Alternative titles; symbols
HGNC Approved Gene Symbol: EXOC6B
SNOMEDCT: 1286834000;
Cytogenetic location: 2p13.2 Genomic coordinates (GRCh38) : 2:72,175,984-72,826,033 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2p13.2 | Spondyloepimetaphyseal dysplasia with joint laxity, type 3 | 618395 | Autosomal recessive | 3 |
In yeast and rat, Sec15 is part of a multiprotein complex that is required for targeted exocytosis.
By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1999) cloned SEC15B, which they designated KIAA0919. The deduced protein contains 710 amino acids, and the 3-prime untranslated region of the mRNA contains 4 MIR sequences. SEC15B shares 69.2% amino acid identity over 668 amino acids with rat Sec15. RT-PCR ELISA detected low to moderate expression in most tissues and specific adult brain regions tested. Highest expression was detected in testis, ovary, and amygdala. Little or no expression was detected in skeletal muscle, pancreas, spleen, fetal liver, and fetal brain.
By radiation hybrid analysis, Nagase et al. (1999) mapped the SEC15B gene to chromosome 2.
Brymora et al. (2001) determined that rat brain synaptosome Sec15b associated with RalA (179550) in a GTP-dependent manner as part of an exocyst complex.
In 2 brothers with spondyloepimetaphyseal dysplasia and multiple joint dislocations (SEMDJL3; 618395), Girisha et al. (2016) identified homozygosity for a nonsense mutation in the EXOC6B gene (Y302X; 607880.0001), for which their unaffected first-cousin parents were heterozygous.
In 2 sisters with SEMDJL3, Campos-Xavier et al. (2018) identified homozygosity for an approximately 220-kb deletion within the EXOC6B gene (607880.0002).
In 2 brothers with spondyloepimetaphyseal dysplasia and multiple joint dislocations (SEMDJL3; 618395), Girisha et al. (2016) identified homozygosity for a c.906T-A transversion (c.906T-A, NM_015189.1) in the EXOC6B gene, resulting in a tyr302-to-ter (Y302X) substitution. Their unaffected first-cousin parents were heterozygous for the mutation. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database.
In 2 sisters with spondyloepimetaphyseal dysplasia and multiple joint dislocations (SEMDJL3; 618395), originally reported by Spranger et al. (2006) (patients 2 and 3), Campos-Xavier et al. (2018) identified homozygosity for a 219,248-bp deletion (c.915+20070_2197-135947del, NM_0013217333.1)in the EXOC6B gene, joining intron 8 to intron 20 and removing 12 of 22 exons (exons 9-20, inclusive) while preserving the reading frame from exon 8 to exon 21. The deletion predicts the loss of amino acids 305 to 732 (Gly305_Gln732del) of the EXOC6B protein. The deletion was identified by array-CGH.
Brymora, A., Valova, V. A., Larsen, M. R., Roufogalis, B. D., Robinson, P. J. The brain exocyst complex interacts with RalA in a GTP-dependent manner: identification of a novel mammalian Sec3 gene and a second Sec15 gene. J. Biol. Chem. 276: 29792-29797, 2001. [PubMed: 11406615] [Full Text: https://doi.org/10.1074/jbc.C100320200]
Campos-Xavier, B., Rogers, R. C., Niel-Butschi, F., Ferreira, C., Unger, S., Spranger, J., Superti-Furga, A. Confirmation of spondylo-epi-metaphyseal dysplasia with joint laxity, EXOC6B type. (Letter) Am. J. Med. Genet. 176A: 2934-2935, 2018. [PubMed: 30284759] [Full Text: https://doi.org/10.1002/ajmg.a.40631]
Girisha, K. M., Kortum, F., Shah, H., Alawi, M., Dalal, A., Bhavani, G. S., Kutsche, K. A novel multiple joint dislocation syndrome associated with a homozygous nonsense variant in the EXOC6B gene. Europ. J. Hum. Genet. 24: 1206-1210, 2016. [PubMed: 26669664] [Full Text: https://doi.org/10.1038/ejhg.2015.261]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 63-70, 1999. [PubMed: 10231032] [Full Text: https://doi.org/10.1093/dnares/6.1.63]
Spranger, J., Lebel, R. R., Rogers, R. C. Spondyloepimetaphyseal dysplasia, leptodactylic type: variability, familial cases and differential diagnosis. Proc. Greenwood Genet. Center 25: 15-25, 2006.