CDG2P
MCID: CNG504
MIFTS: 38

Congenital Disorder of Glycosylation, Type Iip (CDG2P)

Categories: Blood diseases, Bone diseases, Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Immune diseases, Liver diseases, Mental diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases, Smell/Taste diseases

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Iip

MalaCards integrated aliases for Congenital Disorder of Glycosylation, Type Iip:

Name: Congenital Disorder of Glycosylation, Type Iip 56 73 29 6
Cdg2p 56 12 58 73
Congenital Disorder of Glycosylation Type Iip 12 58 15
Cdg Iip 56 12 73
Carbohydrate Deficient Glycoprotein Syndrome Type Iip 12 58
Congenital Disorder of Glycosylation Type 2p 12 58
Cdg Syndrome Type Iip 12 58
Tmem199-Cdg 12 58
Cdg-Iip 58 73
Cdgiip 56 73
Congenital Disorder of Glycosylation 2p 73
Cdg Iip; Cdgiip 56
Cdgiidp 12

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in adolescence
mild disorder
some laboratory abnormalities may fluctuate or improve with time
four patients from 3 unrelated families have been reported (last curated february 2016)


HPO:

31
congenital disorder of glycosylation, type iip:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0070268
OMIM 56 616829
OMIM Phenotypic Series 56 PS212066
MeSH 43 D018981
Orphanet 58 ORPHA466703

Summaries for Congenital Disorder of Glycosylation, Type Iip

UniProtKB/Swiss-Prot : 73 Congenital disorder of glycosylation 2P: A form of congenital disorder of glycosylation, a genetically heterogeneous group of autosomal recessive, multisystem disorders caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG2P is characterized by mild metabolic dysfunction, primarily affecting the liver. Psychomotor development is normal.

MalaCards based summary : Congenital Disorder of Glycosylation, Type Iip, also known as cdg2p, is related to liver disease and myopathy, x-linked, with excessive autophagy. An important gene associated with Congenital Disorder of Glycosylation, Type Iip is TMEM199 (Transmembrane Protein 199), and among its related pathways/superpathways are Metabolism and Transport to the Golgi and subsequent modification. Affiliated tissues include liver, and related phenotypes are global developmental delay and generalized hypotonia

Disease Ontology : 12 A congenital disorder of glycosylation type II that has material basis in an autosomal recessive mutation of TMEM199 on chromosome 17q11.2.

OMIM : 56 Congenital disorder of glycosylation type IIp (CDG2P) is an autosomal recessive metabolic disorder characterized by mild liver dysfunction, which may be found incidentally during adolescence. Laboratory abnormalities include elevated liver enzymes and alkaline phosphatase, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016). For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066). (616829)

Related Diseases for Congenital Disorder of Glycosylation, Type Iip

Diseases in the Disorder of Multiple Glycosylation family:

Congenital Disorder of Glycosylation, Type Ia Congenital Disorder of Glycosylation, Type Iia
Congenital Disorder of Glycosylation, Type I/iix Congenital Disorder of Glycosylation, Type Iic
Congenital Disorder of Glycosylation, Type Iim Congenital Disorder of Glycosylation, Type Iy
Congenital Disorder of Glycosylation, Type Id Congenital Disorder of Glycosylation, Type Ib
Congenital Disorder of Glycosylation, Type Ic Congenital Disorder of Glycosylation, Type Iif
Congenital Disorder of Glycosylation, Type Iib Congenital Disorder of Glycosylation, Type Iid
Congenital Disorder of Glycosylation, Type Ig Congenital Disorder of Glycosylation, Type Ii
Congenital Disorder of Glycosylation, Type Ij Congenital Disorder of Glycosylation, Type Ih
Congenital Disorder of Glycosylation, Type Ik Congenital Disorder of Glycosylation, Type Il
Congenital Disorder of Glycosylation, Type Ie Congenital Disorder of Glycosylation, Type if
Congenital Disorder of Glycosylation, Type Im Congenital Disorder of Glycosylation, Type Iih
Congenital Disorder of Glycosylation, Type Iig Congenital Disorder of Glycosylation, Type in
Congenital Disorder of Glycosylation, Type Iq Congenital Disorder of Glycosylation, Type Iij
Congenital Disorder of Glycosylation, Type Iii Congenital Disorder of Glycosylation, Type Ip
Congenital Disorder of Glycosylation, Type Ir Congenital Disorder of Glycosylation, Type Iil
Congenital Disorder of Glycosylation, Type Iik Congenital Disorder of Glycosylation, Type It
Congenital Disorder of Glycosylation, Type Iu Congenital Disorder of Glycosylation, Type Iw
Congenital Disorder of Glycosylation, Type Ix Congenital Disorder of Glycosylation, Type Iin
Congenital Disorder of Glycosylation, Type Iio Congenital Disorder of Glycosylation, Type Iip
Congenital Disorder of Glycosylation, Type Iiq

Diseases related to Congenital Disorder of Glycosylation, Type Iip via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 liver disease 10.3
2 myopathy, x-linked, with excessive autophagy 10.1 TMEM199 CCDC115
3 congenital disorder of glycosylation, type iib 9.8 ALG2 ALG1
4 congenital disorder of glycosylation, type iin 9.8 TMEM199 CCDC115 ALG8
5 congenital disorder of glycosylation, type iia 9.8 ALG2 ALG1
6 congenital disorder of glycosylation, type ih 9.8 ALG8 ALG2
7 protein-losing enteropathy 9.7 ALG8 ALG6
8 esotropia 9.7 ALG9 ALG6
9 congenital disorders of n-linked glycosylation and multiple pathway 9.6 ALG6 ALG2 ALG1
10 polycystic liver disease 9.5 ALG9 ALG8
11 congenital disorder of glycosylation, type iig 9.4 ALG9 ALG8 ALG2
12 congenital disorder of glycosylation, type iih 9.4 ALG9 ALG8 ALG2
13 carbohydrate metabolic disorder 9.2 PGM1 ALG6 ALG2
14 congenital disorder of glycosylation, type iik 9.2 ALG8 ALG6 ALG2 ALG1
15 congenital disorder of glycosylation, type iim 9.2 ALG9 ALG6 ALG2 ALG1
16 congenital disorder of glycosylation, type iif 9.2 ALG8 ALG6 ALG2 ALG1
17 congenital disorder of glycosylation, type iii 9.1 ALG9 ALG8 ALG6 ALG2
18 congenital disorder of glycosylation, type ii 8.0 TMEM199 CCDC115 ATP6AP1 ALG9 ALG8 ALG6
19 congenital disorder of glycosylation, type iio 8.0 TMEM199 CCDC115 ATP6AP1 ALG9 ALG8 ALG6
20 congenital disorder of glycosylation, type in 7.4 TMEM199 PGM1 CCDC115 ATP6AP1 ALG9 ALG8

Graphical network of the top 20 diseases related to Congenital Disorder of Glycosylation, Type Iip:



Diseases related to Congenital Disorder of Glycosylation, Type Iip

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Iip

Human phenotypes related to Congenital Disorder of Glycosylation, Type Iip:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 generalized hypotonia 31 occasional (7.5%) HP:0001290
3 hepatic steatosis 31 very rare (1%) HP:0001397
4 elevated hepatic transaminase 31 very rare (1%) HP:0002910
5 increased ldl cholesterol concentration 31 very rare (1%) HP:0003141
6 hypercholesterolemia 31 very rare (1%) HP:0003124
7 elevated alkaline phosphatase 31 very rare (1%) HP:0003155
8 abnormal protein n-linked glycosylation 31 very rare (1%) HP:0012347
9 abnormal protein o-linked glycosylation 31 very rare (1%) HP:0012358
10 decreased liver function 31 HP:0001410
11 decreased serum ceruloplasmin 31 HP:0010837

Symptoms via clinical synopsis from OMIM:

56
Laboratory Abnormalities:
hypercholesterolemia
increased alkaline phosphatase
abnormal liver enzymes
type 2 pattern of transferrin, indicating n-glycosylation defect
abnormal apoc-iii glycosylation, indicating o-glycosylation defect
more
Muscle Soft Tissue:
hypotonia (1 patient)

Hematology:
decreased serum coagulation factors

Abdomen Liver:
liver dysfunction
liver steatosis
copper accumulation (in some patients)
liver fibrosis, mild

Neurologic Central Nervous System:
delayed psychomotor development (1 patient)

Clinical features from OMIM:

616829

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Iip

Search Clinical Trials , NIH Clinical Center for Congenital Disorder of Glycosylation, Type Iip

Genetic Tests for Congenital Disorder of Glycosylation, Type Iip

Genetic tests related to Congenital Disorder of Glycosylation, Type Iip:

# Genetic test Affiliating Genes
1 Congenital Disorder of Glycosylation, Type Iip 29 TMEM199

Anatomical Context for Congenital Disorder of Glycosylation, Type Iip

MalaCards organs/tissues related to Congenital Disorder of Glycosylation, Type Iip:

40
Liver

Publications for Congenital Disorder of Glycosylation, Type Iip

Articles related to Congenital Disorder of Glycosylation, Type Iip:

# Title Authors PMID Year
1
TMEM199 Deficiency Is a Disorder of Golgi Homeostasis Characterized by Elevated Aminotransferases, Alkaline Phosphatase, and Cholesterol and Abnormal Glycosylation. 56 6
26833330 2016
2
Long-standing mild hypertransaminasaemia caused by congenital disorder of glycosylation (CDG) type IIx. 56 6
19067230 2008
3
CCDC115-CDG: A new rare and misleading inherited cause of liver disease. 61
29759592 2018
4
Clinical glycomics for the diagnosis of congenital disorders of glycosylation. 61
29497882 2018
5
Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal glycosylation. 61
29321044 2018
6
Liver involvement in congenital disorders of glycosylation (CDG). A systematic review of the literature. 61
28108845 2017

