TRAM2

Chr 6

translocation associated membrane protein 2

NCBI Gene: 9697ENSG00000065308UniProt: Q15035

Necessary for collagen type I synthesis. May couple the activity of the ER Ca(2+) pump SERCA2B with the activity of the translocon. This coupling may increase the local Ca(2+) concentration at the site of collagen synthesis, and a high Ca(2+) concentration may be necessary for the function of molecular chaperones involved in collagen folding. Required for proper insertion of the first transmembrane helix N-terminus of TM4SF20 into the ER lumen, may act as a ceramide sensor for regulated alternative translocation (RAT) (PubMed:27499293)

0
ClinVar variants
0
Pathogenic / LP
0.94
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRAM2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.35LOEUF
pLI 0.944
Z-score 3.79
OE 0.13 (0.06–0.35)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.76Z-score
OE missense 0.66 (0.58–0.76)
145 obs / 218.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.06–0.35)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.58–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.96
0≤1.21.6
LoF obs/exp: 3 / 22.3Missense obs/exp: 145 / 218.2Syn Z: 0.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TRAM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Exosomes-loaded thermosensitive hydrogels for corneal epithelium and stroma regeneration.
Tang Q et al.·Biomaterials
2022
Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma.
Xu F et al.·Front Immunol
2022
Identification of Four Enhancer-Associated Genes as Risk Signature for Diffuse Glioma Patients.
Wang J et al.·J Mol Neurosci
2022Cohort
Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer.
Jiang W et al.·Can J Gastroenterol Hepatol
2022Functional
Three de novo losses and one insertion within a pericentric inversion of chromosome 6 in a patient with complete absence of expressive speech and reduced pain perception.
Poot M et al.·Eur J Med Genet
2009Case report
Anti-cyclic citrullinated peptide antibodies are associated with radiographic damage but not disease activity in early rheumatoid arthritis diagnosed in 2006-2011.
Ziegelasch M et al.·Scand J Rheumatol
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools