Report of the committee on nomenclature Prepared by: E.R. Giblett Committee members: E. R. Giblett, Seattle (chairman) W. J. Mellman, Philadelphia H. Harris, London C. W. H. Partridge, New Haven P. Meera Khan, Leiden T. B.. Shows, Buffalo E. W. Lovrien, Portland The guidelines outlined below are based on the decisions made at an interim meeting of the committee held on April 3-4, 1975. These guidelines, including a list of suggested names for enzyme loci, were approved during a plenary session of the Gene Mapping Workshop in Baltimore, 1975. Consideration was confined to enzyme nomenclature because the blood group antigens have been dealt with in the standard text by Race and Sanger (1), while participants in the Histocompatibility Testing workshops have handled the terminology problems in that area (2). In general, the guidelines for naming enzymes can also be applied to the plasma proteins. Guidelines for Genetic Nomenclature of Human Enzymes Essential to a satisfactory terminology are that it be pre- that cise and unambiguous, At clearly distinguish between genotypes and that phenotypes, and/as far as possible, the symbols used should readily identify the particular enzyme. In addition it should be sufficiently flexible to which were permit some unusual symbols/used to designate certain en- zymes in the original papers and have subsequently been widely adopted in the literature, It should also be capable of incorporating new ve . aiscoveries as they are reported, The following general scheme appears to meet these requirements and is reasonably convenient in practice. I. Genotypes Genotypic symbols, i.e. for loci or alleles, are italicised (or un- derlined in typescript) to distinguish them clearly from symbols used to designate phenotypes, which are not italicised or underlined. A. Loci 1. Loci are designated by letters, either all capitalized (pre- ferred) or just the first letter. Usually two or three letters will suffice, but sometimes four or even five may be required. Examples: ADA for adenosine deaminase UMPK for uridine monophosphate kinase Gd for glucose-6-phosphate dehydrogenase (Obviously, when lower case letters are used to designate one locus, it is undesirable to use the same letters but in capi- tals (e.g. GD) to designate another locus.) The letters chosen for locus names are preferably based on the recommended name given by the Enzyme Commission on Nomenclature, However, this is sometimes inconvenient or confusing because of past usage, Thus, GOT is preferred for glutamic-oxaloacetic transaminase, although the E.C. recommended name is aspartate aminotransfer- ase, In some cases, Greek letters are also needed for clarity. Example: aGAL for a-galactosidase to distinguish it from B-galactosidase (8GAL). 2. There are often two or more loci coding for different poly- peptide chains which are contained in separate enzyme proteins having very similar or identical catalytic properties. Sucn leci are best differentiated by appropriate subscripts. Examples: PGM), PCM, and PGM3 for the three phosphoglucomutase loci ADH), ADH and ADH3 for the three alcohol dehydrogenase loci Although /mmerical subscripts are often most convenient, _some~ times because of past usage or sas e/identification, letters are preferred to avoid confusion. Examples: LDHa, LDHp and LDHe for the three lactate dehydrogenase loci PGAM, and PGAM, for the two phosphoglycerate mutase loci which are active in muscle and brain, respect— ively. Some enzymes occur in a so-called soluble (or supernatant or cytosol) form and also in a mitochondrial fomn, with the two forms being catalytically similar but coded at separate loci. © In such