Preferred Label : Left-right determination factor 2;
Symbol : LEFTY2;
CISMeF acronym : EBAF; LEFTA; LEFTY2; TGFB4;
Type : Gene;
Alternative titles and symbols : Endometrial bleeding-associated factor; Left-right determination, factor a; Lefty a; Lefty2, mouse, homolog of; Transforming growth factor, beta-4; EBAF; LEFTA; TGFB4;
Description : Human endometrium is unique since it is the only tissue in the body that bleeds at
regular intervals. Abnormal endometrial bleeding is one of the most common manifestations
of gynecologic diseases. Kothapalli et al. (1997) reported a novel human gene, designated
endometrial bleeding-associated factor (EBAF) by them, whose strong expression in
endometrium was associated with abnormal endometrial bleeding. In normal human endometrium,
this gene is transiently expressed before and during menstrual bleeding. In situ hybridization
showed that the mRNA of EBAF is expressed in the stroma without any significant mRNA
expression in the endometrial glands or endothelial cells. The predicted protein sequence
of EBAF showed homology with and structural features of the members of TGF-beta superfamily
(see 190180). Fluorescence in situ hybridization showed that the EBAF gene is located
on 1q42.1. Despite the knowledge that steroid hormones are responsible for normal
and abnormal endometrial bleeding, the identity of the local and specific endometrial
factors that are implicated had remained largely unknown. It is for this reason that
the study was undertaken. Kothapalli et al. (1997) used differential display of cDNAs
prepared from total RNAs isolated from endometria from various phases of the menstrual
cycle. All vertebrates lateralize unpaired organs of the chest and abdomen during
embryogenesis. This process leads, for example, to the characteristic positions of
the heart apex, stomach, and spleen to the left of the midline. Several genes are
expressed asymmetrically prior to the appearance of anatomic left-right (L-R) differences.
Meno et al. (1996, 1997) identified 2 transforming growth factor-beta-related genes,
Lefty1 (603037) and Lefty2, that are expressed on the left side of developing mouse
embryos. These genes are expressed exclusively on the left side of the mouse embryo
by 8.0 days postcoitum. The asymmetry is lost or reversed in 2 murine models of abnormal
L-R axis specification, inversus viscerum (iv; see 603339) and inversion of embryonic
turning (INV; 243305). Furthermore, mice homozygous for a Lefty1 null allele manifest
L-R malformations and misexpress Lefty2. Because of the possibility that Lefty mutations
may be associated with human L-R axis malformations, Kosaki et al. (1999) characterized
2 human homologs of mouse Lefty1 and Lefty2, which they called LEFTY B and LEFTY A,
respectively. PCR screening of a PAC genomic library identified a clone that contained
both LEFTY A and LEFTY B genes. Restriction mapping showed that the genes are separated
by approximately 50 kb and are oriented in tandem. The 2 genes were localized by FISH
to 1q42, a region syntenic to the location to which the mouse Lefty genes have been
mapped at 1H5 (Meno et al., 1997). Both LEFTY A and LEFTY B contain 4 exons which
are spliced at identical positions, and both genes encode proteins with 366 amino
acids. LEFTY A was found to be identical to EBAF, the cDNA previously identified by
Kothapalli et al. (1997). The deduced amino acid sequences of LEFTY A and LEFTY B
are more similar to each other than to Lefty1 or Lefty2 of the mouse. Analysis of
126 human cases of L-R axis malformation showed 1 nonsense and 1 missense mutation
in the LEFTY A gene. Both mutations lay in the cystine knot region of the;
Ensembl ID : ENSG00000143768;
Prefixed ID : *601877;
Origin ID : 601877;
UMLS CUI : C1537561;
Automatic exact mappings (from CISMeF team)
- Currated CISMeF NLP mapping
- HGNC gene
- NCIt concept(s)
- ORDO concept(s)
- Semantic type(s)
- UMLS correspondences (same concept)
