MRD57
MCID: MNT334
MIFTS: 26

Mental Retardation, Autosomal Dominant 57 (MRD57)

Categories: Ear diseases, Eye diseases, Fetal diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mental Retardation, Autosomal Dominant 57

MalaCards integrated aliases for Mental Retardation, Autosomal Dominant 57:

Name: Mental Retardation, Autosomal Dominant 57 57 72 29 6
Mrd57 57 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy
highly variable phenotype
de novo mutation (in most patients) percentages noted above are estimates from reijnders et al. (2018)


HPO:

31
mental retardation, autosomal dominant 57:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset


Classifications:



Summaries for Mental Retardation, Autosomal Dominant 57

UniProtKB/Swiss-Prot : 72 Mental retardation, autosomal dominant 57: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD57 is characterized by delayed psychomotor development apparent in infancy or early childhood, and a variety of behavioral abnormalities. Affected individuals may have severe gastro-intestinal problems, and facial dysmorphism. MRD57 inheritance is autosomal dominant.

MalaCards based summary : Mental Retardation, Autosomal Dominant 57, is also known as mrd57. An important gene associated with Mental Retardation, Autosomal Dominant 57 is TLK2 (Tousled Like Kinase 2). Affiliated tissues include eye, and related phenotypes are intellectual disability and scoliosis

OMIM® : 57 MRD57 is an autosomal dominant neurodevelopmental disorder with a highly variable phenotype. Most affected individuals have delayed psychomotor development apparent in infancy or early childhood, language delay, and behavioral abnormalities. Additional features may include hypotonia, feeding problems, gastrointestinal issues, and dysmorphic facial features (summary by Reijnders et al., 2018). (618050) (Updated 20-May-2021)

Related Diseases for Mental Retardation, Autosomal Dominant 57

Diseases in the Mental Retardation, Autosomal Dominant 7 family:

Mental Retardation, Autosomal Recessive 2 Mental Retardation, Autosomal Recessive 5
Mental Retardation, Autosomal Dominant 22 Mental Retardation, Autosomal Dominant 20
Mental Retardation, Autosomal Recessive 14 Mental Retardation, Autosomal Recessive 16
Mental Retardation, Autosomal Recessive 18 Mental Retardation, Autosomal Dominant 10
Mental Retardation, Autosomal Dominant 11 Mental Retardation, Autosomal Recessive 31
Mental Retardation, Autosomal Recessive 29 Mental Retardation, Autosomal Recessive 27
Mental Retardation, Autosomal Recessive 33 Mental Retardation, Autosomal Recessive 30
Mental Retardation, Autosomal Recessive 19 Mental Retardation, Autosomal Recessive 23
Mental Retardation, Autosomal Recessive 24 Mental Retardation, Autosomal Recessive 25
Mental Retardation, Autosomal Recessive 28 Mental Retardation, Autosomal Dominant 13
Mental Retardation, Autosomal Recessive 35 Mental Retardation, Autosomal Recessive 36
Mental Retardation, Autosomal Recessive 37 Mental Retardation, Autosomal Dominant 21
Mental Retardation, Autosomal Recessive 38 Mental Retardation, Autosomal Recessive 39
Mental Retardation, Autosomal Recessive 40 Mental Retardation, Autosomal Recessive 41
Mental Retardation, Autosomal Dominant 23 Mental Retardation, Autosomal Recessive 42
Mental Retardation, Autosomal Recessive 43 Mental Retardation, Autosomal Dominant 26
Mental Retardation, Autosomal Recessive 44 Mental Retardation, Autosomal Recessive 45
Mental Retardation, Autosomal Dominant 29 Mental Retardation, Autosomal Dominant 30
Mental Retardation, Autosomal Recessive 46 Mental Retardation, Autosomal Dominant 31
Mental Retardation, Autosomal Recessive 47 Mental Retardation, Autosomal Recessive 48
Mental Retardation, Autosomal Dominant 33 Mental Retardation, Autosomal Dominant 34
Mental Retardation, Autosomal Dominant 35 Mental Retardation, Autosomal Dominant 36
Mental Retardation, Autosomal Dominant 38 Mental Retardation, Autosomal Recessive 50
Mental Retardation, Autosomal Dominant 39 Mental Retardation, Autosomal Dominant 40
Mental Retardation, Autosomal Recessive 51 Mental Retardation, Autosomal Recessive 52
Mental Retardation, Autosomal Recessive 53 Mental Retardation, Autosomal Dominant 41
Mental Retardation, Autosomal Dominant 42 Mental Retardation, Autosomal Dominant 43
Mental Retardation, Autosomal Recessive 54 Mental Retardation, Autosomal Recessive 56
Mental Retardation, Autosomal Recessive 57 Mental Retardation, Autosomal Recessive 58
Mental Retardation, Autosomal Recessive 59 Mental Retardation, Autosomal Recessive 60
Mental Retardation, Autosomal Dominant 45 Mental Retardation, Autosomal Dominant 46
Mental Retardation, Autosomal Dominant 47 Mental Retardation, Autosomal Dominant 48
Mental Retardation, Autosomal Recessive 61 Mental Retardation, Autosomal Dominant 50
Mental Retardation, Autosomal Dominant 51 Mental Retardation, Autosomal Dominant 52
Mental Retardation, Autosomal Dominant 53 Mental Retardation, Autosomal Dominant 54
Mental Retardation, Autosomal Dominant 56 Mental Retardation, Autosomal Dominant 57
Mental Retardation, Autosomal Recessive 63 Mental Retardation, Autosomal Recessive 64
Mental Retardation, Autosomal Dominant 58 Mental Retardation, Autosomal Recessive 65
Mental Retardation, Autosomal Recessive 66 Autosomal Dominant Mental Retardation 55

Symptoms & Phenotypes for Mental Retardation, Autosomal Dominant 57

Human phenotypes related to Mental Retardation, Autosomal Dominant 57:

31 (show all 36)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 HP:0001249
2 scoliosis 31 HP:0002650
3 ptosis 31 HP:0000508
4 constipation 31 HP:0002019
5 kyphosis 31 HP:0002808
6 high palate 31 HP:0000218
7 global developmental delay 31 HP:0001263
8 delayed speech and language development 31 HP:0000750
9 pes planus 31 HP:0001763
10 microcephaly 31 HP:0000252
11 short stature 31 HP:0004322
12 strabismus 31 HP:0000486
13 attention deficit hyperactivity disorder 31 HP:0007018
14 anxiety 31 HP:0000739
15 epicanthus 31 HP:0000286
16 toe walking 31 HP:0040083
17 motor delay 31 HP:0001270
18 joint hypermobility 31 HP:0001382
19 narrow mouth 31 HP:0000160
20 upslanted palpebral fissure 31 HP:0000582
21 obsessive-compulsive behavior 31 HP:0000722
22 long face 31 HP:0000276
23 otitis media 31 HP:0000388
24 prominent nasal bridge 31 HP:0000426
25 telecanthus 31 HP:0000506
26 blepharophimosis 31 HP:0000581
27 craniosynostosis 31 HP:0001363
28 feeding difficulties 31 HP:0011968
29 posteriorly rotated ears 31 HP:0000358
30 autistic behavior 31 HP:0000729
31 diarrhea 31 HP:0002014
32 broad nasal tip 31 HP:0000455
33 generalized hypotonia 31 HP:0001290
34 hypertrichosis 31 HP:0000998
35 tall chin 31 HP:0400000
36 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Skeletal Spine:
scoliosis
kyphosis

Abdomen Gastrointestinal:
constipation
feeding difficulties
diarrhea

Neurologic Central Nervous System:
global developmental delay
toe walking
motor delay
language delay
intellectual disability, mild to moderate
more
Neurologic Behavioral Psychiatric Manifestations:
anxiety
autism spectrum disorder
obsessive-compulsive disorder
tantrums
attention deficit-hyperactivity disorder (adhd)

Head And Neck Face:
long face
asymmetric face
pointed tall chin

Head And Neck Nose:
prominent nasal bridge
broad nasal tip

Muscle Soft Tissue:
hypotonia

Growth Height:
short stature (37%)

Skeletal Skull:
craniosynostosis (11%)

Head And Neck Eyes:
ptosis
strabismus
telecanthus
blepharophimosis
epicanthal folds
more
Head And Neck Mouth:
high palate
narrow mouth
thin vermilion of the upper lip

Skeletal Feet:
pes planus

Skeletal:
joint hypermobility

Head And Neck Ears:
otitis media
posteriorly rotated ears

Skin Nails Hair Hair:
hypertrichosis

Skeletal Hands:
finger contractures

Head And Neck Head:
microcephaly (24%)

Clinical features from OMIM®:

