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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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ANOS1
anosmin 1
Chromosome X Β· Xp22.31
NCBI Gene: 3730Ensembl: ENSG00000011201.13HGNC: HGNC:6211UniProt: P23352
91PubMed Papers
21Diseases
0Drugs
95Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingcell surfaceneuron differentiationaxon guidancehypogonadotropic hypogonadism 1 with or without anosmiaKallmann syndromehypogonadotropic hypogonadismgenetic disorder
✦AI Summary

ANOS1 encodes anosmin-1, an extracellular glycoprotein that functions as a cell adhesion molecule with dual roles in neuronal development and reproductive axis formation 1. The protein exhibits chemoattractant activity for olfactory epithelial cells and promotes axon guidance, particularly in patterning olfactory neuron projections to the cortex. During fetal development, GnRH and olfactory neurons migrate together from the olfactory placode, with anosmin-1 facilitating this coordinated migration 2. ANOS1 mutations cause X-linked recessive Kallmann syndrome, characterized by hypogonadotropic hypogonadism combined with anosmia or hyposmia 13. This results from impaired GnRH neuron migration to the hypothalamus, leading to gonadotropin deficiency and absent puberty. ANOS1 variants account for a substantial fraction of congenital hypogonadotropic hypogonadism cases 4. Clinically, patients present with delayed puberty, infertility, and olfactory dysfunction; treatment with testosterone or GnRH/gonadotropin therapy can restore sexual development and fertility 2. Beyond reproductive development, elevated ANOS1 expression has been associated with gastric cancer progression, correlating with increased proliferation, invasion, and worse prognosis 5, suggesting broader biological significance in cell adhesion and migration processes.

Sources cited
1
ANOS1 (KAL1) encodes anosmin-1, an extracellular glycoprotein responsible for X-linked recessive Kallmann syndrome; mutations cause hypogonadotropic hypogonadism with anosmia
PMID: 18985070
2
GnRH and olfactory neurons migrate together from the olfactory placode during fetal development; KAL1 mutations cause idiopathic hypogonadotropic hypogonadism with treatment options including GnRH or gonadotropin therapy
PMID: 17543719
3
ANOS1 was the first gene identified for Kallmann syndrome; variants account for significant proportion of hypogonadotropic hypogonadism cases with X-linked recessive inheritance
PMID: 34062169
4
ANOS1 variants are frequent genetic causes of congenital hypogonadotropic hypogonadism/Kallmann syndrome, presenting with delayed puberty and anosmia
PMID: 41312956
5
ANOS1 functions as a cell adhesion molecule; elevated expression in gastric cancer associates with increased proliferation, invasion, and worse prognosis
PMID: 26270236
6
ANOS1 is the unified nomenclature for KAL1 gene and anosmin-1 protein, reflecting standardized naming conventions
PMID: 27899353
7
Novel ANOS1 mutations identified in Kallmann syndrome patients; mutations can affect splicing and disrupt protein function
PMID: 36859276
Disease Associationsβ“˜21
hypogonadotropic hypogonadism 1 with or without anosmiaOpen Targets
0.83Strong
Kallmann syndromeOpen Targets
0.73Strong
hypogonadotropic hypogonadismOpen Targets
0.47Moderate
genetic disorderOpen Targets
0.42Moderate
congenital anomaly of kidney and urinary tractOpen Targets
0.37Weak
MicropenisOpen Targets
0.34Weak
Cataract - intellectual disability - hypogonadismOpen Targets
0.34Weak
Delayed pubertyOpen Targets
0.27Weak
amenorrheaOpen Targets
0.15Weak
neoplasmOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
achalasia-alacrima syndromeOpen Targets
0.07Suggestive
cholangiocarcinomaOpen Targets
0.07Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.07Suggestive
Hepatic steatosisOpen Targets
0.07Suggestive
non-alcoholic steatohepatitisOpen Targets
0.05Suggestive
brain neoplasmOpen Targets
0.04Suggestive
