AFP

alpha fetoprotein

Basic information

Region (hg38): 4:73431138-73456174

Previous symbols: [ "HPAFP" ]

Links

ENSG00000081051 ∙ NCBI:174 ∙ OMIM:104150 ∙ HGNC:317 ∙ Uniprot:P02771 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital deficiency in alpha-fetoprotein (No Known Disease Relationship), mode of inheritance: AR
• hereditary persistence of alpha-fetoprotein (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
AFP deficiency, congenital; Hereditary persistence of AFP	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	General	1690155; 1379776; 7684942; 15280901; 18854864

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AFP gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AFP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	2	6
missense		1	26	2	2	31
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					2	2
Total	0	1	26	6	6

Variants in AFP

This is a list of pathogenic ClinVar variants found in the AFP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-73436100-G-A		Alpha-fetoprotein, hereditary persistence of	Affects (Jan 01, 2004)
4-73436164-C-A		Alpha-fetoprotein, hereditary persistence of	Affects (Jan 01, 2004)
4-73436294-T-C		not specified	Uncertain significance (Aug 01, 2024)
4-73437192-G-A		not specified	Uncertain significance (May 02, 2024)
4-73438182-T-C		not specified	Uncertain significance (Aug 12, 2024)
4-73438185-T-A		AFP-related disorder	Likely benign (Feb 09, 2022)
4-73438203-A-G		not specified	Uncertain significance (Mar 20, 2024)
4-73440617-G-A		not specified	Uncertain significance (Jan 06, 2023)
4-73440656-G-C			Benign (Aug 16, 2018)
4-73440725-A-C		not specified	Uncertain significance (Dec 28, 2023)
4-73440730-A-G			Likely benign (Apr 25, 2018)
4-73440732-C-T		not specified	Uncertain significance (Jun 29, 2023)
4-73440737-A-T		not specified	Uncertain significance (Aug 04, 2023)
4-73440749-C-A		not specified	Uncertain significance (Dec 13, 2021)
4-73440759-A-C		not specified	Uncertain significance (Feb 13, 2024)
4-73442356-G-A		Alpha-fetoprotein deficiency	Pathogenic (Mar 01, 2009)
4-73442363-C-T		not specified	Uncertain significance (Apr 07, 2022)
4-73443426-C-T		not specified	Uncertain significance (Oct 08, 2024)
4-73443443-A-C		not specified	Uncertain significance (Jun 26, 2023)
4-73444988-C-T			Likely benign (Jul 17, 2018)
4-73445078-G-A		not specified	Uncertain significance (Nov 13, 2024)
4-73445102-C-G		not specified	Uncertain significance (Mar 21, 2023)
4-73447452-T-C		AFP-related disorder	Benign (Oct 28, 2019)
4-73447476-C-T			Benign (Dec 31, 2019)
4-73447498-ACT-A		Alpha-fetoprotein deficiency	Pathogenic (Mar 01, 2009)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AFP	protein_coding	protein_coding	ENST00000395792	14	25037

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.14e-11	0.913	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.185	302	311	0.970	0.0000148	4007
Missense in Polyphen		70	97.289	0.71951		1326
Synonymous	0.371	106	111	0.955	0.00000542	1096
Loss of Function	1.99	23	35.8	0.642	0.00000178	448

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000423	0.000420
Ashkenazi Jewish	0.00	0.00
East Asian	0.00147	0.00147
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000239	0.000237
Middle Eastern	0.00147	0.00147
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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.
• Disease: DISEASE: Alpha-fetoprotein deficiency (AFPD) [MIM:615969]: A benign condition characterized by undetectable AFP levels in the amniotic fluid. Affected individuals are asymptomatic and present normal development. {ECO:0000269|PubMed:15280901, ECO:0000269|PubMed:18854864}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Alpha-fetoprotein, hereditary persistence (HPAFP) [MIM:615970]: A benign autosomal dominant condition characterized by continued expression of alpha-fetoprotein in adult life. {ECO:0000269|PubMed:7684942}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hippo signaling pathway - Homo sapiens (human);Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;p73 transcription factor network;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Glucocorticoid receptor regulatory network;Direct p53 effectors;FOXA2 and FOXA3 transcription factor networks (Consensus)

Recessive Scores

• pRec: 0.750

Intolerance Scores

• loftool: 0.859
• rvis_EVS: 0.29
• rvis_percentile_EVS: 71.57

Haploinsufficiency Scores

• pHI: 0.580
• hipred: N
• hipred_score: 0.469
• ghis: 0.512

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.928

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Afp
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm

Gene ontology

• Biological process: ovulation from ovarian follicle;progesterone metabolic process;post-translational protein modification;cellular protein metabolic process;SMAD protein signal transduction
• Cellular component: extracellular space;endoplasmic reticulum lumen
• Molecular function: protein binding;metal ion binding