TBRG1

Chr 11

FYRN and FYRC domains INO80 complex interactor 1

Also known as: NIAM, TB-5, TBRG1

NCBI Gene: 84897 ENSG00000154144 UniProt: Q3YBR2 OMIM: 610614

TBRG1 encodes a growth inhibitor protein that activates p53, causes G1 cell cycle arrest, and maintains chromosomal stability by redistributing CDKN2A into the nucleoplasm. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and microcephaly. The gene is highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Involved in several processes, including DNA replication; protein localization to nucleoplasm; and protein stabilization. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.000

Z-score 1.99

OE 0.50 (0.30–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.81Z-score

OE missense 0.84 (0.74–0.95)

175 obs / 207.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.30–0.86)

0≤0.351.4

Missense OE?0.84 (0.74–0.95)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 9 / 18.2Missense obs/exp: 175 / 207.9Syn Z: 1.38

Background carrier burden — how many people carry a rare variant somewhere in TBRG1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

525 rare PASS variants

Rare truncating (LoF)

1 in 1,600

84 rare PASS variants

Rare synonymous (reference)

1 in 180

184 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TBRG1. 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 140	1 in 1,600
South Asian	~43k	1 in 71	1 in 4,500
Remaining (unassigned)	~30k	1 in 120	1 in 3,000
European (Finnish)	~27k	1 in 2,500	≈ 1 in 8,600
Admixed American	~22k	1 in 110	1 in 3,300
African / African American	~21k	1 in 93	1 in 1,400
East Asian	~20k	1 in 85	1 in 2,200
Ashkenazi Jewish	~13k	1 in 1,800	none seen
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,800

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 9.? see exons ↓