TDRD3

Chr 13

tudor domain containing 3

NCBI Gene: 81550 ENSG00000083544 UniProt: Q9H7E2

TDRD3 encodes a scaffolding protein that binds dimethylated arginine-containing proteins and functions as a transcriptional coactivator in the nucleus and an antiviral factor in stress granule assembly in the cytoplasm. This gene is highly constrained against loss-of-function variants (pLI near 1, LOEUF 0.624), but associated diseases from mutations have not been well-characterized in the clinical literature. Additional phenotypic data is needed to define the clinical spectrum of TDRD3-related disorders.

ResearchSummary from RefSeq, UniProt

Enables chromatin binding activity; histone reader activity; and transcription coactivator activity. Predicted to be involved in siRNA-mediated heterochromatin formation. Located in cytosol; exon-exon junction complex; and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.62

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.62LOEUF

pLI 0.000

Z-score 3.41

OE 0.41 (0.28–0.62)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.43Z-score

OE missense 0.79 (0.72–0.87)

306 obs / 385.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.28–0.62)

0≤0.351.4

Missense OE?0.79 (0.72–0.87)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 16 / 38.9Missense obs/exp: 306 / 385.1Syn Z: 0.75

Background carrier burden — how many people carry a rare variant somewhere in TDRD3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 96

870 rare PASS variants

Rare truncating (LoF)

1 in 1,600

101 rare PASS variants

Rare synonymous (reference)

1 in 190

318 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TDRD3. 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 130	1 in 1,500
South Asian	~43k	1 in 63	1 in 1,500
Remaining (unassigned)	~30k	1 in 88	1 in 1,600
European (Finnish)	~27k	1 in 270	1 in 4,100
Admixed American	~22k	1 in 79	1 in 2,000
African / African American	~21k	1 in 63	1 in 1,300
East Asian	~20k	1 in 97	1 in 1,700
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 100	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): 10 of 13 coding exons well covered in gnomAD exomes; exons 1, 2, 3 marginal. Genomes: all 13.? see exons ↓