SHORT COMMUNICATION Cloning of a Novel Human Putative Type Ia Integral Membrane Protein Mapping to 21q22.3 Marie-Laure Yaspo,* ,1 Johanna Aaltonen,† Nina Horelli-Kuitunen,‡ Leena Peltonen,† and Hans Lehrach * * Max Planck Institute fuer Molekulare Genetik, Ihnestrasse 73, D-14195 Berlin, Germany; †Department of Human Molecular Genetics, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland; and ‡Department of Clinical Chemistry and Department of Biomedicine, University of Helsinki, Haartmaninkatu 4, 00290 Helsinki, Finland Received May 7, 1997; accepted January 15, 1998 264 bp) and one trapped exon (exIII-4H7) were used to The distal part of human chromosome 21q22.3 is ex- search for the corresponding cDNAs. The clone fi1H15 ceptionally gene rich and contains several loci that have was used to probe 60,000 arrayed clones from a been linked to hereditary disorders. In the course of poly(dT)-primed human fetal thymus cDNA library constructing an extensive transcript map for chromo- (M.L.Y, unpublished; cDNA library filters available at some 21, we have isolated numerous coding segments RZPD, Berlin, http://www.rzpd.de). Two positive cDNA in 21q22.3 that represent potential candidate genes in clones were identified. One of them (HTE-1N15; 2635 this region. Following this approach, we have cloned a bp) was chosen for further analysis. cDNA HTE-1N15 novel single-copy gene (C21orf3) (HGMW-approved sym- was sequenced by the shotgun method using both dye- bol C21orf1) expressed as a unique 2.69-kb mRNA in a primer and dye-terminator chemistries on an ABI 373 wide range of tissues. We have precisely mapped sequencer. Reads were assembled with the XBAP pro- C21orf3 by fiber FISH distal to marker D21S171. The gram from the Staden package (7, 19). The cDNA se- C21orf3 gene encodes a predicted protein of 180 resi- quence is shown in Fig. 1 and has been deposited in dues that does not share any sequence homology with EMBL (Accession No. Z50022). Conceptual translation other known proteins. C21orf3 harbors predicted struc- of HTE-1N15 identified an open reading frame of 180 tural features of a type Ia integral membrane protein amino acids (Fig. 1). A canonical initiation codon was and contains a tetrapeptide motif (YXRF) observed in found at nucleotide 94, and the 3  untranslated region several cell surface proteins involved in signal trans- is 2002 bp long. The partial cDNA fi1H15 and the duction. Although the function of C21orf3 is still un- trapped-exon exIII-4H7 sequences were found in the known, this novel gene may play an important role in 3  untranslated region (nucleotides 756 – 1020) and in a cell trafficking mechanism.  1998 Academic Press the coding region (nucleotides 49 – 89), respectively, of cDNA HTE-1N15. Transcription units (TUs) identified along chromo- Homology searches against public databases were some 21 by exon-trapping and cDNA selection (4, 5, 20, performed with the HTE-1N15 nucleotide sequence us- 23) or EST mapping (16) are estimated to represent ing Blastn, Blastx, and tBlastx programs with the de- signatures for 40–60% of the total number of genes fault matrix and with the translated sequence using encoded by 21q (between 600 and 700 genes). This re- Blastp with both default and PAM250 matrices (2). Se- source shows a bias in favor of expressed loci mapping quence comparison with Blastx and Blastp against the to 21q22.3 (8, 18), providing a pool for isolating genes nonredundant protein database failed to detect any sig- in distal 21q. Several hereditary disorders have been nificant similarities with known proteins, and this novel linked to 21q22.3: autoimmune polyglandular disease gene was named C21orf3. 2 Nucleotide sequence compar- type I (APECED) (1), one form of congenital nonsyn- ison against dbEST identified more than 60 human dromic deafness (3), holoprosencephaly (13), a suscepti- ESTs derived from fetal heart, fetal liver/spleen, para- bility locus for bipolar affective disorder (23), and thyroid gland, melanocyte, fetal cochlea, infant brain, Knobloch syndrome (17). fibroblast, olfactory epithelium, placenta, and multiple To clone novel genes in this region, we have analyzed sclerosis lesion tissues [reported also in the Unigene in more detail the transcription unit TU6 mapping to dataset from (16)]. Interestingly, an identity match was YAC 94E4 in 21q22.3 (23). A partial cDNA (fi1H15; found with an EST (U46326) corresponding to a cDNA overexpressed in pancreatic cancer (11). Rodent homo- Sequence data from this article have been deposited with the logues of cDNA HTE-1N15 were identified with tBlastx. EMBL Data Library under Accession No. Z50022. 1 To whom correspondence should be addressed. Telephone: 49-30- 8413-1356. Fax: 49-30-8413-1380. E-mail: yaspo@mpimg-berlin 2 The HGMW-approved symbol for the gene described in this paper is C21orf1. dahlem.mpg.de. 133 GENOMICS 49, 133–136 (1998) ARTICLE NO. GE985217 0888-7543/98 $25.00 Copyright  1998 by Academic Press All rights of reproduction in any form reserved.