TOM1L2

Chr 17

target of myb1 like 2 membrane trafficking protein

NCBI Gene: 146691ENSG00000175662UniProt: Q6ZVM7

This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

203
ClinVar variants
121
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TOM1L2
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
121 Pathogenic / Likely Pathogenic· 79 VUS of 203 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.56LOEUF
pLI 0.002
Z-score 3.53
OE 0.34 (0.21–0.56)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.68Z-score
OE missense 0.89 (0.81–0.98)
280 obs / 313.8 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.0.34 (0.21–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.81–0.98)
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.1.08
0≤1.21.6
LoF obs/exp: 11 / 32.8Missense obs/exp: 280 / 313.8Syn Z: -0.73

ClinVar Variant Classifications

203 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic120
Likely Pathogenic1
VUS79
Likely Benign3
120
Pathogenic
1
Likely Pathogenic
79
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
120
0
120
Likely Pathogenic
0
0
1
0
1
VUS
0
74
5
0
79
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total0761270203

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

View in ClinVar →

Protein Context — Lollipop Plot

TOM1L2 · 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
Pinpointing Novel Plasma and Brain Proteins for Common Ocular Diseases: A Comprehensive Cross-Omics Integration Analysis.
Mo Q et al.·Int J Mol Sci
2024
Genetic Variant Overlap Analysis Identifies Established and Putative Genes Involved in Pulmonary Fibrosis.
Groen K et al.·Int J Mol Sci
2023
Evidence That Non-Syndromic Familial Tall Stature Has an Oligogenic Origin Including Ciliary Genes.
Weiss B et al.·Front Endocrinol (Lausanne)
2021
Post-mortem cytogenomic investigations in patients with congenital malformations.
Dias AT et al.·Exp Mol Pathol
2016Cohort
COPS3 amplification and clinical outcome in osteosarcoma.
Yan T et al.·Cancer
2007
The t(1;10)(p22;q24) TGFBR3/MGEA5 Translocation in Pleomorphic Hyalinizing Angiectatic Tumor, Myxoinflammatory Fibroblastic Sarcoma, and Hemosiderotic Fibrolipomatous Tumor.
Liu H et al.·Arch Pathol Lab Med
2019
Smith-Magenis Syndrome Patients Often Display Antibody Deficiency but Not Other Immune Pathologies.
Perkins T et al.·J Allergy Clin Immunol Pract
2017Cohort
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