CMPK2

protein-coding

cytidine/uridine monophosphate kinase 2

Gene summary

This gene encodes one of the enzymes in the nucleotide synthesis salvage pathway that may participate in terminal differentiation of monocytic cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

MANE transcript

NM_207315.4

Inheritance

ClinVar variants

P:4U:96B:11

Top phenotype

Basal ganglia calcification, idiopathic, 10, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr2:6,840,570-6,866,635

External References & Databases

Ensembl (ENSG00000134326)

Transcript & Mutation Effects

hg38 • Region Span ~26.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

basal ganglia calcification, idiopathic, 10, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0975875

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Basal ganglia calcification, idiopathic, 10, autosomal recessiveAR

Manifestation: 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: 36443312

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CMPK2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 96

CMPK2-related disorderTotal: 5

not providedTotal: 4

Basal ganglia calcification, idiopathic, 10, autosomal recessiveTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207315.4. 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	1 clinvar		96 clinvar	9 clinvar		106
nonsense						0
start loss	2 clinvar					2
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)						0
Total	3	1	96	11	0	111

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207315.4	RefSeq	NP_997198.2	5	MANE Select
ENST00000256722.10	Ensembl	ENSP00000256722.5	5	MANE Select
NM_001256477.1	RefSeq	NP_001243406.1	4	Standard
NM_001256478.1	RefSeq	NP_001243407.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyrimidine metabolism - Homo sapiens (human)
Pyrimidine Metabolism
UMP Synthase Deiciency (Orotic Aciduria)
MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy)
Beta Ureidopropionase Deficiency

Biological Process

nucleoside diphosphate phosphorylation
dUDP biosynthetic process
dTDP biosynthetic process
dTTP biosynthetic process
nucleoside triphosphate biosynthetic process

Molecular Function

cytidylate kinase activity
nucleoside diphosphate kinase activity
thymidylate kinase activity
ATP binding
uridylate kinase activity

Cellular Component

cytoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000256722
Coding exons: 5
Length: 26066
Individuals with no LoFs: 124763
Homozygous LoFs: 1
Heterozygous LoFs: 35
Defined: 124799
p: 0.000144

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.274	170	180	0.943	0.00000943	2788
Missense (PolyPhen)		70	75.095	0.93215		986
Synonymous	0.171	75	76.9	0.975	0.00000398	985
Loss of Function	0.472	10	11.7	0.851	5.00e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00084	0.00084	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00039	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000071	rare
South Asian	0.00013	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May participate in dUTP and dCTP synthesis in mitochondria. Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP; CMP and UMP are poor substrates. May be involved in mtDNA depletion caused by long term treatment with ddC or other pyrimidine analogs. Also displays broad nucleoside diphosphate kinase activity. {ECO:0000269|PubMed:17999954, ECO:0000269|PubMed:23416111}.;

Recessive Scores

pRec: 0.111

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.575

Gene Damage Prediction

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