TRIM49C

Chr 11

tripartite motif containing 49C

Also known as: TRIM49L2

NCBI Gene: 642612 ENSG00000204449 UniProt: P0CI26

TRIM49C encodes a protein predicted to function as a ubiquitin protein ligase involved in innate immune response and regulation of gene expression in the cytoplasm. This gene is highly tolerant to loss-of-function variants based on population data (pLI 0.0001, LOEUF 1.7), and no established human disease associations have been reported. Clinical significance of variants in this gene remains uncertain.

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

1.70

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.70LOEUF

pLI 0.000

Z-score 0.20

OE 0.92 (0.50–1.70)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.98 (0.85–1.12)

151 obs / 154.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.50–1.70)

0≤0.351.4

Missense OE?0.98 (0.85–1.12)

0≤0.61.4

Synonymous OE?1.25

0≤1.21.6

LoF obs/exp: 6 / 6.6Missense obs/exp: 151 / 154.5Syn Z: -1.41

Background carrier burden — how many people carry a rare variant somewhere in TRIM49C?

gnomAD v4 · ~727k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

215 rare PASS variants

Rare truncating (LoF)

1 in 2,600

33 rare PASS variants

Rare synonymous (reference)

1 in 430

77 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM49C. 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)	~554k	1 in 160	1 in 4,200
South Asian	~43k	1 in 89	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 6,800
European (Finnish)	~26k	1 in 430	≈ 1 in 26,000
Admixed American	~22k	1 in 220	1 in 1,200
African / African American	~20k	1 in 81	1 in 1,500
East Asian	~20k	1 in 190	1 in 1,200
Ashkenazi Jewish	~13k	1 in 320	≈ 1 in 6,400
Middle Eastern	~2,856	1 in 200	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): 1 of 6 coding exons well covered in gnomAD exomes; exons 4, 5, 6, 7 poorly covered; exon 3 marginal. Genomes: 0 of 6 (exons 3, 4, 5, 6, 7, 8 below).? see exons ↓