ANOS1
anosmin 1, the group of Fibronectin type III domain containing|WAP four-disulfide core domain containing
Basic information
Region (hg38): X:8528874-8732137
Previous symbols: [ "KAL", "ADMLX", "KAL1" ]
Links
Phenotypes
GenCC
Source:
- hypogonadotropic hypogonadism 1 with or without anosmia (Strong), mode of inheritance: XL
- Kallmann syndrome (Supportive), mode of inheritance: AD
- hypogonadotropic hypogonadism 1 with or without anosmia (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) | XL/Digenic | Audiologic/Otolaryngologic; Endocrine | Surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required; As the condition may include hearing loss, recognition and interventions related to speech and language development may be beneficial | Audiologic/Otolaryngologic; Craniofacial; Dental; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal | 6772660; 3312278; 3101500; 8504298; 7677154; 8989261; 9713559; 10944855; 11297579; 15001591; 8768867; 16882753; 8160472; 20301509; 20949504; 23533228 |
| Digenic inheritance (with PROKR2) has been reported |
ClinVar
This is a list of variants' phenotypes submitted to
- Hypogonadotropic_hypogonadism_1_with_or_without_anosmia (205 variants)
- not_provided (79 variants)
- Inborn_genetic_diseases (59 variants)
- not_specified (15 variants)
- ANOS1-related_disorder (14 variants)
- Hypogonadotropic_hypogonadism (3 variants)
- Amenorrhea (3 variants)
- See_cases (2 variants)
- Hypogonadotropic_hypogonadism_7_with_or_without_anosmia (1 variants)
- Delayed_puberty (1 variants)
- Micropenis (1 variants)
- Martsolf_syndrome_1 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANOS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000216.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 20 | 31 | ||||
| missense | 115 | 27 | 157 | |||
| nonsense | 21 | 25 | ||||
| start loss | 3 | 3 | ||||
| frameshift | 30 | 36 | ||||
| splice donor/acceptor (+/-2bp) | 14 | |||||
| Total | 60 | 23 | 120 | 47 | 16 |
Highest pathogenic variant AF is 0.0000100918
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ANOS1 | protein_coding | protein_coding | ENST00000262648 | 14 | 203313 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00207 | 125730 | 5 | 3 | 125738 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.885 | 221 | 261 | 0.846 | 0.0000205 | 4384 |
| Missense in Polyphen | 53 | 81.317 | 0.65177 | 1462 | ||
| Synonymous | 0.0928 | 107 | 108 | 0.989 | 0.00000916 | 1371 |
| Loss of Function | 4.69 | 3 | 31.3 | 0.0958 | 0.00000283 | 408 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000731 | 0.0000731 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000626 | 0.0000462 |
| European (Non-Finnish) | 0.0000616 | 0.0000440 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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}.;
- Disease
- DISEASE: Hypogonadotropic hypogonadism 1 with or without anosmia (HH1) [MIM:308700]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:11297579, ECO:0000269|PubMed:15001591, ECO:0000269|PubMed:15471890, ECO:0000269|PubMed:15605412, ECO:0000269|PubMed:17054399, ECO:0000269|PubMed:17213338, ECO:0000269|PubMed:17223984, ECO:0000269|PubMed:19696444, ECO:0000269|PubMed:20530987, ECO:0000269|PubMed:21168128, ECO:0000269|PubMed:23643382, ECO:0000269|PubMed:25077900, ECO:0000269|PubMed:8504298, ECO:0000269|PubMed:8989261, ECO:0000269|PubMed:9589672}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in ANOS1 as well as in other HH-associated genes including FGFR1 and TACR3 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.;
- Pathway
- Signal Transduction;Signaling by FGFR;Signaling by Receptor Tyrosine Kinases;FGFR1c ligand binding and activation;FGFR1 ligand binding and activation;Negative regulation of FGFR1 signaling;Signaling by FGFR1
(Consensus)
Recessive Scores
- pRec
- 0.206
Intolerance Scores
- loftool
- rvis_EVS
- 0.15
- rvis_percentile_EVS
- 64.74
Haploinsufficiency Scores
- pHI
- 0.494
- hipred
- Y
- hipred_score
- 0.784
- ghis
- 0.413
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
Zebrafish Information Network
- Gene name
- anos1a
- Affected structure
- neuromast hair cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- chemotaxis;cell adhesion;axon guidance;fibroblast growth factor receptor signaling pathway;negative regulation of endopeptidase activity
- Cellular component
- extracellular region;extracellular space;plasma membrane;extracellular matrix
- Molecular function
- serine-type endopeptidase inhibitor activity;extracellular matrix structural constituent;protein binding;heparin binding