 |
CHRDL1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- CHRDL1 (HGNC:29861) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- chordin like 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MGC1
- Alias symbols
- NRLN1, CHL
- %HI
- 24.72(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.22(Read more about gnomAD pLI score)
- LOEUF
- 0.52(Read more about gnomAD LOEUF score)
- Cytoband
- Xq23
- Genomic Coordinates
-
GRCh37/hg19: chrX:109917084-110039045 NCBI Ensembl UCSC GRCh38/hg38: chrX:110673856-110795817 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001143981.2 ENST00000372042.6 (Read more about MANE Select)
- Function
- Antagonizes the function of BMP4 by binding to it and preventing its interaction with receptors. Alters the fate commitment of neural stem cells from gliogenesis to neurogenesis. Contributes to neuronal differentiation of neural stem cells in the brain by preventing the adoption of a glial fate. May play a crucial role in dorsoventral axis formation. May play a role in embryonic bone formation (By similarity). May also play an important role in regulating retinal angiogenesis through modulation ... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- isolated congenital megalocornea Monarch
-
PUBMED:
22284829
CHRDL1 (Chordin-like 1) gene is composed of 12 exons and maps to Xq23. CHRDL1 encodes ventropin, a bone morphorphogenic protein antagonist which is known to play a crucial role anteroposterior and dorsoventral axes in the retina and tectum during development. Loss of function variants in CHRDL1 are associated with X-linked megalocornea (MGC1, OMIM 309300) which is characterized by an increased corneal diameter and deep anterior chamber evident at birth with later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. Webb et al. 2012: Discusses 7 different variants in CHRDL1 in families with X-linked megalocornea (MGC1), including two microdeletions, one of which contained only CHRDL1, as well as one nonsense mutation (p.Arg218X) and two frameshifts (c.872delG [p.Cys291LeufsX25] and c.101delAG [p.Glu34AspfsX14]). The microdeletion segregating with the phenotype in that family and the frameshift and nonsense mutations were found in the patients' unaffected mothers.
-
PUBMED:
25093588
Davidson et al (2014) performed whole exome sequencing, Sanger sequencing, and PCR to identify mutations in 10 new families with a diagnosis of MGC1. In all families, mutations of CHRDL1 segregated with affected males and carrier females were unaffected. Structural variants were identified which included whole gene deletions (2 families), nonsense mutations (4 families), and missense mutations (4 families).
-
PUBMED:
26020825
Mangialavori et al (2015) studied 2 families with MGC1 from the same region of Italy. These families apparently are unrelated despite attempts to identify a common ancestor. Between the two families, 5 affected males were identified. All affected individuals in both families family had the same 11-base pair deletion that leads to a stop codon in the second coding exon of the CHRDL1 gene. The mothers of the probands were found to be heterozygous carriers and this mutation was not detected in unaffected male family members.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
