KLEFS2
MCID: KLF005
MIFTS: 35

Kleefstra Syndrome 2 (KLEFS2)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Kleefstra Syndrome 2

MalaCards integrated aliases for Kleefstra Syndrome 2:

Name: Kleefstra Syndrome 2 57 12 72 29 6 15
Klefs2 57 72
Syndrome, Kleefstra, Type 2 39

Characteristics:

OMIM®:

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

Miscellaneous:
de novo mutation



Classifications:



Summaries for Kleefstra Syndrome 2

OMIM® : 57 Kleefstra syndrome-2 is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features (summary by Koemans et al., 2017). For a discussion of genetic heterogeneity of Kleefstra syndrome, see KLEFS1 (610253). (617768) (Updated 20-May-2021)

MalaCards based summary : Kleefstra Syndrome 2, also known as klefs2, is related to kleefstra syndrome and agenesis of corpus callosum, cardiac, ocular, and genital syndrome. An important gene associated with Kleefstra Syndrome 2 is KMT2C (Lysine Methyltransferase 2C), and among its related pathways/superpathways are Chromatin organization and PKMTs methylate histone lysines. Affiliated tissues include breast, and related phenotypes are intellectual disability and scoliosis

Disease Ontology : 12 A Kleefstra syndrome that is characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features and has material basis in heterozygous mutation in the KMT2C gene on chromosome 7q36.

UniProtKB/Swiss-Prot : 72 Kleefstra syndrome 2: A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable mental retardation, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms.

Related Diseases for Kleefstra Syndrome 2

Diseases in the Kleefstra Syndrome family:

Kleefstra Syndrome 1 Kleefstra Syndrome 2
Kleefstra Syndrome Due to a Point Mutation

Diseases related to Kleefstra Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 kleefstra syndrome 9.9 KMT2C AGMO
2 agenesis of corpus callosum, cardiac, ocular, and genital syndrome 9.6 KMT2E KMT2C
3 kabuki syndrome 1 9.3 SETD1A KMT2E KMT2C

Symptoms & Phenotypes for Kleefstra Syndrome 2

Human phenotypes related to Kleefstra Syndrome 2:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 very rare (1%) HP:0001249
2 scoliosis 31 very rare (1%) HP:0002650
3 kyphosis 31 very rare (1%) HP:0002808
4 self-injurious behavior 31 very rare (1%) HP:0100716
5 global developmental delay 31 very rare (1%) HP:0001263
6 everted lower lip vermilion 31 very rare (1%) HP:0000232
7 midface retrusion 31 very rare (1%) HP:0011800
8 plagiocephaly 31 very rare (1%) HP:0001357
9 bifid uvula 31 very rare (1%) HP:0000193
10 autistic behavior 31 very rare (1%) HP:0000729
11 generalized hypotonia 31 very rare (1%) HP:0001290
12 seizure 31 very rare (1%) HP:0001250
13 hypotonia 31 very rare (1%) HP:0001252
14 delayed speech and language development 31 HP:0000750
15 abnormal facial shape 31 HP:0001999
16 microcephaly 31 HP:0000252
17 thick eyebrow 31 HP:0000574
18 growth delay 31 HP:0001510

Symptoms via clinical synopsis from OMIM®:

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

Neurologic Central Nervous System:
seizures (in some patients)
speech delay
delayed psychomotor development
intellectual disability, mild to severe

Growth Other:
poor growth

Head And Neck Face:
dysmorphic facial features, variable
flattened midface

Growth Height:
decreased height (in some patients)

Head And Neck Ears:
thick ear helices

Neurologic Behavioral Psychiatric Manifestations:
behavioral abnormalities
autistic features

Head And Neck Mouth:
everted lower lip

Head And Neck Eyes:
prominent eyebrows

Muscle Soft Tissue:
hypotonia (in some patients)

Head And Neck Head:
microcephaly, mild (up to -2 sd in some patients)

Clinical features from OMIM®:

617768 (Updated 20-May-2021)

Drugs & Therapeutics for Kleefstra Syndrome 2

Search Clinical Trials , NIH Clinical Center for Kleefstra Syndrome 2

Genetic Tests for Kleefstra Syndrome 2

Genetic tests related to Kleefstra Syndrome 2:

# Genetic test Affiliating Genes
1 Kleefstra Syndrome 2 29 KMT2C

Anatomical Context for Kleefstra Syndrome 2

MalaCards organs/tissues related to Kleefstra Syndrome 2:

40
Breast

Publications for Kleefstra Syndrome 2

Articles related to Kleefstra Syndrome 2:

# Title Authors PMID Year
1
Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder. 57 6
29069077 2017
2
Disruption of an EHMT1-associated chromatin-modification module causes intellectual disability. 57 6
22726846 2012
3
Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA. 6
30981987 2019
4
DNA Sequencing of Small Bowel Adenocarcinomas Identifies Targetable Recurrent Mutations in the ERBB2 Signaling Pathway. 6
30352910 2019
5
Breast cancer in women with neurofibromatosis type 1 (NF1): a comprehensive case series with molecular insights into its aggressive phenotype. 6
29926297 2018
6
Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders. 57
29276005 2018
7
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 6
25741868 2015
8
Dissecting the genomic complexity underlying medulloblastoma. 6
22832583 2012

Variations for Kleefstra Syndrome 2

ClinVar genetic disease variations for Kleefstra Syndrome 2:

6 (show all 35)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KMT2C NM_170606.3(KMT2C):c.5216del (p.Pro1739fs) Deletion Pathogenic 446223 rs1554505381 GRCh37: 7:151880108-151880108
GRCh38: 7:152183023-152183023
2 KMT2C NM_170606.3(KMT2C):c.10812_10815del (p.Lys3605fs) Deletion Pathogenic 446226 rs1554477105 GRCh37: 7:151859847-151859850
GRCh38: 7:152162762-152162765
3 KMT2C NM_170606.3(KMT2C):c.1951_1952del (p.Glu651fs) Deletion Pathogenic 807440 rs1588571802 GRCh37: 7:151945567-151945568
GRCh38: 7:152248482-152248483
4 KMT2C NM_170606.3(KMT2C):c.12415C>T (p.Arg4139Ter) SNV Pathogenic 975272 GRCh37: 7:151849901-151849901
GRCh38: 7:152152816-152152816
5 KMT2C NM_170606.3(KMT2C):c.2961C>G (p.Tyr987Ter) SNV Likely pathogenic 694634 rs58528565 GRCh37: 7:151927023-151927023
GRCh38: 7:152229938-152229938
6 KMT2C NM_170606.3(KMT2C):c.7550C>G (p.Ser2517Ter) SNV Likely pathogenic 446224 rs779659766 GRCh37: 7:151874988-151874988
GRCh38: 7:152177903-152177903
7 KMT2C NM_170606.3(KMT2C):c.1690A>T (p.Lys564Ter) SNV Likely pathogenic 446225 rs1554580083 GRCh37: 7:151947983-151947983
GRCh38: 7:152250898-152250898
8 KMT2C NM_170606.3(KMT2C):c.7613dup (p.Gln2539fs) Duplication Likely pathogenic 559406 rs1554496813 GRCh37: 7:151874924-151874925
GRCh38: 7:152177839-152177840
9 KMT2C NM_170606.3(KMT2C):c.4299_4307del (p.Asp1433_Ser1435del) Deletion Likely pathogenic 635469 rs1588119681 GRCh37: 7:151893063-151893071
GRCh38: 7:152195978-152195986
10 KMT2C Deletion Likely pathogenic 638598 GRCh37: 7:151838641-151973850
GRCh38:
11 KMT2C NM_170606.3(KMT2C):c.5088dup (p.Ala1697fs) Duplication Likely pathogenic 982915 GRCh37: 7:151880235-151880236
GRCh38: 7:152183150-152183151
12 KMT2C NM_170606.3(KMT2C):c.13198C>T (p.Arg4400Trp) SNV Likely pathogenic 1033180 GRCh37: 7:151845814-151845814
GRCh38: 7:152148729-152148729
13 KMT2C NM_170606.3(KMT2C):c.4441C>T (p.Arg1481Ter) SNV Likely pathogenic 88895 rs587777073 GRCh37: 7:151891591-151891591
GRCh38: 7:152194506-152194506
14 KMT2C NM_170606.3(KMT2C):c.4918G>C (p.Glu1640Gln) SNV Uncertain significance 1064557 GRCh37: 7:151884437-151884437
GRCh38: 7:152187352-152187352
15 KMT2C NM_170606.3(KMT2C):c.6589C>T (p.Gln2197Ter) SNV Uncertain significance 982955 GRCh37: 7:151878356-151878356
GRCh38: 7:152181271-152181271
16 KMT2C NM_170606.3(KMT2C):c.8045C>T (p.Ser2682Phe) SNV Uncertain significance 982956 GRCh37: 7:151874493-151874493
GRCh38: 7:152177408-152177408
17 KMT2C NM_170606.3(KMT2C):c.7841G>T (p.Gly2614Val) SNV Uncertain significance 996875 GRCh37: 7:151874697-151874697
GRCh38: 7:152177612-152177612
18 AGMO Deletion Uncertain significance 1012221 GRCh37: 7:15238956-15248946
GRCh38: 7:15199331-15209321
19 KMT2C NM_170606.3(KMT2C):c.1331G>A (p.Arg444Gln) SNV Uncertain significance 1027365 GRCh37: 7:151949769-151949769
GRCh38: 7:152252684-152252684
20 KMT2C NM_170606.3(KMT2C):c.10054C>G (p.Gln3352Glu) SNV Uncertain significance 1027838 GRCh37: 7:151860608-151860608
GRCh38: 7:152163523-152163523
21 KMT2C NM_170606.3(KMT2C):c.10301A>C (p.His3434Pro) SNV Uncertain significance 1027839 GRCh37: 7:151860361-151860361
GRCh38: 7:152163276-152163276
22 KMT2C NM_170606.3(KMT2C):c.10789A>G (p.Ile3597Val) SNV Uncertain significance 1027840 GRCh37: 7:151859873-151859873
GRCh38: 7:152162788-152162788
23 KMT2C NM_170606.3(KMT2C):c.1522C>G (p.Leu508Val) SNV Uncertain significance 1027841 GRCh37: 7:151949123-151949123
GRCh38: 7:152252038-152252038
24 KMT2C NM_170606.3(KMT2C):c.577A>G (p.Arg193Gly) SNV Uncertain significance 1027842 GRCh37: 7:152012236-152012236
GRCh38: 7:152315151-152315151
25 KMT2C NM_170606.3(KMT2C):c.6638G>C (p.Gly2213Ala) SNV Uncertain significance 1027843 GRCh37: 7:151878307-151878307
GRCh38: 7:152181222-152181222
26 KMT2C NM_170606.3(KMT2C):c.9905C>T (p.Pro3302Leu) SNV Uncertain significance 1027844 GRCh37: 7:151860757-151860757
GRCh38: 7:152163672-152163672
27 KMT2C NM_170606.3(KMT2C):c.2961C>G (p.Tyr987Ter) SNV Uncertain significance 694634 rs58528565 GRCh37: 7:151927023-151927023
GRCh38: 7:152229938-152229938
28 KMT2C NM_170606.3(KMT2C):c.162-1G>T SNV Uncertain significance 802382 rs1177551329 GRCh37: 7:152055761-152055761
GRCh38: 7:152358676-152358676
29 KMT2C NM_170606.3(KMT2C):c.10874C>T (p.Pro3625Leu) SNV Uncertain significance 930481 GRCh37: 7:151859788-151859788
GRCh38: 7:152162703-152162703
30 KMT2C NM_170606.3(KMT2C):c.4382T>C (p.Ile1461Thr) SNV Uncertain significance 930736 GRCh37: 7:151891650-151891650
GRCh38: 7:152194565-152194565
31 KMT2C NM_170606.3(KMT2C):c.4030A>G (p.Ile1344Val) SNV Uncertain significance 931616 GRCh37: 7:151900081-151900081
GRCh38: 7:152202996-152202996
32 KMT2C NM_170606.3(KMT2C):c.3874C>G (p.Arg1292Gly) SNV Uncertain significance 932912 GRCh37: 7:151902278-151902278
GRCh38: 7:152205193-152205193
33 KMT2C NM_170606.3(KMT2C):c.11651C>T (p.Thr3884Met) SNV Uncertain significance 982790 GRCh37: 7:151855967-151855967
GRCh38: 7:152158882-152158882
34 KMT2C NM_170606.3(KMT2C):c.7207C>T (p.Arg2403Ter) SNV Uncertain significance 982818 GRCh37: 7:151877154-151877154
GRCh38: 7:152180069-152180069
35 KMT2C NM_170606.3(KMT2C):c.2657G>A (p.Arg886His) SNV Uncertain significance 915310 GRCh37: 7:151933014-151933014
GRCh38: 7:152235929-152235929

