TRIM49

Chr 11

tripartite motif containing 49

Also known as: RNF18, TRIM49A, TRIM49L2

NCBI Gene: 57093 ENSG00000168930 UniProt: P0CI25 OMIM: 606124

The TRIM49 protein contains a RING zinc finger domain involved in protein-protein interactions and is preferentially expressed in testis. This gene is extremely intolerant to loss-of-function variation (pLI near 1.0), but no definitive disease associations have been established in the current literature. Additional research is needed to determine if TRIM49 mutations cause human disease.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This gene has been found to be preferentially expressed in testis. Related pseudogenes and gene duplicates have also been identified on chromosome 11. [provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.82

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.000

Z-score -0.38

OE 1.15 (0.68–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.41Z-score

OE missense 1.09 (0.96–1.23)

186 obs / 170.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.15 (0.68–1.82)

0≤0.351.4

Missense OE?1.09 (0.96–1.23)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 9 / 7.8Missense obs/exp: 186 / 170.9Syn Z: -1.01

Background carrier burden — how many people carry a rare variant somewhere in TRIM49?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

250 rare PASS variants

Rare truncating (LoF)

1 in 770

42 rare PASS variants

Rare synonymous (reference)

1 in 450

90 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM49. 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 210	1 in 1,700
South Asian	~43k	1 in 120	1 in 1,700
Remaining (unassigned)	~30k	1 in 85	≈ 1 in 30,000
European (Finnish)	~27k	1 in 900	1 in 5,300
Admixed American	~22k	1 in 100	1 in 1,100
African / African American	~20k	1 in 74	1 in 240
East Asian	~20k	1 in 95	1 in 530
Ashkenazi Jewish	~13k	1 in 680	1 in 520
Middle Eastern	~2,874	1 in 110	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): 2 of 6 coding exons well covered in gnomAD exomes; exon 5 poorly covered; exons 4, 6, 7 marginal. Genomes: 0 of 6 (exons 3, 4, 5, 6, 7, 8 below).? see exons ↓