The reference OMIM entry for this protein is 300205

Emopamil-binding protein; ebp
3-@beta-hydroxysteroid-delta-8,delta-7 isomerase

DESCRIPTION

The EBP gene encodes an integral membrane protein located mainly in the endoplasmic reticulum that functions as a key enzyme in the final steps of the sterol biosynthesis pathway (summary by Hartill et al., 2014).

CLONING

EBP was originally cloned as a delta-receptor binding target for the phenylalkylamine calcium-ion antagonist emopamil, an antiischemic drug in animal models of stroke (Hanner et al., 1995).

GENE FUNCTION

EBP was shown to bind a number of structurally diverse molecules, including the immunosuppressant SR31747A (Labit-Le Bouteiller et al., 1998) and the chemotherapeutic agent tamoxifen (Cho et al., 1998). EBP was shown to function as a delta(8)-delta(7) sterol isomerase by complementation of a yeast erg2 mutant (Silve et al., 1996).

MAPPING

Hanner et al. (1995) and Schindelhauer et al. (1996) mapped the EBP gene to Xp11.23-p11.22 by radiation hybrid and FISH analysis. Obviously an earlier assignment of CDPX2 to Xq28 was an error. Traupe et al. (1992) had claimed exclusion of Xp11 as the site of the mutation in X-linked dominant chondrodysplasia punctata (CDPX2; 302960); molecular studies in this family by Derry et al. (1999) demonstrated that Xp11 is, in fact, not excluded.

BIOCHEMICAL FEATURES

Derry et al. (1999) suggested that the loss of males in utero may be related to the presence of toxic sterol intermediates. The fact that mutations in the gene encoding 7-dehydrocholesterol reductase (DHCR7; 602858), the final enzyme of cholesterol biosynthesis, cause Smith-Lemli-Opitz syndrome (SLOS; 270400), suggests a direct involvement for abnormal cholesterol biosynthesis in some features of the Td/CDPX2 phenotype.

MOLECULAR GENETICS

- X-linked Dominant Chondrodysplasia Punctata 2 Derry et al. (1999) identified heterozygous mutations in the EBP gene (see, e.g., 300205.0001-300205.0002) in 7 of 8 female patients with X-linked dominant chondrodysplasia punctata-2 CDPX2 (302960). Of the 7, 5 mutations were predicted to be complete null alleles (4 nonsense single-base substitutions and 1 intragenic deletion producing a frameshift and truncated protein). An in-frame 3-bp deletion and 2 identical nonsense mutations (R63X) involved the same potential methylated CpG dinucleotide, which may represent a 'hotspot' for mutations. The single missense mutation R110Q, like Td, altered a conserved amino acid; it was positioned only 3 amino acids distal to the Td substitution in the same cytoplasmic domain of the isomerase protein. One of the families with CDPX2 investigated by Derry et al. (1999) had been reported by Traupe et al. (1992) and by Clayton et al. (1989); another family had been reported by Holmes et al. (1987). Simultaneously and independently, Braverman et al. (1999) used SSCP analysis and sequencing of genomic DNA to find heterozygous EBP mutations in all 7 cases of CDPX2 studied. They confirmed the functional significance of 2 missense alleles by expressing them in a sterol-delta(8)-isomerase-deficient yeast strain. Because of the clinical similarities between X-linked dominant chondrodysplasia punctata-2 and CHILD syndrome (308050), Grange et al. (2000) analyzed plasma sterols in a patient with typical CHILD syndrome. The levels of 8-dehydrocholesterol and 8(9)-cholestenol were increased in this patient to the same degree as in CDPX2 patients. The authors subsequently identified a nonsense mutation in exon 3 of the patient's 3-beta-hydroxysteroid-d ... More on the omim web site

Subscribe to this protein entry history

Nov. 16, 2018: Protein entry updated
Automatic update: OMIM entry 300205 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).