TRIM69

Chr 15

tripartite motif containing 69

Also known as: HSD-34, HSD34, RNF36, Trif

NCBI Gene: 140691 ENSG00000185880 UniProt: Q86WT6

This gene encodes a member of the RING-B-box-coiled-coil (RBCC) family and encodes a protein with an N-terminal RING finger motif, a PRY domain and a C-terminal SPRY domain. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

Multiple*

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?

1.15LOEUF

pLI 0.000

Z-score 1.05

OE 0.75 (0.51–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.40Z-score

OE missense 1.07 (0.97–1.19)

270 obs / 252.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.75 (0.51–1.15)

0≤0.351.4

Missense OE?1.07 (0.97–1.19)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 16 / 21.2Missense obs/exp: 270 / 252.1Syn Z: 1.30

Background carrier burden — how many people carry a rare variant somewhere in TRIM69?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

654 rare PASS variants

Rare truncating (LoF)

1 in 1,800

94 rare PASS variants

Rare synonymous (reference)

1 in 160

219 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRIM69. 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 110	1 in 2,200
South Asian	~43k	1 in 120	1 in 550
Remaining (unassigned)	~30k	1 in 91	1 in 420
European (Finnish)	~27k	1 in 630	1 in 1,500
Admixed American	~22k	1 in 120	1 in 3,200
African / African American	~21k	1 in 82	1 in 620
East Asian	~20k	1 in 92	1 in 700
Ashkenazi Jewish	~13k	1 in 380	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,500

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): 7 of 7 coding exons well covered in gnomAD exomes. Genomes: 6 of 7 (exon 1 below).? see exons ↓