CDT1

Chr 16

chromatin licensing and DNA replication factor 1

Also known as: DUP, RIS2

NCBI Gene: 81620 ENSG00000167513 UniProt: Q9H211

CDT1 encodes a DNA replication licensing factor required for pre-replication complex assembly and also promotes stable kinetochore-microtubule attachments during mitosis. Mutations cause Meier-Gorlin syndrome 4, an autosomal recessive disorder characterized by microcephaly, short stature, and underdeveloped ears. The gene shows extremely low tolerance to loss-of-function variants (pLI near zero, LOEUF 1.2), indicating it is highly constrained and critical for normal cellular function.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.22

Clinical Summary— CDT1

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Gene-Disease Validity (ClinGen)

Meier-Gorlin syndrome 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 245 VUS of 549 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.22LOEUF

pLI 0.000

Z-score 0.81

OE 0.81 (0.55–1.22)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.90Z-score

OE missense 1.29 (1.19–1.40)

435 obs / 336.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.81 (0.55–1.22)

0≤0.351.4

Missense OE?1.29 (1.19–1.40)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 17 / 21.0Missense obs/exp: 435 / 336.9Syn Z: -2.81

ClinVar Variant Classifications

549 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21

Likely Pathogenic8

VUS245

Likely Benign200

Benign47

Conflicting16

Pathogenic

Likely Pathogenic

245

VUS

200

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	15	3	3	0	21
Likely Pathogenic	6	2	0	0	8
VUS	1	231	12	1	245
Likely Benign	0	11	76	113	200
Benign	0	10	25	12	47
Conflicting	—				16
Total	22	257	116	126	537

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

View in ClinVar →

69 pathogenic / likely-pathogenic (of 93) ClinVar copy-number / structural variants overlap CDT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →