Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma

Table 1 Hepatitis B virus - encoded X protein mutants and their role in liver injury and hepatocellular carcinoma

No.	Putative mutation	Function/significance of the mutation	Ref.
1	Insert mutation at position 204	Associated with the nuclear localization of HBx protein	[88]
2	Mutations at aa 127, 130, and 131	HBx deletions may be implicated in HCC	[89]
3	Distal COOH-terminal region deletion	COOH-terminal truncated HBx plays critical role in the HCC carcinogenesis via the activation of cell proliferation	[45,93]
4	HBx-A31 mutation	Development of this mutant represent a strategy of escape immune surveillance and thus may contribute to the process of multiple-step HCC	[101]
5	Truncation mutation at 3′ end of HBx	Potential role in HBV related HCC	[91]
6	Point mutations at X gene codons 130 (AAG - ATG) and 131 (GTC - ATC)	Modification in the transactivation function of HBx	[102,103]
7	Deletion from 382 to 401 base pairs (HBxDelta127)	HBxÄ127 promotes hepatoma cell growth through activating SREBP-1c involving 5-LOX	[96,104]
8	HBx M130K and V131I (T-A) mutations in HBV genotype F	Associated with severe liver damage and HCC, can acts as prognostic marker for HCC	[49]
9	aa 52 to 65 and 88 to 154	Regions are important for augmentation function of HBX in HBV replication	[105]
10	Five types of “hot-spot” mutations of genotype B or C	Affects antiproliferation and transactivation of genotype B or C of HBx	[106]
11	A1762T/G1764A	Associated with development of HCC in Thai patients	[107]
12	and G1899A mutationsNatural HBx mutant truncated 27 amino acids at the COOH terminal	Promotes cell proliferation	[108]
13	TP53 R249S mutation, genetic variations in HBx	Associated with diagnosis of HCC or liver cirrhosis	[109]
14	A truncated mutant (residues 58-140) of the HBx	Participate in transactivation function	[94]
15	Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C	Codon-38 change in genotype C is an independent risk factor for HCC development	[110]
16	Ser-101, Met-130 Mutation	Have differential effect on the expression of cyclin dependent kinase inhibitor	[111]
17	HBx 120 and 121	Inhibits DNA repair	[112]

aa: Amino acid; A31: Alanine 31; M-130: Methionine 130; I: Isoleucine; V: Valine; Ser: Serine(S); Met: Methionine; R: Arginine; LOX-5: Arachidonate 5-lipoxygenase; SREBP: Sterol Regulatory Element-Binding Protein; HBV: Hepatitis B virus; HBx: HBV-encoded X protein; HCC: Hepatocellular carcinoma.