Table 1.

Mutations of the hemochromatosis gene (HFE)^{1, 2}

Exon	cDNA alteration	Protein alteration	Phenotype3	Reference
5’UTR	c.−20G→A	fs	1	[78]
2	88C→T	L30L	0	[79]
2	4128G→A + 187C→G	G43D + H63D	1	[80]
2	138T→G	L46W	1	[81]
2	c.del149–170	L50fs	0	[82,83]
2	128G→A	G43D	1	[84]
2	157G→A	V53M	0	[85]
2	175G→A	V59M	0	[85]
2	187C→G	H63D	1	[13]
2,4	4187C→G + 845G→C	H63D + C282Y	1	[86,87]
2	189T→C	H63H	0	[85]
2	193A→T	S65C	1	[88]
2	196C→T	R66C	1	[79]
2	199C→T	R67C	1	[83]
2	c.del203	V68fs	2	[89]
2	211C→T	R74X	2	[90]
2	277G→C	G93R	2	[91]
2	277del	G93fs	2	[92]
2	314T→C	I105T	1	[91]
2	340G→A	E114K	1	[83]
	IVS2(+4)T→C	—	0	[90]
3	381A→C	Q127H	1	[85]
3	385G→A	D129N	0	[81]
3	414C→G	Y138X	2	[81]
3	471del	A158fs	2	[93]
3	478del	P160fs	2	[94]
3	502G→C	E168Q	1	[95]
3	502G→T	E168X	2	[96]
3, 2	4502G→C + 187C→G	E168Q + H63D	1	[97]
3	506G→A	W169X	2	[96]
3	527C→T	A176V	1	[98]
3	548T→C	L183P	2	[99]
	IVS3(+1)G→T	(null allele)	2	[100]
	IVS3(+21)T→C	G43D	1	[79]
	IVS3(+21)T→C	—	0	[79]
	IVS3(−48)C→G	—	0	[101]
4	c.del616–48C→T	—	0	[102]
4	636G→C	V212V	0	[103]
4	671G→A	R224G	1	[79]
4	676C→G	R226G	1	[104]
4	689A→T	Y230F	2	[81]
4	c.del691–693	Y231X	2	[105]
4	696C→T	P232P	0	[79]
4	697C→T	Q233X	2	[106]
4	c.dup794	W267fs	2	[107]
4	724G→A	D242D	0	[102]
4	747G→A	K249K	0	[102]
4	814G→T	V272L	0	[108]
4	829G→A	E277K	0	[103]
4	845G→A	C282Y	2	[13]
4	845G→C	C282S	2	[109]
4	4845G→A + 842C→A	C282Y + T281K	1	[110]
4	847C→T	G283X	2	[111]
4	848A→C	Q283P	2	[112]
4	867C→G	L289L	0	[79]
4	884T→A	V295E	1	[102]
4	884T→C	V295A	?	[89]
4	867G→C	L289L	0	[79]
	IVS4(+37)A→G	—	0	[85]
	IVS4(+48)G→A	—	0	[113]
	IVS4(+109)A→G	—	0	[85]
	IVS4(−44)T→C	—	?	[114]
	IVS4(−50)A→G	—	?	[115]
	IVS4(+115)T→C	—	0	[85]
	942T→C	A314A	0	[98]
5	989G→T	R330M	2	[85]
	IVS5(+1)G→A	—	1	[116]
	IVS5(−47)G→A	—	?	[114]
6	c.1022–1034del13	H341X	2	[83]
—	5HFEdel	—	1 or 2	[117]

¹Modified from C.Q. Edwards, J.C. Barton, Hemochromatosis in: J.P. Greer, D.A. Arber, B. Glader, A.F. List, R.T. Means Jr., F. Paraskevas, and G.M. Rodgers (Eds.), Wintrobe’s Clinical Hematology, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, 2014, pp. 662–81. Permission to publish requested from publisher.

²Most alleles were identified in persons with hemochromatosis phenotypes or their family members. HFE Y231X was identified in a hemochromatosis cell line.

³Phenotype: 0 = none known; 1 = probably weak effect on iron homeostasis; 2 = probably strong effect on iron homeostasis.

⁴Complex allele with two mutations in cis.

⁵An Alu-mediated recombination caused loss of the complete HFE gene sequence. Homozygosity for the corresponding chromosome 6p is a common cause of hemochromatosis in Sardinia [118].