Genetic variants of human serum albumin

# Namea [ref.] Alternative name [ref.] Base changeb  DNA or protein sequencingc Intron/Exon Protein changed Notes and functional effects [ref.]
1 Malmö I [1] Kaikoura, Tradate [1], Redhill (see also residue 320) [2-4], Sweden [5], Ildut [6] c.67C>T D/P E-1 –2Arg→Cys Malmö I: 3% proalbumin, 30% Arg-albumin (due to aberrant signal peptide cleavage) with the rest as normal albumin (Alb A) [1]. Sweden: 3 homozygotes [5]
2 Lille [7] Pollibauer [8],Somalia, Tokushima [9],Taipei [10], Fukuoka-2 [11],Varese [12], Wu Yang [13], Mayo EW220, Komagone-3 [14], Stirling [15] c.68G>A P E-1 –2Arg→His
3 Christchurch [16] Gainesville, Y [10,17], Honolulu-2 [18],  Fukuoka-3 [11], Mayo JW180 [14], Shizuoka [19], Kamloops [15], Zagreb [20,21] c.71G>A P E-1 –1Arg→ Gln
4 Takefu [10] Honolulu-1 [18] c.71G>C P E-1 –1Arg→Pro
5 Jaffna [22] c.71G>T P E-1 –1Arg→ Leu
6 Blenheim[23] Bremen [18], Malmö II, Iowa City-2 [14] c.74A>T P E-1 1Asp→ Val Blenheim: 10% proalbumin, 38% Val- [23]. Bremen: 20% Arg-Alb, 30% Val- [1]. In both cases, the remaining is Alb A. Blenheim: decreased α-helical content [24].
7 Larino [25] c.79C>T D/P E-1 3His→Tyr Low in vivo stability [25]
8 Nagasaki-3 [10] c.81C>A/G P E-2 3His→Gln
9 Torino [12] c.250G>A P E-3 60Glu→Lys
10 Dalakarlia-1 [5,26] Sweden-1, Malmö-95 c.259G>A D/P E-3 63Asp→Asn; N-glycosylated at 63Asn CHO next to a Cys. High thermal stability [24]. Decreased α-helical content [24]
11 FDH-T3 [27] c.269T>C D E-3 66Leu→Pro High T3 binding. Identified in a Thai family.
12 Vibo Valentia [12] c.316G>A P E-4 82Glu→Lys
13 Yanomama-2 [28] c.412C>G P E-4 114Arg→Gly Low bilirubin binding [29]
14 Nagoya [18] c.427G>A P E-4 119Glu→Lys
15 Tregasio [30] c.437T>A P E-4 122Val→Glu Decreased plasma half-life [31]
16 Komagome-2 [14] c.455A>G P E-4 128His→Arg
17 Asola [32] c.491A>G D/P E-5 140Tyr→Cys 20-25% variant [32]
18 Korea [33] c.593A>T D E-5 174Lys→Ile
19 Hawkes Bay [34] c.602G>T D/P E-5 177Cys→Phe 5% variant [34]. Decreased α-helical content [24]. Decreased plasma half-life [31]
20 Ilam [88] c.643G>A D/P E-6 191Ala→Thr Identified by a new high resolution on-line reverse phase time-of-flight mass spectrometry procedure.
21 FDH-3 [89] c.724C>A D E-7 218Arg→Ser High free T4 andT3. Identified in a Canadian family of Bangladeshi extraction.
22 FDH-1 [35,36] c.725G>A D E-7 218Arg→His High T4 binding [35-37]. Low warfarin binding [38].The most common causal variant in Caucasians [35].
23 FDH-2 [39,40] c.725G>C D E-7 218Arg→Pro High T4 binding [39,40]. Low warfarin binding [38]]. Identified in Japanese and Swiss subjects [39,40].
24 FDH-4 [90] c.737G>T D E-7 222Arg→Ile High T4 binding. Identified in three unrelated African (Somali) families and one East European (Croatian) family.
25 Tradate-2 [25] Vera Cruz [41] c.745A>C D/P E-7 225Lys→Gln
26 Herborn [42] c.790A>G P E-7 240Lys→Glu
27 Skaane [5] c.875A>G D/P E-8 268Gln→Arg
28 Niigata [43] Nagasaki-1 [19] c.878A>G P E-8 269 Asp→Gly High prostaglandin binding [44]
29 Caserta [25] c.900G>C D/P E-8 276 Lys→Asn 60-70% variant [25]
30 Tagliacozzo [25,45] Cuneo [25], Cooperstown [46], Canterbury [47], New Guinea [18], Reading [48], IRE-1 [49], Sweden [5] c.1011G>T D/P E-8 313 Lys→Asn Low drug binding [50].      Low thermal stability [24]. High progesterone binding [44]
31 Bergamo [30] c.1013A>G P E-8 314 Asp→Gly
32 Brest [6] c.1013A>T P E-8 314Asp→Val High fatty acid binding [6]
33 Orebro [5] Malmo-4 [5] c.1026C>G D/P E-8 318 Asn→Lys
34 Redhill    [2-4] c.[67C>T (=Malmö-I); 1030G>A] D/P E-1; E-8 ‒2Arg→Cys (=Malmö-I);  320 Ala→Thr; N-glycosylated at 318Asn (AsnTyrThr) [4,51] High fatty acid binding [52]
35 Roma [53] c.1033G>A P E-8 321Glu→Lys Low testosterone binding [44]
36 Sondrio [54,55] c.1069G>A P E-9 333Glu→Lys
37 Hiroshima-1 [19] c.1132G>A P E-9 354Glu→Lys
38 Coari I [56] Porto Alegre I [56] c.1144G>A D/P E-9 358Glu→Lys
39 Trieste [57] c.1149G>T/C P E-9 359 Lys→Asn Low thermal stability [24]
40 Parklands [58] c.1165G>C P E-9 365Asp→His Low drug binding [50]
