CDG2K
MCID: CNG383
MIFTS: 44

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, Smell/Taste 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 56 13 71
Congenital Disorder of Glycosylation Type Iik 12 58 73 15
Congenital Disorder of Glycosylation Type 2k 12 58 29 6
Cdg2k 56 12 58 73
Cdg Iik 56 12 73
Carbohydrate Deficient Glycoprotein Syndrome Type Iik 12 58
Cdg Syndrome Type Iik 12 58
Cdg-Iik 58 73
Cdgiik 56 73
Glycosylation, Congenital Disorder of, Type Iik 39
Congenital Disorder of Glycosylation 2k 73
Cdg Iik; Cdgiik 56
Tmem165-Cdg 58
Cdgiidk 12

Characteristics:

Orphanet epidemiological data:

58
tmem165-cdg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

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


HPO:

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


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare bone diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Congenital Disorder of Glycosylation, Type Iik

UniProtKB/Swiss-Prot : 73 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 ih, 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 Metabolism and Metabolism of proteins. Affiliated tissues include eye, liver and bone, and related phenotypes are malar flattening and midface retrusion

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 : 56 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 Iir 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 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 Congenital Disorder of Glycosylation, Type Iit

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

(show all 27)
# Related Disease Score Top Affiliating Genes
1 congenital disorders of n-linked glycosylation and multiple pathway 30.0 ALG6 ALG2 ALG11
2 congenital disorder of glycosylation, type ih 10.0 ALG8 ALG2
3 congenital disorder of glycosylation, type iin 10.0 PMM2 PGM1
4 galactosemia i 10.0 PMM2 PGM1 ALG2
5 congenital disorder of glycosylation, type iia 10.0 SLC35C1 PMM2 ALG2
6 kahrizi syndrome 9.9 DOLK ALG2
7 congenital disorder of glycosylation, type iim 9.8 PGM1 MAN1B1 ALG2
8 congenital disorder of glycosylation, type iij 9.8 COG1 ALG2
9 congenital disorder of deglycosylation 9.8 SLC35C1 PMM2 ALG11
10 congenital disorder of glycosylation, type ic 9.8 PMM2 ALG6
11 fructose intolerance, hereditary 9.8 SLC35C1 MAN1B1 ALG2
12 congenital disorder of glycosylation, type iio 9.7 MAN1B1 ALG8 ALG2
13 congenital muscular dystrophy-dystroglycanopathy type a2 9.7 ALG6 ALG2
14 congenital disorder of glycosylation, type im 9.7 DOLK ALG6
15 congenital disorder of glycosylation, type iib 9.6 SLC35C1 PMM2 MAN1B1 ALG2
16 walker-warburg syndrome 9.6 PMM2 DOLK ALG2 ALG11
17 congenital disorder of glycosylation, type iid 9.5 SLC35C1 PMM2 COG1 ALG2
18 congenital disorder of glycosylation, type iip 9.5 PGM1 MAN1B1 ALG8 ALG2
19 congenital disorder of glycosylation, type iih 9.5 PMM2 COG1 ALG8 ALG2
20 protein-losing enteropathy 9.5 PMM2 ALG8 ALG6
21 granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type ii 9.4 PMM2 ALG6
22 congenital disorder of glycosylation, type iig 9.3 COG1 ALG8 ALG2 ALG11
23 congenital disorder of glycosylation, type ie 9.0 PMM2 DOLK ALG6 ALG2 ALG11
24 congenital disorder of glycosylation, type iii 8.9 PMM2 COG1 ALG8 ALG6 ALG2
25 congenital disorder of glycosylation, type iif 8.8 SLC35C1 PMM2 MAN1B1 COG1 ALG8 ALG2
26 congenital disorder of glycosylation, type in 6.8 TMEM165 SLC35C1 PMM2 PGM1 MAN1B1 DOLK
27 immunodeficiency 47 6.8 TMEM165 SLC35C1 PMM2 PGM1 MAN1B1 DOLK

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:

31 (show all 24)
# Description HPO Frequency HPO Source Accession
1 malar flattening 31 occasional (7.5%) HP:0000272
2 midface retrusion 31 occasional (7.5%) HP:0011800
3 unexplained fevers 31 occasional (7.5%) HP:0001955
4 amelogenesis imperfecta 31 occasional (7.5%) HP:0000705
5 seizure 31 occasional (7.5%) HP:0001250
6 global developmental delay 31 HP:0001263
7 hepatomegaly 31 HP:0002240
8 short stature 31 HP:0004322
9 muscle weakness 31 HP:0001324
10 failure to thrive 31 HP:0001508
11 elevated serum creatine kinase 31 HP:0003236
12 epiphyseal dysplasia 31 HP:0002656
13 osteoporosis 31 HP:0000939
14 low-set ears 31 HP:0000369
15 elevated hepatic transaminase 31 HP:0002910
16 thrombocytopenia 31 HP:0001873
17 joint laxity 31 HP:0001388
18 kyphoscoliosis 31 HP:0002751
19 posteriorly rotated ears 31 HP:0000358
20 postnatal microcephaly 31 HP:0005484
21 abnormality of the cerebral white matter 31 HP:0002500
22 generalized hypotonia 31 HP:0001290
23 metaphyseal dysplasia 31 HP:0100255
24 diaphyseal dysplasia 31 HP:0100252

Symptoms via clinical synopsis from OMIM:

56
Abdomen Liver:
hepatomegaly

Muscle Soft Tissue:
muscle weakness
hypotonia
abnormal fat distribution

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

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

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)

Growth Weight:
short stature

Growth Other:
failure to thrive
growth retardation

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:

40
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. 56 6
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. 56 61
23430531 2013
3
Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview 6
20301507 2005
4
Fetal bovine serum impacts the observed N-glycosylation defects in TMEM165 KO HEK cells. 61
31415112 2020
5
Dissection of TMEM165 function in Golgi glycosylation and its Mn2+ sensitivity. 61
31351090 2019
6
Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases. 61
31319631 2019
7
CDG Therapies: From Bench to Bedside. 61
29702557 2018
8
Manganese-induced turnover of TMEM165. 61
28270545 2017
9
Galactose Supplementation in Patients With TMEM165-CDG Rescues the Glycosylation Defects. 61
28323990 2017
10
TMEM165 Deficiency: Postnatal Changes in Glycosylation. 61
26238249 2016
11
Abnormal cartilage development and altered N-glycosylation in Tmem165-deficient zebrafish mirrors the phenotypes associated with TMEM165-CDG. 61
25609749 2015
12
Antisense-mediated therapeutic pseudoexon skipping in TMEM165-CDG. 61
24720419 2015
13
Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation. 61
23928051 2013

