CDK19

protein-coding

cyclin dependent kinase 19, the group of Cyclin dependent kinases|Mediator complex

Gene summary

This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

Previous symbols:

CDK11
CDC2L6

MANE transcript

NM_015076.5

Inheritance

ClinVar variants

P:10U:86B:13

Top phenotype

Developmental and epileptic encephalopathy 87

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr6:110,609,978-110,815,958

External References & Databases

Ensembl (ENSG00000155111)

Transcript & Mutation Effects

hg38 • Region Span ~206.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 87STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030059

Submitter: G2P

developmental and epileptic encephalopathy, 87STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030059

Submitter: Labcorp Genetics (formerly Invitae)

developmental and epileptic encephalopathy, 87LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0030059

Submitter: Ambry Genetics

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

Clinical Genomic Database (CGD)

Developmental and epileptic encephalopathy 87AD

Manifestation: Craniofacial; 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: 32330417

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDK19 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 45

Inborn genetic diseasesTotal: 29

Developmental and epileptic encephalopathy, 87Total: 22

CDK19-related disorderTotal: 7

not specifiedTotal: 7

See casesTotal: 2

Neurodevelopmental disorderTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015076.5. 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				11 clinvar		11
missense	4 clinvar	6 clinvar	74 clinvar	2 clinvar		86
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	4	6	86	13	0	109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015076.5	RefSeq	NP_055891.1	13	MANE Select
ENST00000368911.8	Ensembl	ENSP00000357907.3	13	MANE Select
NM_001300960.2	RefSeq	NP_001287889.1	12	Standard
NM_001300963.2	RefSeq	NP_001287892.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Transcriptional regulation of white adipocyte differentiation

Biological Process

protein phosphorylation
positive regulation of apoptotic process
positive regulation of inflammatory response
regulation of cell cycle
cellular response to lipopolysaccharide

Molecular Function

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

Cellular Component

nucleus
cytosol
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368911
Coding exons: 13
Length: 205981
Individuals with no LoFs: 125660
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125663
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.56	114	283	0.403	0.0000145	3311
Missense (PolyPhen)		20	100.68	0.19864		1213
Synonymous	0.871	93	104	0.891	0.00000572	925
Loss of Function	4.82	1	29.0	0.0345	0.00000143	337

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0850

Intolerance Scores

LoFtool: 0.0675
RVIS EVS: -0.23
RVIS percentile EVS: 36.86

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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