TIPIN

Chr 15

TIMELESS interacting protein

NCBI Gene: 54962 ENSG00000075131 UniProt: Q9BVW5 OMIM: 610716

The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.44

OE 0.58 (0.34–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.30Z-score

OE missense 0.93 (0.81–1.07)

140 obs / 150.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.34–1.05)

0≤0.351.4

Missense OE?0.93 (0.81–1.07)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 8 / 13.8Missense obs/exp: 140 / 150.3Syn Z: 0.18

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

319 rare PASS variants

Rare truncating (LoF)

1 in 1,700

73 rare PASS variants

Rare synonymous (reference)

1 in 410

111 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TIPIN. 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 320	1 in 1,800
South Asian	~43k	1 in 300	1 in 1,900
Remaining (unassigned)	~30k	1 in 120	1 in 2,500
European (Finnish)	~27k	1 in 720	≈ 1 in 8,900
Admixed American	~22k	1 in 190	1 in 1,200
African / African American	~21k	1 in 170	1 in 860
East Asian	~20k	1 in 240	1 in 1,300
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	≈ 1 in 950	≈ 1 in 1,400

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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