AMN (amnion associated transmembrane protein)

Gene

• Entrez ID: 81693
• Gene name: Amnion associated transmembrane protein
• Gene symbol: AMN
• Synonyms: IGS2, PRO1028, amnionless
• Chromosome: 14
• Chromosome location: 14q32.32
• Summary: The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs119478058	C>A,T	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs144077391	G>A,C	Likely-pathogenic	Intron variant
rs386834160	CCATCCCGCCCCGCC>-	Likely-pathogenic	Intron variant
rs386834161	CCTCGCCCCGCCGCG>-	Likely-pathogenic	Intron variant
rs386834162	TCGCCCCGCCGCGGG>-	Likely-pathogenic	Intron variant
rs386834163	CCTCGGCG>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs386834164	C>T	Uncertain-significance, benign, likely-pathogenic	Intron variant
rs386834165	->A	Likely-pathogenic	Frameshift variant, coding sequence variant
rs386834166	C>T	Likely-pathogenic	Intron variant
rs386834167	CA>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs386834168	G>-	Likely-pathogenic, pathogenic	Upstream transcript variant, genic upstream transcript variant, coding sequence variant, frameshift variant, 5 prime UTR variant
rs386834169	G>C	Likely-pathogenic	Splice acceptor variant
rs386834170	A>G	Likely-pathogenic	Splice acceptor variant
rs386834171	G>-	Likely-pathogenic	Splice donor variant, coding sequence variant
rs386834172	G>T	Likely-pathogenic	Upstream transcript variant, splice donor variant, 5 prime UTR variant, genic upstream transcript variant
rs386834173	->T	Likely-pathogenic	Frameshift variant, coding sequence variant
rs386834174	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs386834175	AGCCCCTGGGCGGCCGCTGCCCCCAGGCCGCCTGCCACAGCGCCCTCC>-	Likely-pathogenic	Inframe deletion, coding sequence variant
rs386834176	G>T	Likely-pathogenic	Coding sequence variant, missense variant
rs386834177	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs386834178	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs386834179	->CCCG	Likely-pathogenic	Frameshift variant, coding sequence variant
rs969552874	G>C	Likely-pathogenic	Splice acceptor variant
rs1555380625	->GT	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555381324	->CT	Pathogenic	Coding sequence variant, frameshift variant
rs1555381485	G>A	Likely-pathogenic	Splice donor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IPI	14576052
GO:0005515	Function	Protein binding	IPI	30523278
GO:0005615	Component	Extracellular space	IDA	14576052
GO:0005886	Component	Plasma membrane	TAS
GO:0005905	Component	Clathrin-coated pit	IEA
GO:0006898	Process	Receptor-mediated endocytosis	IBA	21873635
GO:0006898	Process	Receptor-mediated endocytosis	IDA	14576052
GO:0006898	Process	Receptor-mediated endocytosis	IMP	20088845
GO:0007275	Process	Multicellular organism development	IEA
GO:0007588	Process	Excretion	IEA
GO:0008104	Process	Protein localization	IBA	21873635
GO:0009235	Process	Cobalamin metabolic process	TAS
GO:0010008	Component	Endosome membrane	TAS
GO:0015889	Process	Cobalamin transport	IDA	14576052
GO:0016021	Component	Integral component of membrane	IEA
GO:0016324	Component	Apical plasma membrane	IBA	21873635
GO:0016324	Component	Apical plasma membrane	IDA	14576052
GO:0030139	Component	Endocytic vesicle	IBA	21873635
GO:0030139	Component	Endocytic vesicle	IDA	14576052
GO:0031526	Component	Brush border membrane	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0034384	Process	High-density lipoprotein particle clearance	TAS
GO:0043001	Process	Golgi to plasma membrane protein transport	IDA	14576052
GO:0070062	Component	Extracellular exosome	HDA	19056867

Other IDs

• MIM: 605799
• HGNC: 14604
• e!Ensembl: ENSG00000166126

Protein

• UniProt ID: Q9BXJ7
• Protein name: Protein amnionless [Cleaved into: Soluble protein amnionless]
• Protein function: Membrane-bound component of the endocytic receptor formed by AMN and CUBN (PubMed:14576052, PubMed:30523278, PubMed:29402915). Required for normal CUBN glycosylation and trafficking to the cell surface (PubMed:14576052, PubMed:29402915). The complex formed by AMN and CUBN is required for efficient absorption of vitamin B12 (PubMed:12590260, PubMed:14576052, PubMed:26040326). Required for normal CUBN-mediated protein transport in the kidney (Probable).
• PDB: 6GJE
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14828	Amnionless	21 → 447	Amnionless	Family

• Sequence:

  MGVLGRVLLWLQLCALTQAVSKLWVPNTDFDVAANWSQNRTPCAGGAVEFPADKMVSVLV
  QEGHAVSDMLLPLDGELVLASGAGFGVSDVGSHLDCGAGEPAVFRDSDRFSWHDPHLWRS
  GDEAPGLFFVDAERVPCRHDDVFFPPSASFRVGLGPGASPVRVRSISALGRTFTRDEDLA
  VFLASRAGRLRFHGPGALSVGPEDCADPSGCVCGNAEAQPWICAALLQPLGGRCPQAACH
  SALRPQGQCCDLCGAVVLLTHGPAFDLERYRARILDTFLGLPQYHGLQVAVSKVPRSSRL
  READTEIQVVLVENGPETGGAGRLARALLADVAENGEALGVLEATMRESGAHVWGSSAAG
  LAGGVAAAVLLALLVLLVAPPLLRRAGRLRWRRHEAAAPAGAPLGFRNPVFDVTASEELP
  LPRRLSLVPKAAADSTSHSYFVNPLFAGAEAEA

• Sequence length: 453

Pathways

KEGG:

Vitamin digestion and absorption

Reactome:

Cobalamin (Cbl, vitamin B12) transport and metabolism
Defective AMN causes hereditary megaloblastic anemia 1
Defective CUBN causes hereditary megaloblastic anemia 1
HDL clearance

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Anemia	Anemia, Megaloblastic, Megaloblastic anemia due to inborn errors of metabolism, Megaloblastic Anemia 1	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505	21750092, 26040326, 12590260, 22929189, 29402915, 17285242, 30523278, 22631584, 15024727
Imerslund-grasbeck syndrome	Imerslund-Gräsbeck syndrome	rs119478058, rs121434430, rs1205598688, rs386833766, rs386833767, rs386833768, rs386833769, rs386833770, rs386833771, rs182512508, rs386833772, rs386833773, rs386833774, rs386833775, rs386833776, rs386833777, rs386833778, rs386833779, rs386833780, rs386833781, rs386833783, rs386833784, rs386833785, rs386833786, rs386833787, rs386833788, rs386833789, rs386833790, rs386833791, rs386834160, rs386834161, rs386834162, rs386834163, rs386834165, rs386834167, rs386834168, rs386834169, rs386834170, rs386834171, rs386834172, rs386834173, rs144077391, rs386834174, rs386834175, rs386834176, rs386834177, rs386834178, rs386834179, rs386833782, rs757649673, rs566060177, rs374695194, rs1168074679, rs1554790861, rs-1, rs1555381485, rs143944436, rs146047781, rs1564435943, rs145661597, rs969552874, rs137998687, rs754704005, rs1564379463, rs752843169, rs368697251, rs747417629, rs1564435513, rs1564443979, rs765301342, rs769881615, rs770921101, rs1588639188, rs374417889, rs1588511533, rs147730705, rs557208468, rs2131458620, rs202153130, rs2131820786, rs2139312594, rs1566829097, rs769770182, rs375774640

Unknown
Disease name	Disease term	dbSNP ID	References
Cobalamin deficiency	Vitamin B 12 Deficiency
Dementia	Dementia
Kidney failure	Kidney Failure, Acute		20514524
Acute kidney insufficiency	Acute Kidney Insufficiency		20514524