F11R

Summary

F11R (F11 receptor, HGNC:14685) is a protein-coding gene on chromosome 1q23.3, encoding Junctional adhesion molecule A (Q9Y624). Seems to play a role in epithelial tight junction formation.

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. The protein encoded by this immunoglobulin superfamily gene member is an important regulator of tight junction assembly in epithelia. In addition, the encoded protein can act as (1) a receptor for reovirus, (2) a ligand for the integrin LFA1, involved in leukocyte transmigration, and (3) a platelet receptor. Multiple 5’ alternatively spliced variants, encoding the same protein, have been identified but their biological validity has not been established.

Source: NCBI Gene 50848 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_016946

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14685
Approved symbol	F11R
Name	F11 receptor
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	PAM-1, JCAM, JAM-1, JAM-A, JAMA, CD321
Ensembl gene	ENSG00000158769
Ensembl biotype	protein_coding
OMIM	605721
Entrez	50848

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000335772, ENST00000368026, ENST00000472573, ENST00000537746, ENST00000602966, ENST00000890886, ENST00000942779, ENST00000942780

RefSeq mRNA: 6 — MANE Select: NM_016946 NM_001348091, NM_001382727, NM_001382730, NM_001382733, NM_001382734, NM_016946

CCDS: CCDS1213, CCDS86026

Canonical transcript exons

ENST00000368026 — 10 exons

Exon	Start	End
ENSE00001353809	160995211	160998906
ENSE00003306692	161021010	161021152
ENSE00003459101	160999043	160999091
ENSE00003467624	161000146	161000348
ENSE00003521634	160999396	160999408
ENSE00003530301	160999876	160999978
ENSE00003584894	160999640	160999747
ENSE00003615572	161001285	161001353
ENSE00003638604	161001020	161001127
ENSE00003649157	161000631	161000777

Expression profiles

Bgee: expression breadth ubiquitous, 209 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.1214 / max 739.7051, expressed in 1529 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15561	41.3020	1504
15563	23.0518	1339
15562	6.5238	1293
15560	5.3809	1068
15559	0.4022	199
15558	0.3328	139
15564	0.1628	81
15557	0.0170	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	96.74	gold quality
right lung	UBERON:0002167	96.45	gold quality
rectum	UBERON:0001052	96.34	gold quality
islet of Langerhans	UBERON:0000006	96.32	gold quality
esophagus mucosa	UBERON:0002469	95.88	gold quality
lower esophagus mucosa	UBERON:0035834	95.88	gold quality
upper lobe of left lung	UBERON:0008952	95.78	gold quality
mucosa of transverse colon	UBERON:0004991	95.13	gold quality
minor salivary gland	UBERON:0001830	94.94	gold quality
gall bladder	UBERON:0002110	94.65	gold quality
upper lobe of lung	UBERON:0008948	94.36	gold quality
skin of abdomen	UBERON:0001416	94.05	gold quality
left lobe of thyroid gland	UBERON:0001120	93.61	gold quality
body of pancreas	UBERON:0001150	93.45	gold quality
right uterine tube	UBERON:0001302	93.20	gold quality
right lobe of thyroid gland	UBERON:0001119	93.11	gold quality
colonic epithelium	UBERON:0000397	93.05	gold quality
right lobe of liver	UBERON:0001114	92.98	gold quality
skin of leg	UBERON:0001511	92.95	gold quality
pancreas	UBERON:0001264	92.88	gold quality
thyroid gland	UBERON:0002046	92.57	gold quality
mouth mucosa	UBERON:0003729	92.20	gold quality
saliva-secreting gland	UBERON:0001044	92.00	gold quality
monocyte	CL:0000576	91.73	gold quality
vagina	UBERON:0000996	91.49	gold quality
leukocyte	CL:0000738	91.36	gold quality
mononuclear cell	CL:0000842	91.35	gold quality
adrenal tissue	UBERON:0018303	91.28	gold quality
transverse colon	UBERON:0001157	90.39	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.39	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	78.59
E-HCAD-13	yes	22.33
E-MTAB-6678	yes	16.27
E-HCAD-10	yes	15.08
E-MTAB-9388	yes	6.58
E-GEOD-130148	yes	5.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YBX3

miRNA regulators (miRDB)

110 targeting F11R, 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-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 40)

• The F11 receptor (F11R) was discovered in 1990 (Kornecki et al.), partially sequenced (1995) and cloned (Sobocka, et al) by this group. A 100% homology exists between platelet F11R and JAM. (PMID:10753840)
• Two domains in the N-terminus and 1st Ig-fold of F11R were found, through which M.Ab.F11 triggers platelet aggregation. These 2 regions form an active site within the conformation of this cell adhesion molecule. (PMID:12008956)
• Effect of gene on proliferation arrest in a non-small cell bronchopulmonary cancer line. (PMID:12174908)
• platelets adhere specifically to F11R of cytokine- (TNF-alpha, INF-gamma) stimulated vascular endothelial cells (PMID:12428104)
• signaling through JAM-1 and alphavbeta3 is necessary for bFGF-induced angiogenesis. (PMID:12750158)
• JAM-1 is required for basic fibroblast growth factor-induced extracellular signal-related kinase activation that leads to endothelial cell migration on vitronectin. (PMID:12958043)
• homodimer formation may be important for localization of JAM1 at tight junctions and for regulation of epithelial barrier function (PMID:14749337)
• JAM1 structure, role and tissue distribution (review) (PMID:15065765)
• analysis of F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa in human platelets (PMID:15344881)
• JAM1 regulates epithelial cell morphology and beta1 integrin expression by modulating activity of the small GTPase Rap1. (PMID:15677455)
• functional contribution of JAM-A to atherogenesis (PMID:15681301)
• JAM-A transgene is prominently expressed in embryonic vasculature and the epithelial components of several organ systems of transgenic mice and may have an important role in their development (PMID:15977176)
• signaling through JAM-A is necessary for alpha(v)beta(3)-dependent endothelial cells migration and implicate JAM-A in the regulation of vascular function. (PMID:16418218)
• Data show that reovirus engages JAM-A monomers via residues found on beta-strands of the dimer and suggest that the distinct disease phenotypes produced by different strains of reovirus are in part due to differences in contacts with JAM-A. (PMID:17452315)
• Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells (PMID:17623668)
• the apparent occurrence of an unusual TG 3’ splice site in intron 3 is discussed (PMID:17672918)
• Examine JAM-1 expression in normal/inflammed lymphatic endothelium. (PMID:17822725)
• Detection of JAM-A in human sperm proteins indicates that its role may be conserved in sperm motility. (PMID:18022613)
• JAM-A plays a role in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation (PMID:18039951)
• Single nucleotide polymorphisms (SNPs) in the F11 receptor gene (F11R) are associated with hypertension and obesity in Hong Kong Chinese. (PMID:18067551)
• JAM-A is essential for the development of polarity in cultured hepatic cells (PMID:18096610)
• JAM-1 is expressed by human corneal epithelial and endothelial cells, but not by keratocytes, although its expression is induced in corneal myofibroblasts. (PMID:18158589)
• results that an immunoglobulin superfamily cell adhesion protein, JAM-A, expressed at tight junctions could serve as a key negative regulator of breast cancer cell invasion and possibly metastasis. (PMID:18381425)
• nonredundant and novel role of JAM-A in controlling mucosal homeostasis by regulating the integrity and permeability of epithelial barrier function (PMID:18514073)
• LFA-1 binding to JAM-A destabilizes the JAM-A homophilic interaction and the greater strength of the LFA-1/JAM-A complex permits it to support the tension needed to disrupt the JAM-A homophilic interaction, allowing leukocyte transendothelial migration (PMID:18849408)
• study reports the crystal structure of reovirus attachment protein sigma1 in complex with a soluble form of JAM-A (PMID:19079583)
• These data indicate that JAM-A is required for the correct internalization and recycling of integrins during cell migration. (PMID:19118219)
• JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates beta1 integrin levels and cell migration. (PMID:19176753)
• A seven-locus haplotype, present in 2.1% of the subjects, was associated with higher sF11R level. results further support a role of F11 receptor in the pathophysiology of human hypertension. (PMID:19214165)
• Downregulation of JAM-A is an early event in the development of renal cancer and increases the migration of renal cancer cells. (PMID:19250634)
• Junctional adhesion molecule A expression seems to be reduced in high-grade or advanced endometrial carcinoma and may be a prognostic factor. (PMID:19395995)
• JAM-A overexpression is associated with invasive breast cancer. (PMID:19533747)
• These findings indicated that the induction of JAM-A occurred during differentiation of human THP-1 DCs and was independent of PPAR-gamma and the p38 MAPK pathway. (PMID:19748485)
• JAM-A expressed on CD34(+) progenitor cells regulates their adhesion to platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. (PMID:20378847)
• In addition to the previously reported role of F11R in the initiation of plaque formation, F11R plays also an important role in the subsequent growth of atherosclerotic plaques. (PMID:20627246)
• these data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. (PMID:20818426)
• findings provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation of Rap1 GTPase and beta1-integrin (PMID:21429211)
• downregulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis (PMID:21695058)
• de novo synthesis of F11R in endothelial cells (EC) is required for the adhesion of platelets to inflamed ECs. (PMID:21703019)
• Low expression of junctional adhesion molecule A is associated with metastasis in pancreatic cancer (PMID:22549289)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	f11r.1	ENSDARG00000017320
danio_rerio	f11r.2	ENSDARG00000068114
mus_musculus	F11r	ENSMUSG00000038235
rattus_norvegicus	F11r	ENSRNOG00000004414
rattus_norvegicus	AABR07006111.1	ENSRNOG00000020409

Paralogs (14): VSIG2 (ENSG00000019102), VSIG1 (ENSG00000101842), VSIR (ENSG00000107738), GPA33 (ENSG00000143167), IGSF11 (ENSG00000144847), ESAM (ENSG00000149564), CXADR (ENSG00000154639), JAM2 (ENSG00000154721), MXRA8 (ENSG00000162576), JAM3 (ENSG00000166086), CLMP (ENSG00000166250), MUC15 (ENSG00000169550), VSTM2B (ENSG00000187135), VSIG8 (ENSG00000243284)

Protein

Protein identifiers

Junctional adhesion molecule A — Q9Y624 (reviewed: Q9Y624)

Alternative names: Junctional adhesion molecule 1, Platelet F11 receptor, Platelet adhesion molecule 1

All UniProt accessions (2): Q9Y624, Q6FIB4

UniProt curated annotations — full annotation on UniProt →

Function. Seems to play a role in epithelial tight junction formation. Appears early in primordial forms of cell junctions and recruits PARD3. The association of the PARD6-PARD3 complex may prevent the interaction of PARD3 with JAM1, thereby preventing tight junction assembly. Plays a role in regulating monocyte transmigration involved in integrity of epithelial barrier. Ligand for integrin alpha-L/beta-2 involved in memory T-cell and neutrophil transmigration. Involved in platelet activation. (Microbial infection) Acts as a receptor for Mammalian reovirus sigma-1. (Microbial infection) Acts as a receptor for Human Rotavirus strain Wa.

Subunit / interactions. Interacts with the ninth PDZ domain of MPDZ. Interacts with the first PDZ domain of PARD3. The association between PARD3 and PARD6B probably disrupts this interaction. Interacts with ITGAL (via I-domain). Interacts with CD151. (Microbial infection) Interacts with mammalian reovirus outer capsid protein sigma-1 (via the head region); this interaction leads to the disruption of F11R/JAM1 homodimers by sigma-1. (Microbial infection) Interacts with Human Rotavirus strain Wa vp4 capsid protein.

Subcellular location. Cell junction. Tight junction. Cell membrane.

Tissue specificity. Expressed in endothelium, epithelium and leukocytes (at protein level).

Post-translational modifications. N-glycosylated. (Microbial infection) Cleaved by H.pylori virulence factor PqqE. Cleavage leads to altered tight junction functions.