618050 (Updated 20-May-2021)

Drugs & Therapeutics for Mental Retardation, Autosomal Dominant 57

Search Clinical Trials , NIH Clinical Center for Mental Retardation, Autosomal Dominant 57

Genetic Tests for Mental Retardation, Autosomal Dominant 57

Genetic tests related to Mental Retardation, Autosomal Dominant 57:

# Genetic test Affiliating Genes
1 Mental Retardation, Autosomal Dominant 57 29 TLK2

Anatomical Context for Mental Retardation, Autosomal Dominant 57

MalaCards organs/tissues related to Mental Retardation, Autosomal Dominant 57:

40
Eye

Publications for Mental Retardation, Autosomal Dominant 57

Articles related to Mental Retardation, Autosomal Dominant 57:

# Title Authors PMID Year
1
De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder. 6 57
29861108 2018
2
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability. 6 57
27479843 2016
3
Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis. 61
33323470 2020

Variations for Mental Retardation, Autosomal Dominant 57

ClinVar genetic disease variations for Mental Retardation, Autosomal Dominant 57:

6 (show all 31)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TLK2 NM_006852.4(TLK2):c.1720+1G>T SNV Pathogenic 548933 rs1555660806 GRCh37: 17:60678182-60678182
GRCh38: 17:62600821-62600821
2 TLK2 NM_006852.4(TLK2):c.989C>A (p.Ser330Ter) SNV Pathogenic 548935 rs1555644480 GRCh37: 17:60650596-60650596
GRCh38: 17:62573235-62573235
3 TLK2 NM_006852.4(TLK2):c.1460+2T>G SNV Pathogenic 548936 rs1555651572 GRCh37: 17:60663589-60663589
GRCh38: 17:62586228-62586228
4 TLK2 NM_006852.4(TLK2):c.784C>T (p.Arg262Ter) SNV Pathogenic 617919 rs1567920209 GRCh37: 17:60637440-60637440
GRCh38: 17:62560079-62560079
5 TLK2 NM_001284333.2(TLK2):c.777C>A (p.Tyr259Ter) SNV Pathogenic 617921 rs1567920106 GRCh37: 17:60637433-60637433
GRCh38: 17:62560072-62560072
6 TLK2 NM_001330418.2(TLK2):c.-150G>T SNV Pathogenic 617923 rs1567844114 GRCh37: 17:60599613-60599613
GRCh38: 17:62522252-62522252
7 TLK2 NM_006852.4(TLK2):c.907C>T (p.Arg303Ter) SNV Pathogenic 617933 rs138247472 GRCh37: 17:60642437-60642437
GRCh38: 17:62565076-62565076
8 TLK2 NM_001330418.2(TLK2):c.-461C>T SNV Pathogenic 617935 rs1567758622 GRCh37: 17:60558523-60558523
GRCh38: 17:62481162-62481162
9 TLK2 NM_006852.4(TLK2):c.1651C>T (p.Gln551Ter) SNV Pathogenic 617937 rs1568003569 GRCh37: 17:60678112-60678112
GRCh38: 17:62600751-62600751
10 TLK2 NM_006852.4(TLK2):c.2107C>T (p.Arg703Ter) SNV Pathogenic 689792 rs1598940393 GRCh37: 17:60689780-60689780
GRCh38: 17:62612419-62612419
11 TLK2 NM_006852.6(TLK2):c.968+1G>C SNV Pathogenic 807711 rs1598620094 GRCh37: 17:60642499-60642499
GRCh38: 17:62565138-62565138
12 TLK2 NM_006852.6(TLK2):c.968+1G>A SNV Pathogenic 828197 rs1598620094 GRCh37: 17:60642499-60642499
GRCh38: 17:62565138-62565138
13 TLK2 NM_001330418.2(TLK2):c.-171C>T SNV Pathogenic 617928 rs1567844041 GRCh37: 17:60599592-60599592
GRCh38: 17:62522231-62522231
14 TLK2 NM_006852.6(TLK2):c.1357G>T (p.Glu453Ter) SNV Pathogenic 978814 GRCh37: 17:60657542-60657542
GRCh38: 17:62580181-62580181
15 TLK2 NM_006852.6(TLK2):c.1586A>G (p.Asp529Gly) SNV Pathogenic 978815 GRCh37: 17:60678047-60678047