41 Iowa City-1 [14] c.1166A>T P E-9 365Asp→Val
42 Benkovac [59] c.1175A>G D E-9 368Glu→Gly
43 Naskapi [60] Mersin [61], Komagone-1 [14] c.1186A>G D/P E-9 372Lys→Glu
44 Nagasaki-2 [28] Passo Fundo [41] c.1195G>A P E-10 375 Asp→Asn
45 Milano slow [57] c.1195G>C D/P E-10 375Asp→His
46 Tochigi [19] c.1198G>A P E-10 376Glu→Lys
47 Malmo-3 [5] c.1198G>C D/P E-10 376Glu→Gln
48 Hiroshima-2 [19] c.1216G>A P E-10 382Glu→Lys
49 Liprizzi [57,62] c.1300C>T D/P E-11 410 Arg→Cys High S-nitrosylation [63]
50 Dublin [49] c.1507G>A P E-12 479Glu→Lys
51 Casebrook [64] Besana Brianza [30] c.1552G>A D/P E-12 494 Asp→Asn; N-glycosylated at 494Asn (AsnGluThr) [65] High fatty acid binding [52]. Decreased α-helical content [66]
52 Vancouver [67] Birmingham, Adana [67], Porto Alegre II [56], Manaus I [18], Lambadi [18], Kashmir [68,69], Fortaleza [41] c.1573G>A D/P E-12 501Glu→Lys
53 Ortonovo [70] c.1585G>A P E-12 505Glu→Lys
54 Lyon [71] c.1601A>G D/P E-12 510His→Arg
55 Maddaloni [30] c.1669G>A P E-13 533Val→Met
56 Castel di Sangro [72] c.1678A>G P E-13 536Lys→Glu
57 South Pacific (see also residue 546) [73] c.1690A>G D/P E-13 540 Thr→Ala
58 Maku, (Wapishana) [28] Oriximina I [56] c.1693A>G D/P E-13 541Lys→Glu High fatty acid binding [52]. High thermal stability [24]
59 South Pacific [73] c.1708G>T D/P E-13 546 Ala→Ser
60 Mexico [61] c.1721A>G D/P E-13 550 Asp→Gly
61 Dalakarlia-2 [5] Malmö-62 [5] c.1721A>C D/P E-13 550Asp→Ala
62 Church Bay [74] c.1750A>G D/P E-13 560Lys→Glu
63 Fukuoka-1 [18] Ube-1 [18], Varese-2 [75], Paris-2 [25,55] c.1759G>A D/P E-13 563 Asp→Asn High fatty acid binding [52]. Decreased α-helical content [24]
64 Osaka-1 [18] c.1765G>A D/P E-13 565Glu→Lys
65 Bazzano [25] c.1771delT D/P E-13 (567)CFAEEGKKLVAASQAALGL (585) → (567)ALPRRVKNLLLQVKLP(582) High fatty acid binding [52]. Decreased α-helical content [66]
66 B [76,77,11] Oliphant, Ann Arbor [78], Verona [25,79], Osaka-2, Phnom Penh, Nagano, London (Ontario), Lübeck, Tokyo-1, Shinanomachi-1 [11], Iowa City-3, Mayo (MT610, RW246 and SH420), Victoria (East India), [14], Saitama-1 [19], Sweden [5], Amsterdam [15] c.1780G>A D/P E-13 570Glu→Lys Low thermal stability [24]
67 Rugby Park [80] c.1785+1G>C D/P I-13 (572)GKKLVAASQAALGL (585) → (572)LLQFSSF(578) 8% variant [80]. High fatty acid binding [52]
68 Banks Peninsula [81] c.1786-15T>A D/P I-13 (572)GKKLVAASQAALGL (585) → (572)SLCSG(576)
69 Milano fast (Mi/Fg)  [82, 25] Krapina [21] c.1789A>G D/P E-14 573Lys→Glu This variant was recently identified in a 4-year-old Yemeni girl with growth hormone deficiency [91].
70 Vanves [79] c.1794A>T/C D/P E-14 574 Lys→Asn
71 Kénitra [83] c.1794dupA D/P E-14 (575)LVAASQAALGL (585) →(575)TCCCKSSCLRLITSHLKASQPTMRIRERK(603), 2 new SS bonds, T596 is half O-glycosylated 15% variant [83]. Low thermal stability [24]
72 Catania (Ge/Ct) [84,85] c.1810delC D/P E-14 (580)QAALGL(585) → (580)KLP (582)
73 Venezia [85,86] c.1786_1814+1 delinsAAAAT D/P E-14/ I-14 (572)GKKLVAASQAALGL(585) → (572)PTMRIRE (R)(K)(580) 30% variant [86]. Low thermal stability [24]. Increased α-helical content [66]. Decreased plasma half-life [66]
A general feature of the variants modified close to the normal N-terminus (#1-8) is a low affinity for metal ions such as Cu++ and Ni++ [75]. For additional effects of a propeptide on the structure, stability and function on Alb A, see [75].

aThe variants have usually been named after the place from where the first detected carrier originates.

bCodon numbering according to HGVS rules and based on the cDNA sequence NM_000477.7. For converting the present numbering to that of Minghetti et al. [87], see [75].

cThe structural changes have been determined by DNA (D) or protein (P) sequence analysis.

dThe positions of proalbumin are from –6 to –1 (the juxtaposition to albumin itself), and those of the mature albumin molecule (Alb A) are from 1 to 585. Addition of 24 to these numbers converts them to a number according to HGVS rules, which is based on the preproalbumin sequence (NCBI Reference Sequence: NP_000468.1).
REVISED 22.01.2021