ANOS1 |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ANOS1 (HGNC:6211) HGNC Entrez Ensembl OMIM Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- anosmin 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- KAL, ADMLX, KAL1
- Alias symbols
- KALIG-1, WFDC19
- %HI
- 60.51(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.25(Read more about gnomAD LOEUF score)
- Cytoband
- Xp22.31
- Genomic Coordinates
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GRCh37/hg19: chrX:8496915-8700178 NCBI Ensembl UCSC GRCh38/hg38: chrX:8528874-8732137 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000216.4 ENST00000262648.8 (Read more about MANE Select)
- Function
- Has a dual branch-promoting and guidance activity, which may play an important role in the patterning of mitral and tufted cell collaterals to the olfactory cortex (By similarity). Chemoattractant for fetal olfactory epithelial cells. {ECO:0000250, ECO:0000269|PubMed:19696444}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- hypogonadotropic hypogonadism 1 with or without anosmia Monarch
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PUBMED:
28122887
Goncalves et al. (2017) The ANOS1 gene (also known as Kallmann syndrome 1 gene, or KAL1), is the most commonly involved gene in congenital hypogonadotropic hypogonadism (CHH) and responsible for X-linked Kallmann syndrome. Authors performed sequencing on 42 unrelated males with CHH (20 with KS and 22 with normosmic CHH) in order to determine prevalence of ANOS1 variants . Three different ANOS1 variants were identified: Family 1: Splice acceptor site variant (c.542-IG>C)-exon skipping, production of abnormal mRNA. This variant was shown to lead to skipping of exon 5 in the ANOS1 transcript in a patient with self-reported normosmia (but hyposmic upon testing). Absent in 85 normal controls. Family 2: Nonsense variant (c.571C>T; p.Arg191*) Family 3: 4.8 Mb contiguous gene deletion Xp22.31-p22.32 region including ANOS1 (deleted genes ANOS1, VCX3B, VCX2, PNPLA4, VCX, STS, HDHD1, VCX3A and NLGN4X).
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PUBMED:
12050219
Soderlund et al. (2002) sequenced the entire ANOS1 gene in 12 males with Kallmann syndrome. Three variants were identified: Patient 5: nucleotides 158-168 were duplicated in exon 1. The 11 bp insertion causes a termination codon within the same exon (19 codons after the insertion). Patient 6: Deletion of exon 5 Patient 12: C->T change codon 262 from CGA (arginine) to TGA (premature termination signal)
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PUBMED:
24232061
Marlin et al. (2013) described two brothers with variable severity of sensorineural hearing loss (severe unilateral for one and profound bilateral for the other), cryptorchidism, hyposmia, and mirror movements of the upper limbs. One of them also presented with unilateral renal agenesis and metatarsus of one foot. Array analysis showed 570 kb deletion containing the entire VCS3B and ANOS1 gene. The deletion arr Xp22.31 (8,112,876-8,665,494)x0 was found to be inherited from a mother with a mosaic deletion.
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PUBMED:
21717404
Kryminska et al (2011) described a family in which the male proband and his maternal uncle with Kallmann syndrome were found to have an intragenic deletion of the ANOS1 (KAL1) gene from exons 4-14 (c.469-?_6314+?del) identified by MLPA. Three carrier females were also identified in this family.
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PUBMED:
25328414
Husny et al. (2014) identified a c.612G>A ( p.Trp204*) in a family of 4 brothers with a diagnosis of Kallmann syndrome and five heterozygous female family members.
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PUBMED:
18463157
Pendersen-White et al. (2008): Kallmann syndrome (KS) consists of idopathic hypogonadotrophic hypogonadism (IHH) with anosmia. Authors performed MLPA analysis of the ANOS1( all 14 exons), FGFR1, GNRH1, GNRHR, GPR54 or NELF genes on 112 probands both male and female with IHH/KS. A total of 4/54 patients (male and female) had ANOS1 deletions (7.4%) When only anosmic males were considered 4/33 (12.1 %) were found to have ANOS1 deletions. Three of these deletions were determined to be whole gene and one was a 3 bp deletion Cys164del.
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
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PUBMED: 18657637
Mencarelli et al. performed oligo arrays on 84 patients with mild to severe intellectual disability and multiple congenital anomalies. They described a 0.8 MB duplication at Xp22.31 including the ANOS1 (KAL1), FAM8A, and FAM9B genes in a female with autism, skeletal defects, short stature, facial asymmetry, and heart defect in inherited from a clinically normal father.
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.