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TBC1D4

Synonyms
AS160, NIDDM5
External resources
Summary
This gene is a member of the Tre-2/BUB2/CDC16 domain family. The protein encoded by this gene is a Rab-GTPase-activating protein, and contains two phopshotyrosine-binding domains (PTB1 and PTB2), a calmodulin-binding domain (CBD), a Rab-GTPase domain, and multiple AKT phosphomotifs. This protein is thought to play an important role in glucose homeostasis by regulating the insulin-dependent trafficking of the glucose transporter 4 (GLUT4), important for removing glucose from the bloodstream into skeletal muscle and fat tissues. Reduced expression of this gene results in an increase in GLUT4 levels at the plasma membrane, suggesting that this protein is important in intracellular retention of GLUT4 under basal conditions. When exposed to insulin, this protein is phosphorylated, dissociates from GLUT4 vesicles, resulting in increased GLUT4 at the cell surface, and enhanced glucose transport. Phosphorylation of this protein by AKT is required for proper translocation of GLUT4 to the cell surface. Individuals homozygous for a mutation in this gene are at higher risk for type 2 diabetes and have higher levels of circulating glucose and insulin levels after glucose ingestion. Alternative splicing results in multiple transcript variants encoding different isoforms.

Variant Counts

Variant classification counts, according to ACMG guideline on all identified variants among our tested samples, are listed. The variants with over 5% variant frequency in population genome databases ( gnomAD, dbSNP, etc.) are excluded.

Pathogenic
16
Likely pathogenic
0
VUS
9,116
Likely benign
3,825
Benign
0

Patient Phenotypes

Proportions of phenotypes among 13 patients carrying pathogenic or likely pathogenic variants on TBC1D4 gene are displayed below. The following symptoms were found in patients with a variant in TBC1D4. However, patients may have been diagnosed with a different variant.

Phenotype class
Patients in 3billion (%)
Abnormality of the nervous system
46.2%
Abnormality of the eye
38.5%
Abnormality of the musculoskeletal system
38.5%
Abnormality of head or neck
30.8%
Abnormality of the ear
23.1%
Abnormality of limbs
15.4%
Abnormality of the cardiovascular system
15.4%
Growth abnormality
15.4%
Abnormality of the digestive system
7.7%
Abnormality of the integument
7.7%
Abnormality of the voice
7.7%
Constitutional symptom
7.7%
Abnormal cellular phenotype
0%
Abnormality of blood and blood forming tissues
0%
Abnormality of metabolism homeostasis
0%
Abnormality of prenatal development or birth
0%
Abnormality of the breast
0%
Abnormality of the endocrine system
0%
Abnormality of the genitourinary system
0%
Abnormality of the immune system
0%
Abnormality of the respiratory system
0%
Abnormality of the thoracic cavity
0%
Neoplasm
0%

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