Variations for Congenital Disorder of Glycosylation, Type Iip

ClinVar genetic disease variations for Congenital Disorder of Glycosylation, Type Iip:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TMEM199 NM_152464.3(TMEM199):c.92G>C (p.Arg31Pro)SNV Pathogenic 218964 rs782531869 17:26684785-26684785 17:28357762-28357762
2 TMEM199 NM_152464.3(TMEM199):c.20C>A (p.Ala7Glu)SNV Pathogenic 218965 rs369488804 17:26684713-26684713 17:28357690-28357690
3 TMEM199 NM_152464.3(TMEM199):c.40G>C (p.Ala14Pro)SNV Pathogenic 223000 rs869025586 17:26684733-26684733 17:28357710-28357710
4 TMEM199 NM_152464.3(TMEM199):c.376-1G>ASNV Pathogenic 223001 rs869025587 17:26687551-26687551 17:28360528-28360528

UniProtKB/Swiss-Prot genetic disease variations for Congenital Disorder of Glycosylation, Type Iip:

73
# Symbol AA change Variation ID SNP ID
1 TMEM199 p.Ala7Gly VAR_075770 rs369488804
2 TMEM199 p.Ala14Pro VAR_075771 rs869025586
3 TMEM199 p.Arg31Pro VAR_075772 rs782531869

Expression for Congenital Disorder of Glycosylation, Type Iip

Search GEO for disease gene expression data for Congenital Disorder of Glycosylation, Type Iip.

Pathways for Congenital Disorder of Glycosylation, Type Iip

Pathways related to Congenital Disorder of Glycosylation, Type Iip according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.45 PGM1 ATP6AP1 ALG9 ALG8 ALG6 ALG2
2
Show member pathways
12.44 ALG9 ALG8 ALG6 ALG2 ALG1
3
Show member pathways
11.64 ALG9 ALG8 ALG6 ALG2 ALG1
4
Show member pathways
11.03 ALG9 ALG8 ALG6 ALG2 ALG1

GO Terms for Congenital Disorder of Glycosylation, Type Iip

Cellular components related to Congenital Disorder of Glycosylation, Type Iip according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.5 TMEM199 CCDC115 ATP6AP1 ALG9 ALG8 ALG6
2 endoplasmic reticulum-Golgi intermediate compartment membrane GO:0033116 9.26 TMEM199 ATP6AP1
3 endoplasmic reticulum membrane GO:0005789 9.17 TMEM199 ATP6AP1 ALG9 ALG8 ALG6 ALG2
4 vacuolar proton-transporting V-type ATPase complex GO:0016471 9.16 TMEM199 CCDC115

Biological processes related to Congenital Disorder of Glycosylation, Type Iip according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein glycosylation GO:0006486 9.72 ALG9 ALG8 ALG6 ALG2 ALG1
2 cellular iron ion homeostasis GO:0006879 9.58 TMEM199 CCDC115 ATP6AP1
3 protein N-linked glycosylation GO:0006487 9.48 ALG8 ALG6
4 lysosomal lumen acidification GO:0007042 9.46 TMEM199 CCDC115
5 vacuolar proton-transporting V-type ATPase complex assembly GO:0070072 9.43 TMEM199 CCDC115
6 cellular response to increased oxygen levels GO:0036295 9.43 TMEM199 CCDC115 ATP6AP1
7 lysosomal protein catabolic process GO:1905146 9.37 TMEM199 CCDC115
8 oligosaccharide-lipid intermediate biosynthetic process GO:0006490 9.33 ALG8 ALG6 ALG2
9 mannosylation GO:0097502 9.26 ALG9 ALG8 ALG2 ALG1
10 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.02 ALG9 ALG8 ALG6 ALG2 ALG1

Molecular functions related to Congenital Disorder of Glycosylation, Type Iip according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.8 ALG9 ALG8 ALG6 ALG2 ALG1
2 transferase activity, transferring hexosyl groups GO:0016758 9.37 ALG8 ALG6
3 mannosyltransferase activity GO:0000030 9.32 ALG9 ALG1
4 dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity GO:0004583 9.26 ALG8 ALG6
5 alpha-1,3-mannosyltransferase activity GO:0000033 9.16 ALG8 ALG2
6 transferase activity, transferring glycosyl groups GO:0016757 9.02 ALG9 ALG8 ALG6 ALG2 ALG1
7 dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity GO:0042281 8.96 ALG8 ALG6

Sources for Congenital Disorder of Glycosylation, Type Iip

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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