GRCh38: 17:62600686-62600686
16 TLK2 NM_006852.6(TLK2):c.1784C>T (p.Ser595Leu) SNV Pathogenic 978817 GRCh37: 17:60679466-60679466
GRCh38: 17:62602105-62602105
17 TLK2 NM_006852.6(TLK2):c.1579G>A (p.Gly527Arg) SNV Likely pathogenic 1048781 GRCh37: 17:60678040-60678040
GRCh38: 17:62600679-62600679
18 TLK2 NM_006852.4(TLK2):c.1487A>G (p.His496Arg) SNV Likely pathogenic 617930 rs1567995650 GRCh37: 17:60673972-60673972
GRCh38: 17:62596611-62596611
19 overlap with 2 genes Deletion Likely pathogenic 978816 GRCh37: 17:60683462-60722398
GRCh38:
20 TLK2 NM_006852.4(TLK2):c.1636C>T (p.Arg546Trp) SNV Likely pathogenic 617931 rs1283838287 GRCh37: 17:60678097-60678097
GRCh38: 17:62600736-62600736
21 TLK2 NM_006852.4(TLK2):c.1819G>A (p.Asp607Asn) SNV Likely pathogenic 617906 rs1568006217 GRCh37: 17:60679501-60679501
GRCh38: 17:62602140-62602140
22 TLK2 NM_006852.4(TLK2):c.1412A>G (p.His471Arg) SNV Likely pathogenic 617910 rs1567974030 GRCh37: 17:60663539-60663539
GRCh38: 17:62586178-62586178
23 TLK2 NM_006852.4(TLK2):c.1973C>G (p.Pro658Arg) SNV Likely pathogenic 617915 rs1568018905 GRCh37: 17:60685403-60685403
GRCh38: 17:62608042-62608042
24 TLK2 NM_006852.4(TLK2):c.1016G>A (p.Arg339Gln) SNV Uncertain significance 617916 rs1567948287 GRCh37: 17:60650623-60650623
GRCh38: 17:62573262-62573262
25 TLK2 NM_006852.4(TLK2):c.890G>A (p.Gly297Asp) SNV Uncertain significance 548937 rs1555639254 GRCh37: 17:60642420-60642420
GRCh38: 17:62565059-62565059
26 TLK2 NM_006852.4(TLK2):c.2092C>T (p.Arg698Ter) SNV Uncertain significance 489247 rs1555669421 GRCh37: 17:60689765-60689765
GRCh38: 17:62612404-62612404
27 TLK2 NM_006852.4(TLK2):c.1015C>T (p.Arg339Trp) SNV Uncertain significance 617926 rs1567948262 GRCh37: 17:60650622-60650622
GRCh38: 17:62573261-62573261
28 TLK2 NM_006852.4(TLK2):c.2170C>T (p.Arg724Ter) SNV Uncertain significance 617922 rs1568028078 GRCh37: 17:60689843-60689843
GRCh38: 17:62612482-62612482
29 TLK2 NM_006852.4(TLK2):c.1273G>A (p.Glu425Lys) SNV Uncertain significance 617932 rs1567959483 GRCh37: 17:60655922-60655922
GRCh38: 17:62578561-62578561
30 TLK2 NM_006852.6(TLK2):c.34C>T (p.Arg12Trp) SNV Uncertain significance 992409 GRCh37: 17:60558520-60558520
GRCh38: 17:62481159-62481159
31 TLK2 NM_006852.6(TLK2):c.367C>T (p.Arg123Ter) SNV not provided 816982 rs758726258 GRCh37: 17:60613534-60613534
GRCh38: 17:62536173-62536173

UniProtKB/Swiss-Prot genetic disease variations for Mental Retardation, Autosomal Dominant 57:

72
# Symbol AA change Variation ID SNP ID
1 TLK2 p.His493Arg VAR_081028 rs156797403
2 TLK2 p.His518Arg VAR_081029 rs156799565
3 TLK2 p.Arg568Trp VAR_081030 rs128383828
4 TLK2 p.Asp629Asn VAR_081032 rs156800621
5 TLK2 p.Pro680Arg VAR_081033 rs156801890

Expression for Mental Retardation, Autosomal Dominant 57

Search GEO for disease gene expression data for Mental Retardation, Autosomal Dominant 57.

Pathways for Mental Retardation, Autosomal Dominant 57

GO Terms for Mental Retardation, Autosomal Dominant 57

Sources for Mental Retardation, Autosomal Dominant 57

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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