TICRR

Chr 15

TOPBP1 interacting checkpoint and replication regulator

Also known as: C15orf42, SLD3, Treslin

NCBI Gene: 90381 ENSG00000140534 UniProt: Q7Z2Z1 OMIM: 613298

TICRR encodes a protein that regulates DNA replication initiation and cell cycle checkpoints by facilitating the transition from pre-replication to pre-initiation complexes at replication origins. Mutations cause Meier-Gorlin syndrome, an autosomal recessive disorder characterized by primordial dwarfism, microtia, and absent or underdeveloped patellae. The gene is highly intolerant to loss-of-function variants (LOEUF 0.599), reflecting the essential nature of proper DNA replication control.

OMIM ResearchSummary from RefSeq, UniProt

Enables chromatin binding activity. Involved in regulation of DNA-templated DNA replication initiation. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.60

Clinical Summary— TICRR

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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

319 VUS of 382 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.60LOEUF

pLI 0.000

Z-score 4.51

OE 0.45 (0.35–0.60)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-1.45Z-score

OE missense 1.13 (1.07–1.18)

1150 obs / 1019.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.45 (0.35–0.60)

0≤0.351.4

Missense OE?1.13 (1.07–1.18)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 36 / 79.4Missense obs/exp: 1150 / 1019.6Syn Z: -1.59

ClinVar Variant Classifications

382 submitted variants in ClinVar

ClinVar

Classification Summary

VUS319

Likely Benign30

Benign5

319

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	318	1	0	319
Likely Benign	27	0	3	30
Benign	3	0	2	5
Total	348	1	5	354

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

View in ClinVar →

36 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap TICRR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →