone marrow showed a maturation arrest in the myeloid and lymphoid lineage. The underlying genetic defect for most cases of RD have been identified in the gene encoding adenylate kinase 2 (AK2).

UniProtKB/Swiss-Prot : 73 Reticular dysgenesis: A fatal form of severe combined immunodeficiency, characterized by absence of granulocytes, almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immunity, leading to fatal septicemia within days after birth. In bone marrow of individuals with reticular dysgenesis, myeloid differentiation is blocked at the promyelocytic stage, whereas erythro- and megakaryocytic maturation is generally normal. Inheritance is autosomal recessive.

Wikipedia : 74 Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in... more...

More information from OMIM: 267500

Related Diseases for Reticular Dysgenesis

Diseases related to Reticular Dysgenesis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 332)
# Related Disease Score Top Affiliating Genes
1 severe combined immunodeficiency 29.1 RAG1 PNP NHEJ1 JAK3 IL2RG DCLRE1C
2 lymphopenia 28.5 RAG1 PNP JAK3 IL2RG ADA
3 immune deficiency disease 27.8 RAG1 PNP JAK3 IL2RG DCLRE1C ADA
4 omenn syndrome 27.2 RAG1 PNP NHEJ1 JAK3 IL2RG DCLRE1C
5 respiratory distress syndrome in premature infants 12.3
6 restrictive dermopathy, lethal 12.0
7 refsum disease, classic 11.9
8 immunoerythromyeloid hypoplasia 11.8
9 radin blood group antigen 11.7
10 respiratory distress syndrome, infant 11.7
11 bronchopulmonary dysplasia 11.5
12 choroidal dystrophy, central areolar, 1 11.5
13 adult respiratory distress syndrome 11.2
14 renal hypodysplasia/aplasia 1 11.2
15 renal hypodysplasia/aplasia 2 11.2
16 surfactant dysfunction 11.2
17 retinal degeneration 10.9
18 retinitis pigmentosa 10.8
19 neuroretinitis 10.8
20 retinitis 10.8
21 haemophilus influenzae 10.7
22 combined t and b cell immunodeficiency 10.6
23 rhabdomyosarcoma 10.6
24 retinal disease 10.5
25 macular degeneration, age-related, 1 10.4
26 yemenite deaf-blind hypopigmentation syndrome 10.4
27 pattern dystrophy 10.4
28 neutropenia 10.3
29 fundus dystrophy 10.3
30 inherited retinal disorder 10.3
31 macular dystrophy, patterned, 1 10.3
32 retinitis pigmentosa 7 10.3
33 butterfly-shaped pigment dystrophy 10.3
34 branchiootic syndrome 1 10.3
35 granulocytopenia 10.3
36 cerebral artery occlusion 10.2
37 patent ductus arteriosus 1 10.2
38 choroidal dystrophy, central areolar 2 10.2
39 graft-versus-host disease 10.2
40 alcohol dependence 10.2
41 ischemia 10.2
42 pneumocystosis 10.2
43 measles 10.2
44 cone-rod dystrophy 2 10.2
45 retinal detachment 10.2
46 macular dystrophy, vitelliform, 3 10.2
47 respiratory failure 10.2
48 48,xyyy 10.2
49 attention deficit-hyperactivity disorder 10.1
50 vitelliform macular dystrophy 10.1

Graphical network of the top 20 diseases related to Reticular Dysgenesis:



Diseases related to Reticular Dysgenesis

Symptoms & Phenotypes for Reticular Dysgenesis

Human phenotypes related to Reticular Dysgenesis:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000365
2 chronic otitis media 58 31 hallmark (90%) Very frequent (99-80%) HP:0000389
3 recurrent respiratory infections 58 31 hallmark (90%) Very frequent (99-80%) HP:0002205
4 anemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001903
5 cellular immunodeficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0005374
6 aplasia/hypoplasia of the thymus 58 31 hallmark (90%) Very frequent (99-80%) HP:0010515
7 sepsis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100806
8 abnormality of neutrophils 58 31 hallmark (90%) Very frequent (99-80%) HP:0001874
9 diarrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002014
10 leukopenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001882
11 severe combined immunodeficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0004430
12 abnormality of mitochondrial metabolism 58 31 hallmark (90%) Very frequent (99-80%) HP:0003287
13 decreased circulating antibody level 31 hallmark (90%) HP:0004313
14 malabsorption 58 31 frequent (33%) Frequent (79-30%) HP:0002024
15 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
16 fever 58 31 frequent (33%) Frequent (79-30%) HP:0001945
17 weight loss 58 31 frequent (33%) Frequent (79-30%) HP:0001824
18 dehydration 58 31 occasional (7.5%) Occasional (29-5%) HP:0001944
19 skin rash 58 31 occasional (7.5%) Occasional (29-5%) HP:0000988
20 skin ulcer 58 31 occasional (7.5%) Occasional (29-5%) HP:0200042
21 decreased antibody level in blood 58 Very frequent (99-80%)
22 lymphopenia 31 HP:0001888
23 hypoplasia of the thymus 31 HP:0000778
24 impaired t cell function 31 HP:0005435
25 lack of t cell function 31 HP:0005354
26 combined immunodeficiency 31 HP:0005387
27 congenital agranulocytosis 31 HP:0005541

Symptoms via clinical synopsis from OMIM:

56
Hematology:
lymphopenia
leukopenia
congenital agranulocytosis
absent bone marrow myeloid elements

Immunology:
thymic hypoplasia
lymphoid hypoplasia
absent cellular immunity
absent humoral immunity

Clinical features from OMIM:

267500

GenomeRNAi Phenotypes related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

26 (show all 35)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-103 9.96 AK1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.96 AK3
3 Increased shRNA abundance (Z-score > 2) GR00366-A-11 9.96 JAK3
4 Increased shRNA abundance (Z-score > 2) GR00366-A-121 9.96 DCLRE1C
5 Increased shRNA abundance (Z-score > 2) GR00366-A-122 9.96 DCLRE1C
6 Increased shRNA abundance (Z-score > 2) GR00366-A-123 9.96 AK3
7 Increased shRNA abundance (Z-score > 2) GR00366-A-139 9.96 AK3
8 Increased shRNA abundance (Z-score > 2) GR00366-A-145 9.96 DCLRE1C
9 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.96 DCLRE1C
10 Increased shRNA abundance (Z-score > 2) GR00366-A-149 9.96 JAK3
11 Increased shRNA abundance (Z-score > 2) GR00366-A-164 9.96 AK8
12 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.96 AK3
13 Increased shRNA abundance (Z-score > 2) GR00366-A-173 9.96 AK2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-190 9.96 AK2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-20 9.96 AK1 JAK3
16 Increased shRNA abundance (Z-score > 2) GR00366-A-204 9.96 DCLRE1C
17 Increased shRNA abundance (Z-score > 2) GR00366-A-211 9.96 AK3
18 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.96 AK2
19 Increased shRNA abundance (Z-score > 2) GR00366-A-215 9.96 AK2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-216 9.96 AK2 DCLRE1C
21 Increased shRNA abundance (Z-score > 2) GR00366-A-40 9.96 AK3
22 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.96 AK1
23 Increased shRNA abundance (Z-score > 2) GR00366-A-42 9.96 AK3
24 Increased shRNA abundance (Z-score > 2) GR00366-A-46 9.96 AK8
25 Increased shRNA abundance (Z-score > 2) GR00366-A-52 9.96 AK3
26 Increased shRNA abundance (Z-score > 2) GR00366-A-60 9.96 AK3 AK8 JAK3
27 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.96 AK3
28 Increased shRNA abundance (Z-score > 2) GR00366-A-73 9.96 AK1
29 Increased shRNA abundance (Z-score > 2) GR00366-A-78 9.96 AK1
30 Increased shRNA abundance (Z-score > 2) GR00366-A-85 9.96 AK1 AK2 AK3 AK8 DCLRE1C JAK3
31 Increased shRNA abundance (Z-score > 2) GR00366-A-87 9.96 DCLRE1C
32 Increased shRNA abundance (Z-score > 2) GR00366-A-88 9.96 AK2
33 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.96 DCLRE1C
34 Increased shRNA abundance (Z-score > 2) GR00366-A-96 9.96 JAK3
35 Decreased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 9.26 AK2 AK3 AK4 JAK3

MGI Mouse Phenotypes related to Reticular Dysgenesis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.81 ADA AK1 DCLRE1C GFI1 IL2RG JAK3
2 endocrine/exocrine gland MP:0005379 9.56 ADA DCLRE1C GFI1 IL2RG JAK3 NHEJ1
3 hematopoietic system MP:0005397 9.23 ADA DCLRE1C GFI1 IL2RG JAK3 NHEJ1

Drugs & Therapeutics for Reticular Dysgenesis

Drugs for Reticular Dysgenesis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID Since January 1,1968 (RDCRN PIDTC-6902) Recruiting NCT01346150
2 A Prospective Natural History Study of Diagnosis, Treatment and Outcomes of Children With SCID Disorders (RDCRN PIDTC-6901) Recruiting NCT01186913

Search NIH Clinical Center for Reticular Dysgenesis

Cochrane evidence based reviews: reticular dysgenesis

Genetic Tests for Reticular Dysgenesis

Genetic tests related to Reticular Dysgenesis:

# Genetic test Affiliating Genes
1 Reticular Dysgenesis 29 AK2

Anatomical Context for Reticular Dysgenesis

MalaCards organs/tissues related to Reticular Dysgenesis:

40
Myeloid, Bone, Bone Marrow, Thymus, Nk Cells, T Cells, Skin

Publications for Reticular Dysgenesis

Articles related to Reticular Dysgenesis:

(show top 50) (show all 62)
# Title Authors PMID Year
1
Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness. 54 6 56 61
19043416 2009
2
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2. 61 6 54 56
19043417 2009
3
Severe congenital leukopenia (reticular dysgenesis). Immunologic and morphologic characterizations of leukocytes. 61 56
3875278 1985
4
Successful bone-marrow transplantation for reticular dysgenesis. 61 56
6132037 1983
5
Reticular dysgenesis: report of two brothers. 56 61
535190 1979
6
Severe combined immunodeficiency with leukopenia (reticular dysgenesis) in siblings: immunologic and histopathologic findings. 56 61
956962 1976
7
Congenital immunodeficiency and agranulocytosis (reticular dysgenesia). 56
141193 1977
8
A proposed classification of primary immunologic deficiencies. 56
5722637 1968
9
THYMIC ALYMPHOPLASIA AND CONGENITAL ALEUKOCYTOSIS. 56
14117373 1964
10
Reticular dysgenesia. 56
13840590 1959
11
Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing. 61 54
19468337 2009
12
Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. 61 54
9063412 1997
13
Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. 54 61
8410508 1993
14
Frequency of pathogenic/likely pathogenic germline variants in cancer-related genes among children with acute leukemia in Saudi Arabia. 61
32359129 2020
15
Reticular dysgenesis caused by an intronic pathogenic variant in AK2. 61
32532877 2020
16
Hypomorphic variants in AK2 reveal the contribution of mitochondrial function to B-cell activation. 61
31862378 2019
17
A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress. 61
31727854 2019
18
Reticular Dysgenesis and Mitochondriopathy Induced by Adenylate Kinase 2 Deficiency with Atypical Presentation. 61
31673062 2019
19
Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India. 61
30778343 2019
20
[Rheumatological manifestations in primary immunodeficiency diseases]. 61
29860881 2018
21
Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency. 61
28938259 2018
22
Recent advances in understanding the pathogenesis and management of reticular dysgenesis. 61
29270983 2018
23
Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors. 61
29462620 2018
24
Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. 61
29021228 2017
25
Reticular dysgenesis: international survey on clinical presentation, transplantation, and outcome. 61
28331055 2017
26
Postpartum HLA-Matched Bone Marrow Donation from Mother to Neonate for Reticular Dysgenesis. 61
27913909 2017
27
AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages. 61
26270350 2015
28
Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress. 61
26150473 2015
29
Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. 61
24290292 2014
30
Adenylate kinase 2 deficiency limits survival and regulates various genes during larval stages of Drosophila melanogaster. 61
24705759 2014
31
Differential expression of adenine nucleotide converting enzymes in mitochondrial intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil differentiation. 61
24587121 2014
32
Skeletal abnormalities and successful hematopoietic stem cell transplantation in patients with reticular dysgenesis. 61
23763981 2013
33
First reported case of Omenn syndrome in a patient with reticular dysgenesis. 61
23014587 2013
34
Occurrence of myelodysplastic syndrome in 2 patients with reticular dysgenesis. 61
21458044 2011
35
Adenylate kinase 2 links mitochondrial energy metabolism to the induction of the unfolded protein response. 61
20876536 2011
36
Reticular dysgenesis in a preterm infant: a case report. 61
20863163 2010
37
Altered functional balance of Gfi-1 and Gfi-1b as an alternative cause of reticular dysgenesis? 61
19896777 2010
38
Early defects in human T-cell development severely affect distribution and maturation of thymic stromal cells: possible implications for the pathophysiology of Omenn syndrome. 61
19414857 2009
39
Successful haploidentical bone marrow transplantation in a patient with reticular dysgenesis: three-year follow-up. 61
17854878 2007
40
Successful cord blood transplantation in a premature and dysmature neonate of 1700 g with reticular dysgenesis. 61
17262063 2007
41
Fatal GvHD as a complication of liver transplantation for undetermined fulminant hepatic failure and associated aplastic anemia. 61
17058230 2006
42
Reticular dysgenesis: HLA non-identical bone marrow transplants in a series of 10 patients. 61
12040473 2002
43
Neutropenia associated with primary immunodeficiency syndromes. 61
11957193 2002
44
Umbilical cord blood transplantation in severe T-cell immunodeficiency disorders: two-year experience. 61
11202237 2000
45
Langerhans cell deficiency in reticular dysgenesis. 61
10891430 2000
46
[Reticular dysgenesis]. 61
11212742 2000
47
Association of reticular dysgenesis (thymic alymphoplasia and congenital aleukocytosis) with bilateral sensorineural deafness. 61
10484810 1999
48
Kinetics of T-cell development of umbilical cord blood transplantation in severe T-cell immunodeficiency disorders. 61
10329816 1999
49
[Reticular dysgenesis]. 61
9833481 1998
50
Recent advances in the pathogenesis and treatment of nonimmune neutropenias in the neonate. 61
9515201 1998

Variations for Reticular Dysgenesis

ClinVar genetic disease variations for Reticular Dysgenesis:

6 (show top 50) (show all 57) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AK2 NM_001625.4(AK2):c.523del (p.Arg175fs)deletion Pathogenic 446366 rs1553150995 1:33478979-33478979 1:33013378-33013378
2 AK2 NM_013411.4(AK2):c.636_*2601deldeletion Pathogenic 18250
3 AK2 NM_001625.4(AK2):c.118del (p.Cys40fs)deletion Pathogenic 18251 rs387906581 1:33490144-33490144 1:33024543-33024543
4 AK2 NM_001625.4(AK2):c.1A>G (p.Met1Val)SNV Pathogenic 18252 rs137853206 1:33502429-33502429 1:33036828-33036828
5 AK2 NM_001625.4(AK2):c.331-1G>ASNV Pathogenic 18253 1:33487063-33487063 1:33021462-33021462
6 AK2 NM_001625.4(AK2):c.453del (p.Tyr152fs)deletion Pathogenic 18254 rs1553151177 1:33480168-33480168 1:33014567-33014567
7 AK2 NM_001625.4(AK2):c.498+1G>ASNV Pathogenic 18255 1:33480122-33480122 1:33014521-33014521
8 AK2 NM_001625.4(AK2):c.494A>G (p.Asp165Gly)SNV Pathogenic 18256 rs267606643 1:33480127-33480127 1:33014526-33014526
9 AK2 NM_001625.4(AK2):c.556C>T (p.Arg186Cys)SNV Pathogenic 18258 rs267606645 1:33478946-33478946 1:33013345-33013345
10 AK2 AK2, EX2 DELdeletion Pathogenic 18259
11 AK2 NM_001625.4(AK2):c.697A>T (p.Lys233Ter)SNV Pathogenic 18261 rs267606646 1:33478805-33478805 1:33013204-33013204
12 AK2 NM_001625.4(AK2):c.25G>T (p.Glu9Ter)SNV Pathogenic 18262 rs267606647 1:33502405-33502405 1:33036804-33036804
13 AK2 NM_001625.4(AK2):c.307C>T (p.Arg103Trp)SNV Likely pathogenic 18260 rs267606648 1:33487217-33487217 1:33021616-33021616
14 AK2 NM_001625.4(AK2):c.524G>C (p.Arg175Pro)SNV Likely pathogenic 836023 1:33478978-33478978 1:33013377-33013377
15 AK2 NM_001625.4(AK2):c.386G>A (p.Ser129Asn)SNV Conflicting interpretations of pathogenicity 517906 rs61750965 1:33487007-33487007 1:33021406-33021406
16 AK2 NM_001625.4(AK2):c.330+5G>ASNV Conflicting interpretations of pathogenicity 661953 1:33487189-33487189 1:33021588-33021588
17 AK2 NM_001625.4(AK2):c.277A>G (p.Lys93Glu)SNV Uncertain significance 460287 rs767276648 1:33487247-33487247 1:33021646-33021646
18 AK2 NM_001625.4(AK2):c.433C>G (p.His145Asp)SNV Uncertain significance 839132 1:33480188-33480188 1:33014587-33014587
19 AK2 NM_001625.4(AK2):c.336_338del (p.Asp113del)deletion Uncertain significance 840748 1:33487055-33487057 1:33021454-33021456
20 AK2 NM_001625.4(AK2):c.229G>A (p.Glu77Lys)SNV Uncertain significance 850228 1:33487295-33487295 1:33021694-33021694
21 AK2 NM_001625.4(AK2):c.37C>T (p.Pro13Ser)SNV Uncertain significance 840047 1:33502393-33502393 1:33036792-33036792
22 AK2 NM_001625.4(AK2):c.199A>G (p.Thr67Ala)SNV Uncertain significance 529734 rs771799826 1:33490063-33490063 1:33024462-33024462
23 AK2 NC_000001.11:g.(?_33024422)_(33024587_?)deldeletion Uncertain significance 584028 1:33490023-33490188 1:33024422-33024587
24 AK2 NM_001625.4(AK2):c.631G>A (p.Asp211Asn)SNV Uncertain significance 578484 rs143825456 1:33478871-33478871 1:33013270-33013270
25 AK2 NM_001625.4(AK2):c.457C>G (p.His153Asp)SNV Uncertain significance 581432 rs1164598375 1:33480164-33480164 1:33014563-33014563
26 AK2 NM_001625.4(AK2):c.670C>G (p.Leu224Val)SNV Uncertain significance 567959 rs771562640 1:33478832-33478832 1:33013231-33013231
27 AK2 NM_001625.4(AK2):c.247A>G (p.Ile83Val)SNV Uncertain significance 577089 rs184683619 1:33487277-33487277 1:33021676-33021676
28 AK2 NM_001625.4(AK2):c.636_*791del (p.Ala212_Ter240delinsXaa)deletion Uncertain significance 657641 1:33477991-33478866 1:33012390-33013265
29 AK2 NM_001625.4(AK2):c.720A>G (p.Ter240=)SNV Uncertain significance 655501 1:33478782-33478782 1:33013181-33013181
30 AK2 NM_001625.4(AK2):c.655G>A (p.Val219Met)SNV Uncertain significance 664531 1:33478847-33478847 1:33013246-33013246
31 AK2 NM_001625.4(AK2):c.638C>A (p.Ser213Tyr)SNV Uncertain significance 644601 1:33478864-33478864 1:33013263-33013263
32 AK2 NM_001625.4(AK2):c.625G>T (p.Ala209Ser)SNV Uncertain significance 662703 1:33478877-33478877 1:33013276-33013276
33 AK2 NM_001625.4(AK2):c.488T>C (p.Met163Thr)SNV Uncertain significance 652357 1:33480133-33480133 1:33014532-33014532
34 AK2 NM_001625.4(AK2):c.471C>G (p.Asn157Lys)SNV Uncertain significance 654886 1:33480150-33480150 1:33014549-33014549
35 AK2 NM_001625.4(AK2):c.470A>G (p.Asn157Ser)SNV Uncertain significance 643382 1:33480151-33480151 1:33014550-33014550
36 AK2 NM_001625.4(AK2):c.462G>T (p.Glu154Asp)SNV Uncertain significance 659463 1:33480159-33480159 1:33014558-33014558
37 AK2 NM_001625.4(AK2):c.419C>T (p.Thr140Ile)SNV Uncertain significance 659858 1:33486974-33486974 1:33021373-33021373
38 AK2 NM_001625.4(AK2):c.376A>G (p.Ile126Val)SNV Uncertain significance 645331 1:33487017-33487017 1:33021416-33021416
39 AK2 NM_001625.4(AK2):c.307C>A (p.Arg103=)SNV Uncertain significance 665542 1:33487217-33487217 1:33021616-33021616
40 AK2 NM_001625.4(AK2):c.224G>T (p.Ser75Ile)SNV Uncertain significance 655866 1:33487300-33487300 1:33021699-33021699
41 AK2 NM_001625.4(AK2):c.94G>A (p.Ala32Thr)SNV Uncertain significance 660097 1:33490168-33490168 1:33024567-33024567
42 AK2 NM_001625.4(AK2):c.55G>A (p.Val19Met)SNV Uncertain significance 651057 1:33502375-33502375 1:33036774-33036774
43 AK2 NM_001625.4(AK2):c.460G>A (p.Glu154Lys)SNV Likely benign 702342 1:33480161-33480161 1:33014560-33014560
44 AK2 NM_001625.4(AK2):c.202A>G (p.Met68Val)SNV Likely benign 724864 1:33490060-33490060 1:33024459-33024459
45 AK2 NM_001625.4(AK2):c.117C>T (p.Phe39=)SNV Likely benign 732482 1:33490145-33490145 1:33024544-33024544
46 AK2 NM_001625.4(AK2):c.49C>G (p.Arg17Gly)SNV Likely benign 460288 rs138577419 1:33502381-33502381 1:33036780-33036780
47 AK2 NM_001625.4(AK2):c.504C>T (p.Thr168=)SNV Likely benign 529739 rs61750964 1:33478998-33478998 1:33013397-33013397
48 AK2 NM_001625.4(AK2):c.220-5deldeletion Likely benign 529736 rs752085550 1:33487309-33487309 1:33021708-33021708
49 AK2 NM_001625.4(AK2):c.630C>T (p.Ile210=)SNV Likely benign 529735 rs746330303 1:33478872-33478872 1:33013271-33013271
50 AK2 NM_001625.4(AK2):c.603C>T (p.Tyr201=)SNV Likely benign 529738 rs138151595 1:33478899-33478899 1:33013298-33013298

UniProtKB/Swiss-Prot genetic disease variations for Reticular Dysgenesis:

73
# Symbol AA change Variation ID SNP ID
1 AK2 p.Arg103Trp VAR_054630 rs267606648
2 AK2 p.Asp165Gly VAR_054631 rs267606643

Expression for Reticular Dysgenesis

Search GEO for disease gene expression data for Reticular Dysgenesis.

Pathways for Reticular Dysgenesis

Pathways related to Reticular Dysgenesis according to KEGG:

36
# Name Kegg Source Accession
1 Purine metabolism hsa00230

Pathways related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.44 PNP AK9 AK8 AK4 AK3 AK2
2
Show member pathways
11.84 PNP AK8 AK4 AK2 AK1 ADA
3 11.7 PNP AK4 AK2 AK1 ADA
4 11.27 JAK3 IL2RG GFI1
5 11.03 RAG1 JAK3 IL2RG
6 10.93 RAG1 JAK3 IL2RG DCLRE1C ADA
7 10.83 AK8 AK4 AK2 AK1
8 10.42 AK9 AK8 AK4 AK2 AK1
9 10.36 AK4 AK2

GO Terms for Reticular Dysgenesis

Cellular components related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nonhomologous end joining complex GO:0070419 8.96 NHEJ1 DCLRE1C
2 sperm flagellum GO:0036126 8.8 AK8 AK2 AK1

Biological processes related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 10 JAK3 AK9 AK8 AK4 AK3 AK2
2 B cell differentiation GO:0030183 9.78 RAG1 NHEJ1 JAK3 DCLRE1C
3 nucleobase-containing small molecule interconversion GO:0015949 9.72 AK9 AK8 AK4 AK2 AK1
4 nucleoside triphosphate biosynthetic process GO:0009142 9.71 AK8 AK4 AK3 AK1
5 ATP metabolic process GO:0046034 9.69 AK4 AK2 AK1
6 nucleoside diphosphate phosphorylation GO:0006165 9.67 AK8 AK4 AK1
7 AMP metabolic process GO:0046033 9.67 AK4 AK3 AK2 AK1
8 nucleotide metabolic process GO:0009117 9.63 AK9 ADA
9 T cell homeostasis GO:0043029 9.63 RAG1 JAK3
10 interleukin-7-mediated signaling pathway GO:0038111 9.62 JAK3 IL2RG
11 positive regulation of T cell differentiation GO:0045582 9.62 RAG1 ADA
12 regulation of T cell differentiation GO:0045580 9.61 RAG1 ADA
13 GTP metabolic process GO:0046039 9.61 AK4 AK3
14 negative regulation of thymocyte apoptotic process GO:0070244 9.61 RAG1 JAK3 ADA
15 purine-containing compound salvage GO:0043101 9.6 PNP ADA
16 interleukin-15-mediated signaling pathway GO:0035723 9.59 JAK3 IL2RG
17 interleukin-2-mediated signaling pathway GO:0038110 9.58 JAK3 IL2RG
18 V(D)J recombination GO:0033151 9.58 RAG1 DCLRE1C
19 positive regulation of alpha-beta T cell differentiation GO:0046638 9.57 PNP ADA
20 interleukin-9-mediated signaling pathway GO:0038113 9.56 JAK3 IL2RG
21 ADP biosynthetic process GO:0006172 9.56 AK4 AK3 AK2 AK1
22 interleukin-21-mediated signaling pathway GO:0038114 9.55 JAK3 IL2RG
23 nucleoside monophosphate phosphorylation GO:0046940 9.55 AK8 AK4 AK3 AK2 AK1
24 interleukin-4-mediated signaling pathway GO:0035771 9.54 JAK3 IL2RG
25 nucleoside diphosphate metabolic process GO:0009132 9.52 AK9 AK2
26 nucleobase-containing compound metabolic process GO:0006139 9.5 PNP AK9 AK8 AK4 AK3 AK2
27 purine nucleotide metabolic process GO:0006163 9.1 AK9 AK8 AK4 AK3 AK2 AK1

Molecular functions related to Reticular Dysgenesis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10.02 JAK3 AK9 AK8 AK4 AK3 AK2
2 transferase activity GO:0016740 10.02 RAG1 PNP JAK3 AK9 AK8 AK4
3 ATP binding GO:0005524 10 JAK3 AK9 AK8 AK4 AK3 AK2
4 kinase activity GO:0016301 9.87 JAK3 AK9 AK8 AK4 AK3 AK2
5 nucleoside diphosphate kinase activity GO:0004550 9.46 AK9 AK8 AK4 AK1
6 nucleoside monophosphate kinase activity GO:0050145 9.43 AK9 AK4
7 phosphotransferase activity, phosphate group as acceptor GO:0016776 9.43 AK4 AK3 AK2
8 nucleobase-containing compound kinase activity GO:0019205 9.43 AK9 AK8 AK4 AK3 AK2 AK1
9 nucleoside triphosphate adenylate kinase activity GO:0046899 9.4 AK4 AK3
10 adenylate kinase activity GO:0004017 9.1 AK9 AK8 AK4 AK3 AK2 AK1

Sources for Reticular Dysgenesis

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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