TRAM1L1

Chr 4

translocation associated membrane protein 1 like 1

NCBI Gene: 133022 ENSG00000174599 UniProt: Q8N609 OMIM: 617505

Predicted to be involved in protein insertion into ER membrane. Predicted to be located in membrane. Predicted to be active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.39

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.39LOEUF

pLI 0.007

Z-score 0.90

OE 0.62 (0.30–1.39)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.95 (0.85–1.07)

191 obs / 200.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.30–1.39)

0≤0.351.4

Missense OE?0.95 (0.85–1.07)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 4 / 6.5Missense obs/exp: 191 / 200.5Syn Z: 0.48

Background carrier burden — how many people carry a rare variant somewhere in TRAM1L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

489 rare PASS variants

Rare truncating (LoF)

1 in 3,300

70 rare PASS variants

Rare synonymous (reference)

1 in 390

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAM1L1. 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 220	1 in 3,400
South Asian	~43k	1 in 100	1 in 1,100
Remaining (unassigned)	~30k	1 in 140	1 in 4,300
European (Finnish)	~27k	1 in 810	≈ 1 in 8,900
Admixed American	~22k	1 in 240	1 in 2,800
African / African American	~21k	1 in 240	≈ 1 in 4,200
East Asian	~20k	1 in 170	1 in 2,000
Ashkenazi Jewish	~13k	1 in 410	≈ 1 in 4,400
Middle Eastern	~2,884	1 in 410	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): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