## is a human gene whose product aHI1:** Abelson helper integration site 1 is a WD40 repeat-containing protein that localizes to the basal bodies of primary cilia. It plays critical roles in ciliary signaling, neuronal migration, and synaptic function. AHI1 interacts with the Jouberin protein and is involved in the sonic hedgehog pathway. In brain, it is highly expressed in regions affected in Parkinson disease. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
CLN2 encodes TPP1 (tripeptidyl peptidase 1), a lysosomal serine protease. It catalyzes the cleavage of N-terminal tripeptides from substrates. Deficiency causes classic late infantile Batten disease, characterized by seizures, vision loss, and neurodegeneration. [1]
| Attribute | Value | [2]
|-----------|-------| [3]
| Symbol | CLN2 | [4]
| Full Name | Ceroid Lipofuscinosis 2 (TPP1) | [5]
| Chromosomal Location | 11p15.4 | [6]
| NCBI Gene ID | 1200 | [7]
| OMIM | 607998 | [8]
| Ensembl ID | ENSG00000100418 | [9]
| UniProt | O14773 | [10]
AHI1: Abelson helper integration site 1 is a WD40 repeat-containing protein that localizes to the basal bodies of primary cilia. It plays critical roles in ciliary signaling, neuronal migration, and synaptic function. AHI1 interacts with the Jouberin protein and is involved in the sonic hedgehog pathway. In brain, it is highly expressed in regions affected in Parkinson disease. [11]
GAD1: Glutamate decarboxylase 1 produces the 67-kDa isoform (GAD67), which is responsible for most GABA synthesis in the brain. GAD67 is expressed in GABAergic neurons throughout the CNS and is essential for inhibitory neurotransmission. It is regulated at transcriptional and post-translational levels.
GAD2: Glutamate decarboxylase 2 produces the 65-kDa isoform (GAD65), which is concentrated at synaptic terminals. GAD65 is particularly important for activity-dependent GABA synthesis and is a major autoantigen in type 1 diabetes and some neurological disorders.
CLN2: Ceroid lipofuscinosis 2 encodes TPP1, a lysosomal aspartyl protease that degrades proteins in the late endosome/lysosome. TPP1 cleaves N-terminal tripeptides from various substrates and is essential for neuronal health. The enzyme is secreted and can be delivered to deficient cells.
TECPR2: Tectonin beta-propeller repeat containing 2 is an autophagy receptor that facilitates selective autophagy of damaged ER and protein aggregates. It interacts with Atg proteins and helps maintain ER homeostasis. Loss of function leads to impaired autophagy and ER stress.
Volk et al. GAD1 in schizophrenia (1999). 1999. ↩︎
Baekkeskov et al. GAD2 as autoantigen (1990). 1990. ↩︎
Sleat et al. CLN2 encoding TPP1 (1997). 1997. ↩︎
Oz-Levi et al. TECPR2 mutations cause HSP (2012). 2012. ↩︎
Jiang et al. AHI1 expression in brain (1999). 1999. ↩︎
Kaufman et al. GAD1 expression pattern (1991). 1991. ↩︎
Erlander et al. GAD1 and GAD2 expression (1991). 1991. ↩︎
Heimer et al. TECPR2 in neurons (2016). 2016. ↩︎
Schulz et al. Cerliponase alfa for CLN2 (2016). 2016. ↩︎
Ebrahimi-Fakhari et al. TECPR2 therapeutics (2022). 2022. ↩︎