DTYMK

Chr 2AR

deoxythymidylate kinase

Also known as: CDC8, CONPM, PP3731, TMPK, TYMK

NCBI Gene: 1841 ENSG00000168393 UniProt: P23919 OMIM: 188345

The protein catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), an essential step in producing DNA building blocks within mitochondria. Mutations cause autosomal recessive neurodegeneration with childhood onset and progressive microcephaly. The gene is highly tolerant to loss-of-function variants in the general population (pLI 0.00006, LOEUF 1.54).

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables ATP binding activity and dTMP kinase activity. Involved in dTDP biosynthetic process and thymidine biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodegeneration, childhood-onset, with progressive microcephalyMIM #619847

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Neurodegeneration, childhood-onset, with progressive microcephaly; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

gnomad: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in DTYMK?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

379 rare PASS variants

Rare truncating (LoF)

1 in 1,100

72 rare PASS variants

Rare synonymous (reference)

1 in 330

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for DTYMK. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,500
South Asian	~43k	1 in 75	1 in 1,600
Remaining (unassigned)	~30k	1 in 120	1 in 230
European (Finnish)	~27k	1 in 1,000	≈ 1 in 13,000
Admixed American	~22k	1 in 140	1 in 2,500
African / African American	~21k	1 in 110	1 in 2,600
East Asian	~20k	1 in 180	1 in 1,100
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 3,500
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 5 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 5.? see exons ↓