TRIM49D1

Chr 11

tripartite motif containing 49D1

The TRIM49D1 protein is predicted to function as a ubiquitin protein ligase involved in innate immune response and gene regulation. Pathogenic variants in this gene have not been definitively associated with human disease, and the gene shows relatively low constraint to loss-of-function variation (pLI 0.29, LOEUF 1.89).

ResearchSummary from RefSeq

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

—

Mechanism

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.291

Z-score 0.29

OE 0.00 (0.00–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.95Z-score

OE missense 0.35 (0.19–0.70)

6 obs / 17.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.89)

0≤0.351.4

Missense OE?0.35 (0.19–0.70)

0≤0.61.4

Synonymous OE?0.00

0≤1.21.6

LoF obs/exp: 0 / 0.1Missense obs/exp: 6 / 17.0Syn Z: 1.91

Background carrier burden — how many people carry a rare variant somewhere in TRIM49D1?

gnomAD v4 · ~563k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 7,100

2 rare PASS variants

Rare truncating (LoF)

1 in 5,300

11 rare PASS variants

Rare synonymous (reference)

none observed

0 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRIM49D1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 6 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~460k	none seen	1 in 4,200
South Asian	~26k	1 in 770	none seen
Remaining (unassigned)	~23k	none seen	≈ 1 in 23,000
African / African American	~18k	≈ 1 in 3,700	none seen
East Asian	~15k	1 in 2,300	none seen
Admixed American	~11k	≈ 1 in 6,600	1 in 1,600

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): 0 of 6 coding exons well covered in gnomAD exomes; exons 3, 4, 5, 6, 7, 8 poorly covered. Genomes: 0 of 6 (exons 3, 4, 5, 6, 7, 8 below).? see exons ↓