MCPH3
MCID: MCR248
MIFTS: 38

Microcephaly 3, Primary, Autosomal Recessive (MCPH3)

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

Aliases & Classifications for Microcephaly 3, Primary, Autosomal Recessive

MalaCards integrated aliases for Microcephaly 3, Primary, Autosomal Recessive:

Name: Microcephaly 3, Primary, Autosomal Recessive 58 76 13
Primary Autosomal Recessive Microcephaly 3 12 30 6 15
Mcph3 58 12 76
Microcephaly, Primary Autosomal Recessive, 3 74

Characteristics:

OMIM:

58
Inheritance:
autosomal recessive


HPO:

33
microcephaly 3, primary, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0070286
OMIM 58 604804
MeSH 45 D008831
MedGen 43 C1858108
UMLS 74 C1858108

Summaries for Microcephaly 3, Primary, Autosomal Recessive

UniProtKB/Swiss-Prot : 76 Microcephaly 3, 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 3, Primary, Autosomal Recessive, also known as primary autosomal recessive microcephaly 3, is related to microcephaly and primary microcephaly. An important gene associated with Microcephaly 3, Primary, Autosomal Recessive is CDK5RAP2 (CDK5 Regulatory Subunit Associated Protein 2), and among its related pathways/superpathways are Cell Cycle, Mitotic and Organelle biogenesis and maintenance. Affiliated tissues include cortex, brain and eye, and related phenotypes are sensorineural hearing impairment and proptosis

Disease Ontology : 12 A primary autosomal recessive microcephaly that has material basis in homozygous or compound heterozygous mutation in the CDK5RAP2 gene on chromosome 9q33.

Description from OMIM: 604804

Related Diseases for Microcephaly 3, 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 Microcephaly 24, Primary, Autosomal Recessive
Microcephaly 25, Primary, Autosomal Recessive Primary Autosomal Recessive Microcephaly
Primary Microcephaly

Diseases related to Microcephaly 3, Primary, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 microcephaly 29.5 CDK5RAP2 CENPJ CEP152 MCPH1 PNKP
2 primary microcephaly 29.5 CDK5RAP2 CENPJ CEP152 MCPH1 PNKP
3 seckel syndrome 5 10.0 CENPJ CEP152
4 seckel syndrome 1 9.9 CENPJ CEP152
5 seckel syndrome 2 9.9 CENPJ CEP152
6 seckel syndrome 4 9.8 CENPJ CNTLN
7 physical disorder 9.8 CDK5RAP2 CENPJ MCPH1
8 microcephalic osteodysplastic primordial dwarfism, type ii 9.7 CDK5RAP2 CENPJ CNTLN
9 corneal dystrophy, meesmann 9.7 CEP152 CNTLN
10 microcephaly 12, primary, autosomal recessive 9.6 CDK5RAP2 CENPJ CEP152 MCPH1
11 primary autosomal recessive microcephaly 9.6 CDK5RAP2 CENPJ CEP152 MCPH1
12 microcephaly 18, primary, autosomal dominant 9.6 CDK5RAP2 CENPJ CEP152 MCPH1
13 congenital nervous system abnormality 9.6 CDK5RAP2 CENPJ CEP152 MCPH1
14 seckel syndrome 9.4 CENPJ CEP152 CNTLN MCPH1
15 microcephaly 6, primary, autosomal recessive 9.3 CDK5RAP2 CENPJ CEP152 CNTLN MCPH1
16 microcephaly 4, primary, autosomal recessive 9.3 CDK5RAP2 CENPJ CEP152 CNTLN MCPH1
17 microcephaly 2, primary, autosomal recessive, with or without cortical malformations 9.3 CDK5RAP2 CENPJ CEP152 CNTLN MCPH1
18 microcephaly 5, primary, autosomal recessive 9.3 CDK5RAP2 CENPJ CEP152 CNTLN MCPH1
19 microcephaly 7, primary, autosomal recessive 9.3 CDK5RAP2 CENPJ CEP152 CNTLN MCPH1
20 microcephaly 17, primary, autosomal recessive 8.9 CDK5 CDK5RAP2 CENPJ CEP152 MCPH1 PNKP

Graphical network of the top 20 diseases related to Microcephaly 3, Primary, Autosomal Recessive:



Diseases related to Microcephaly 3, Primary, Autosomal Recessive

Symptoms & Phenotypes for Microcephaly 3, Primary, Autosomal Recessive

Human phenotypes related to Microcephaly 3, Primary, Autosomal Recessive:

33 (show all 8)
# Description HPO Frequency HPO Source Accession
1 sensorineural hearing impairment 33 occasional (7.5%) HP:0000407
2 proptosis 33 occasional (7.5%) HP:0000520
3 cortical gyral simplification 33 occasional (7.5%) HP:0009879
4 global developmental delay 33 HP:0001263
5 microcephaly 33 HP:0000252
6 intellectual disability, moderate 33 HP:0002342
7 sloping forehead 33 HP:0000340
8 small cerebral cortex 33 HP:0002472

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
sloping forehead
microcephaly, severe (-4 to -8 sds)

Head And Neck Ears:
hearing loss, sensorineural (in some patients)

Head And Neck Teeth:
conical-shaped teeth (in one patient)

Neurologic Central Nervous System:
developmental delay
mental retardation, mild to moderate
small but structurally normal cerebral cortex
simplified gyral pattern (in one patient)
small frontal lobes (in one patient)
more
Head And Neck Eyes:
prominent eyes (in one patient)

Clinical features from OMIM:

604804

GenomeRNAi Phenotypes related to Microcephaly 3, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability with poly (ADPa89ribose)a89polymerasea891 (PARP) inhibitor GR00114-A 8.62 CDK5 PNKP

MGI Mouse Phenotypes related to Microcephaly 3, Primary, Autosomal Recessive:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.43 BIRC5 CDK5RAP2 CENPJ CEP152 MCPH1 PNKP
2 nervous system MP:0003631 9.1 CDK5 CDK5RAP2 CENPJ CEP152 MCPH1 PNKP

Drugs & Therapeutics for Microcephaly 3, Primary, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Microcephaly 3, Primary, Autosomal Recessive

Genetic Tests for Microcephaly 3, Primary, Autosomal Recessive

Genetic tests related to Microcephaly 3, Primary, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Primary Autosomal Recessive Microcephaly 3 30 CDK5RAP2

Anatomical Context for Microcephaly 3, Primary, Autosomal Recessive

MalaCards organs/tissues related to Microcephaly 3, Primary, Autosomal Recessive:

42
Cortex, Brain, Eye

Publications for Microcephaly 3, Primary, Autosomal Recessive

Variations for Microcephaly 3, Primary, Autosomal Recessive

ClinVar genetic disease variations for Microcephaly 3, Primary, Autosomal Recessive:

6 (show top 50) (show all 124)
# Gene Variation Type Significance SNP ID Assembly Location
1 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5448G> A (p.Glu1816=) single nucleotide variant Conflicting interpretations of pathogenicity rs587783396 GRCh37 Chromosome 9, 123163023: 123163023
2 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5448G> A (p.Glu1816=) single nucleotide variant Conflicting interpretations of pathogenicity rs587783396 GRCh38 Chromosome 9, 120400745: 120400745
3 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5413C> T (p.Leu1805Phe) single nucleotide variant Uncertain significance rs545543130 GRCh37 Chromosome 9, 123163058: 123163058
4 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5413C> T (p.Leu1805Phe) single nucleotide variant Uncertain significance rs545543130 GRCh38 Chromosome 9, 120400780: 120400780
5 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5359A> C (p.Lys1787Gln) single nucleotide variant Uncertain significance rs587783395 GRCh37 Chromosome 9, 123163112: 123163112
6 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5359A> C (p.Lys1787Gln) single nucleotide variant Uncertain significance rs587783395 GRCh38 Chromosome 9, 120400834: 120400834
7 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5227C> T (p.Gln1743Ter) single nucleotide variant Pathogenic rs587783392 GRCh37 Chromosome 9, 123165164: 123165164
8 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5227C> T (p.Gln1743Ter) single nucleotide variant Pathogenic rs587783392 GRCh38 Chromosome 9, 120402886: 120402886
9 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5152C> G (p.Leu1718Val) single nucleotide variant Uncertain significance rs141004029 GRCh37 Chromosome 9, 123165239: 123165239
10 CDK5RAP2 NM_018249.5(CDK5RAP2): c.5152C> G (p.Leu1718Val) single nucleotide variant Uncertain significance rs141004029 GRCh38 Chromosome 9, 120402961: 120402961
11 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4822A> G (p.Ser1608Gly) single nucleotide variant Uncertain significance rs372057183 GRCh37 Chromosome 9, 123169431: 123169431
12 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4822A> G (p.Ser1608Gly) single nucleotide variant Uncertain significance rs372057183 GRCh38 Chromosome 9, 120407153: 120407153
13 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4441C> T (p.Arg1481Ter) single nucleotide variant Pathogenic/Likely pathogenic rs587783390 GRCh37 Chromosome 9, 123171568: 123171568
14 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4441C> T (p.Arg1481Ter) single nucleotide variant Pathogenic/Likely pathogenic rs587783390 GRCh38 Chromosome 9, 120409290: 120409290
15 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4425G> T (p.Lys1475Asn) single nucleotide variant Uncertain significance rs587783389 GRCh37 Chromosome 9, 123171584: 123171584
16 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4425G> T (p.Lys1475Asn) single nucleotide variant Uncertain significance rs587783389 GRCh38 Chromosome 9, 120409306: 120409306
17 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4393A> G (p.Met1465Val) single nucleotide variant Uncertain significance rs201864352 GRCh37 Chromosome 9, 123173657: 123173657
18 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4393A> G (p.Met1465Val) single nucleotide variant Uncertain significance rs201864352 GRCh38 Chromosome 9, 120411379: 120411379
19 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4338T> A (p.Ser1446Arg) single nucleotide variant Uncertain significance rs143341041 GRCh37 Chromosome 9, 123173712: 123173712
20 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4338T> A (p.Ser1446Arg) single nucleotide variant Uncertain significance rs143341041 GRCh38 Chromosome 9, 120411434: 120411434
21 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4325C> T (p.Ser1442Leu) single nucleotide variant Uncertain significance rs376138280 GRCh37 Chromosome 9, 123173725: 123173725
22 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4325C> T (p.Ser1442Leu) single nucleotide variant Uncertain significance rs376138280 GRCh38 Chromosome 9, 120411447: 120411447
23 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4055A> G (p.Glu1352Gly) single nucleotide variant Uncertain significance rs587783388 GRCh37 Chromosome 9, 123182188: 123182188
24 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4055A> G (p.Glu1352Gly) single nucleotide variant Uncertain significance rs587783388 GRCh38 Chromosome 9, 120419910: 120419910
25 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4005-1G> A single nucleotide variant Pathogenic rs587783387 GRCh37 Chromosome 9, 123182239: 123182239
26 CDK5RAP2 NM_018249.5(CDK5RAP2): c.4005-1G> A single nucleotide variant Pathogenic rs587783387 GRCh38 Chromosome 9, 120419961: 120419961
27 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3859G> T (p.Ala1287Ser) single nucleotide variant Uncertain significance rs587783386 GRCh37 Chromosome 9, 123199669: 123199669
28 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3859G> T (p.Ala1287Ser) single nucleotide variant Uncertain significance rs587783386 GRCh38 Chromosome 9, 120437391: 120437391
29 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3686A> G (p.Asn1229Ser) single nucleotide variant Uncertain significance rs148403620 GRCh37 Chromosome 9, 123201713: 123201713
30 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3686A> G (p.Asn1229Ser) single nucleotide variant Uncertain significance rs148403620 GRCh38 Chromosome 9, 120439435: 120439435
31 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3679A> T (p.Ile1227Phe) single nucleotide variant Uncertain significance rs139203975 GRCh37 Chromosome 9, 123201720: 123201720
32 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3679A> T (p.Ile1227Phe) single nucleotide variant Uncertain significance rs139203975 GRCh38 Chromosome 9, 120439442: 120439442
33 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3285G> C (p.Met1095Ile) single nucleotide variant Uncertain significance rs587783385 GRCh37 Chromosome 9, 123202114: 123202114
34 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3285G> C (p.Met1095Ile) single nucleotide variant Uncertain significance rs587783385 GRCh38 Chromosome 9, 120439836: 120439836
35 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3258T> C (p.Ser1086=) single nucleotide variant Uncertain significance rs587783384 GRCh37 Chromosome 9, 123202141: 123202141
36 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3258T> C (p.Ser1086=) single nucleotide variant Uncertain significance rs587783384 GRCh38 Chromosome 9, 120439863: 120439863
37 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3034C> G (p.Pro1012Ala) single nucleotide variant Uncertain significance rs141496431 GRCh37 Chromosome 9, 123206012: 123206012
38 CDK5RAP2 NM_018249.5(CDK5RAP2): c.3034C> G (p.Pro1012Ala) single nucleotide variant Uncertain significance rs141496431 GRCh38 Chromosome 9, 120443734: 120443734
39 CDK5RAP2 NM_018249.5(CDK5RAP2): c.2644C> G (p.Leu882Val) single nucleotide variant Uncertain significance rs587783383 GRCh37 Chromosome 9, 123215883: 123215883
40 CDK5RAP2 NM_018249.5(CDK5RAP2): c.2644C> G (p.Leu882Val) single nucleotide variant Uncertain significance rs587783383 GRCh38 Chromosome 9, 120453605: 120453605
41 CDK5RAP2 NM_018249.5(CDK5RAP2): c.1433T> C (p.Val478Ala) single nucleotide variant Uncertain significance rs587783382 GRCh37 Chromosome 9, 123253634: 123253634
42 CDK5RAP2 NM_018249.5(CDK5RAP2): c.1433T> C (p.Val478Ala) single nucleotide variant Uncertain significance rs587783382 GRCh38 Chromosome 9, 120491356: 120491356
43 CDK5RAP2 NM_018249.5(CDK5RAP2): c.1183C> T (p.His395Tyr) single nucleotide variant Uncertain significance rs587783380 GRCh37 Chromosome 9, 123280833: 123280833
44 CDK5RAP2 NM_018249.5(CDK5RAP2): c.1183C> T (p.His395Tyr) single nucleotide variant Uncertain significance rs587783380 GRCh38 Chromosome 9, 120518555: 120518555
45 CDK5RAP2 NM_018249.5(CDK5RAP2): c.923C> T (p.Thr308Ile) single nucleotide variant Uncertain significance rs145272328 GRCh37 Chromosome 9, 123290160: 123290160
46 CDK5RAP2 NM_018249.5(CDK5RAP2): c.923C> T (p.Thr308Ile) single nucleotide variant Uncertain significance rs145272328 GRCh38 Chromosome 9, 120527882: 120527882
47 CDK5RAP2 NM_018249.5(CDK5RAP2): c.749C> T (p.Pro250Leu) single nucleotide variant Uncertain significance rs568558844 GRCh37 Chromosome 9, 123292332: 123292332
48 CDK5RAP2 NM_018249.5(CDK5RAP2): c.749C> T (p.Pro250Leu) single nucleotide variant Uncertain significance rs568558844 GRCh38 Chromosome 9, 120530054: 120530054
49 CDK5RAP2 NM_018249.5(CDK5RAP2): c.574C> T (p.Arg192Trp) single nucleotide variant Uncertain significance rs369568564 GRCh37 Chromosome 9, 123298738: 123298738
50 CDK5RAP2 NM_018249.5(CDK5RAP2): c.574C> T (p.Arg192Trp) single nucleotide variant Uncertain significance rs369568564 GRCh38 Chromosome 9, 120536460: 120536460

Expression for Microcephaly 3, Primary, Autosomal Recessive

Search GEO for disease gene expression data for Microcephaly 3, Primary, Autosomal Recessive.

Pathways for Microcephaly 3, Primary, Autosomal Recessive

Pathways related to Microcephaly 3, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.18 BIRC5 CDK5RAP2 CENPJ CEP152 MCPH1
2
Show member pathways
12.06 CDK5RAP2 CENPJ CEP152
3 11.6 CDK5 MCPH1 PNKP

GO Terms for Microcephaly 3, Primary, Autosomal Recessive

Cellular components related to Microcephaly 3, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.98 BIRC5 CDK5 CDK5RAP2 CENPJ CEP152 CNTLN
2 nucleoplasm GO:0005654 9.7 BIRC5 CDK5 CENPJ CEP152 CNTLN MCPH1
3 centrosome GO:0005813 9.67 CDK5RAP2 CENPJ CEP152 CNTLN
4 microtubule organizing center GO:0005815 9.56 CDK5RAP2 CENPJ CEP152 MCPH1
5 centriole GO:0005814 9.5 CENPJ CEP152 CNTLN
6 pericentriolar material GO:0000242 9.4 CDK5RAP2 CEP152
7 microtubule GO:0005874 9.26 BIRC5 CDK5 CDK5RAP2 CENPJ
8 cytoskeleton GO:0005856 9.17 BIRC5 CDK5 CDK5RAP2 CENPJ CEP152 CNTLN

Biological processes related to Microcephaly 3, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell division GO:0051301 9.58 BIRC5 CDK5 CENPJ
2 microtubule cytoskeleton organization GO:0000226 9.48 CDK5 CDK5RAP2
3 chromosome segregation GO:0007059 9.46 BIRC5 CDK5RAP2
4 cerebral cortex development GO:0021987 9.43 CDK5 MCPH1
5 G2/M transition of mitotic cell cycle GO:0000086 9.43 CDK5RAP2 CENPJ CEP152
6 establishment of mitotic spindle orientation GO:0000132 9.37 CDK5RAP2 MCPH1
7 ciliary basal body-plasma membrane docking GO:0097711 9.33 CDK5RAP2 CENPJ CEP152
8 centrosome duplication GO:0051298 9.32 CENPJ CEP152
9 regulation of G2/M transition of mitotic cell cycle GO:0010389 9.13 CDK5RAP2 CENPJ CEP152
10 centriole replication GO:0007099 8.8 CDK5RAP2 CENPJ CEP152

Molecular functions related to Microcephaly 3, Primary, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tubulin binding GO:0015631 9.16 CDK5RAP2 CENPJ
2 microtubule binding GO:0008017 9.13 BIRC5 CDK5 CDK5RAP2
3 protein kinase binding GO:0019901 9.02 CDK5 CDK5RAP2 CENPJ CEP152 CNTLN

Sources for Microcephaly 3, Primary, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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