CDK10

protein-coding

cyclin dependent kinase 10, the group of Spliceosomal P complex|Cyclin dependent kinases|Spliceosomal C complex

Gene summary

The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

MANE transcript

NM_052988.5

Inheritance

ClinVar variants

P:32U:92B:20

Top phenotype

Al Kaissi syndrome

gnomAD constraint

pLI —, LoF o/e 1.03

Max pathogenic AF

—

Genomic locus

chr16:89,680,737-89,696,354

External References & Databases

Ensembl (ENSG00000185324)

Transcript & Mutation Effects

hg38 • Region Span ~15.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Al Kaissi syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044324

Submitter: Labcorp Genetics (formerly Invitae)

Al Kaissi syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044324

Submitter: G2P

Clinical Genomic Database (CGD)

Al Kaissi syndromeAR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28886341

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDK10 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 80

Al Kaissi syndromeTotal: 43

not providedTotal: 42

not specifiedTotal: 11

CDK10-related disorderTotal: 8

Abnormal brain morphologyTotal: 2

Fetal anomalies with a likely genetic causeTotal: 1

Global developmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052988.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	3 clinvar	13 clinvar	1 clinvar	18
missense	2 clinvar	2 clinvar	85 clinvar	6 clinvar		95
nonsense	2 clinvar	7 clinvar				9
start loss						0
frameshift	5 clinvar	7 clinvar				12
splice donor/acceptor (+/-2bp)	3 clinvar	3 clinvar	4 clinvar			10
Total	12	20	92	19	1	144

Highest pathogenic variant AF is 0.000061365135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 106 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052988.5	RefSeq	NP_443714.3	13	MANE Select
ENST00000353379.12	Ensembl	ENSP00000338673.7	13	MANE Select
NM_001098533.3	RefSeq	NP_001092003.2	11	Standard
NM_001160367.2	RefSeq	NP_001153839.1	11	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cdk10	Danio rerio	Structure: retinal ganglion cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

cdk10

Danio rerio

Structure: retinal ganglion cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein phosphorylation
traversing start control point of mitotic cell cycle
negative regulation of cell population proliferation
peptidyl-threonine phosphorylation
cell projection organization

Molecular Function

protein serine/threonine kinase activity
cyclin-dependent protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
ciliary basal body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000353379
Coding exons: 13
Length: 15628
Individuals with no LoFs: 125648
Homozygous LoFs: 0
Heterozygous LoFs: 99
Defined: 125747
p: 0.000394

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.461	252	232	1.09	0.0000151	2302
Missense (PolyPhen)		67	81.483	0.82226		797
Synonymous	-2.61	130	97.3	1.34	0.00000636	712
Loss of Function	-0.149	24	23.2	1.03	0.00000127	249

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00025	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.0036	0.0036	notable
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00030	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cyclin-dependent kinase that phosphorylates the transcription factor ETS2 (in vitro) and positively controls its proteasomal degradation (in cells) (PubMed:24218572). Involved in the regulation of actin cytoskeleton organization through the phosphorylation of actin dynamics regulators such as PKN2. Is a negative regulator of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling (PubMed:27104747). {ECO:0000269|PubMed:24218572, ECO:0000269|PubMed:27104747}.;
Disease: DISEASE: Al Kaissi syndrome (ALKAS) [MIM:617694]: An autosomal recessive developmental disorder characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delay. {ECO:0000269|PubMed:28886341}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.863
RVIS EVS: 0.07
RVIS percentile EVS: 58.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.987

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium