DTYMK

deoxythymidylate kinase

Basic information

Region (hg38): 2:241675747-241686944

Links

ENSG00000168393 ∙ NCBI:1841 ∙ OMIM:188345 ∙ HGNC:3061 ∙ Uniprot:P23919 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodegeneration, childhood-onset, with progressive microcephaly (Strong), mode of inheritance: AR
• mitochondrial DNA depletion syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodegeneration, childhood-onset, with progressive microcephaly	AR	General	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	Genitourinary; Neurologic	31271740; 34918187

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DTYMK gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DTYMK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			17	1	1	19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	18	2	1

Variants in DTYMK

This is a list of pathogenic ClinVar variants found in the DTYMK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-241676149-G-A		not specified	Uncertain significance (Jan 26, 2022)
2-241676173-G-A		not specified	Uncertain significance (Dec 01, 2022)
2-241676174-C-T		not specified	Likely benign (Dec 06, 2022)
2-241676224-G-A		not specified	Uncertain significance (Jul 26, 2021)
2-241678467-C-T			Likely benign (May 01, 2023)
2-241678505-G-A		not specified	Uncertain significance (Jul 09, 2021)
2-241678547-C-T		not specified	Uncertain significance (Jul 31, 2023)
2-241678553-G-A		not specified	Uncertain significance (Oct 25, 2023)
2-241678591-A-C		not specified	Uncertain significance (Aug 08, 2024)
2-241678598-C-T		Neurodegeneration, childhood-onset, with progressive microcephaly	Pathogenic (Apr 28, 2022)
2-241678616-C-T		not specified	Uncertain significance (Nov 22, 2022)
2-241680238-ACCGGTGAAGGCCACACCAGAAAATGCGTATCTGT-A		Neurodegeneration, childhood-onset, with progressive microcephaly	Pathogenic (Apr 28, 2022)
2-241680257-G-C		not specified	Uncertain significance (Nov 21, 2023)
2-241680264-C-T		Neurodegeneration, childhood-onset, with progressive microcephaly	Pathogenic (Oct 06, 2022)
2-241680317-G-A		Neurodegeneration, childhood-onset, with progressive microcephaly	Pathogenic (Oct 06, 2022)
2-241684718-CAACATT-C		Neurodegeneration, childhood-onset, with progressive microcephaly	Uncertain significance (Mar 26, 2024)
2-241685819-C-T			Likely benign (Oct 01, 2024)
2-241685825-A-C		not specified	Uncertain significance (Nov 21, 2023)
2-241685863-T-G		not specified	Uncertain significance (Feb 28, 2024)
2-241686678-G-C		not specified	Uncertain significance (Nov 11, 2024)
2-241686681-G-A			Benign (Mar 29, 2018)
2-241686698-G-C		not specified	Uncertain significance (Jan 26, 2022)
2-241686699-C-A		not specified	Uncertain significance (Jul 14, 2023)
2-241686732-C-T		not specified	Uncertain significance (Jul 20, 2021)
2-241686747-C-T		not specified	Uncertain significance (Apr 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DTYMK	protein_coding	protein_coding	ENST00000305784	5	11250

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000615	0.488	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.251	122	130	0.938	0.00000856	1362
Missense in Polyphen		32	44.096	0.72569		480
Synonymous	-0.309	62	59.0	1.05	0.00000421	427
Loss of Function	0.451	7	8.41	0.832	3.56e-7	103

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000239	0.000239
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.0000939	0.0000924
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.000217	0.000217
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of dTMP to dTDP.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics;Pyrimidine metabolism;pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;Metabolism of nucleotides;Interconversion of nucleotide di- and triphosphates;Metabolism;superpathway of pyrimidine deoxyribonucleoside salvage;Pyrimidine nucleotides nucleosides metabolism;pyrimidine deoxyribonucleotide phosphorylation;superpathway of pyrimidine deoxyribonucleotides <i>de novo</i> biosynthesis;pyrimidine deoxyribonucleotides biosynthesis from CTP (Consensus)

Recessive Scores

• pRec: 0.272

Intolerance Scores

• loftool: 0.368
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.376
• ghis: 0.701

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.966

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dtymk

Gene ontology

• Biological process: nucleoside diphosphate phosphorylation;dUDP biosynthetic process;dTDP biosynthetic process;dTTP biosynthetic process;cell population proliferation;nucleobase-containing small molecule interconversion;response to estrogen;myoblast differentiation;response to cadmium ion;nucleoside monophosphate phosphorylation;cellular response to growth factor stimulus
• Cellular component: nucleus;cytoplasm;mitochondrion;mitochondrial intermembrane space;mitochondrial matrix;cytosol
• Molecular function: nucleoside diphosphate kinase activity;thymidylate kinase activity;ATP binding;uridylate kinase activity;nucleoside monophosphate kinase activity