CDG2K
MCID: CNG383
MIFTS: 37

Congenital Disorder of Glycosylation, Type Iik (CDG2K)

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

Aliases & Classifications for Congenital Disorder of Glycosylation, Type Iik

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

Name: Congenital Disorder of Glycosylation, Type Iik 57 13 72
Congenital Disorder of Glycosylation Type Iik 12 59 74 15
Congenital Disorder of Glycosylation Type 2k 12 59 29 6
Cdg2k 57 12 59 74
Cdg Iik 57 12 74
Carbohydrate Deficient Glycoprotein Syndrome Type Iik 12 59
Cdg Syndrome Type Iik 12 59
Cdg-Iik 59 74
Cdgiik 57 74
Glycosylation, Congenital Disorder of, Type Iik 40
Congenital Disorder of Glycosylation 2k 74
Cdg Iik; Cdgiik 57
Tmem165-Cdg 59
Cdgiidk 12

Characteristics:

Orphanet epidemiological data:

59
tmem165-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
onset in early childhood
five patients have been reported (last curated december 2014)


HPO:

32
congenital disorder of glycosylation, type iik:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070263
MeSH 44 D018981
ICD10 via Orphanet 34 E77.8
Orphanet 59 ORPHA314667
UMLS 72 C3553571

Summaries for Congenital Disorder of Glycosylation, Type Iik

UniProtKB/Swiss-Prot : 74 Congenital disorder of glycosylation 2K: An autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Congenital disorders of glycosylation are caused by a defect in glycoprotein biosynthesis and characterized by under- glycosylated serum glycoproteins and a wide variety of clinical features. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.

MalaCards based summary : Congenital Disorder of Glycosylation, Type Iik, also known as congenital disorder of glycosylation type iik, is related to congenital disorders of n-linked glycosylation and multiple pathway and congenital disorder of glycosylation, type iio, and has symptoms including muscle weakness An important gene associated with Congenital Disorder of Glycosylation, Type Iik is TMEM165 (Transmembrane Protein 165), and among its related pathways/superpathways are Synthesis of substrates in N-glycan biosythesis and Amino sugar and nucleotide sugar metabolism. Affiliated tissues include eye, liver and bone, and related phenotypes are malar flattening and seizures

Disease Ontology : 12 A congenital disorder of glycosylation type II that has material basis in an autosomal recessive mutation of TMEM165 on chromosome 4q12.

OMIM : 57 CDG2K is an autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern (summary by Foulquier et al., 2012). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). (614727)

Related Diseases for Congenital Disorder of Glycosylation, Type Iik

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 Iik via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 congenital disorders of n-linked glycosylation and multiple pathway 10.5
2 congenital disorder of glycosylation, type iio 9.7 PGM1 ATP6V0A2
3 epileptic encephalopathy, early infantile, 36 9.7 SLC35C1 PMM2 DOLK
4 congenital disorder of glycosylation, type iip 9.7 PGM1 ATP6V0A2
5 congenital disorder of glycosylation, type iif 9.6 PMM2 PGM1
6 congenital disorder of glycosylation, type iii 9.5 PMM2 APOC3
7 congenital disorder of glycosylation, type iim 8.6 PMM2 PGM1 ATP6V0A2 APOC3
8 congenital disorder of glycosylation, type ii 8.0 TMEM165 SLC35C1 PMM2 GOLPH3 ATP6V0A2 APOC3
9 congenital disorder of glycosylation, type in 7.6 TMEM165 SLC35C1 PMM2 PGM1 DOLK ATP6V0A2

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



Diseases related to Congenital Disorder of Glycosylation, Type Iik

Symptoms & Phenotypes for Congenital Disorder of Glycosylation, Type Iik

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

32 (show all 24)
# Description HPO Frequency HPO Source Accession
1 malar flattening 32 occasional (7.5%) HP:0000272
2 seizures 32 occasional (7.5%) HP:0001250
3 midface retrusion 32 occasional (7.5%) HP:0011800
4 amelogenesis imperfecta 32 occasional (7.5%) HP:0000705
5 unexplained fevers 32 occasional (7.5%) HP:0001955
6 low-set ears 32 HP:0000369
7 muscle weakness 32 HP:0001324
8 failure to thrive 32 HP:0001508
9 global developmental delay 32 HP:0001263
10 hepatomegaly 32 HP:0002240
11 short stature 32 HP:0004322
12 osteoporosis 32 HP:0000939
13 generalized hypotonia 32 HP:0001290
14 epiphyseal dysplasia 32 HP:0002656
15 elevated hepatic transaminase 32 HP:0002910
16 thrombocytopenia 32 HP:0001873
17 joint laxity 32 HP:0001388
18 kyphoscoliosis 32 HP:0002751
19 posteriorly rotated ears 32 HP:0000358
20 postnatal microcephaly 32 HP:0005484
21 metaphyseal dysplasia 32 HP:0100255
22 abnormality of the cerebral white matter 32 HP:0002500
23 diaphyseal dysplasia 32 HP:0100252
24 elevated serum creatine kinase 32 HP:0003236

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
posteriorly rotated ears

Growth Other:
failure to thrive
growth retardation

Growth Weight:
short stature

Skeletal Limbs:
epiphyseal dysplasia
metaphyseal dysplasia
diaphyseal dysplasia
hypoplasia of the femoral heads (1 patient)

Skeletal Spine:
kyphoscoliosis
dysplastic vertebrae

Laboratory Abnormalities:
increased serum creatine kinase
abnormal liver enzymes
n-glycosylation defect
decreased levels of certain coagulation factors

Head And Neck Face:
dysmorphic features
midface hypoplasia (1 patient)

Head And Neck Eyes:
eye abnormalities

Chest Ribs Sternum Clavicles And Scapulae:
dysplastic ribs (1 patient)

Skeletal Feet:
dysplastic fourth metatarsals (1 patient)

Muscle Soft Tissue:
muscle weakness
hypotonia
abnormal fat distribution

Abdomen Liver:
hepatomegaly

Skeletal:
osteoporosis
joint laxity

Hematology:
thrombocytopenia

Neurologic Central Nervous System:
delayed psychomotor development
white matter abnormalities
seizures (1 patient)

Abdomen Gastrointestinal:
feeding problems in infancy

Head And Neck Head:
microcephaly, acquired

Head And Neck Teeth:
amelogenesis imperfecta (1 patient)

Skeletal Hands:
dysplastic fourth metacarpals (1 patient)

Metabolic Features:
unexplained fevers (2 patients)

Clinical features from OMIM:

614727

UMLS symptoms related to Congenital Disorder of Glycosylation, Type Iik:


muscle weakness

Drugs & Therapeutics for Congenital Disorder of Glycosylation, Type Iik

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

Genetic Tests for Congenital Disorder of Glycosylation, Type Iik

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

# Genetic test Affiliating Genes
1 Congenital Disorder of Glycosylation Type 2k 29 TMEM165

Anatomical Context for Congenital Disorder of Glycosylation, Type Iik

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

41
Eye, Liver, Bone

Publications for Congenital Disorder of Glycosylation, Type Iik

Articles related to Congenital Disorder of Glycosylation, Type Iik:

(show all 13)
# Title Authors PMID Year
1
TMEM165 deficiency causes a congenital disorder of glycosylation. 8 71
22683087 2012
2
Bone Dysplasia as a Key Feature in Three Patients with a Novel Congenital Disorder of Glycosylation (CDG) Type II Due to a Deep Intronic Splice Mutation in TMEM165. 38 8
23430531 2013
3
Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview 71
20301507 2005
4
Fetal Bovine Serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. 38
31415112 2019
5
Dissection of TMEM165 function in Golgi glycosylation and its Mn2+ sensitivity. 38
31351090 2019
6
Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases. 38
31319631 2019
7
CDG Therapies: From Bench to Bedside. 38
29702557 2018
8
Manganese-induced turnover of TMEM165. 38
28270545 2017
9
Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects. 38
28323990 2017
10
TMEM165 Deficiency: Postnatal Changes in Glycosylation. 38
26238249 2016
11
Abnormal cartilage development and altered N-glycosylation in Tmem165-deficient zebrafish mirrors the phenotypes associated with TMEM165-CDG. 38
25609749 2015
12
Antisense-mediated therapeutic pseudoexon skipping in TMEM165-CDG. 38
24720419 2015
13
Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation. 38
23928051 2013

Variations for Congenital Disorder of Glycosylation, Type Iik

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TMEM165 NM_018475.5(TMEM165): c.792+182G> A single nucleotide variant Pathogenic rs793888506 4:56284334-56284334 4:55418167-55418167
2 TMEM165 NM_018475.5(TMEM165): c.377G> A (p.Arg126His) single nucleotide variant Pathogenic rs387907221 4:56277950-56277950 4:55411783-55411783
3 TMEM165 NM_018475.5(TMEM165): c.910G> A (p.Gly304Arg) single nucleotide variant Pathogenic rs886037631 4:56291554-56291554 4:55425387-55425387
4 TMEM165 NM_018475.5(TMEM165): c.892A> G (p.Arg298Gly) single nucleotide variant Uncertain significance rs1310344895 4:56290804-56290804 4:55424637-55424637
5 TMEM165 NM_018475.5(TMEM165): c.376C> T (p.Arg126Cys) single nucleotide variant Uncertain significance rs387907222 4:56277949-56277949 4:55411782-55411782

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

74
# Symbol AA change Variation ID SNP ID
1 TMEM165 p.Arg126Cys VAR_068446 rs387907222
2 TMEM165 p.Arg126His VAR_068447 rs387907221
3 TMEM165 p.Gly304Arg VAR_068448 rs886037631

Expression for Congenital Disorder of Glycosylation, Type Iik

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

Pathways for Congenital Disorder of Glycosylation, Type Iik

GO Terms for Congenital Disorder of Glycosylation, Type Iik

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

# Name GO ID Score Top Affiliating Genes
1 endosome GO:0005768 8.8 TMEM165 GOLPH3 ATP6V0A2

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

# Name GO ID Score Top Affiliating Genes
1 protein N-linked glycosylation GO:0006487 8.62 TMEM165 PMM2

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

# Name GO ID Score Top Affiliating Genes
1 isomerase activity GO:0016853 8.62 PMM2 PGM1

Sources for Congenital Disorder of Glycosylation, Type Iik

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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