Domain organisation. The Ig-like V-type 2 domain is necessary and sufficient for interaction with integrin alpha-L/beta-2.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y624-1	1	yes
Q9Y624-2	2

RefSeq proteins (6): NP_001335020, NP_001369656, NP_001369659, NP_001369662, NP_001369663, NP_058642* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR042456	F11R	Family

Pfam: PF07686, PF13927

UniProt features (39 total): strand 20, modified residue 3, disulfide bond 2, topological domain 2, turn 2, helix 2, domain 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, transmembrane region 1, site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3TSZ	X-RAY DIFFRACTION	2.5
1NBQ	X-RAY DIFFRACTION	2.9
4ODB	X-RAY DIFFRACTION	3.2
3EOY	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y624-F1	87.18	0.73

Functional residue map

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

Catalytic / active sites (1): 285–286 ((microbial infection) cleavage; by h.pylori pqqe)

Post-translational modifications (3): 287, 281, 284

Disulfide bonds (2): 50–109, 153–212

Glycosylation sites (1): 185

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-2173791	TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
R-HSA-420029	Tight junction interactions
R-HSA-109582	Hemostasis
R-HSA-1474244	Extracellular matrix organization
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 332 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_ENDOTHELIAL_INTESTINAL_BARRIER, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_PLATELET_ACTIVATION, GOBP_APICAL_JUNCTION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP

GO Biological Process (28): regulation of cytokine production (GO:0001817), inflammatory response (GO:0006954), leukocyte cell-cell adhesion (GO:0007159), regulation of cell shape (GO:0008360), actomyosin structure organization (GO:0031032), regulation of actin cytoskeleton organization (GO:0032956), positive regulation of Rho protein signal transduction (GO:0035025), maintenance of blood-brain barrier (GO:0035633), memory T cell extravasation (GO:0035683), intestinal absorption (GO:0050892), regulation of cytoskeleton organization (GO:0051493), negative regulation of stress fiber assembly (GO:0051497), cellular response to mechanical stimulus (GO:0071260), protein localization to plasma membrane (GO:0072659), establishment of endothelial intestinal barrier (GO:0090557), regulation of membrane permeability (GO:0090559), cell-cell adhesion (GO:0098609), positive regulation of platelet aggregation (GO:1901731), protein localization to bicellular tight junction (GO:1902396), positive regulation of establishment of endothelial barrier (GO:1903142), regulation of bicellular tight junction assembly (GO:2000810), system process (GO:0003008), cell adhesion (GO:0007155), cell differentiation (GO:0030154), epithelial cell differentiation (GO:0030855), symbiont entry into host cell (GO:0046718), leukocyte migration (GO:0050900), regulation of biological quality (GO:0065008)

GO Molecular Function (6): virus receptor activity (GO:0001618), integrin binding (GO:0005178), PDZ domain binding (GO:0030165), protein homodimerization activity (GO:0042803), cadherin binding (GO:0045296), protein binding (GO:0005515)

GO Cellular Component (9): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), cell junction (GO:0030054), protein-containing complex (GO:0032991), extracellular exosome (GO:0070062), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Hemostasis	1
Extracellular matrix organization	1
Signaling by TGF-beta Receptor Complex	1
Cell-cell junction organization	1
Signaling by TGFB family members	1
Cell junction organization	1
Cell-Cell communication	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of biological quality	2
actin cytoskeleton organization	2
establishment of endothelial barrier	2
cell adhesion molecule binding	2
cellular anatomical structure	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
defense response	1
cell-cell adhesion	1
regulation of cell morphogenesis	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
tissue homeostasis	1
T cell extravasation	1
digestive system process	1
cytoskeleton organization	1
regulation of organelle organization	1
negative regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
response to mechanical stimulus	1
cellular response to abiotic stimulus	1
cellular response to external stimulus	1
protein localization to membrane	1
protein localization to cell periphery	1
cell adhesion	1
positive regulation of homotypic cell-cell adhesion	1
platelet aggregation	1
regulation of platelet aggregation	1
protein localization to cell-cell junction	1
positive regulation of endothelial cell development	1
regulation of establishment of endothelial barrier	1
symbiont entry into host cell	1
exogenous protein binding	1
signaling receptor binding	1
protein-containing complex binding	1

