FYB2

Summary

FYB2 (FYN binding protein 2, HGNC:27295) is a protein-coding gene on chromosome 1p32.2, encoding FYN-binding protein 2 (Q5VWT5). Adapter protein that plays a role in T-cell receptor (TCR)-mediated activation of signaling pathways.

Involved in T cell receptor signaling pathway and cell adhesion mediated by integrin. Located in immunological synapse and membrane raft.

Source: NCBI Gene 199920 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001004303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27295
Approved symbol	FYB2
Name	FYN binding protein 2
Location	1p32.2
Locus type	gene with protein product
Status	Approved
Aliases	RP4-758N20.2, FLJ43208, ARAP
Ensembl gene	ENSG00000187889
Ensembl biotype	protein_coding
OMIM	618478
Entrez	199920

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000343433, ENST00000371240, ENST00000484327, ENST00000493000, ENST00000497991, ENST00000867602, ENST00000969682

RefSeq mRNA: 1 — MANE Select: NM_001004303 NM_001004303

CCDS: CCDS30729

Canonical transcript exons

ENST00000343433 — 20 exons

Exon	Start	End
ENSE00001818974	56718789	56719692
ENSE00001926774	56819282	56819404
ENSE00003462976	56751044	56751203
ENSE00003467610	56726497	56726583
ENSE00003473991	56738625	56738653
ENSE00003498813	56758716	56758750
ENSE00003504943	56744152	56744266
ENSE00003550254	56744026	56744066
ENSE00003562591	56767829	56767938
ENSE00003567534	56723588	56723681
ENSE00003567824	56737087	56737147
ENSE00003574905	56742161	56742221
ENSE00003611809	56720022	56720055
ENSE00003612616	56753839	56753935
ENSE00003617013	56787175	56787208
ENSE00003619168	56740697	56740795
ENSE00003622189	56792056	56792803
ENSE00003648779	56788973	56789134
ENSE00003660039	56755896	56755927
ENSE00003667316	56720173	56720329

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 98.35.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8687 / max 75.3994, expressed in 263 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12537	0.3726	171
12539	0.3527	126
12538	0.0961	54
12536	0.0473	15

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.35	gold quality
bronchial epithelial cell	CL:0002328	98.03	gold quality
germinal epithelium of ovary	UBERON:0001304	97.19	gold quality
bronchus	UBERON:0002185	96.07	gold quality
right lobe of liver	UBERON:0001114	93.66	gold quality
pigmented layer of retina	UBERON:0001782	93.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.31	gold quality
oviduct epithelium	UBERON:0004804	91.64	gold quality
liver	UBERON:0002107	90.06	gold quality
apex of heart	UBERON:0002098	89.51	gold quality
metanephros cortex	UBERON:0010533	87.21	gold quality
fallopian tube	UBERON:0003889	86.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.16	gold quality
heart left ventricle	UBERON:0002084	84.80	gold quality
left ventricle myocardium	UBERON:0006566	84.70	gold quality
cardiac ventricle	UBERON:0002082	84.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.34	gold quality
secondary oocyte	CL:0000655	79.41	gold quality
buccal mucosa cell	CL:0002336	78.63	gold quality
right lung	UBERON:0002167	78.22	gold quality
adult mammalian kidney	UBERON:0000082	77.72	gold quality
cortex of kidney	UBERON:0001225	77.23	gold quality
oocyte	CL:0000023	76.01	gold quality
gastrocnemius	UBERON:0001388	75.82	gold quality
kidney	UBERON:0002113	75.28	gold quality
heart right ventricle	UBERON:0002080	75.13	gold quality
pituitary gland	UBERON:0000007	74.53	gold quality
endometrium	UBERON:0001295	74.39	gold quality
renal medulla	UBERON:0000362	74.27	gold quality
kidney epithelium	UBERON:0004819	74.18	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	39.74
E-CURD-114	yes	10.01
E-ANND-3	yes	6.41
E-MTAB-7381	no	147.38
E-MTAB-6386	no	34.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting FYB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 1)

• results of this study indicate that a novel T cell adaptor protein, activation-dependent, raft-recruited ADAP-like phosphoprotein (ARAP), plays a unique role in T cells as a part of both the proximal activation signaling and inside-out signaling pathways that result in integrin activation and T cell adhesion (PMID:27335501)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-188c16.1	ENSDARG00000077288
danio_rerio	si:ch211-232i5.3	ENSDARG00000086874
mus_musculus	Fyb2	ENSMUSG00000078612
rattus_norvegicus	Fyb2	ENSRNOG00000030938

Paralogs (2): FYB1 (ENSG00000082074), PRAM1 (ENSG00000133246)

Protein

Protein identifiers

FYN-binding protein 2 — Q5VWT5 (reviewed: Q5VWT5)

Alternative names: Activation-dependent, raft-recruited ADAP-like phosphoprotein

All UniProt accessions (1): Q5VWT5

UniProt curated annotations — full annotation on UniProt →

Function. Adapter protein that plays a role in T-cell receptor (TCR)-mediated activation of signaling pathways. Required for T-cell activation and integrin-mediated T-cell adhesion in response to TCR stimulation.

Subunit / interactions. Interacts with SKAP1, LCK and FYN. The phosphorylated form interacts with LCP2.

Subcellular location. Membrane raft.

Tissue specificity. Expressed in T-cells (at protein level). Widely expressed.

Post-translational modifications. Phosphorylation is required for its function in T-cell activation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VWT5-1	1	yes
Q5VWT5-2	2

RefSeq proteins (1): NP_001004303* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR029294	hSH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR043443	FYB1/2-like	Family

Pfam: PF14603

UniProt features (19 total): sequence conflict 3, region of interest 3, compositionally biased region 3, modified residue 2, splice variant 2, mutagenesis site 2, chain 1, domain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWT5-F1	53.54	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 587, 491

Mutagenesis-validated functional residues (2):

Position	Phenotype
491	decrease in phosphorylation and interaction with lcp2. significant decrease in phosphorylation and loss of interaction w
587	decrease in phosphorylation and interaction with lcp2. significant decrease in phosphorylation and loss of interaction w

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 82 (showing top): GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_CELL_ADHESION_MEDIATED_BY_INTEGRIN, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_INTEGRIN_MEDIATED_SIGNALING_PATHWAY, GOCC_IMMUNOLOGICAL_SYNAPSE, DODD_NASOPHARYNGEAL_CARCINOMA_DN, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, GOBP_ACTIVATION_OF_IMMUNE_RESPONSE, GOBP_IMMUNE_RESPONSE_REGULATING_SIGNALING_PATHWAY, GOBP_PROTEIN_LOCALIZATION_TO_PLASMA_MEMBRANE, MIR616_5P

GO Biological Process (4): integrin-mediated signaling pathway (GO:0007229), cell adhesion mediated by integrin (GO:0033627), T cell receptor signaling pathway (GO:0050852), protein localization to plasma membrane (GO:0072659)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): immunological synapse (GO:0001772), plasma membrane (GO:0005886), membrane raft (GO:0045121), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell surface receptor signaling pathway	1
cell adhesion	1
antigen receptor-mediated signaling pathway	1
protein localization to membrane	1
protein localization to cell periphery	1
binding	1
plasma membrane	1
membrane	1
cell periphery	1
membrane microdomain	1

Protein interactions and networks

STRING

382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FYB2	C1orf105	O95561	479
FYB2	C1orf226	A1L170	447
FYB2	CLBA1	Q96F83	447
FYB2	RALGAPA2	Q2PPJ7	417
FYB2	CREBZF	Q9NS37	392
FYB2	C1orf141	Q5JVX7	374
FYB2	TMC3	Q7Z5M5	370
FYB2	DYNLT5	Q8N7M0	368
FYB2	DNAJC5B	Q9UF47	358
FYB2	ANKRD54	Q6NXT1	355
FYB2	UBE2U	Q5VVX9	348
FYB2	RAVER2	Q9HCJ3	348
FYB2	TM2D1	Q9BX74	324
FYB2	EFCAB7	A8K855	322
FYB2	MPPED1	O15442	321

IntAct

10 interactions, top by confidence:

A	B	Type	Score
FYB2	MRPS9	psi-mi:“MI:0915”(physical association)	0.400
FYB2	SKAP2	psi-mi:“MI:0915”(physical association)	0.400
FYB2	FDFT1	psi-mi:“MI:0915”(physical association)	0.000
DNAJC13	FYB2	psi-mi:“MI:0915”(physical association)	0.000
NMT1	FYB2	psi-mi:“MI:0915”(physical association)	0.000
MLF1	FYB2	psi-mi:“MI:0915”(physical association)	0.000
TBCE	FYB2	psi-mi:“MI:0915”(physical association)	0.000
EDRF1	FYB2	psi-mi:“MI:0915”(physical association)	0.000
IRF2BP1	FYB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): C1orf168 (Affinity Capture-MS), C1orf168 (Affinity Capture-MS), C1orf168 (Affinity Capture-MS), C1orf168 (Affinity Capture-MS), C1orf168 (Affinity Capture-MS), C1orf168 (Affinity Capture-MS), C1orf168 (Proximity Label-MS), SKAP2 (Affinity Capture-MS), HSP90AB1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A096MK47, A2A995, A2ALU4, A4IGN8, A6NGG8, A6NMK8, B1AXH1, B2RQL2, D3ZMK9, D3ZUI5, E9Q309, O14513, O60303, O75128, Q0P5X5, Q14B48, Q1W617, Q2M1Z3, Q3UMF0, Q499V8, Q569L8, Q571I4, Q5BQN8, Q5DTX6, Q5HYW2, Q5T1N1, Q5VWT5, Q5ZJ26, Q62394, Q68DA7, Q69ZL1, Q6GQV1, Q6INC4, Q6PAC4, Q6ZRS4, Q6ZV73, Q6ZVD7, Q7TP36, Q7TS75, Q86YV5

Diamond homologs: A2A995, D3ZIE4, O15117, O35601, Q5VWT5, Q6BCL1, Q96QH2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

33 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2839 predictions. Top by Δscore:

Variant	Effect	Δscore
1:56720020:A:AC	donor_gain	1.0000
1:56720021:C:CC	donor_gain	1.0000
1:56720168:CTTA:C	donor_loss	1.0000
1:56720169:TTACA:T	donor_loss	1.0000
1:56720170:TA:T	donor_loss	1.0000
1:56720171:A:AC	donor_gain	1.0000
1:56720172:C:CT	donor_gain	1.0000
1:56720172:CA:C	donor_gain	1.0000
1:56720172:CATT:C	donor_gain	1.0000
1:56720172:CATTT:C	donor_gain	1.0000
1:56720177:G:A	donor_gain	1.0000
1:56720229:T:TA	donor_gain	1.0000
1:56720325:TCGTA:T	acceptor_gain	1.0000
1:56720326:CGTA:C	acceptor_gain	1.0000
1:56720326:CGTAC:C	acceptor_gain	1.0000
1:56720327:GTA:G	acceptor_gain	1.0000
1:56720327:GTAC:G	acceptor_loss	1.0000
1:56720328:TA:T	acceptor_gain	1.0000
1:56720328:TACTG:T	acceptor_loss	1.0000
1:56720329:AC:A	acceptor_loss	1.0000
1:56720330:C:CC	acceptor_gain	1.0000
1:56742157:TCACT:T	donor_loss	1.0000
1:56742158:CAC:C	donor_loss	1.0000
1:56742159:A:AC	donor_gain	1.0000
1:56742160:C:CC	donor_gain	1.0000
1:56742160:CT:C	donor_gain	1.0000
1:56742160:CTCT:C	donor_gain	1.0000
1:56742222:C:CC	acceptor_gain	1.0000
1:56744067:C:CC	acceptor_gain	1.0000
1:56744146:ACTT:A	donor_loss	1.0000

AlphaMissense

4823 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:56720190:C:G	R705P	0.996
1:56720192:A:C	C704W	0.991
1:56720256:A:G	L683S	0.989
1:56720194:A:G	C704R	0.988
1:56720232:A:G	L691S	0.987
1:56720226:A:T	V693D	0.983
1:56720298:G:T	A669E	0.983
1:56720299:C:G	A669P	0.983
1:56723591:A:C	F657L	0.982
1:56723591:A:T	F657L	0.982
1:56723593:A:G	F657L	0.982
1:56720052:C:T	G712E	0.981
1:56720193:C:T	C704Y	0.981
1:56720046:A:T	V714E	0.979
1:56720031:A:G	L719P	0.976
1:56720191:G:T	R705S	0.972
1:56720052:C:A	G712V	0.969
1:56720256:A:C	L683W	0.969
1:56720186:A:C	N706K	0.967
1:56720186:A:T	N706K	0.967
1:56792765:A:C	F16L	0.966
1:56792765:A:T	F16L	0.966
1:56792767:A:G	F16L	0.966
1:56720024:G:C	F721L	0.963
1:56720024:G:T	F721L	0.963
1:56720026:A:G	F721L	0.963
1:56720223:A:T	I694N	0.962
1:56720196:A:T	I703K	0.960
1:56723604:A:G	F653S	0.959
1:56720173:A:G	Y711H	0.957

dbSNP variants (sampled 300 via entrez): RS1000010970 (1:56788591 G>T), RS1000017251 (1:56758072 C>A), RS1000037932 (1:56746081 T>C), RS1000055927 (1:56807438 T>C), RS1000066736 (1:56816686 TG>T), RS1000100252 (1:56740073 T>A,C), RS1000122682 (1:56721892 T>C), RS1000136970 (1:56817161 G>A), RS1000168037 (1:56769837 G>A,C), RS1000228233 (1:56771498 G>A), RS1000238616 (1:56782529 T>A), RS1000272039 (1:56752222 G>A), RS1000342310 (1:56777613 C>T), RS1000348399 (1:56734020 A>G), RS1000360830 (1:56758205 G>A)

Disease associations

OMIM: gene MIM:618478 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001620_1	Resistin levels	5.000000e-07
GCST001762_478	Obesity-related traits	9.000000e-06
GCST002761_8	Hippocampal volume	4.000000e-06
GCST008114_29	Type 2 diabetes	5.000000e-06
GCST010397_57	Gut microbiota (bacterial taxa, rank normal transformation method)	3.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004819	resistin measurement
EFO:0003939	energy intake
EFO:0005035	hippocampal volume
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	affects expression, decreases methylation	3
methylmercuric chloride	decreases expression	2
Resveratrol	decreases expression, increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
sotorasib	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Cytarabine	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.