ClinGen Dosage Sensitivity Curation Page
ANOS1
- Curation Status: Complete
- id: ISCA-32917
- Date last evaluated: 2012-06-28
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about ANOS1 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/3730
- OMIM: https://omim.org/entry/300836
- Gene Reviews: https://www.ncbi.nlm.nih.gov/books/NBK1334/?term=KAL1
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 0.939
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
- Haploinsufficiency Phenotype: HYPOGONADOTROPIC HYPOGONADISM 1 WITH OR WITHOUT ANOSMIA; HH1
Haploinsufficiency phenotype comments:
Loss of function mutations in KAL1, including whole or partial gene deletions, cause Kallmann syndrome in males. Female carriers are typically unaffected. See GeneReviews.
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 score: 0
- Strength of Evidence (disclaimer): No evidence for dosage pathogenicity
Triplosensitivity phenotype comment:
There have been no focal duplications of KAL1 reported. Mencarelli et al (2008) report a female patient who had autism, skeletal defects, short stature, facial asymmetry, and heart valve defects. She had a 0.8 Mb duplication that included KAL1 and other genes and that was inherited from a healthy father (PMID: 18657637).
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.