CAMKK1

protein-coding

calcium/calmodulin dependent protein kinase kinase 1

Gene summary

The product of this gene belongs to the Serine/Threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This protein plays a role in the calcium/calmodulin-dependent (CaM) kinase cascade. Three transcript variants encoding two distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_032294.3

Inheritance

—

ClinVar variants

U:82B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr17:3,860,315-3,894,891

External References & Databases

Ensembl (ENSG00000004660)

Transcript & Mutation Effects

hg38 • Region Span ~34.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CAMKK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 76

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032294.3. 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				2 clinvar		2
missense			77 clinvar	1 clinvar		78
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	82	3	0	85

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032294.3	RefSeq	NP_115670.1	15	MANE Select
ENST00000348335.7	Ensembl	ENSP00000323118.3	15	MANE Select
NM_172206.2	RefSeq	NP_757343.2	16	Standard
NM_172207.3	RefSeq	NP_757344.2	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alcoholism - Homo sapiens (human)
AMP-activated Protein Kinase (AMPK) Signaling
regulation of pgc-1a
nfat and hypertrophy of the heart
Neuronal System

Biological Process

protein phosphorylation
intracellular signal transduction
positive regulation of protein kinase activity

Molecular Function

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

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000158166
Coding exons: 15
Length: 34577
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.34	254	322	0.790	0.0000196	3359
Missense (PolyPhen)		93	137.91	0.67438		1390
Synonymous	1.13	122	139	0.878	0.00000948	1042
Loss of Function	3.06	11	28.7	0.383	0.00000132	341

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Calcium/calmodulin-dependent protein kinase that belongs to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Phosphorylates CAMK1, CAMK1D, CAMK1G and CAMK4. Involved in regulating cell apoptosis. Promotes cell survival by phosphorylating AKT1/PKB that inhibits pro-apoptotic BAD/Bcl2-antagonist of cell death. {ECO:0000269|PubMed:12935886}.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.729
RVIS EVS: -0.58
RVIS percentile EVS: 18.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.917

Gene Damage Prediction

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