Expression for Kleefstra Syndrome 2

Search GEO for disease gene expression data for Kleefstra Syndrome 2.

Pathways for Kleefstra Syndrome 2

Pathways related to Kleefstra Syndrome 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.18 SETD1A KMT2E KMT2C
2
Show member pathways
11.28 SETD1A KMT2E KMT2C
3 10.6 SETD1A KMT2E KMT2C

GO Terms for Kleefstra Syndrome 2

Cellular components related to Kleefstra Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromosome GO:0005694 9.33 SETD1A KMT2E EPOP
2 Set1C/COMPASS complex GO:0048188 8.96 WDR82 SETD1A
3 histone methyltransferase complex GO:0035097 8.8 WDR82 SETD1A KMT2C

Biological processes related to Kleefstra Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin organization GO:0006325 9.5 SETD1A KMT2E KMT2C
2 methylation GO:0032259 9.37 SETD1A KMT2C
3 histone H3-K4 methylation GO:0051568 9.26 WDR82 KMT2C
4 histone H3-K4 trimethylation GO:0080182 9.16 WDR82 SETD1A
5 histone H3-K4 monomethylation GO:0097692 8.96 SETD1A KMT2C
6 regulation of megakaryocyte differentiation GO:0045652 8.8 SETD1A KMT2E KMT2C

Molecular functions related to Kleefstra Syndrome 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 methyltransferase activity GO:0008168 9.16 SETD1A KMT2C
2 histone-lysine N-methyltransferase activity GO:0018024 8.96 SETD1A KMT2E
3 histone methyltransferase activity (H3-K4 specific) GO:0042800 8.8 WDR82 SETD1A KMT2C

Sources for Kleefstra Syndrome 2

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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