CMPK1

Chr 1

cytidine/uridine monophosphate kinase 1

Also known as: CK, CMK, CMPK, UMK, UMP-CMPK, UMPK

NCBI Gene: 51727 ENSG00000162368 UniProt: P30085 OMIM: 191710

The protein catalyzes the phosphorylation of pyrimidine nucleoside monophosphates using ATP, playing an important role in de novo pyrimidine nucleotide biosynthesis with preference for UMP and CMP substrates. Mutations cause autosomal recessive immunodeficiency with severe reduction in B and T cell numbers. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes one of the enzymes required for cellular nucleic acid biosynthesis. This enzyme catalyzes the transfer of a phosphate group from ATP to CMP, UMP, or dCMP, to form the corresponding diphosphate nucleotide. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Feb 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.45

Clinical Summary— CMPK1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.85) — some intolerance to loss-of-function variants.

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ClinVar Variants

12 VUS of 21 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.45LOEUF

pLI 0.848

Z-score 2.73

OE 0.09 (0.03–0.45)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.93Z-score

OE missense 0.48 (0.38–0.60)

52 obs / 108.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.09 (0.03–0.45)

0≤0.351.4

Missense OE?0.48 (0.38–0.60)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 1 / 10.6Missense obs/exp: 52 / 108.6Syn Z: 0.97

This gene — mechanism propensity

0.6162th %ile

GOF

0.5269th %ile

LOF

0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS12

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	11	1	12
Likely Benign	0	0	0
Benign	0	0	0
Total	11	1	12

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap CMPK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →