TOM1

Chr 22AD

target of myb1 membrane trafficking protein

Also known as: IMD85

NCBI Gene: 10043ENSG00000100284UniProt: O60784

This gene was identified as a target of the v-myb oncogene. The encoded protein shares its N-terminal domain in common with proteins associated with vesicular trafficking at the endosome. It is recruited to the endosomes by its interaction with endofin. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

?Immunodeficiency 85 and autoimmunityMIM #619510
AD
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TOM1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.04LOEUF
pLI 0.000
Z-score 1.38
OE 0.72 (0.51–1.04)
Tolerant

Highly tolerant — LoF variants common in population

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.
1.08Z-score
OE missense 0.83 (0.75–0.92)
255 obs / 308.3 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.0.72 (0.51–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.75–0.92)
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.0.89
0≤1.21.6
LoF obs/exp: 21 / 29.0Missense obs/exp: 255 / 308.3Syn Z: 1.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TOM1 · 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

?Immunodeficiency 85 and autoimmunity

MIM #619510

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A TOM1 variant impairs interaction with TOLLIP, autophagosome-lysosome fusion and regulation of innate immunity.
Lång HKM et al.·Dis Model Mech
2025
Whole exome sequencing for identifying rare genetic variants related to idiopathic granulomatous mastitis.
Ozer L et al.·Clin Rheumatol
2025
Ubiquitin-binding proteins: similar, but different.
Andersen KM et al.·Essays Biochem
2005Review
TOM1 Regulates Neuronal Accumulation of Amyloid-β Oligomers by FcγRIIb2 Variant in Alzheimer's Disease.
Gwon Y et al.·J Neurosci
2018
Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management.
Baxter SK et al.·J Allergy Clin Immunol
2022
Proteomic Analysis of FFPE Tissue Samples Identifies Potential Molecular Mechanisms Mediating Resistance to Radiotherapy in Rectal Cancer.
Zott T et al.·J Proteome Res
2025Functional
Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology.
McKiernan PJ et al.·Int J Nanomedicine
2013
Escherichia coli producing CNF1 toxin hijacks Tollip to trigger Rac1-dependent cell invasion.
Visvikis O et al.·Traffic
2011
Comparative proteomic analyses of two reovirus T3D subtypes and comparison to T1L identifies multiple novel proteins in key cellular pathogenic pathways.
Berard AR et al.·Proteomics
2015
WNT5A, a putative tumour suppressor of lymphoid malignancies, is inactivated by aberrant methylation in acute lymphoblastic leukaemia.
Roman-Gomez J et al.·Eur J Cancer
2007
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