TRAM1

Chr 8

translocation associated membrane protein 1

Also known as: PNAS8, TRAM, TRAMP

The protein facilitates translocation of nascent proteins across the endoplasmic reticulum membrane and regulates proper positioning at the SEC61 channel, playing a critical role in protein processing and quality control. Mutations cause autosomal recessive intellectual disability with congenital malformations affecting multiple organ systems. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

Summary from RefSeq, UniProt
Research Assistant →
1
Active trials
2
Pubs (1 yr)
33
P/LP submissions
0%
P/LP missense
0.36
LOEUF
Mechanism
Clinical SummaryTRAM1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.93). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 34 VUS of 94 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.36LOEUF
pLI 0.925
Z-score 3.70
OE 0.14 (0.060.36)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.54Z-score
OE missense 0.69 (0.600.80)
134 obs / 194.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.14 (0.060.36)
00.351.4
Missense OE0.69 (0.600.80)
00.61.4
Synonymous OE1.24
01.21.6
LoF obs/exp: 3 / 21.5Missense obs/exp: 134 / 194.5Syn Z: -1.58

ClinVar Variant Classifications

94 submitted variants in ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS34
Likely Benign4
Benign1
32
Pathogenic
1
Likely Pathogenic
34
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
0
30
4
0
34
Likely Benign
0
3
0
1
4
Benign
0
1
0
0
1
Total03437172

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRAM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC