TRAM1

Chr 8

translocation associated membrane protein 1

Also known as: PNAS8, TRAM, TRAMP

NCBI Gene: 23471 ENSG00000067167 UniProt: Q15629

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a multi-pass membrane protein that is part of the mammalian endoplasmic reticulum. The encoded protein influences glycosylation and facilitates the translocation of secretory proteins across the endoplasmic reticulum membrane by regulating which domains of the nascent polypeptide chain are visible to the cytosol during a translocational pause. [provided by RefSeq, Oct 2009]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.36

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.36LOEUF

pLI 0.925

Z-score 3.70

OE 0.14 (0.06–0.36)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.54Z-score

OE missense 0.69 (0.60–0.80)

134 obs / 194.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.36)

0≤0.351.4

Missense OE?0.69 (0.60–0.80)

0≤0.61.4

Synonymous OE?1.24

0≤1.21.6

LoF obs/exp: 3 / 21.5Missense obs/exp: 134 / 194.5Syn Z: -1.58

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Recurrent Breast CarcinomaStage III Breast Cancer AJCC v7Stage IIIA Breast Cancer AJCC v7

Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer

ACTIVE NOT RECRUITING

NCT02311933Phase PHASE2National Cancer Institute (NCI)Started 2015-05-28

Endoxifen HydrochlorideLaboratory Biomarker AnalysisPharmacological Study

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Quantitative Mass Spectrometry Characterizes Client Spectra of Components for Targeting of Membrane Proteins to and Their Insertion into the Membrane of the Human ER

Jung M et al.·Int J Mol Sci

2023