CKMT2

protein-coding

creatine kinase, mitochondrial 2

Gene summary

Mitochondrial creatine kinase (MtCK) is responsible for the transfer of high energy phosphate from mitochondria to the cytosolic carrier, creatine. It belongs to the creatine kinase isoenzyme family. It exists as two isoenzymes, sarcomeric MtCK and ubiquitous MtCK, encoded by separate genes. Mitochondrial creatine kinase occurs in two different oligomeric forms: dimers and octamers, in contrast to the exclusively dimeric cytosolic creatine kinase isoenzymes. Sarcomeric mitochondrial creatine kinase has 80% homology with the coding exons of ubiquitous mitochondrial creatine kinase. This gene contains sequences homologous to several motifs that are shared among some nuclear genes encoding mitochondrial proteins and thus may be essential for the coordinated activation of these genes during mitochondrial biogenesis. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001099735.2

Inheritance

—

ClinVar variants

U:66B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.06

Max pathogenic AF

—

Genomic locus

chr5:81,233,320-81,266,398

External References & Databases

Ensembl (ENSG00000131730)

Transcript & Mutation Effects

hg38 • Region Span ~33.1 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 CKMT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099735.2. 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						0
missense			66 clinvar	1 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	66	1	0	67

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099735.2	RefSeq	NP_001093205.1	9	MANE Select
ENST00000254035.9	Ensembl	ENSP00000254035.4	9	MANE Select
NM_001099736.2	RefSeq	NP_001093206.1	9	Standard
NM_001825.3	RefSeq	NP_001816.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Arginine and proline metabolism - Homo sapiens (human)
creatine-phosphate biosynthesis
Metabolism of polyamines
Metabolism of amino acids and derivatives
Metabolism

Biological Process

creatine metabolic process
muscle contraction
phosphorylation

Molecular Function

creatine kinase activity
ATP binding

Cellular Component

mitochondrion
mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000424301
Coding exons: 9
Length: 33113
Individuals with no LoFs: 125634
Homozygous LoFs: 0
Heterozygous LoFs: 114
Defined: 125748
p: 0.000453

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.30	212	272	0.778	0.0000173	2728
Missense (PolyPhen)		92	119.06	0.77273		1219
Synonymous	-0.206	109	106	1.03	0.00000679	856
Loss of Function	-0.251	25	23.7	1.06	0.00000153	232

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00041	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00060	0.00053	rare
South Asian	0.00046	0.00046	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa.;

Recessive Scores

pRec: 0.615

Intolerance Scores

LoFtool: 0.945
RVIS EVS: -0.62
RVIS percentile EVS: 17.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.979

Gene Damage Prediction

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