Details for: AFM

Gene ID: 173

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: AFM

Ensembl ID: ENSG00000079557

Description: afamin

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • midzonal region hepatocyte CL0019028
    CSI 4.39
    rCSI 10.29%
    PRS 98.25
  • hepatocyte CL0000182
    CSI 3.85
    rCSI 6.89%
    PRS 98.35
  • Kupffer cell CL0000091
    CSI 3.65
    rCSI 8.35%
    PRS 99.37
  • periportal region hepatocyte CL0019026
    CSI 2.68
    rCSI 10.43%
    PRS 98.14
  • centrilobular region hepatocyte CL0019029
    CSI 2.38
    rCSI 6.21%
    PRS 97.91
  • epithelial cell of proximal tubule CL0002306
    CSI 2.31
    rCSI 5.64%
    PRS 97.36
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 0.87
    rCSI 9.19%
    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 [AFM](/details-gene/173), also known as Afamin, is a protein-coding gene located on chromosome 4q13.3. It belongs to the albumin gene family, which also includes albumin, alpha-fetoprotein, and vitamin D-binding protein [Link](https://doi.org/10.1016/s0021-9258(17)32429-8). [AFM](/details-gene/173) is a secreted glycoprotein primarily expressed in the liver, with its highest significance observed in various subpopulations of [hepatocytes](/details-cell/CL0000182). Functionally, it is recognized as a vitamin E-binding protein, playing a key role in the transport and stabilization of vitamin E and other lipophilic molecules in the extracellular space [Link](https://doi.org/10.1021/pr0500105), [Link](https://doi.org/10.1021/bi026513v). Its primary function is associated with protein stabilization ([GO:0050821](https://www.ebi.ac.uk/QuickGO/term/GO:0050821)) and vitamin transport ([GO:0051180](https://www.ebi.ac.uk/QuickGO/term/GO:0051180)). ## Cellular Roles and Expression Landscape The expression profile of [AFM](/details-gene/173) strongly indicates a central role in liver biology. **Overall**, the gene shows the highest significance in liver parenchymal cells, particularly [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 4.39) and undifferentiated [hepatocytes](/details-cell/CL0000182) (CSI: 3.85). Significant expression is also observed across other hepatic zones, including [periportal region hepatocytes](/details-cell/CL0019026) (CSI: 2.68) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 2.38), suggesting a ubiquitous and critical function throughout the liver lobule. Beyond hepatocytes, [AFM](/details-gene/173) is also a significant marker for [Kupffer cells](/details-cell/CL0000091) (CSI: 3.65), the resident macrophages of the liver, which may suggest a role in local immune surveillance or lipid metabolism within the liver sinusoids. A secondary site of notable expression is the kidney, specifically in the [epithelial cell of proximal tubule](/details-cell/CL0002306) (CSI: 2.31), which is consistent with the role of these cells in reabsorption and transport processes. The gene's synthesis has also been identified in cerebrovascular endothelial cells, where it is implicated in transporting vitamin E across the blood-brain barrier [Link](https://doi.org/10.1111/j.1471-4159.2008.05796.x). ## Pathways and Molecular Function The molecular function of [AFM](/details-gene/173) is primarily linked to its role as a transport protein in the extracellular environment. Gene Ontology annotations highlight its involvement in the extracellular region ([GO:0005576](https://www.ebi.ac.uk/QuickGO/term/GO:0005576)) and space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)), including its presence in [blood microparticles](/details-cell/GO:0072562) and [extracellular exosomes](/details-cell/GO:0070062). This is consistent with its function as a secreted protein synthesized predominantly by [hepatocytes](/details-cell/CL0000182). The key molecular function is its ability to bind and transport vitamins ([GO:0051180](https://www.ebi.ac.uk/QuickGO/term/GO:0051180)), with a specific, demonstrated capacity for vitamin E binding ([GO:0008431](https://www.ebi.ac.uk/QuickGO/term/GO:0008431)) [Link](https://doi.org/10.1021/pr0500105). By binding lipophilic molecules, it contributes to protein stabilization ([GO:0050821](https://www.ebi.ac.uk/QuickGO/term/GO:0050821)) and facilitates their transport within the bloodstream and other extracellular fluids. This transport function is critical for delivering essential, non-polar nutrients like vitamin E to peripheral tissues. ## Research Directions The specific role of [AFM](/details-gene/173) in health and disease remains an active area of investigation. Its high expression in the liver suggests its potential as a biomarker for hepatic function or disease. Based on its known biology, several testable hypotheses can be proposed. 1. **Hypothesis:** The expression of [AFM](/details-gene/173) by [hepatocytes](/details-cell/CL0000182) is dynamically regulated by metabolic state and oxidative stress. Conditions such as non-alcoholic fatty liver disease (NAFLD) or high-fat diets may alter [AFM](/details-gene/173) synthesis and secretion as a compensatory mechanism to manage lipid peroxidation by transporting vitamin E. 2. **Hypothesis:** Dysregulation of [AFM](/details-gene/173) expression or function in cerebrovascular endothelial cells impairs vitamin E transport into the central nervous system, thereby increasing neuronal vulnerability to oxidative stress and contributing to the pathology of neurodegenerative diseases. To test the first hypothesis, a compelling experimental approach would be to use an *in vivo* mouse model of diet-induced NAFLD. Mice could be fed a high-fat diet, and liver tissue and serum samples would be collected at various time points. The expression of [AFM](/details-gene/173) in the liver would be quantified using qPCR and immunohistochemistry, while serum Afamin protein levels would be measured by ELISA. These results could then be correlated with markers of liver injury (ALT/AST), steatosis, and oxidative stress to determine if [AFM](/details-gene/173) levels change in response to metabolic disease progression. **Therapeutic Potential:** As a secreted protein, [AFM](/details-gene/173) is more likely to be a diagnostic or prognostic biomarker rather than a direct therapeutic target for inhibition. Circulating levels of Afamin could serve as a sensitive indicator of liver health, metabolic syndrome, or systemic oxidative stress. However, in conditions of severe vitamin E deficiency or malabsorption, recombinant Afamin protein could potentially be explored as a therapeutic vehicle for targeted vitamin E delivery, representing a strategy of supplementation or activation of a native transport pathway.

Genular Protein ID: 1924026511

Symbol: AFAM_HUMAN

Name: Afamin

UniProtKB Accession Codes:

P43652 A8K3E1 Q32MR3 Q4W5C5

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 5 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 11 Ensembl 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 3 PIRSF 1 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7517938

Title: Afamin is a new member of the albumin, alpha-fetoprotein, and vitamin D-binding protein gene family.

PubMed ID: 7517938

DOI: 10.1016/s0021-9258(17)32429-8

PubMed ID: 8755513

Title: Complete structure of the human alpha-albumin gene, a new member of the serum albumin multigene family.

PubMed ID: 8755513

DOI: 10.1073/pnas.93.15.7557

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 7875606

Title: Identification of rat alpha-albumin and cDNA cloning of its human ortholog.

PubMed ID: 7875606

DOI: 10.1016/0378-1119(94)00745-e

PubMed ID: 15952736

Title: Afamin is a novel human vitamin E-binding glycoprotein characterization and in vitro expression.

PubMed ID: 15952736

DOI: 10.1021/pr0500105

PubMed ID: 12463752

Title: Characterization of the vitamin E-binding properties of human plasma afamin.

PubMed ID: 12463752

DOI: 10.1021/bi026513v

PubMed ID: 14760718

Title: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.

PubMed ID: 14760718

DOI: 10.1002/pmic.200300556

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 16740002

Title: Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.

PubMed ID: 16740002

DOI: 10.1021/pr050492k

PubMed ID: 19046407

Title: Afamin is synthesized by cerebrovascular endothelial cells and mediates alpha-tocopherol transport across an in vitro model of the blood-brain barrier.

PubMed ID: 19046407

DOI: 10.1111/j.1471-4159.2008.05796.x

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 19139490

Title: A strategy for precise and large scale identification of core fucosylated glycoproteins.

PubMed ID: 19139490

DOI: 10.1074/mcp.m800504-mcp200

PubMed ID: 19838169

Title: Enrichment of glycopeptides for glycan structure and attachment site identification.

PubMed ID: 19838169

DOI: 10.1038/nmeth.1392

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 26902720

Title: Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/alpha-albumin.

PubMed ID: 26902720

DOI: 10.7554/elife.11621

PubMed ID: 29153507

Title: Structural Evidence for a Role of the Multi-functional Human Glycoprotein Afamin in Wnt Transport.

PubMed ID: 29153507

DOI: 10.1016/j.str.2017.10.006

Sequence Information:

  • Length: 599
  • Mass: 69069
  • Checksum: D594E75E20D308AB
  • Sequence:
    • MKLLKLTGFI FFLFFLTESL TLPTQPRDIE NFNSTQKFIE DNIEYITIIA FAQYVQEATF 
EEMEKLVKDM VEYKDRCMAD KTLPECSKLP NNVLQEKICA MEGLPQKHNF SHCCSKVDAQ 
RRLCFFYNKK SDVGFLPPFP TLDPEEKCQA YESNRESLLN HFLYEVARRN PFVFAPTLLT 
VAVHFEEVAK SCCEEQNKVN CLQTRAIPVT QYLKAFSSYQ KHVCGALLKF GTKVVHFIYI 
AILSQKFPKI EFKELISLVE DVSSNYDGCC EGDVVQCIRD TSKVMNHICS KQDSISSKIK 
ECCEKKIPER GQCIINSNKD DRPKDLSLRE GKFTDSENVC QERDADPDTF FAKFTFEYSR 
RHPDLSIPEL LRIVQIYKDL LRNCCNTENP PGCYRYAEDK FNETTEKSLK MVQQECKHFQ 
NLGKDGLKYH YLIRLTKIAP QLSTEELVSL GEKMVTAFTT CCTLSEEFAC VDNLADLVFG 
ELCGVNENRT INPAVDHCCK TNFAFRRPCF ESLKADKTYV PPPFSQDLFT FHADMCQSQN 
EELQRKTDRF LVNLVKLKHE LTDEELQSLF TNFANVVDKC CKAESPEVCF NEESPKIGN