Alt. symbols: Tp44

Approved name: CD28 molecule
Alt. names: CD28 antigen (Tp44) | T-cell-specific surface glycoprotein

Location: 2q33.2: 203706517 - 203739756 (+)
Gene type: protein_coding, 4 transcripts.

Scores: LoFtool: 0.254000 | pLI: 0.51198920 | LOEUF: 0.711

HGNC: 1653

NCBI: 940, RefSeq: NG_029618.1

Ensembl: ENSG00000178562.19

LRG_ | Status: none

OMIM: 186760

Expression | ProteinAtlas

To date, only one homozygous variant in the gene has been linked to disease (p.G18R) in one family (PMID:34214472). This variant was thought to possibly affect splicing. Indeed, patient-derived T cells showed significantly decreased CD28 mRNA levels compared to controls. About 79% of the transcripts used the canonical splicing donor site (containing the p.G18R change), whereas 21% of the transcripts used an alternative donor splice site, which led to the creation of frame-shifted transcripts tha t were predicted to have a premature stop codon. These alternative transcripts were likely subjected to nonsense-mediated mRNA decay. HEK293 cells transiently overexpressing the CD28-G18R variant showed that CD28 was normally expressed on the cell surface, whereas truncated isoforms were not detected. Functional studies showed that the CD28-G18R variant retained the ability to induce NF-kB activation upon binding to an anti-CD28 antibody; however, patient cells had extremely low levels (less than 1% of normal) of functional G18R CD28 protein. Patient T-cell blasts lacked CD28 expression and showed no CD28-dependent downstream signaling responses, indicating that the mutation is a loss-of-function allele (PMID:34214472). [Load More]