CKMT1A

protein-coding

creatine kinase, mitochondrial 1A

Gene summary

Mitochondrial creatine (MtCK) kinase 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. Many malignant cancers with poor prognosis have shown overexpression of ubiquitous mitochondrial creatine kinase; this may be related to high energy turnover and failure to eliminate cancer cells via apoptosis. Ubiquitous mitochondrial creatine kinase has 80% homology with the coding exons of sarcomeric mitochondrial creatine kinase. Two genes located near each other on chromosome 15 have been identified which encode identical mitochondrial creatine kinase proteins. [provided by RefSeq, Jul 2008]

Previous symbols:

CKMT1

MANE transcript

NM_001321926.2

Inheritance

—

ClinVar variants

U:26B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr15:43,692,886-43,699,222

External References & Databases

Ensembl (ENSG00000223572)

Transcript & Mutation Effects

hg38 • Region Span ~6.3 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 CKMT1A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 25

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001321926.2. 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				2 clinvar		2
missense			26 clinvar			26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	26	2	0	28

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001321926.2	RefSeq	NP_001308855.1	9	MANE Select
ENST00000413453.7	Ensembl	ENSP00000406577.3	9	MANE Select
NM_001015001.2	RefSeq	NP_001015001.1	9	Standard
NM_001321927.1	RefSeq	NP_001308856.1	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
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: ENST00000413453
Coding exons: 9
Length: 6337
Individuals with no LoFs: 125703
Homozygous LoFs: 2
Heterozygous LoFs: 38
Defined: 125743
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.631	94	113	0.833	0.00000678	2669
Missense (PolyPhen)		45	53.967	0.83384		1184
Synonymous	0.390	35	38.1	0.920	0.00000184	887
Loss of Function	0.131	10	10.5	0.956	6.54e-7	225

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00075	0.00074	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00020	0.00016	rare
Other	0	0.0	absent

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: 0.676

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.787

Gene Damage Prediction

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