Details for: AMN

Gene ID: 81693

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: AMN

Ensembl ID: ENSG00000166126

Description: amnion associated transmembrane protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • intestinal epithelial cell CL0002563
    CSI 30.78
    rCSI 32.17%
    PRS 95.92
  • colonocyte CL1000347
    CSI 28.28
    rCSI 40.54%
    PRS 95.9
  • colon epithelial cell CL0011108
    CSI 18.7
    rCSI 19.59%
    PRS 96.01
  • enterocyte CL0000584
    CSI 17.32
    rCSI 27.93%
    PRS 94.8
  • secretory cell CL0000151
    CSI 15.75
    rCSI 16.43%
    PRS 96.63
  • precursor B cell CL0000817
    CSI 13.59
    rCSI 11.9%
    PRS 98.41
  • intestine goblet cell CL0019031
    CSI 12.45
    rCSI 11.05%
    PRS 95.88
  • transit amplifying cell of colon CL0009011
    CSI 11.99
    rCSI 14.08%
    PRS 97.51
  • immature B cell CL0000816
    CSI 11.5
    rCSI 8.54%
    PRS 98.86
  • BEST4+ enteroycte CL4030026
    CSI 10.23
    rCSI 12.72%
    PRS 96.39
  • hepatocyte CL0000182
    CSI 9.67
    rCSI 17.3%
    PRS 95.53
  • fallopian tube secretory epithelial cell CL4030006
    CSI 9.46
    rCSI 9.1%
    PRS 96.23
  • stem cell CL0000034
    CSI 9.09
    rCSI 8.77%
    PRS 95.79
  • M cell of gut CL0000682
    CSI 9
    rCSI 9.56%
    PRS 97.37
  • type L enteroendocrine cell CL0002279
    CSI 8.8
    rCSI 16.51%
    PRS 96.7
  • enterocyte of epithelium of large intestine CL0002071
    CSI 8.24
    rCSI 43.29%
    PRS 97.52
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 7.95
    rCSI 21.43%
    PRS 97.67
  • colon goblet cell CL0009039
    CSI 7.92
    rCSI 18.82%
    PRS 97.29
  • epithelial cell of proximal tubule CL0002306
    CSI 7.85
    rCSI 19.18%
    PRS 93.29
  • paneth cell CL0000510
    CSI 7.6
    rCSI 11.22%
    PRS 98.45
  • small pre-B-II cell CL0000954
    CSI 7.06
    rCSI 6.79%
    PRS 98.88
  • periportal region hepatocyte CL0019026
    CSI 6.94
    rCSI 26.98%
    PRS 94.34
  • transit amplifying cell CL0009010
    CSI 6.94
    rCSI 10.61%
    PRS 98.02
  • goblet cell CL0000160
    CSI 6.49
    rCSI 6.13%
    PRS 95.88
  • lung ciliated cell CL1000271
    CSI 6.42
    rCSI 7.42%
    PRS 94.21
  • ionocyte CL0005006
    CSI 6.38
    rCSI 6.83%
    PRS 97.53
  • enteroendocrine cell CL0000164
    CSI 6.06
    rCSI 8.29%
    PRS 95.44
  • small intestine goblet cell CL1000495
    CSI 5.71
    rCSI 12.5%
    PRS 97.43
  • brush cell CL0002204
    CSI 5.04
    rCSI 9.97%
    PRS 97.09
  • foveolar cell of stomach CL0002179
    CSI 5
    rCSI 10.64%
    PRS 97.38
  • type EC enteroendocrine cell CL0000577
    CSI 4.56
    rCSI 16.19%
    PRS 96.62
  • pulmonary ionocyte CL0017000
    CSI 4.07
    rCSI 4.96%
    PRS 97.96
  • tracheal goblet cell CL1000329
    CSI 4.06
    rCSI 8.85%
    PRS 97.42
  • renal alpha-intercalated cell CL0005011
    CSI 4.01
    rCSI 5.36%
    PRS 97.97
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.94
    rCSI 3.05%
    PRS 98.29
  • enteroendocrine cell of small intestine CL0009006
    CSI 3.87
    rCSI 8.51%
    PRS 97.14
  • transit amplifying cell of small intestine CL0009012
    CSI 3.4
    rCSI 14.95%
    PRS 97.9
  • mucous neck cell CL0000651
    CSI 3.04
    rCSI 4.38%
    PRS 97.52
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3
    rCSI 7.76%
    PRS 96.05
  • IgA plasma cell CL0000987
    CSI 2.9
    rCSI 2.97%
    PRS 95.8
  • paneth cell of epithelium of small intestine CL1000343
    CSI 2.54
    rCSI 7.11%
    PRS 97.79
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.93
    rCSI 29.85%
    PRS 97.14
  • pancreatic ductal cell CL0002079
    CSI 1.9
    rCSI 3.69%
    PRS 97.17
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.8
    rCSI 2.18%
    PRS 82.97
  • paneth cell of colon CL0009009
    CSI 1.74
    rCSI 17.06%
    PRS 97.63
  • large pre-B-II cell CL0000957
    CSI 1.59
    rCSI 4.54%
    PRS 96.3
  • intestinal crypt stem cell of colon CL0009043
    CSI 1.51
    rCSI 11.31%
    PRS 98.57
  • pancreatic epsilon cell CL0005019
    CSI 1.22
    rCSI 5.69%
    PRS 97.3
  • parietal epithelial cell CL1000452
    CSI 1.17
    rCSI 3.13%
    PRS 95.12
  • bronchial goblet cell CL1000312
    CSI 0.93
    rCSI 3.73%
    PRS 98.22
  • respiratory goblet cell CL0002370
    CSI 0.7
    rCSI 7.65%
    PRS 98.08

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [AMN](/details-gene/81693) (Amnion Associated Transmembrane Protein) is a protein-coding gene located on chromosome 14 that encodes the amnionless protein. This type I transmembrane protein is a critical component of the cubam receptor complex, which also includes cubilin (CUBN). The primary function of this complex is the endocytosis of intrinsic factor-vitamin B12 (cobalamin) in the terminal ileum and the reabsorption of filtered proteins in the renal proximal tubules ([Link](https://doi.org/10.1182/blood-2003-08-2852); [Link](https://doi.org/10.1038/s41467-018-07468-4)). Consistent with this role, [AMN](/details-gene/81693) shows its highest significance in absorptive epithelial cells, such as [intestinal epithelial cell](/details-cell/CL0002563) and [colonocyte](/details-cell/CL1000347). Pathogenic mutations in [AMN](/details-gene/81693) disrupt this uptake mechanism, leading to Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by megaloblastic anemia and proteinuria ([Link](https://doi.org/10.1038/ng1098); [Link](https://doi.org/10.1186/s12881-015-0181-2)). ## Cellular Roles and Expression Landscape The expression profile of [AMN](/details-gene/81693) underscores its specialized function in nutrient absorption and metabolic homeostasis. **Overall**, the gene's significance is overwhelmingly concentrated in the epithelial cells of the gastrointestinal tract. It is a top marker for [intestinal epithelial cell](/details-cell/CL0002563) (CSI: 30.78), [colonocyte](/details-cell/CL1000347) (CSI: 28.28), and [enterocyte](/details-cell/CL0000584) (CSI: 17.32), the primary sites for dietary vitamin B12 absorption. Its high significance extends to related secretory and support cells within the intestinal lining, including [secretory cell](/details-cell/CL0000151), [intestine goblet cell](/details-cell/CL0019031), and [M cell of gut](/details-cell/CL0000682), suggesting a coordinated role within the intestinal mucosa. Beyond the gut, [AMN](/details-gene/81693) is also significantly expressed in [hepatocyte](/details-cell/CL0000182), which is consistent with the liver's central role in cobalamin storage and metabolism. Interestingly, a notable expression is also observed in several non-canonical cell types. Its significance in [precursor B cell](/details-cell/CL0000817) and [immature B cell](/details-cell/CL0000816) may suggest a previously underappreciated role in cobalamin uptake during the high metabolic demands of lymphopoiesis. Furthermore, its expression in [fallopian tube secretory epithelial cell](/details-cell/CL4030006) suggests potential functions related to nutrient transport in the reproductive tract. ## Pathways and Molecular Function The functional annotations for [AMN](/details-gene/81693) align precisely with its established role as a co-receptor for vitamin B12. It is a key participant in the [Cobalamin transport](/details-go/GO:0015889) and [Cobalamin metabolic process](/details-go/GO:0009235), acting as a [cargo receptor](/details-go/GO:0038024) within a larger [receptor complex](/details-go/GO:0043235). This function is mediated through its localization to the [apical plasma membrane](/details-go/GO:0016324) and specifically the [brush border membrane](/details-go/GO:0031526) of polarized epithelial cells, where it engages in [receptor-mediated endocytosis](/details-go/GO:0006898). Studies have shown that AMN is crucial for the proper glycosylation and trafficking of its partner protein, cubilin, to the cell surface, without which the receptor is non-functional ([Link](https://doi.org/10.1038/s41598-018-20731-4)). Reactome pathway analysis further cements this identity, placing [AMN](/details-gene/81693) at the center of [Cobalamin (cbl, vitamin b12) transport and metabolism](/details-pathway/R-HSA-196741) and specifically in the [Uptake of dietary cobalamins into enterocytes](/details-pathway/R-HSA-9758881). The clinical consequences of its dysfunction are highlighted by its direct link to disease pathways such as [Defective amn causes mga1](/details-pathway/R-HSA-3359462) (megaloblastic anemia 1) and the broader category of [Defects in vitamin and cofactor metabolism](/details-pathway/R-HSA-3296482). ## Research Directions While the primary role of [AMN](/details-gene/81693) in intestinal and renal cobalamin uptake is well-established, its expression in other cell types opens new avenues for investigation. The data suggests several testable hypotheses that could expand our understanding of its biological scope. 1. **Hypothesis 1:** The significant expression of [AMN](/details-gene/81693) in [precursor B cell](/details-cell/CL0000817) and [immature B cell](/details-cell/CL0000816) suggests it may play a critical, cell-intrinsic role in supplying cobalamin to support the rapid proliferation and metabolic demands of B-lymphopoiesis in the bone marrow. 2. **Hypothesis 2:** The presence of [AMN](/details-gene/81693) in [fallopian tube secretory epithelial cell](/details-cell/CL4030006) indicates a potential role in transporting cobalamin or other cubilin-binding ligands into the oviductal fluid, which could be essential for supporting gamete viability or early embryonic development prior to implantation. To test the first hypothesis regarding its role in B-cell development, a key experiment could be proposed. A conditional knockout mouse model could be generated using a B-cell-specific Cre recombinase (e.g., CD19-Cre) to delete *Amn* specifically within the B-lymphocyte lineage. The development, proliferation, and survival of B-cell precursors in the bone marrow of these knockout mice would be compared to wild-type littermates, particularly under conditions of dietary cobalamin limitation. Functional validation could be achieved by measuring the uptake of radiolabeled vitamin B12 in sorted B-cell progenitors from both genotypes. From a therapeutic standpoint, [AMN](/details-gene/81693) is not a candidate for inhibition. Loss-of-function mutations are the cause of Imerslund-Grasbeck syndrome, making functional restoration the therapeutic goal. Gene therapy represents a promising future direction, potentially using AAV vectors to deliver a functional copy of the [AMN](/details-gene/81693) cDNA specifically to intestinal [enterocytes](/details-cell/CL0000584). Such an approach could provide a long-term cure and eliminate the need for lifelong parenteral vitamin B12 supplementation, though challenges related to vector delivery and sustained expression in the intestinal epithelium would need to be overcome.

Genular Protein ID: 1200010147

Symbol: AMNLS_HUMAN

Name: Protein amnionless

UniProtKB Accession Codes:

Q9BXJ7 Q6UX83

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 2 DrugCentral 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 19 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11279523

Title: The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain.

PubMed ID: 11279523

DOI: 10.1038/86912

PubMed ID: 12508121

Title: The DNA sequence and analysis of human chromosome 14.

PubMed ID: 12508121

DOI: 10.1038/nature01348

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 12590260

Title: Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia.

PubMed ID: 12590260

DOI: 10.1038/ng1098

PubMed ID: 14576052

Title: The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless.

PubMed ID: 14576052

DOI: 10.1182/blood-2003-08-2852

PubMed ID: 30523278

Title: Structural assembly of the megadalton-sized receptor for intestinal vitamin B12 uptake and kidney protein reabsorption.

PubMed ID: 30523278

DOI: 10.1038/s41467-018-07468-4

PubMed ID: 22929189

Title: Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns.

PubMed ID: 22929189

DOI: 10.1186/1750-1172-7-56

PubMed ID: 26040326

Title: Novel compound heterozygous mutations in AMN cause Imerslund-Graesbeck syndrome in two half-sisters: a case report.

PubMed ID: 26040326

DOI: 10.1186/s12881-015-0181-2

PubMed ID: 22631584

Title: Imerslund-Grasbeck syndrome: new mutation in amnionless.

PubMed ID: 22631584

DOI: 10.1111/j.1442-200x.2011.03482.x

PubMed ID: 29402915

Title: Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.

PubMed ID: 29402915

DOI: 10.1038/s41598-018-20731-4

Sequence Information:

  • Length: 453
  • Mass: 47754
  • Checksum: 40AA14EF186A6009
  • Sequence:
    • MGVLGRVLLW LQLCALTQAV SKLWVPNTDF DVAANWSQNR TPCAGGAVEF PADKMVSVLV 
QEGHAVSDML LPLDGELVLA SGAGFGVSDV GSHLDCGAGE PAVFRDSDRF SWHDPHLWRS 
GDEAPGLFFV DAERVPCRHD DVFFPPSASF RVGLGPGASP VRVRSISALG RTFTRDEDLA 
VFLASRAGRL RFHGPGALSV GPEDCADPSG CVCGNAEAQP WICAALLQPL GGRCPQAACH 
SALRPQGQCC DLCGAVVLLT HGPAFDLERY RARILDTFLG LPQYHGLQVA VSKVPRSSRL 
READTEIQVV LVENGPETGG AGRLARALLA DVAENGEALG VLEATMRESG AHVWGSSAAG 
LAGGVAAAVL LALLVLLVAP PLLRRAGRLR WRRHEAAAPA GAPLGFRNPV FDVTASEELP 
LPRRLSLVPK AAADSTSHSY FVNPLFAGAE AEA

Genular Protein ID: 1883879028

Symbol: B3KP64_HUMAN

Name: N/A

UniProtKB Accession Codes:

B3KP64

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 4 GO 2 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 ProteomicsDB 1 RefSeq 2 SAM 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

Sequence Information:

  • Length: 399
  • Mass: 41913
  • Checksum: 8591CE6F965BD2F2
  • Sequence:
    • MVSVLVQEGH AVSDMLLPLD GELVLASGAG FGVSDVGSHL DCGAGEPAVF RDSDRFSWHD 
PHLWRSGDEA PGLFFVDAER VPCRHDDVFF PPSASFRVGL GPGASPVRVR SISALGRTFT 
RDEDLAVFLA SRAGRLRFHG PGALSVGPED CADPSGCVCG NAEAQPWICA ALLQPLGGRC 
PQAACHSALR PQGQCCDLCG AVVLLTHGPA FDLERYRARI LDTFLGLPQY HGLQVAVSKV 
PRSSRLREAD TEIQVVLVEN GPETGGAGRL ARALLADVAE NGEALGVLEA TMRESGAHVW 
GSSAAGLAGG VAAAVLLALL VLLVAPPLLR RAGRLRWRRH EAAAPAGAPL GFRNPVFDVT 
ASEELPLPRR LSLVPKAAAD STSHSYFVNP LFAGAEAEA