Variations for Congenital Disorder of Glycosylation, Type Iik

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

6 (show all 20) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TMEM165 NM_018475.5(TMEM165):c.792+182G>ASNV Pathogenic 35518 rs793888506 4:56284334-56284334 4:55418167-55418167
2 TMEM165 NM_018475.5(TMEM165):c.377G>A (p.Arg126His)SNV Pathogenic 35519 rs387907221 4:56277950-56277950 4:55411783-55411783
3 TMEM165 NM_018475.5(TMEM165):c.910G>A (p.Gly304Arg)SNV Pathogenic 35521 rs886037631 4:56291554-56291554 4:55425387-55425387
4 TMEM165 NM_018475.5(TMEM165):c.433+15C>ASNV Conflicting interpretations of pathogenicity 349065 rs370138167 4:56278021-56278021 4:55411854-55411854
5 TMEM165 NM_018475.5(TMEM165):c.294C>T (p.Val98=)SNV Conflicting interpretations of pathogenicity 380191 rs11542641 4:56277867-56277867 4:55411700-55411700
6 TMEM165 NM_018475.5(TMEM165):c.602A>G (p.Asp201Gly)SNV Uncertain significance 349067 rs372893311 4:56283407-56283407 4:55417240-55417240
7 TMEM165 NM_018475.5(TMEM165):c.*236A>GSNV Uncertain significance 349070 rs548381906 4:56291855-56291855 4:55425688-55425688
8 TMEM165 NM_018475.5(TMEM165):c.506T>C (p.Ile169Thr)SNV Uncertain significance 349066 rs150519910 4:56283311-56283311 4:55417144-55417144
9 TMEM165 NM_018475.5(TMEM165):c.376C>T (p.Arg126Cys)SNV Uncertain significance 35520 rs387907222 4:56277949-56277949 4:55411782-55411782
10 TMEM165 NM_018475.5(TMEM165):c.892A>G (p.Arg298Gly)SNV Uncertain significance 473210 rs1310344895 4:56290804-56290804 4:55424637-55424637
11 TMEM165 NM_018475.5(TMEM165):c.351A>G (p.Ala117=)SNV Uncertain significance 905839 4:56277924-56277924 4:55411757-55411757
12 TMEM165 NM_018475.5(TMEM165):c.617G>A (p.Arg206Gln)SNV Uncertain significance 906352 4:56283977-56283977 4:55417810-55417810
13 TMEM165 NM_018475.5(TMEM165):c.*121T>ASNV Uncertain significance 906353 4:56291740-56291740 4:55425573-55425573
14 TMEM165 NM_018475.5(TMEM165):c.*436T>CSNV Uncertain significance 907357 4:56292055-56292055 4:55425888-55425888
15 TMEM165 NM_018475.5(TMEM165):c.*627A>CSNV Uncertain significance 904023 4:56292246-56292246 4:55426079-55426079
16 TMEM165 NM_018475.5(TMEM165):c.*643A>GSNV Uncertain significance 904024 4:56292262-56292262 4:55426095-55426095
17 TMEM165 NM_018475.5(TMEM165):c.921T>G (p.Val307=)SNV Benign 702600 4:56291565-56291565 4:55425398-55425398
18 TMEM165 NM_018475.5(TMEM165):c.-147T>CSNV Benign 907295 4:56262210-56262210 4:55396043-55396043
19 TMEM165 NM_018475.5(TMEM165):c.*505T>ASNV Benign 349074 rs73151843 4:56292124-56292124 4:55425957-55425957
20 TMEM165 NM_018475.5(TMEM165):c.*2_*3deldeletion Benign 349069 rs35154686 4:56291621-56291622 4:55425454-55425455

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

73
# 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

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.63 PMM2 PGM1 MAN1B1 DOLK ATP6V0A2 ALG8
2
Show member pathways
13.34 SLC35C1 PMM2 MAN1B1 DOLK COG1 ALG8
3
Show member pathways
12.7 SLC35C1 PMM2 MAN1B1 DOLK COG1 ALG8
4
Show member pathways
11.46 SLC35C1 PMM2 DOLK ALG8 ALG6 ALG2
5
Show member pathways
11.44 MAN1B1 DOLK ALG8 ALG6 ALG2 ALG11

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 membrane GO:0016020 9.96 TMEM165 SLC35C1 MAN1B1 DOLK COG1 ATP6V0A2
2 integral component of membrane GO:0016021 9.61 TMEM165 SLC35C1 MAN1B1 DOLK ATP6V0A2 ALG8
3 endoplasmic reticulum GO:0005783 9.55 MAN1B1 DOLK ALG8 ALG6 ALG11
4 endoplasmic reticulum membrane GO:0005789 9.1 MAN1B1 DOLK ALG8 ALG6 ALG2 ALG11

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 glycosylation GO:0006486 9.55 PMM2 MAN1B1 ALG8 ALG6 ALG2
2 mannosylation GO:0097502 9.5 ALG8 ALG2 ALG11
3 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.43 ALG8 ALG6 ALG2
4 protein N-linked glycosylation GO:0006487 9.35 TMEM165 PMM2 ALG8 ALG6 ALG11
5 oligosaccharide-lipid intermediate biosynthetic process GO:0006490 8.92 ALG8 ALG6 ALG2 ALG11

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

# Name GO ID Score Top Affiliating Genes
1 transferase activity, transferring glycosyl groups GO:0016757 9.56 ALG8 ALG6 ALG2 ALG11
2 transferase activity, transferring hexosyl groups GO:0016758 9.32 ALG8 ALG6
3 dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity GO:0004583 9.16 ALG8 ALG6
4 alpha-1,3-mannosyltransferase activity GO:0000033 8.96 ALG8 ALG2
5 dolichyl pyrophosphate Man9GlcNAc2 alpha-1,3-glucosyltransferase activity GO:0042281 8.62 ALG8 ALG6

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 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
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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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