Alt. symbols: HRG4 | POC7 | POC7A

Approved name: unc-119 lipid binding chaperone
Alt. names: unc119 (C.elegans) homolog, unc-119 homolog (C. elegans) | POC7 centriolar protein homolog A (Chlamydomonas)

Location: 17q11.2: 28546708 - 28552631 (-)
Gene type: protein_coding, 8 transcripts.

Scores: LoFtool: 0.346000 | pLI: 0.00971742 | LOEUF: 1.327

HGNC: 12565

NCBI: 9094, RefSeq: NG_012302.1

Ensembl: ENSG00000109103.12

LRG_341 | Status: public

OMIM: 604011

Expression | ProteinAtlas

UNC119 encodes a ciliary protein with important roles in mediating Src family kinase signals for the completion of cytokinesis via RAB11A. As such, it was recently shown to be a key regulator of TCR activity in human T cells, via LCK transport to immune synapses. It has also been shown to be a lipid-binding chaperone with specificity for a diverse subset of myristoylated proteins, and as such is implicated in G-protein localization and trafficking in sensory neurons. Via its regulation of vesicular trafficking, it is also thought to function in synaptic neurotransmitter release from retinal photoreceptor cells. Its expression is enriched in retinal photoreceptors, skeletal muscle fibroblasts, and Sertoli cells of the testis. Two transcript variants encoding different isoforms have been described for this gene.

Gorska and Alam (2012) identified a heterozygous dominant-negative UNC119 missense mutation in a 32-year-old woman with ?Immunodeficiency 13 [MIM:615518], featuring CD4+ T cell lymphopenia and history of recurrent sinusitis/otitis media, frequent episodes of shingles, fungal nail infection, fungal dermatitis, oral herpetic lesions, and bronchiolitis obliterans organizing pneumonia after 2 episodes of bacterial pneumonia (PMID: 22184408). They showed that patient cells had reduced responses to TC R stimulation, with impairment in LCK localization and activation, resulting in decreased cell proliferation. They further recapitulated the patient cell defects in a cell line model and showed that the mutation disrupts the Unc119-Lck interaction normally needed for stimulation of Lck catalytic activity by TCR and also leads to Lck mislocalization to Rab11(+) perinuclear endosomes. Nagaja Capitani et al. (2024) reported the identification of a heterozygous UNC119 mutation (c.C437A, p.(T146K)) in a patient with T cell lymphopenia and defective mitogen-induced responses. They showed that patient T cells form dysfunctional ISs, with defective centrosome polarization and impaired TCR/CD3 clustering and signaling at the IS. These defects are recapitulated using T cells transfected with UNC119 T146K-GFP, which failed to establish a productive IS, but were rescued by transfection with wild-type UNC119-GFP. Preliminary data show defective accumulation of the active form of Lck (Y394) at the IS in the patient's T cells, suggesting a possible defect in ARL3-mediated Lck activation and release from UNC119. [Publication pending, presented at ESID 2024] [Load More]