cases, the use of S and M as subscripts may be less confusing than numerical or alphabetical designations. Example: | GOT. and GOT), for the soluble and mitochondrial forms of glutamic-oxaloacetic transaminase. Alleles Different alleles at the same locus are designated by superscripts. Example: PGM} , PGMt » PGM3 ‘e PCH? etc., for allelas at the PGM, locus, The superscripts may be numerical or alphabetical. In rare cases, + and - signs, when used extensively in the past, may be retained, Example: B A A- Gd, Gd, Gd for the three alleles at the glu- common cose-6-phosphate dehydrogenase locus/in Black popula— tions. In other cases, place names are best used as the allele superscript to avoid confusion, Example: cdtediterranean | gqlanton. caAthens | gabeattie (Abbreviation of the place name may be more convenient.) So-called "null" or “silent” alleles with little or no associated enzyme activity are best designated by the superscript O (i.e. zero), although the letter s may be retained because of common usage. Examples: Paw, ES C"silent" allele of the serum cholinesterase first locus) When heterogeneity between "null" alleles can be demonstrated, the allele designation should be qualified, as by a place name, Example: ADA’ Calcutta Cc. D. Examples of Genotypes The following are soma typical examples of genotypes written in accordance with the above recommendations and section D (below). 1. Heterozygote for the two common alleles at the ADA locus: ADAtADA2 (or ADA!/ADA2) 2. Heterozygotes for one or the other of these common ADA alleles and a "null" allele not separable from other "null" alleles at this locus: ADA/ADA® and ADAZADA® (or ADA!/ADA® and ADA2/ADA°) . 3. Genotype of an individual heterozygous for the two common al- leles of PGM,, homozygous for the common allele of PGMo and heterozygous for the two common alleles of PGM3 (3 unlinked loci): PGMt /pou?, pcms/PGM}, PoM}/Pom2 or i 1 ] PGM} eve Pom} 2 1 2 PGM? pcm} PGM3 Linkage and Phase A slash, either horizontal or semivertical (— or /) separating al-— leles, implies chromosomal location. The slash may be omitted in designating the genotype at a single locus. However, if two or more loci are involved, a horizontal line is recommended, particularly if the loci are syntenic. 1. Non-syntenic loci may be designated either by an interrupted horizontal line or by individual slashes and separation by commas. Example: ApA! cu} Ss L=E]Loor:s ADA! /apa2, pom! /Pcm2 apa? Pow aii 2. When the loci are in the same linkage group and the phase is known, the horizontal line is continuous. Example: amy amy® (i.e. any? and amy’ are in cis posi- AMY any tion, as are their alleles) ‘3. When the loci are in the same linkage group but the phase is not known, a semicolon is used. Example: AMY; AMY Amy® ? Auy8 4, To designate loci which are syntenic but not in the same linkage group, a colon is used. Example: amyA pq} oe el amyB Pau? TI. Phenotypes A. The phenotypic designation should have the same letters and sub— scripts as the locus (but not italicised or underlined), followed by the numerical, alphabetical or other symbol for the alleles, but not as superscripts. In the case of homozygotes for any allele or heterozygotes for a "null" allele, only one allele symbol is used. Til, Examples: Genotype Phenotype ApAlapa! ADA 1 ADAlADA2 ADA 2-1 ADAZADA? ADA 2 ADA!ADA® ADA 1 ADA2ADA® ADA 2 PGM!/PGN?, PG} /Post ; pom} /PGM2 PGM, 2-1, PGMp 1, PGM3 2-1 For hemizygotes, heterozygotes and homozygotes of the X~linked phosphoglycerate kinase alleles PGK! and PGK2, Genotype Phenotype PGK! PGK 1 PGK? PGK 2 PGK! pcx! PGK 1 PGK! PGK? — PGK 2-1 PGK? PGK? PGK 2 Isozyme Subunits When two or more loci code for different polypeptide chains which occur together as subunits of single isozymes in a set of isozymes, it is useful to designate the subunit structure of the individual isozymes. Greek letters are convenient symbols for the polypeptide chains. A dif-— ferent letter can be used for the peptide product of each locus, by anal— ogy with the a, B, y and 6 chains of hemoglobin. Whenever there are two or more alleles at a given locus coding for structurally different forms of the same polypeptide, superscripts are incorporated which are the same as the superscripts used to designate the corresponding alleles. Example? The three loci of alcohol dehydrogenase, ADH,, ADH and ADH3 are thought to code for three different polypeptide chains: oa, 8 and y. There is evidence for two common alleles at the ADH2 locus: Apri and ADH?. These alleles code for polypeptides 6! and 82. There are also two common alleles at the ADH3 locus: apa} and ApHg, which code for polypeptides y! and y?. All of the ADH isozymes are dimeric and the subunits interact with each other. In adult liver, all three Ioci are active. Thus, some of the isozymes are homodimers and some are hetero-—- dimers. The heteromeric isozymes contain polypeptides coded by alleles at either the same locus or at different loci, Thus, if an individual has the genotype ADH} ADH}; ADH ADH} ; ADH LADH? the phenotype is ADH; 1, ADH2 1, ADH3 2-1 and in the electrophoretic pattern of a liver extract, there are ten isozymes with the following subunit structures: 11 aa Y*Y ay ply} ap yly2 ay? ply2 pg} ¥2y2 References Race, R.-R. and Sanger, R.: Blood Groups in Man. London: Blackwell, 1975 (6th ed.). Svejgaard, A., Hauge, M., Jersild, C., Platz, P., Ryder, L.P., Nielsen, L.S. and Thomsen, M.: The HLA System: An Introductory Survey. Vol. 7 of Monographs in Human Genetics. Basel: S. Karger, 1976. In the following table, the enzyme name given is usually that recommended in 1972 by the Enzyme Commission.* When the E.C. name has not been used as the basis for the symbol, or if another name is much more familiar, the E.C. name is given first, and enclosed in brackets. (In a few instances the E.C. name is not given because it is so similar to the more familiar name.) The locus sym- bol given first is that recommended by this committee. Alternatives are also listed; these are based on systematic or obsolete names which can nearly always be found in the reference.* The computer symbols in the table are meant to be initial suggestions; they may require individual revision. The final column indicates that the given locus has been reported to be polymorphic in at least one large ethnic group. *Enzyme Nomenclature: Recommendations (1972) of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry. Published in 1973 by Elsevier (Amsterdam) and American Elsevier (New York). Table of Phenotypes for which Information on Chromosomal Assignment is Available Name of Phenotype VAM No. TT E.C. No¥* Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol t not appli- or Linkage cable = NA) Group ABO blood group 11030 NA ABO 9 ABO Yes Acid phosphatase-1 17150 3.1.3.2 AcP1l e ACPe=1 Yes Acid phosphatase-2 20095 3.1.3.2 AcpP2 11 ACP-2 Aconitase, ? mitochondrial 10084 4.2.1.3 Aco 3(P) ACO Aconitase, soluble 10085 4.2.1.3 Acog 9(P) ACO-S Adenine phosphoribosyltransferase 10260 2.4.2.7 APRT 16 APRT Adenosine deaminase 10270 3.5.4.4 ADA 20 ADA Adenosine kinase 10275 2.7.1.20 AdK AdoK 10(P) ADK Adenovirus-12 chromosome 10293 NA AdV12-CMS-1 1 ADV1LE-CMS-1 modification site-l Adenovirus-12 chromosome 10297 NA AdV12-CMS-17 17 ADV12-CMS-17 modification site-1L7 Adenylate kinase-1 10300 2.74.3 AK, 9 AK-1 Yes Adenylate kinase-2 10302 2.7.4.3 AK, 1 AK=2 Adenylate kinase=3 10303 2.7.4.3 AK 9(P) AK=3 Amylase, pancreatic 1LO465 3.2.1.1 Amys Amy 1 AMY~2 Yes Amylase, salivary 10470 3.2.1.1 Amy, Amy g 1 AMY-1 Yes Aniridia, type II Baltimore) 10620 NA 1(L) AN-2 qj-antitrypsin LOTHO ? Pi 2(I) or PI 12(L) Anti-viral protein 10745 NA AVP 21 AVP ** Footnotes on last page. Name of Phenotype VAM No. E.C. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol not appli- or Linkage cable = NA) Group Auriculo-osteodysplasia 10900 NA AOD 1(L) AOD B factor (see properdin factor B) Cataract, zonular pulverulent 11620 NA Cae 1 CAE Chido blood group 11043 NA Ch 6 CH Citrate synthase, mitochondrial 11895 4.1.3.7 cs 12(P) cs Complement component-2 12060 NA c2 6 Ce Complement component=4 12080 NA C4 6 ch Complement component-8 12095 NA cs 6 c8 Desmosterol-to-cholesterol enzyme 12565 ? DCE D:CE 20 DCE Diphtheria toxin sensitivity 12615 NA DTS 5(P) DTS Dombrock blood group 11060 NA Do 1(L) DO Duffy blood group 11070 NA Fy 1 FY Echo 11 sensitivity 12915 NA ELIS 19(L) E11s Elliptocytosis-=L 13050 NA El, 1 EL-1 Enolase-L 17243 4.2.1.11 Eno, PPH, 1 ENO=L Enolase=2 13136 4.2.1.11 Eno, PPH 12(P) ENO-2 Esterase activator 13325 ? L(P) or 5 ES-ACT Esterase-A4 13322 3.1.1.1 ESA) Eis=A) LL EsA4 Esterase D 13328 3.1.1.1 EsD 13 ESD Yes Factor B (see properdin factor B) Formylelycinamideribotide 10255 ? adeB 4(P) or 5 ADEB (FGAR) amidotransferase Name of Phenotype VAM No. ELC. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol not appli- or Linkage cable = NA) Group a ~L-fucosidase 23000 3.2.1.51 Q, Fuc 1 A-FUC Yes mitochondrial Fumarate hydratase(fumarase),/ 13685 4.2.1.2 FH, FH l FH-2, FH-M Fumarate hydratase (fumarase), 13686 4.2.1.2 FH, FHS FH-1, FH-S soluble/ Galactokinase 23020 2.7.1.6 Galk GK, GAK L7 GK Galactose + activator 13703 Gal*-Act 2(P) Galactose-l-phosphate uridyltrans- 23040 2.f./.12 Galt Gt, Gal-1-PUT 3 GAPUT, Yes Terase GALT a -galactosidase (Fabry disease) 30150 3.2.1.22 q, Gal x A=GAL, A-GAL Glucose-6-phosphate dehydrogenase 30590 1.1.1.49 Gd G6PD x G6PDH, G6PD Yes g-Glucuronidase 25322 3.2.1.31 Gus B-Gleu, @Gceu 7(I) or 9(I) GUS, B-GLCU Glutamate- y -semialdehyde 13825 2 GSS GSASyt, GSAS 10(P) GSS, GSASYT synthetase Glutamate oxaloacetic transaminase-1 13818 2.6.1.1 GOT « GOT-1, GOT, 10 GOT=1 Glutathione reductase 13830 1.6.4,2 GSR 8(P) GSR Yes Glyceraldehyde-3-phosphate dehy- 13840 1.2.1.12 GAPDH GAPD 12(P) GAPDH, drogenase GAPD Glyoxylase I 13875 WAS GLO GLY-1, Glx-1 6 G+1,GLO-l1 Yes Gm immunoglobulin types 14710- NA 12 (I) Gm Yes (also see immunoglobulin 14719 heavy chains) Guanylate kinase-1 13927 2.7.4.8 Guk, Guk,, GUMPK, 1 GMPK-1, GUMPK-2 Guanylate kinase-2 13928 2.7.4.8 GuK, Guk>, GUMPK 1 GUK-1 & 2 Hageman factor 23400 NA HaF T(P) HAP Name of Phenotype VAM No. E.C. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol not appli- or Linkage cable = NA) Group Haptoglobin, alpha 14010 NA Hp 16 A-HP Hemoglobin,alpha or beta 14180,14190 NA Hb , Hb 2(I) & 4(T) A-HB, B-HB Hexokinase-1 14260 2.7.1.1 He He + 10 HK-=1 Hexosaminidase A 27280 3.2.1.30 Hex 4 NAGA) 15 Hex=A, Hex A Hesosaminidase B 14265 3.2.1.30 Hex p NAGA, 5 Hex-B, Hex B HLA: Major histocompatibility 14280,14283, NA HLA-A, HLA-B (Several) 6 HLA complex 14284, 15785 HLA-C, HLA-D Hypoxanthine-guanine phosphoribo-= 30800 2.4.2.8 HPRT X HGPRT syltransferase Immune response 14685 NA ir 6(L) IR Immunoglobulin hea chains 14710-14719 NA e(L I also See Gn fmmmnozlobulin types) | ¢ 119 (I) g ndophenoloxidase (see superoxide dismutase) Tnosine triphosphatase 14753 3.6.1.19 TTP 20 ITP Interferon-1 14757 NA if. 2(P) IF-1 Interferon=2 14758 NA Ifo 5(P) IF=2 Isocitrate dehydrogenase-1 14770 1.1.1.42 ICD IDE. » IDH=1 2 IcDH-1, IDH-1 Isocitrate dehydrogenase, mito- 14.765 L.1.1.4e ICDy IDH,,, IDH-2 15(P) ICDH-2, IDH-M chondrial Lactate dehydrogenase A 15000 1.1.1.27 LDH, LDE-A Ll LDH=-A Lactate dehydrogenase B L5010 1.1.1.27 DH, LDH=B Le LDH=B Lecithin-cholesterol acyltrans~ 24590 2.3.1.43 LCAT 15 LCAT ferase Name of Phenotype VAM No. H.C. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Synibol not appli- or Linkage cable = NA) Group Lethal antigen 15125-15127 NA al, a2, a3 11 AL Malate dehydrogenase=l 15420 1.1.1.37 MDH q MORg MOR~1, 2 MDH-1. MDH=1 Malate dehydrogenase, mitochondrial 15410 1.1.1.37 MDH), MORy, MOR=2, 7 MDH=2 MDH=2 Malic enzyme=1 15425 L.1.1.40 MEg MODg, MOD-1, 6 ME=1 ME=1 Mannosephosphate isomerase 15455 5.3.1.8 MPI 15 MANPI, MPI 8 2-microglobulin 10970 NA 82M 15 B- 2M MNSs blood group 11130 NA MNSs 2(L) MNS Nail-patella syndrome 16120 NA NPa NP 9 NPA Nucleoside phosphorylase 16405 2.4.2.1 NP 14 NP P blood group 11140 NA P 6(L) P . * Pepsinogen 16970 3.4.23 Pg Pg=5 6 PEPSG, Puc Yes Peptidase A 16980 3.4.11." PepA 18 PEPA Yes Peptidase B 16990 3.4.11." PepB 12 PEPB Peptidase C 17000 3.4.11.” Pep? 1 PEPC Yes Peptidase D 17010 3.4.13.9 PepD 19(P) PEPD Yes Phosphoglucomutase=L 17190 lef Del PGM, 1 PGM=1 Yes Phosphoglucomutase-2 17200 2.7.5.1 PGM 4(P) PGM-2 Yes Phosphoglucomutase=3 17210 2.7.5.1 PGM2 6 PGM=3 Yes Name of Phenotype VAM No. E.C. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol not appli- or Linkage cable = NA) Group 6-phosphogluconate dehydrogenase 17220 1.1.1.44 PGD 6PGD 1 6PGD Yes Phosphoglycerate kinase 31180 2.76263 PGK x PGAK, PGK Phosphohexose isomerase 17240 PEI 19 PHI Phosphopyruvate hydratase (see enolase) Phosphoribosyl glycineamide 13844 6.3.4.13 GAPS 21(P) GAPS synthetase Polio sensitivity 17385 NA PVS 19 pys Properdin factor B 13847 NA BE 6 B Pyrophosphatase, inorganic 17903 3.6.1.1 PP LO PP Pyruvate kinase-=3 (M2) 17905 2.7.1.40 PR PKorp PK 15 PK-M2, PK3 Retinoblastoma-1 18020 NA Rb, 13(L) RB Rhesus blood group 11170 NA Rh 1 RH Ribosomal RNA 18045 NA WA 13, 14, 15, R-RNA 21, 22 Rodgers blood group 11171 NA Rg 6 RG 5S RNA gene(s) 18042 NA RN5S 1 RN5S Scianna blood group 11175 NA Se 1(L) sc Sclerotylosis 18160 NA Tys 2(L) TYS Serine hydroxymethyltransferase 13845 2.1.2.1 SHMT 12(P) SHMT (glycine + A auxotroph complet- ing) Spherocytosis, Denver type 18290 NA Sph, 8(L) or 12(L) Sph-1 Name of Phenotype VAM No. E.C. No. Locus Alternatives Chromosome Computer Polymorphic? (unless Assignment Symbol not appli- or Linkage cable = NA) Group Superoxide dismutase-1 Wh7h5 1.15.1.1 SOD. TPO-A, SOD-A, el SOD-1 SOD-1 Superoxide dismutase-2 14746 1.15.1.1 SOD,, IPO-B, SOD=-B, 6 SOD-2 SOD<2 Sv40-T antigen 18680 NA SV40-T 7(P) SVLO-T Testis determining factor -- NA TDF ¥ TDF Thymidine kinase, mitochondrial 18829 2.7.1.75 TK TK, 16(P) TKSM Thymidine kinase, soluble 18830 2.7.1.75 TK TK, 17 TKS Trisephosphate isomerase 19045 5.3.1.1 TPL 12 TPL Tryptophanyl-tRNA synthetase 19105 6.1.1.2 TrpRS 14, TRPRS Uridyl diphosphate glucose pyro- 19175 2.7279 UGPP 1(P) UGPP phosphorylase Waardenburg syndrome 19350 NA WS, 9(L) WS-1 Xeroderma pigmentosum, Egyptian 27870 NA XP. 9(L) XP-E Xelinked species (or surface) 31345 NA SAX x SAX antigen ¥Y histocompatibility antigen -~ NA H-Y Y HY * Enzyme Nomenclature: Recommendations (1972) of the International Union of Pure and Applied Chemistry and the International Union of Biochemistry, 1973, Elsevier (Amsterdam) and American Elsevier (New York). + When within the capability of the computer, lower case should be used as in the locus symbols. ++ Number assigned to locus in McKusick's Mendelian Inheritance in Man (4th ed., 1975 with additions).