TRIM64B

Chr 11

tripartite motif containing 64B

NCBI Gene: 642446 ENSG00000189253 UniProt: A6NI03

TRIM64B encodes a protein predicted to function as a ubiquitin protein ligase involved in innate immune response and gene regulation. The gene shows low constraint against loss-of-function variants (pLI 0.00001, LOEUF 1.30), suggesting that haploinsufficiency may be well-tolerated. No definitive disease associations have been established for TRIM64B mutations.

ResearchSummary from RefSeq

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.81

OE 0.75 (0.45–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.34Z-score

OE missense 0.72 (0.63–0.83)

136 obs / 187.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.75 (0.45–1.30)

0≤0.351.4

Missense OE?0.72 (0.63–0.83)

0≤0.61.4

Synonymous OE?0.66

0≤1.21.6

LoF obs/exp: 9 / 12.0Missense obs/exp: 136 / 187.7Syn Z: 2.25

Background carrier burden — how many people carry a rare variant somewhere in TRIM64B?

gnomAD v4 · ~700k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

237 rare PASS variants

Rare truncating (LoF)

1 in 290

33 rare PASS variants

Rare synonymous (reference)

1 in 190

78 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM64B. 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)	~539k	1 in 69	1 in 210
South Asian	~40k	1 in 83	1 in 480
Remaining (unassigned)	~29k	1 in 47	1 in 170
European (Finnish)	~25k	1 in 280	1 in 2,600
African / African American	~21k	1 in 80	1 in 230
Admixed American	~18k	1 in 79	1 in 320
East Asian	~18k	1 in 82	1 in 640
Ashkenazi Jewish	~13k	1 in 170	1 in 860
Middle Eastern	~2,851	1 in 420	none seen

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): 4 of 6 coding exons well covered in gnomAD exomes; exons 4, 6 marginal. Genomes: 1 of 6 (exons 2, 3, 4, 5, 6 below).? see exons ↓