ANOS1

Chr XXLR

anosmin 1

Also known as: ADMLX, HH1, HHA, KAL, KAL1, KALIG-1, KMS, WFDC19

NCBI Gene: 3730ENSG00000011201UniProt: P23352OMIM: 300836

The protein functions as a chemoattractant for fetal olfactory epithelial cells and promotes axonal branching and guidance, playing a critical role in olfactory system development. Mutations cause X-linked Kallmann syndrome, characterized by hypogonadotropic hypogonadism with or without anosmia, typically presenting with delayed or absent puberty. This gene shows X-linked recessive inheritance and is highly constrained against loss-of-function variants.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
XLRLOEUF 0.251 OMIM phenotype
Clinical Summary— ANOS1
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Gene-Disease Validity (ClinGen)
hypogonadotropic hypogonadism 1 with or without anosmia · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
141 unique Pathogenic / Likely Pathogenic· 164 VUS of 455 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ANOS1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.998
Z-score 4.69
OE 0.10 (0.04–0.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.89Z-score
OE missense 0.85 (0.76–0.95)
221 obs / 261.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.04–0.25)
0≤0.351.4
Missense OE0.85 (0.76–0.95)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 3 / 31.3Missense obs/exp: 221 / 261.3Syn Z: 0.09

ClinVar Variant Classifications

455 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
Likely Pathogenic25
VUS164
Likely Benign40
Benign13
Conflicting10
116
Pathogenic
25
Likely Pathogenic
164
VUS
40
Likely Benign
13
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
43
2
71
0
116
Likely Pathogenic
18
6
1
0
25
VUS
2
122
36
4
164
Likely Benign
0
9
16
15
40
Benign
0
4
4
5
13
Conflicting
—10
Total6314312824368

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ANOS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients