// Workers AI · dad joke modeDoes anosmin-1 have a sense of smell? No, it's a little "off".

ANOS1
Identifiers
Aliases	ANOS1, ADMLX, HH1, HHA, KAL, KALIG-1, KMS, WFDC19, KAL1, anosmin 1, anosmin-1
External IDs	OMIM: 300836; GeneCards: ANOS1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1ZLG
Gene location (Human) Chr. X chromosome (human) Band Xp22.31 Start 8,528,874 bp End 8,732,137 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in visceral pleura hair follicle Skeletal muscle tissue of rectus abdominis tibia glutes bronchial epithelial cell lower lobe of lung triceps brachii muscle parietal pleura mucosa of paranasal sinus n/a More reference expression data BioGPS n/a
Gene ontology Molecular function peptidase inhibitor activity heparin binding extracellular matrix structural constituent protein binding serine-type endopeptidase inhibitor activity Cellular component plasma membrane membrane extracellular region extracellular space extracellular matrix Biological process negative regulation of peptidase activity cell adhesion negative regulation of endopeptidase activity axon guidance fibroblast growth factor receptor signaling pathway chemotaxis Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 3730 n/a Ensembl ENSG00000011201 n/a UniProt P23352 n/a RefSeq (mRNA) NM_000216 n/a RefSeq (protein) NP_000207 n/a Location (UCSC) Chr X: 8.53 – 8.73 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

Anosmin-1
Identifiers
Symbol	ANOS1
Alt. symbols	KAL1, ADMLX
Alt. names	Adhesion molecule-like X-linked, Kallmann syndrome protein
NCBI gene	3730
HGNC	6211
OMIM	308700
RefSeq	NM_000216
UniProt	P23352
Other data
Locus	Chr. X p22.32
Search for Structures Swiss-model Domains InterPro

Anosmin-1 is a secreted, EM associated glycoprotein found in humans and other organisms responsible for normal development, which is expressed in the brain, spinal cord and kidney. Absence or damage to the protein results in Kallmann syndrome in humans, which is characterized by loss of olfactory bulbs and GnRH secretion leading to anosmia and hypothalamic hypogonadotropic hypogonadism. Anosmin-1 is coded by the ANOS1 gene, which is found on the X chromosome. Anosmin-1 is 100 kilodaltons and is expressed on the outside of cells. Because of this and because of its contribution to normal migration of nerve cells, a role in the extracellular matrix has been postulated.

Function

During neural crest cell development, anosmin-1 plays a role in cranial neural cell formation by spatiotemporal regulation. Secreated anosmin-1 enhances FGF activity by promoting FGF8-FGFR1 complex formation, whereas inhibits both BMP5 and WNT3A activities. As a results, orchestrated regulation of FGF, BMP, and WNT by anosmin-1 control EMT and MET during neural crest cell development. In human retinal pigment epithelial cell (RPE), the expression of anosmin-1 is regulated by TGF-β which remain to be investigated.

Structure and pathology

Anosmin-1 is encoded by a gene ANOS1 (earlier called ADMLX, KAL, KAL1, KALIG1). In human it is located on the X chromosome at Xp22.3 and is affected in some male individuals with Kallmann syndrome. This gene codes for a protein of the extracellular matrix named anosmin-1, which is involved in the migration of certain nerve cell precursors (neuroendocrine GnRH cells) during embryogenesis. Deletion or mutation of this gene results in loss of the functional protein and affects the proper development of the olfactory nerves and olfactory bulbs. In addition, neural cells that produce GnRH fail to migrate to the hypothalamus.

Clinically, mutation results in the X-linked form of Kallmann syndrome. Individuals with Kallmann syndrome experience anosmia (lack of smell) and do not go through puberty (hypothalamic hypogonadotropic hypogonadism).

ANOS1 is made of 14 exons and spans 120-200 kilobases. Mutations of ANOS1 may account for 14% of the cases of familial Kallmann syndrome and 11% of male sporadic cases.

Further reading

• Söderlund D, Canto P, Méndez JP (June 2002). "Identification of three novel mutations in the KAL1 gene in patients with Kallmann syndrome". The Journal of Clinical Endocrinology & Metabolism. 87 (6): 2589–92. doi:10.1210/jcem.87.6.8611. PMID 12050219.
• Dodé C, Levilliers J, Dupont JM, De Paepe A, Le Dû N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pêcheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP (April 2003). "Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome". Nature Genetics. 33 (4): 463–465. doi:10.1038/ng1122. PMID 12627230.
• Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T (March 2004). "Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients". The Journal of Clinical Endocrinology & Metabolism. 89 (3): 1079–88. doi:10.1210/jc.2003-030476. PMID 15001591.
• Lee SH, Han JH, Cho SW, Lee WH, Cha KY, Lee MH (February 2004). "Mutation analysis of the KAL gene in female patients with gonadotropin-releasing hormone deficiency". Yonsei Medical Journal. 45 (1): 107–12. doi:10.3349/ymj.2004.45.1.107. PMID 15004876.
• Hu Y, González-Martínez D, Kim SH, Bouloux PM (December 2004). "Cross-talk of anosmin-1, the protein implicated in X-linked Kallmann's syndrome, with heparan sulphate and urokinase-type plasminogen activator". Biochemical Journal. 384 (Pt 3): 495–505. doi:10.1042/BJ20041078. PMC 1134135. PMID 15324302.
• Cariboni A, Pimpinelli F, Colamarino S, Zaninetti R, Piccolella M, Rumio C, Piva F, Rugarli EI, Maggi R (November 2004). "The product of X-linked Kallmann's syndrome gene (KAL1) affects the migratory activity of gonadotropin-releasing hormone (GnRH)-producing neurons" (PDF). Human Molecular Genetics. 13 (22): 2781–91. doi:10.1093/hmg/ddh309. PMID 15471890. S2CID 5248283. Archived from the original (PDF) on 2019-02-26.
• González-Martínez D, Kim SH, Hu Y, Guimond S, Schofield J, Winyard P, Vannelli GB, Turnbull J, Bouloux PM (November 2004). "Anosmin-1 modulates fibroblast growth factor receptor 1 signaling in human gonadotropin-releasing hormone olfactory neuroblasts through a heparan sulfate-dependent mechanism" (PDF). The Journal of Neuroscience. 24 (46): 10384–92. doi:10.1523/JNEUROSCI.3400-04.2004. PMC 6730313. PMID 15548653.
• Söderlund D, Vilchis F, Méndez JP (September 2004). "Polymorphic changes in the KAL1 gene: not all of them should be classified as polymorphisms". Journal of Endocrinological Investigation. 27 (8): 765–9. doi:10.1007/BF03347520. PMID 15636431. S2CID 24410365.
• Hu Y, Sun Z, Eaton JT, Bouloux PM, Perkins SJ (July 2005). "Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling". Journal of Molecular Biology. 350 (3): 553–70. doi:10.1016/j.jmb.2005.04.031. PMID 15949815.

External links

• GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
• NextBio.com
• GenAtlas