MCPH4
MCID: MCR254
MIFTS: 41

Microcephaly 4, Primary, Autosomal Recessive (MCPH4)

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

Aliases & Classifications for Microcephaly 4, Primary, Autosomal Recessive

MalaCards integrated aliases for Microcephaly 4, Primary, Autosomal Recessive:

Name: Microcephaly 4, Primary, Autosomal Recessive 57 75 13 73
Primary Autosomal Recessive Microcephaly 4 12 29 6 15
Mcph4 57 12 75
Microcephaly, Type 4, Primary, Autosomal Recessive 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable dysmorphic features may be present


HPO:

32
microcephaly 4, primary, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Microcephaly 4, Primary, Autosomal Recessive

UniProtKB/Swiss-Prot : 75 Microcephaly 4, primary, autosomal recessive: A disease defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Affected individuals are mentally retarded. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits due to degenerative brain disorder.

MalaCards based summary : Microcephaly 4, Primary, Autosomal Recessive, also known as primary autosomal recessive microcephaly 4, is related to primary autosomal recessive microcephaly and primary microcephaly. An important gene associated with Microcephaly 4, Primary, Autosomal Recessive is KNL1 (Kinetochore Scaffold 1), and among its related pathways/superpathways are Signaling by Rho GTPases and Cell Cycle, Mitotic. Affiliated tissues include brain and cortex, and related phenotypes are hypertelorism and intellectual disability

Disease Ontology : 12 A primary autosomal recessive microcephaly that has material basis in homozygous or compound heterozygous mutation in the KNL1 gene on chromosome 15q15.

OMIM : 57 Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by Woods et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). (604321)

Related Diseases for Microcephaly 4, Primary, Autosomal Recessive

Diseases in the Microcephaly family:

Microcephaly, Autosomal Dominant Microcephaly 1, Primary, Autosomal Recessive
Microcephaly 4, Primary, Autosomal Recessive Microcephaly 3, Primary, Autosomal Recessive
Microcephaly 6, Primary, Autosomal Recessive Microcephaly 5, Primary, Autosomal Recessive
Microcephaly 7, Primary, Autosomal Recessive Microcephaly 8, Primary, Autosomal Recessive
Microcephaly 9, Primary, Autosomal Recessive Microcephaly 10, Primary, Autosomal Recessive
Microcephaly 11, Primary, Autosomal Recessive Microcephaly 13, Primary, Autosomal Recessive
Microcephaly 12, Primary, Autosomal Recessive Microcephaly 14, Primary, Autosomal Recessive
Microcephaly 15, Primary, Autosomal Recessive Microcephaly 16, Primary, Autosomal Recessive
Microcephaly 17, Primary, Autosomal Recessive Microcephaly 18, Primary, Autosomal Dominant
Microcephaly 19, Primary, Autosomal Recessive Microcephaly 20, Primary, Autosomal Recessive
Microcephaly 21, Primary, Autosomal Recessive Microcephaly 22, Primary, Autosomal Recessive
Microcephaly 23, Primary, Autosomal Recessive Primary Autosomal Recessive Microcephaly
Primary Microcephaly

Diseases related to Microcephaly 4, Primary, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 primary autosomal recessive microcephaly 29.8 CDK5RAP2 CENPJ CEP152 MCPH1 STIL
2 primary microcephaly 29.5 CDK5RAP2 CENPJ CEP152 CEP63 KNL1 MCPH1
3 microcephaly 29.5 BUB1B CDK5RAP2 CENPJ CEP152 CEP63 KNL1
4 seckel syndrome 5 10.1 CENPJ CEP152
5 microcephaly 8, primary, autosomal recessive 10.1 CEP63 CNTLN
6 seckel syndrome 1 10.1 CENPJ CEP152
7 seckel syndrome 2 10.1 CENPJ CEP152
8 seckel syndrome 4 10.1 CENPJ CNTLN
9 corneal dystrophy, meesmann 10.0 CEP152 CNTLN
10 meier-gorlin syndrome 1 10.0 CEP152 CEP63
11 microcephalic osteodysplastic primordial dwarfism, type ii 10.0 CDK5RAP2 CENPJ CNTLN
12 mosaic variegated aneuploidy syndrome 9.9 BUB1 BUB1B
13 physical disorder 9.9 CDK5RAP2 CENPJ CEP63 MCPH1
14 seckel syndrome 9.8 CENPJ CEP152 CEP63 CNTLN MCPH1
15 microcephaly 17, primary, autosomal recessive 9.7 CDK5RAP2 CENPJ CEP152 CEP63 MCPH1 STIL
16 congenital nervous system abnormality 9.7 CDK5RAP2 CENPJ CEP152 CEP63 MCPH1 STIL
17 microcephaly 3, primary, autosomal recessive 9.7 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN MCPH1
18 microcephaly 12, primary, autosomal recessive 9.6 CDK5RAP2 CENPJ CEP152 CEP63 KNL1 MCPH1
19 microcephaly 18, primary, autosomal dominant 9.6 CDK5RAP2 CENPJ CEP152 CEP63 KNL1 MCPH1
20 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 9.6 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN MCPH1
21 microcephaly 6, primary, autosomal recessive 9.6 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN MCPH1
22 microcephaly 5, primary, autosomal recessive 9.6 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN MCPH1
23 microcephaly 7, primary, autosomal recessive 9.6 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN MCPH1

Graphical network of the top 20 diseases related to Microcephaly 4, Primary, Autosomal Recessive:



Diseases related to Microcephaly 4, Primary, Autosomal Recessive

Symptoms & Phenotypes for Microcephaly 4, Primary, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
synophrys
thick eyebrows

Neurologic Central Nervous System:
mental retardation, mild to moderate
speech delay
small brain

Head And Neck Nose:
low columella

Head And Neck Face:
micrognathia
sloping forehead
low hairline

Head And Neck Head:
microcephaly (-4 to -7 sd)


Clinical features from OMIM:

604321

Human phenotypes related to Microcephaly 4, Primary, Autosomal Recessive:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 intellectual disability 32 HP:0001249
3 delayed speech and language development 32 HP:0000750
4 microcephaly 32 HP:0000252
5 thick eyebrow 32 HP:0000574
6 micrognathia 32 HP:0000347
7 aggressive behavior 32 HP:0000718
8 synophrys 32 HP:0000664
9 sloping forehead 32 HP:0000340
10 impulsivity 32 HP:0100710
11 bimanual synkinesia 32 HP:0001335

GenomeRNAi Phenotypes related to Microcephaly 4, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Effect on mitosis GR00257-A-2 8.92 BUB1 BUB1B MCPH1 ZWINT

MGI Mouse Phenotypes related to Microcephaly 4, Primary, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.81 BUB1 BUB1B CDK5RAP2 CENPJ CEP152 CEP63
2 growth/size/body region MP:0005378 9.56 BUB1 BUB1B CDK5RAP2 CENPJ CEP63 MCPH1
3 reproductive system MP:0005389 9.17 BUB1 BUB1B CDK5RAP2 CENPJ CEP63 MCPH1

Drugs & Therapeutics for Microcephaly 4, Primary, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Microcephaly 4, Primary, Autosomal Recessive

Genetic Tests for Microcephaly 4, Primary, Autosomal Recessive

Genetic tests related to Microcephaly 4, Primary, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Primary Autosomal Recessive Microcephaly 4 29 KNL1

Anatomical Context for Microcephaly 4, Primary, Autosomal Recessive

MalaCards organs/tissues related to Microcephaly 4, Primary, Autosomal Recessive:

41
Brain, Cortex

Publications for Microcephaly 4, Primary, Autosomal Recessive

Variations for Microcephaly 4, Primary, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Microcephaly 4, Primary, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 KNL1 p.Met2041Ile VAR_069085 rs763915472

ClinVar genetic disease variations for Microcephaly 4, Primary, Autosomal Recessive:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 KNL1 KNL1, MET2041ILE single nucleotide variant Pathogenic
2 KNL1 NM_170589.4(KNL1): c.772delG (p.Asp258Metfs) deletion Likely pathogenic rs797045430 GRCh37 Chromosome 15, 40913156: 40913156
3 KNL1 NM_170589.4(KNL1): c.772delG (p.Asp258Metfs) deletion Likely pathogenic rs797045430 GRCh38 Chromosome 15, 40620958: 40620958
4 KNL1 NM_170589.4(KNL1): c.6560A> G (p.Asp2187Gly) single nucleotide variant Uncertain significance rs142872154 GRCh38 Chromosome 15, 40654975: 40654975
5 KNL1 NM_170589.4(KNL1): c.6560A> G (p.Asp2187Gly) single nucleotide variant Uncertain significance rs142872154 GRCh37 Chromosome 15, 40947173: 40947173
6 KNL1 NM_170589.4(KNL1): c.5262dupT (p.Ile1755Tyrfs) duplication Pathogenic rs863225127 GRCh37 Chromosome 15, 40917646: 40917646
7 KNL1 NM_170589.4(KNL1): c.5262dupT (p.Ile1755Tyrfs) duplication Pathogenic rs863225127 GRCh38 Chromosome 15, 40625448: 40625448
8 KNL1 NM_170589.4(KNL1): c.4823_4824delTTinsC (p.Leu1608Profs) indel Likely pathogenic GRCh38 Chromosome 15, 40625009: 40625010
9 KNL1 NM_170589.4(KNL1): c.4823_4824delTTinsC (p.Leu1608Profs) indel Likely pathogenic GRCh37 Chromosome 15, 40917207: 40917208
10 KNL1 NM_170589.4(KNL1): c.1599A> G (p.Gln533=) single nucleotide variant Likely pathogenic rs979186313 GRCh37 Chromosome 15, 40913983: 40913983
11 KNL1 NM_170589.4(KNL1): c.1599A> G (p.Gln533=) single nucleotide variant Likely pathogenic rs979186313 GRCh38 Chromosome 15, 40621785: 40621785
12 KNL1 NM_170589.4(KNL1): c.6427G> T (p.Asp2143Tyr) single nucleotide variant Likely pathogenic rs758157294 GRCh38 Chromosome 15, 40652039: 40652039
13 KNL1 NM_170589.4(KNL1): c.6427G> T (p.Asp2143Tyr) single nucleotide variant Likely pathogenic rs758157294 GRCh37 Chromosome 15, 40944237: 40944237

Expression for Microcephaly 4, Primary, Autosomal Recessive

Search GEO for disease gene expression data for Microcephaly 4, Primary, Autosomal Recessive.

Pathways for Microcephaly 4, Primary, Autosomal Recessive

Pathways related to Microcephaly 4, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.58 BUB1 BUB1B KNL1 MIS12 ZWINT
2
Show member pathways
12.52 BUB1 BUB1B CDK5RAP2 CENPJ CEP152 CEP63
3
Show member pathways
12.4 CDK5RAP2 CENPJ CEP152 CEP63
4
Show member pathways
12.38 BUB1 BUB1B KNL1 MIS12 ZWINT
5
Show member pathways
11.89 BUB1 BUB1B KNL1 MIS12 ZWINT
6
Show member pathways
11.12 BUB1 BUB1B
7 10.99 BUB1 CEP63 TP53BP1

GO Terms for Microcephaly 4, Primary, Autosomal Recessive

Cellular components related to Microcephaly 4, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cytoskeleton GO:0005856 9.97 BUB1B CDK5RAP2 CENPJ CEP152 CEP63 CNTLN
2 centrosome GO:0005813 9.91 CDK5RAP2 CENPJ CEP152 CEP63 CNTLN STIL
3 chromosome GO:0005694 9.88 BUB1 BUB1B KNL1 MIS12 TP53BP1 ZWINT
4 microtubule organizing center GO:0005815 9.8 BUB1B CDK5RAP2 CENPJ CEP152 CEP63 MCPH1
5 centriole GO:0005814 9.65 CENPJ CEP152 CEP63 CNTLN STIL
6 chromosome, centromeric region GO:0000775 9.55 BUB1 BUB1B MIS12 TP53BP1 ZWINT
7 pericentriolar material GO:0000242 9.51 CDK5RAP2 CEP152
8 condensed nuclear chromosome kinetochore GO:0000778 9.48 BUB1 BUB1B
9 kinetochore GO:0000776 9.43 BUB1 BUB1B KNL1 MIS12 TP53BP1 ZWINT
10 condensed chromosome kinetochore GO:0000777 9.1 BUB1 BUB1B KNL1 MIS12 TP53BP1 ZWINT
11 cytoplasm GO:0005737 10.22 BUB1B CDK5RAP2 CENPJ CEP152 CEP63 CNTLN
12 cytosol GO:0005829 10.2 BUB1 BUB1B CDK5RAP2 CENPJ CEP152 CEP63
13 nucleoplasm GO:0005654 10.1 BUB1 CENPJ CEP152 CNTLN KNL1 MCPH1

Biological processes related to Microcephaly 4, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 cell cycle GO:0007049 9.88 BUB1 BUB1B CEP63 KNL1 MIS12 ZWINT
2 G2/M transition of mitotic cell cycle GO:0000086 9.73 CDK5RAP2 CENPJ CEP152 CEP63
3 ciliary basal body-plasma membrane docking GO:0097711 9.67 CDK5RAP2 CENPJ CEP152 CEP63
4 mitotic cell cycle checkpoint GO:0007093 9.63 BUB1 BUB1B ZWINT
5 chromosome segregation GO:0007059 9.62 BUB1 CDK5RAP2 KNL1 MIS12
6 DNA damage checkpoint GO:0000077 9.58 CEP63 TP53BP1
7 mitotic sister chromatid segregation GO:0000070 9.57 MIS12 ZWINT
8 mitotic spindle assembly checkpoint GO:0007094 9.56 BUB1 BUB1B
9 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.56 CDK5RAP2 CENPJ CEP152 CEP63
10 establishment of mitotic spindle orientation GO:0000132 9.55 CDK5RAP2 MCPH1
11 protein localization to centrosome GO:0071539 9.54 MCPH1 STIL
12 protein localization to kinetochore GO:0034501 9.52 KNL1 MIS12
13 regulation of centriole replication GO:0046599 9.51 CENPJ STIL
14 cell division GO:0051301 9.5 BUB1 BUB1B CENPJ CEP63 KNL1 MIS12
15 de novo centriole assembly involved in multi-ciliated epithelial cell differentiation GO:0098535 9.49 CEP152 CEP63
16 meiotic sister chromatid cohesion, centromeric GO:0051754 9.48 BUB1 BUB1B
17 centrosome duplication GO:0051298 9.33 CENPJ CEP152 STIL
18 centriole replication GO:0007099 8.92 CDK5RAP2 CENPJ CEP152 CEP63

Molecular functions related to Microcephaly 4, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 9.4 BUB1 BUB1B CDK5RAP2 CENPJ CEP152 CEP63
2 protein kinase binding GO:0019901 9.26 CDK5RAP2 CENPJ CEP152 CNTLN

Sources for Microcephaly 4, Primary, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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