InterPro domain: IPR008429

This entry includes cleft lip and palate transmembrane protein 1 (CLPTM1) and cleft lip and palate transmembrane protein 1-like protein (CLPTM1L, also known as CRR9). This entry also includes uncharacterised proteins from fungi and plants.

Clefts of the lip and/or palate (CL/P) are some of the most common birth defects. They may be categorised into syndromic or non-syndromic types, with syndromic defects having an underlying chromosomal or teratogenic cause. Around 70% of clefts are non-syndromic and individuals have no typical physical or developmental abnormalities; these clefts generally show polygenetic behaviour and complex inheritance [ 1 ]. Studies have identified regions on chromosomes 19 and 11 which may be involved in non-syndromic cleft lip and palates; this included a novel gene on chromosome 19, cleft lip and palate-associated transmembrane protein 1 (CLPTM1) [ 2 ]. The Poliovirus receptor-related 1 gene (PVRL1), which is located on chromosome 11, has also been shown to associate with non-syndromic cleft lip and palates [ 3 , 4 ].

Human CLPTM1L protects non-small cell lung cancer tumour cells from genotoxic apoptosis and may contribute to lung cancer risk [ 5 , 6 ].

1. Mutation analysis of CLPTM 1 and PVRL 1 genes in patients with non-syndromic clefts of lip, alveolus and palate. J Craniomaxillofac Surg 33, 301-6
2. Characterization of a novel gene disrupted by a balanced chromosomal translocation t(2;19)(q11.2;q13.3) in a family with cleft lip and palate. Genomics 54, 231-40
3. Mutation of PVRL1 is associated with sporadic, non-syndromic cleft lip/palate in northern Venezuela. Nat. Genet. 29, 141-2
4. Mutation analysis of the PVRL1 gene in caucasians with nonsyndromic cleft lip/palate. Genet Test Mol Biomarkers 13, 617-21
5. CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis. Cancer Res. 74, 1116-27
6. Functional characterization of CLPTM1L as a lung cancer risk candidate gene in the 5p15.33 locus. PLoS ONE 7, e36116