glioblastomaOpen Targets
0.04Suggestive
cartilage-hair hypoplasiaOpen Targets
0.04Suggestive
Hypogonadotropic hypogonadism 1 with or without anosmiaUniProt
Pathogenic Variants95
NM_000216.4(ANOS1):c.1270C>T (p.Arg424Ter)Pathogenic
not provided|Hypogonadotropic hypogonadism 1 with or without anosmia|Hypogonadotropic hypogonadism
β˜…β˜…β˜†β˜†2026β†’ Residue 424
NM_000216.4(ANOS1):c.1063-1G>CPathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia|not provided
β˜…β˜…β˜†β˜†2025
NM_000216.4(ANOS1):c.256T>A (p.Cys86Ser)Pathogenic
Hypogonadotropic hypogonadism|Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜…β˜†β˜†2025β†’ Residue 86
NM_000216.4(ANOS1):c.784C>T (p.Arg262Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 262
NM_000216.4(ANOS1):c.1449+1G>APathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia|Hypogonadotropic hypogonadism|not provided
β˜…β˜…β˜†β˜†2025
NM_000216.4(ANOS1):c.1137C>G (p.Tyr379Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜…β˜†β˜†2025β†’ Residue 379
NM_000216.4(ANOS1):c.109G>T (p.Glu37Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜…β˜†β˜†2024β†’ Residue 37
NM_000216.4(ANOS1):c.1891C>T (p.Arg631Ter)Pathogenic
not provided|Hypogonadotropic hypogonadism 1 with or without anosmia|Martsolf syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 631
NM_000216.4(ANOS1):c.1369C>T (p.Arg457Ter)Pathogenic
Delayed puberty|Hypogonadotropic hypogonadism 7 with or without anosmia|Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜…β˜†β˜†2024β†’ Residue 457
NM_000216.4(ANOS1):c.1267C>T (p.Arg423Ter)Pathogenic
not provided|Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜…β˜†β˜†2023β†’ Residue 423
NM_000216.4(ANOS1):c.1A>C (p.Met1Leu)Likely pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2026β†’ Residue 1
NM_000216.4(ANOS1):c.709T>C (p.Trp237Arg)Likely pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2026β†’ Residue 237
NM_000216.4(ANOS1):c.257G>T (p.Cys86Phe)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 86
NM_000216.4(ANOS1):c.571C>T (p.Arg191Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 191
NM_000216.4(ANOS1):c.856+1G>TPathogenic
Hypogonadotropic hypogonadism|Familial cancer of breast
β˜…β˜†β˜†β˜†2025
NM_000216.4(ANOS1):c.1156_1157del (p.Lys386fs)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 386
NM_000216.4(ANOS1):c.814C>T (p.Arg272Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 272
NM_000216.4(ANOS1):c.44G>A (p.Trp15Ter)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 15
NM_000216.4(ANOS1):c.1897del (p.Glu633fs)Pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 633
NM_000216.4(ANOS1):c.1863del (p.Asn623fs)Likely pathogenic
Hypogonadotropic hypogonadism 1 with or without anosmia
β˜…β˜†β˜†β˜†2025β†’ Residue 623
View on ClinVar β†—
Related Genes
GNRH1Protein interaction98%FGF8Protein interaction91%CHD7Protein interaction86%GNRHRProtein interaction82%FGFR1Protein interaction82%FGF2Protein interaction78%
Tissue Expression6 tissues
Heart
100%
Lung
78%
Brain
62%
Liver
5%
Ovary
4%
Bone Marrow
1%
Gene Interaction Network
Click a node to explore
ANOS1GNRH1FGF8CHD7GNRHRFGFR1FGF2
PROTEIN STRUCTURE
Preparing viewer…
PDB1ZLG Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.20Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.10 [0.06–0.20]
RankingsWhere ANOS1 stands among ~20K protein-coding genes
  • #5,230of 20,598
    Most Researched91
  • #811of 5,498
    Most Pathogenic Variants95 Β· top quartile
  • #453of 17,882
    Most Constrained (LOEUF)0.20 Β· top 5%
Genes detectedANOS1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J Β· 2022
1.00
2
ANOS1: a unified nomenclature for Kallmann syndrome 1 gene (KAL1) and anosmin-1.
PMID: 27899353
Brief Funct Genomics Β· 2017
0.90
3
PMID: 20301509
0.80
4
Kallmann syndrome.
PMID: 10868244
Adv Otorhinolaryngol Β· 2000
0.70
5
Genetics of hypogonadotropic Hypogonadism-Human and mouse genes, inheritance, oligogenicity, and genetic counseling.
PMID: 34062169
Mol Cell Endocrinol Β· 2021
0.60