Report of the committee on nomenclature Prepared by: E, R. Giblett Committee members: . R. Giblett, Seattle (chairman) W. J. Mellman, Philadelphia » Harris, London C. W. H. Partridge, New Haven - Meera Khan, Leiden T. B. Shows, Buffato . W. Lovrien, Portland mv xm: 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, while participants in the Histocompatibility Testing workshops have handled the terminology problems in that area. In general, the guidelines for naming enzymes can also be applied to the plasma proteins. Guidelines for Genetic Nomenclature of Human Enzymes (as already reported) Addendum: Two enzymes not listed above, adenosine kinase and B-glu- curonidase, were assigned to chromosomal loci at the Baltimore meeting. [t is proposed that their respective loci be designated ADK and BGUS. REPORT OF NOMENCLATURE COMMITTEE On April 3-4, 1975, a meeting was held in Philadelphia by the fotlowing appointed and ad hoc members: Harry Harris, Meera Khan, Everett Lovrien, William Mellman, Chester Partridge and Thomas Shows, with Eloise Giblett as chairman. At the outset, it was decided that this committee should confine itself to enzyme nomenclature, and that the guidelines for naming enzymes could probably be applied to plasma proteins, as well. The nomenclature used for blocd group antigens has been dealt with extensively in the standard text by Race and Sanger, while the participants of the HL-A workshops have worked out their own terminology for the histocompatibility loci and their products. Dr. Harris had already developed a set of guidelines before the cormittee meeting, and it was used as the basis of our deliberations. The consensus emerging from these discussions is presented in the following paragraphs. Guidelines for Genetic Nomenclature of Human Enzymes The essentials of a satisfactory terminology are that it should be pre- cise and unambiguous, it should clearly distinguish between genotypes and phenotypes, and as far as possible, the symbols used should readily identify the particular enzyme. In addition, it should be sufficiently flexible to permit incorporation of some unusual symbols used to designate certain en- zymes in the original papers which have subsequently been widely adopted and embedded in the literature. It should also be capable of incorporating new discoveries as they are reported. The following general scheme appears to mheet 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: oaGAL for ao-galactosidase to distinguish it from 8-palactosidase (BGAL). 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. Such loci are best differentiated by appropriate subscripts. Examples: PGM,, PGMz and PGM3 for the three phosphoglucomutase loci ADH,, ADH2 and ADH3 for the three alcohol dehydrogenase loci Numerical subscripts are often most convenient. However, some- times, because of past usage or easy identification, letters are preferred to avoid confusion. Examples: LDHa, LDHgp and LDHc for the three lactate dehydrogenase loci PG 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 form, 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. B. Alleles Different alleles at the same locus are designated by superscripts. Example: PCM} » PGM?, PGM?, PGM+ etc., for alleles at the PCM, locus. The superscripts may be numerical or alphabetical. In rare cases, + and ~ signs which have been used extensively in the past may be retained. Example: ca®, ca’, ca“ for the three common alleles at the glu- 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: cqliediterranean gq’ anton cqfthens gqeeattie (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 0 (i.e. zero), although the letter s may be retained because of common usage. Examples: Pom’, ES ("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 — C. dD. Examples of Genotypes The following are some 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: ADAlADA2 (or ADA!/ADA2) 2. Heterozygotes for one or the other of these common ADA alleles and a "nuli" 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 PGM»2 and heterozygous for the two common alleles of PGM3 (3 unlinked loci): 1 2 1 1 1 2 PGM}/PGM?, PGM}/PGM}, PoM}/PGMS or sl 1 1 PGM; PGMs PGM 2 1 2 PGM PGM, PGM; 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: ADA! — pc} ADAZ Poms or ADA!/ADA2, pom! /pom? 2. When the loci are in the same linkage group and the phase is known, the horizontal line is continuous. Example: anys awyB (i.e. Amy} and AMy® are in cis posi- Amy amy 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: Any} AMY B > B AMY) AMY, 4, To designate loci which are syntenic but not in the same linkage group, a colon is used. Example: auy> pom} ae pel AMyB = PGMT II, 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. Examples: Genotype . Phenotype ApAlapa! ADA 1 ADAlADA? ADA 2-1 ADA7ADA? ADA 2 ADA1ADA® ADA 1 ADAZADA® ADA 2 pom! /pom<, Pem}/pom}, Pom} /PGMS PGM, 2-1, PGMy 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 PcK!pcK} PGK 1 PGK! PGK? PGK 2-1 PGK? PGK? PGK 2 III. 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, 8, 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: a, 8 and y. There is evidence for two common alleles at the ADH2 locus: ApH} and ADH? . These alleles code for polypeptides 81 and B2. There are also two common alleles at the ADH3 locus: ApH} and ADH, which code for 1 and y?. All of the ADH isozymes are dimeric and the polypeptides y subunits interact with each other. In adult liver, all three Toci 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 1 1. 1 1. 1 2 ADH, ADH) 5 ADH ADH. 5 ADH ADH 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: aw yly! ay! gly} eB! yly2 ay2 — gly2 pig) y2y2 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 syn- 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). . . yAM A omputer |Poly- Enzyme Name of; fbr utp sre pumnlur Es 2 Nos | Locus pasernaeives iy ynbol morphic op plata WA) Acid -phosphatase-1 3.1.3.2 ACP) 2P) ACP~1 Yes Acid. phosphatase-2 3.1.3.2 | ACP, ACP-2 Acid phosphatase-3 3.1.3.2 ACP, ACP~3 ronitate hydratase] 4.2.1.3 Aconitase (sol) | 4.2.1.3 ACON, {ACOc, ACO, ACO~1 Yes Aconitase (mito) | 4.2.1.3 ACON, JACO,,, ACO, ACO~2 Adenine phosphoribosyltrans ferast 2.4.2.7 | APRT APRT Adenosine deaminase 3.5.4.4 [ADA ADA Yes AMP deaminase | 3.5.4.6 | AMPDA AMPDA Adenylate kinase-1 : 2.7.4.3 | AK AK-~1 AK~1 Yes Adenylate kinase-—2 | 2.7.4.3 | AKo AK--2 AK~2 Alcohol dehydrogenase-1 : 1.1.1.1 ADH, ADH-1 Alcohol dehydrogenase~2 | 1.1.1.1 ADH, ADH-2 Yes Alcohol dehydrogenase-—3 : 1.3.1.1 ADH3 ADH-3 Yes uctose-biphosphate aldolase] 4.1.2.13 Aldolase-A : 4.1.2.13 JALD, — JALD, ALD-A Aldolase-B | 4.1.2.13 |ALD, ALD. ALD-B Aldolase-C 4.1.2.13 JALD, ALD. ALD-C Alkaline phosphatase (placental) 3.1.3.1 [PL ALPL Yes a Amylase (salivary) | 3.2.1.1 AMY, AMY AMY-1 Yes a Amylase (pancreatic) 3.2.1.1 | AMY, AMY, AMY-2 Yes Aryl sulfatase 3.1.6.1 JARS ARS rbonate dehydratase] 4.2.1.1 Carbonic anhydrase-1 i 4.2.1.1 |CAy CAp, CAy CA-1 Carbonic anhydrase-2 4.2.1.1 [CAs CAc, CATT CA~2 Yes Catalase 1.11.1.6 j|CAT CAT Cholinesterase (serum) ~1 3.1.1.8 [Ey E-1 Yes Computer | Poly— Enzyme Name E.C. No. | Locus Alternatives Sytibol morphic Cholinesterase (serum) —2 3.1.1.8 | E5 E~2 Yes Citrate synthase 4.1.3.7 | CS CITSY Cytidine deaminase 3.5.4.5 | CDA CDA Yes -ytochrome bs reductase] 1.6.2.2 Diaphorase (NADH) 1.6.2.2 DIA, DIA-A, Dia A DIA-A Diaphorase (NADPH) 1.6.*.* | DIA, DIA-B, Dia B DIA-B Yes 2,3 Diphosphoglyceromutase 2.7.5.4 | DPGM DPGM Enolase-l1 4.2.1.11 ENO, PPH, ENO-1 Enolase-2 4.2.1.11 | ENO» PPH» ENO-2 sarboxylesterase] 3.1.1.1 Esterase Ay 3.1.1.1 | ESA, Es-A, ESA~4 Esterase D 3.1.1.1 | ESD ESD Yes a~L~fucosidase 3.2.1.51 | aFUC A-FUC Yes Fumarate hydratase 4.2.1.2 |FH FUMH Galactokinase 2.7.1.6 [CALK GK, GAK GALK :exose-l-phosphate uridylyltransferase] 2.7.7.12 Galactose~—1—phosphate uridylyItransferase 2.7.7.12 {GALT Gt, Gal-1~PUT GAPUT Yes a Galactosidase 3.2.1.22 | aGAL A-GAL Glucose-6-phosphate dehydrogenase 1.1.1.49 |Gd G6PD G6PDH Yes Glucose phosphate isomerase 5.3.1.9 |GPI PHI GPI a Glucosidase 3.2.1.20 | aGLU A~-GLU Yes Spartate aminotransferase] 2.6.1.1 Glutamic-oxaloacetic transaminase (sol) 2.6.1.1 |G0To GOT-1, GOT) GOT~1 Glutamic-oxaloacetic transaminase (mito) {2.6.1.1 COT, GOT-2, GOT> GOT-2 Yes ‘Lanine aminotransferase] 2.6.1.2 Glutamic~pyruvic transaminase 2.6.1.2 |GPT GPT Yes Glutathione peroxidase 1,11.1.9 | GPX GPX a Computer }|Poly- Enzyme Name E.C. No. | Locus Alternatives Symbol {morphic Glutathione reductase 1.6.4.2 | GSR GSR Yes Glyceraldehyde~3-phosphate dehydrogenase | 1.2.1.12 GAPDH GAPD GAPDH Glycerol—3—phosphate dehydrogenase~1 1.1.1.8 GPD, GPD~1 Glycerol-3-—phosphate dehydrogenase—2 1.1.1.8 GPDo GPD-2 Lactoyl-glutathione lyase] 4.4.1.5 Glyoxylase I 4.4.1.5 | GLO GLY-1, Glx-1 GX—1 Yes aydroxyacylglutathione hydrolase] 3.1.2.6 Glyoxylase II 3.1.2.6 HAGH GLY-2, G1ix~2 GX-2 Guanylate kinase-1 2.7.4.8 GUK, Guk,, GMPK) GMPK~1 Guanylate kinase-2 2.7.4.8 | GUK Guky, GMPK> GMPK--2 Guanylate kinase-3 2.7.4.8 GUK3 Guk3, GPK GMPK-3 Hexokinase-1 2.7.1.1 HK, BK, HK-1 Hexokinase-—2 2.7.1.1 | HK» Ry HK-2 Hexokinase-3 2.7.1.1 HK Bary HK-3 Yes Hexckinase-4 2.7.1.1 EK, EK y HK-4 ~N-acetylglucosaminidase] 3.2.1.30 Hexosaminidase-A 3.2.1.30 HEX, NAGA, HEX-A Hexosaminidase~B 3.2.1.30 HEX, NAGA. HEX-B Hexosaminidase-C 3.2.1.30 HEX, NAGA, HEX-C Hypoxanthine phos phoribosyltransferase 2.4.2.8 HPRT HGPRT HGPRT ucleosidetriphosphate Pyrophosphatase] 3.6.1.19 Inosine triphosphatase 3.6.1.19 ITP ITP Isocitrate dehydrogenase (sol) 1.1.1.42 ICDs IDE, IDH-1 ICDH~-1 tsocitrate dehydrogenase (mito) 1.1.1.42 icb,, IDE» IDH~2 ICDH—2 Lactate dehydrogenase A 1.1.1.27 LDH, LDH-A LDH-A Lactate dehydrogenase B 1.1.1.27 | LDH LDH-B LDH~B Lactate dehydrogenase C ) 1.1.1.27 LDH, LDH-C LDH-C Computer |Poly- Enzyme Name E.C. No. | Locus Alternatives Symbol jfsorphic Lecithin acyltransferase 2.3.1.43 | LCAT LCAT Malate dehydrogenase, NAD (sol) 1.1.1.37 | MDH, MOR,, MOR-1, MDH-1 | MDH-1 Malate dehydrogenase, NAD (mito) 1.1.1.37 | MDHy MOR,,, MOR-2, MDH-2 | MDH-2 falate dehydrogenase, decarb., NADPT] 1.1.1.40 Malic enzyme (sol) 1.1.1.40 |MEo MOD<, MOD-1, ME-1 ME-1 Malic enzyme (mito) 1.1.1.40 |ME,, MODs » MOD~2, ME-2 ME-2 Yeas Mannose phosphate isomerase 5.3.1.8 |MPI MANPI Purine nucleéside phosphorylase] 2.4.2.1 Nucleoside phosphorylase 2.4.2.1 |NP PURNP Pepsinogen (Pepsin) 3.4.23.% |Pg Pg-5 PEPSG Yes Peptidase A 3.4.11.*% |PEPA PEP A Yes Peptidase B 3.4.11.*% |PEPB PEP B Peptidase C 3.4.11.% |PEPC PEP C Yes Proline dipeptidase] 3.4.13.9 Peptidase D 3.4.13.9 |PEPD PEP D Yes 6-Phosphofructokinase A 2.7.1,11 |[PFK, PFK-A 6—-Phosphofructokinase B 2.7.1.11 |PFK, PFK-B 6-Phosphofructokinase C 2.71.11 PFK, PFK-C Phosphoglucomutase 1 227.5.1 PGM, PGM-1 Yes Phosphoglucomutase 2 2.7.5.1 |PGM9 PGM-2 Yes Phosphoglucomutase 3 2.7.5e1 PGM PGM-3 Yes Phosphogluconate dehydrogenase 1.1.1.44 jPGD 6PGD 6PGD Yes Phosphoglycerate kinase 2.7.2.3 |PGK PGAK Phosphoglyceromutase (muscle) 2.725.3 |PGAMsy PGAM-* Phosphoglyceromutase (brain) 2.7.5.3 PGAM, PGAM-5 Pyrophosphatase (inorganic) 3.6.1.1 jPP PP Pyruvate kinase (L) 2.7.1.40 |PK, PK,, PK-1 PK-L Computer | Poly- Enzyme Name E.C. No. | Locus Alternatives Symbol morphic Pyruvate kinase (M1) 2.7.1.40 PK PK-M1 Pyruvate kinase (M2) 2.741240 PR PK ay? PK-3 PK-M2 Ribosephosphate pyrophosphokinase 2.7.6.1 |RPPK RPPPK Iditol dehydrogenase] 1,1.1.14 Sorbitol dehydrogenase 1.1.1.14 | SORDH SORD, SDH SORDH Superoxide dismutase (sol) 1.15.1.1 SOD, TPO-A, SOD~A, SOD-1 SOD-1 Superoxide dismutase (mito) 1.15.1.1 SOD, IPO-B, SOD-B, SOD-2 |] SOD-2 Thymidine kinase’ 2.7.1.75 | TK TK Transaldolase 2.2.1.2 | TRALD TRALD Transketolase 2.2.1.1 |TRKT TRKT Triosephosphate isomerase De3-1,.1 | TPIT TPI ucose-l-phosphate uridylyltransferase] 2.767.9 UDP Glucose pyrophosphorylase 2.747.9 |UGPP UGPP fleoside diphosphate kinase] 2.7.4.6 Uridine diphosphate kinase 2.7.4.6 |UDPK UDPRK Uridine monophosphate kinase 2.7.4,.*% | UMPK UMPK Yes nucleotidase] 3.1.3.5 Uridine monophosphatase 3.1.3.5 | UMPH UMPH