AFP (alpha fetoprotein)

Gene

• Entrez ID: 174
• Gene name: Alpha fetoprotein
• Gene symbol: AFP
• Synonyms (NCBI Gene): AFPD, FETA, HPAFP
• Chromosome: 4
• Chromosome location: 4q13.3
• Summary: This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121912685	G>A	Pathogenic	Stop gained, coding sequence variant
rs387906580	CT>-	Pathogenic	Coding sequence variant, frameshift variant
rs587776861	G>A	Affects	Upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020427	hsa-miR-106b-5p	Microarray	17242205
MIRT737348	hsa-miR-224-3p	RNA-seq, qRT-PCR	32166120
MIRT2168456	hsa-miR-4719	CLIP-seq
MIRT2168457	hsa-miR-4760-3p	CLIP-seq
MIRT2168458	hsa-miR-513b	CLIP-seq
MIRT2168459	hsa-miR-548t	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
CEBPA	Unknown	15924879
HNF4A	Activation	9792724
HNF4G	Activation	9792724
ING1	Repression	14522900
NANOG	Repression	15983365
NF1	Repression	7549116
SIRT2	Activation	14522900
TP53	Repression	14522900
ZFHX3	Repression	14654895;15750593
ZHX2	Repression	23837980

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001542	Process	Ovulation from ovarian follicle	IEA
GO:0005515	Function	Protein binding	IPI	26808496, 39822733
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0006955	Process	Immune response	IEA
GO:0019953	Process	Sexual reproduction	IEA
GO:0031667	Process	Response to nutrient levels	IBA
GO:0036094	Function	Small molecule binding	IBA
GO:0042448	Process	Progesterone metabolic process	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048872	Process	Homeostasis of number of cells	IEA

Other IDs

• MIM: 104150
• HGNC: 317
• e!Ensembl: ENSG00000081051

Protein

• UniProt ID: P02771
• Protein name: Alpha-fetoprotein (Alpha-1-fetoprotein) (Alpha-fetoglobulin)
• Protein function: Binds copper, nickel, and fatty acids as well as, and bilirubin less well than, serum albumin. Only a small percentage (less than 2%) of the human AFP shows estrogen-binding properties.
• PDB: 3MRK, 7RE7, 7RE8, 7YIM, 8X1N
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00273	Serum_albumin	30 → 202	Serum albumin family	Domain
  PF00273	Serum_albumin	222 → 394	Serum albumin family	Domain
  PF00273	Serum_albumin	414 → 592	Serum albumin family	Domain

• Tissue specificity: TISSUE SPECIFICITY: Plasma. Synthesized by the fetal liver and yolk sac.
• Sequence:

  MKWVESIFLIFLLNFTESRTLHRNEYGIASILDSYQCTAEISLADLATIFFAQFVQEATY
  KEVSKMVKDALTAIEKPTGDEQSSGCLENQLPAFLEELCHEKEILEKYGHSDCCSQSEEG
  RHNCFLAHKKPTPASIPLFQVPEPVTSCEAYEEDRETFMNKFIYEIARRHPFLYAPTILL
  WAARYDKIIPSCCKAENAVECFQTKAATVTKELRESSLLNQHACAVMKNFGTRTFQAITV
  TKLSQKFTKVNFTEIQKLVLDVAHVHEHCCRGDVLDCLQDGEKIMSYICSQQDTLSNKIT
  ECCKLTTLERGQCIIHAENDEKPEGLSPNLNRFLGDRDFNQFSSGEKNIFLASFVHEYSR
  RHPQLAVSVILRVAKGYQELLEKCFQTENPLECQDKGEEELQKYIQESQALAKRSCGLFQ
  KLGEYYLQNAFLVAYTKKAPQLTSSELMAITRKMAATAATCCQLSEDKLLACGEGAADII
  IGHLCIRHEMTPVNPGVGQCCTSSYANRRPCFSSLVVDETYVPPAFSDDKFIFHKDLCQA
  QGVALQTMKQEFLINLVKQKPQITEEQLEAVIADFSGLLEKCCQGQEQEVCFAEEGQKLI
  SKTRAALGV

• Sequence length: 609

Pathways

KEGG:

Hippo signaling pathway

Reactome:

Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
Post-translational protein phosphorylation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Alpha-fetoprotein deficiency	Pathogenic	rs387906580, rs121912685	RCV000019799 RCV000019800	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Premature ovarian failure	Likely pathogenic	rs146692547	RCV001270197	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AFP-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alpha-fetoprotein, hereditary persistence of	Affects; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, HEPATOCELLULAR	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFICIENCY IN ALPHA-FETOPROTEIN	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL DEFICIENCY OF ALPHA-FETOPROTEIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATITIS C	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER NEOPLASMS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OVARIAN FAILURE, PREMATURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STOMACH NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations