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. Author manuscript; available in PMC: 2024 Jul 1.

Published in final edited form as: J Clin Immunol. 2023 Feb 21;43(5):847–861. doi: 10.1007/s10875-023-01437-3

Table 2.

Cellular Phenotype.

Gene	NK cell phenotype	Cell cycle	Mouse Model	Reference
MCM4	↓ NK cell frequency ↓ CD56^dim NK cells ↓ CD57⁺ NK cells ↓ Perforin⁺ NK cells ↓ Cell proliferation ↑ Apoptosis (CD56^bright & CD56^dim)	Fewer cells in G1/S phases, more cells in G2/M phases	Chaos3 (hypomorphic); Mcm4^−/− (lethal). ↓ NK cells No growth retardation Chromosomal instability	(8, 10)
GINS1	↓ CD56^bright & CD56^dim NK cells Unresponsive to cytokine stimulation		Gins1^−/− (embryonic lethal)	(9)
MCM10	↓ NK cells ↓ CD56^bright NK cells S phase arrest (MCM10-KD cell line) ↑ doubling time (MCM10-KD cell line) ↑ γH2AX foci Normal cytotoxic function (MCM10-KD cell line; K562 target cells)			(7)
GINS4	↓ NK cells ↑ CD56^bright NK cells ↓ CD57⁺ NK cells ↓ CD94⁺ NK cells ↓ cytotoxic function (K562 target cells) ↓ IFN-γ production ↓ survival when stimulated with PMA	Mild mitotic exit defect		(6)
POLA1	↓ NK cell frequency ↓ lymphocytes ↓ CD56^dim NK cells ↓ CD57⁺ NK cells Normal perforin & granzyme ↓ cytotoxic function (721.221 cells) Normal proliferation Normal TNF+ or IFNγ+ cells ↓ polarization of lytic granules ↑ Degranulation ↓ cytotoxic function (MCM4 and POLA1 KD NK cell lines)	Not investigated	None	(79)
POLE2	↓ NK cell frequency ↑ CD56^bright NK cells	↓ proportion of cells in S phase	None	(81)

KD: knockdown

PMA: phorbol 12-myristate 13-acetate