FYB1

FYN binding protein 1

Basic information

Region (hg38): 5:39105252-39274528

Previous symbols: [ "FYB" ]

Links

ENSG00000082074 ∙ NCBI:2533 ∙ OMIM:602731 ∙ HGNC:4036 ∙ Uniprot:O15117 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombocytopenia 3 (Strong), mode of inheritance: AR
• thrombocytopenia 3 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia 3	AR	Hematologic	Individuals have been described with bleeding tendency, and awareness may allow early diagnosis, preventive measures, and early and aggressive treatment of bleeding episodes	Hematologic	23650215; 25516138; 25876182

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FYB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FYB1 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				10	3	13
missense			56	5	4	65
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding					36	36
Total	0	0	56	15	43

Variants in FYB1

This is a list of pathogenic ClinVar variants found in the FYB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-39107251-T-A			Benign (Jun 18, 2021)
5-39107451-T-A		not specified	Uncertain significance (Feb 10, 2022)
5-39107465-C-T		not specified	Uncertain significance (Jun 09, 2022)
5-39107781-A-G			Benign (Nov 11, 2018)
5-39108207-A-G			Benign (Jun 18, 2021)
5-39108220-A-G			Benign (Nov 11, 2018)
5-39108243-C-T		not specified	Uncertain significance (Jun 07, 2023)
5-39110312-A-T			Benign (Jun 20, 2021)
5-39110357-T-G		Thrombocytopenia 3	Uncertain significance (Apr 09, 2018)
5-39110379-G-A		FYB1-related disorder	Likely benign (May 23, 2019)
5-39118886-C-T		not specified	Uncertain significance (Sep 16, 2021)
5-39118901-C-A		not specified	Uncertain significance (Dec 19, 2022)
5-39118918-G-A		not specified	Uncertain significance (Jul 12, 2023)
5-39118925-T-A		not specified	Uncertain significance (Dec 18, 2023)
5-39118981-G-A		not specified	Uncertain significance (Feb 16, 2023)
5-39118985-T-C		not specified	Uncertain significance (Jul 26, 2022)
5-39118987-A-G		not specified	Uncertain significance (May 08, 2024)
5-39119120-T-G			Benign (Nov 11, 2018)
5-39119142-A-G			Benign (Jun 21, 2021)
5-39119459-T-C			Benign (Nov 11, 2018)
5-39119621-C-A			Benign (Nov 11, 2018)
5-39122338-C-A		not specified	Uncertain significance (Jul 14, 2023)
5-39122399-A-G		not specified	Uncertain significance (Jul 27, 2022)
5-39124256-A-G		not specified	Likely benign (May 04, 2022)
5-39124406-C-T			Benign (Nov 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FYB1	protein_coding	protein_coding	ENST00000540520	19	169293

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.238	0.762	124678	0	18	124696	0.0000722

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.436	437	412	1.06	0.0000204	5465
Missense in Polyphen		98	102.95	0.95189		1407
Synonymous	-0.991	172	156	1.10	0.00000873	1585
Loss of Function	4.37	9	38.1	0.236	0.00000181	564

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000223	0.000223
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000117	0.000115
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells. Modulates the expression of interleukin-2 (IL-2). Involved in platelet activation. Prevents the degradation of SKAP1 and SKAP2. May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton. {ECO:0000269|PubMed:10747096, ECO:0000269|PubMed:15849195, ECO:0000269|PubMed:16980616}.
• Disease: DISEASE: Thrombocytopenia 3 (THC3) [MIM:273900]: Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC3 is an autosomal recessive form characterized by onset in infancy. {ECO:0000269|PubMed:25516138, ECO:0000269|PubMed:25876182}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Rap1 signaling pathway - Homo sapiens (human);T-Cell antigen Receptor (TCR) Signaling Pathway;Generation of second messenger molecules;TCR signaling;TCR;Immune System;Adaptive Immune System;Signal regulatory protein family interactions;Cell-Cell communication;TCR signaling in naïve CD4+ T cells (Consensus)

Recessive Scores

• pRec: 0.197

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.56

Haploinsufficiency Scores

• pHI: 0.0744
• hipred: Y
• hipred_score: 0.655
• ghis: 0.506

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Fyb
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; hematopoietic system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;NLS-bearing protein import into nucleus;immune response;signal transduction;integrin-mediated signaling pathway;biological_process;intracellular signal transduction;T cell receptor signaling pathway;protein localization to plasma membrane
• Cellular component: nucleus;cytosol;plasma membrane;actin cytoskeleton;cell junction
• Molecular function: signaling receptor binding;protein binding;lipid binding;protein-containing complex binding