TSC2

Chr 16p13.3

TSC complex subunit 2

Aliases:: tuberin, LAM, PPP1R160
MANE:: ENST00000219476.9

OMIM: 191092 ↗NCBI: 7249 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

TSC2 · P49815

v62025-08-01

Predicted Aligned Error matrix for TSC2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

67.9/ 100

Low

1,807 residues

Confidence breakdown

Very high(≥ 90)13%
Confident(70–90)51%
Low(50–70)6%
Very low(< 50)30%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult solid tumours cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult solid tumours for rare disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood solid tumours
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Childhood solid tumours cancer susceptibility
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Classical tuberous sclerosis
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cystic kidney disease
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

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Disease associations (Open Targets)

tuberous sclerosis
0.86
tuberous sclerosis 2
0.82
lymphangioleiomyomatosis
0.81
isolated focal cortical dysplasia type II
0.74
hepatocellular carcinoma
0.59
Inherited cancer-predisposing syndrome
0.57
hereditary neoplastic syndrome
0.57
familial adenomatous polyposis 3
0.55
attenuated familial adenomatous polyposis
0.55
tuberous sclerosis 1
0.49

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Tuberin

Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:33436626, PubMed:35772404). Within the TSC-TBC complex, TSC2 acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12172553, PubMed:12820960, PubMed:12842888, PubMed:12906785, PubMed:15340059, PubMed:22819219, PubMed:24529379, PubMed:33436626). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12906785, PubMed:22819219, PubMed:24529379, PubMed:28215400, PubMed:35772404). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity)