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 nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.60

LOEUF

—

Mechanism

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

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 18

2,776 rare PASS variants

Rare truncating (LoF)

1 in 540

368 rare PASS variants

Rare synonymous (reference)

1 in 41

1,062 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TICRR. 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 28	1 in 590
South Asian	~43k	1 in 18	1 in 330
Remaining (unassigned)	~30k	1 in 18	1 in 490
European (Finnish)	~27k	1 in 91	1 in 320
Admixed American	~22k	1 in 18	1 in 450
African / African American	~21k	1 in 17	1 in 640
East Asian	~20k	1 in 22	1 in 500
Ashkenazi Jewish	~13k	1 in 93	1 in 1,300
Middle Eastern	~2,884	1 in 20	≈ 1 in 700

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): 20 of 22 coding exons well covered in gnomAD exomes; exons 9, 13 marginal. Genomes: 21 of 22 (exon 13 below).? see exons ↓