Protein interactions and networks

STRING

1577 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
F11R	OCLN	Q16625	998
F11R	TJP1	Q07157	998
F11R	CLDN1	O95832	991
F11R	ITGB2	P05107	987
F11R	CLDN7	O95471	980
F11R	AFDN	P55196	971
F11R	TJP2	Q9UDY2	968
F11R	CGN	Q9P2M7	963
F11R	ITGAL	P20701	960
F11R	CLDN5	O00501	956
F11R	CLDN4	O14493	919
F11R	MARVELD2	Q8N4S9	918
F11R	PECAM1	P16284	917
F11R	TJP3	O95049	914
F11R	CDH1	P12830	898

IntAct

222 interactions, top by confidence:

A	B	Type	Score
SGTA	F11R	psi-mi:“MI:0915”(physical association)	0.830
F11R	SGTA	psi-mi:“MI:0915”(physical association)	0.830
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
F11R	PICK1	psi-mi:“MI:0407”(direct interaction)	0.690
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
CAMLG	F11R	psi-mi:“MI:0915”(physical association)	0.560
SLC35A1	F11R	psi-mi:“MI:0915”(physical association)	0.560
PGAP2	F11R	psi-mi:“MI:0915”(physical association)	0.560
JAGN1	F11R	psi-mi:“MI:0915”(physical association)	0.560
RABAC1	F11R	psi-mi:“MI:0915”(physical association)	0.560
TMEM147	F11R	psi-mi:“MI:0915”(physical association)	0.560
MARCHF2	F11R	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	F11R	psi-mi:“MI:0915”(physical association)	0.560
TMEM100	F11R	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	F11R	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	F11R	psi-mi:“MI:0915”(physical association)	0.560
SNAP47	F11R	psi-mi:“MI:0915”(physical association)	0.560
MYADM	F11R	psi-mi:“MI:0915”(physical association)	0.560
MMP14	F11R	psi-mi:“MI:0915”(physical association)	0.560
AMBN	F11R	psi-mi:“MI:0915”(physical association)	0.560
LARP4B	F11R	psi-mi:“MI:0915”(physical association)	0.560
MRI1	F11R	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): F11R (Two-hybrid), F11R (Affinity Capture-MS), F11R (Two-hybrid), F11R (Affinity Capture-MS), F11R (Proximity Label-MS), SGTA (Two-hybrid), F11R (Co-localization), TJP1 (Two-hybrid), F11R (Proximity Label-MS), F11R (Affinity Capture-MS), F11R (Affinity Capture-MS), F11R (Affinity Capture-MS), F11R (Affinity Capture-MS), F11R (Proximity Label-MS), F11R (Proximity Label-MS)

ESM2 similar proteins: A0A8M2B818, A3KPA0, A5D7C3, B0JYH6, O35112, O46634, O46651, O88792, P17790, P18461, P18572, P21802, P21803, P26453, P35613, P42292, P57087, P78310, P97792, Q01638, Q13740, Q15198, Q1WIM2, Q2PFX1, Q2WGK2, Q3V3F6, Q5R764, Q5RJP7, Q61490, Q66KX2, Q68FQ2, Q6DJ83, Q6PE55, Q6UWV2, Q7ZXX1, Q8BLQ9, Q8N3J6, Q8WMV3, Q90Y50, Q99795

Diamond homologs: A0A0R4IGV4, P57087, P98160, Q05793, Q1WIM1, Q2WGK2, Q8NFZ8, Q8R464, Q925F2, Q9JI59, Q9XT56, Q9Y624, A3KPA0, F1NY98, O15146, O60469, P29534, Q24372, Q26474, Q61006, Q62838, Q68FQ2, Q8N475, Q8VHZ8, Q967D7, Q9BX67, Q9D8B7, Q9ERC8, A2ASS6, G5EBF1, O88792, O94898, Q52KR2, Q91664, Q96IQ7, Q9JHY1, A2AJ76, D3YXG0, P09564, P0C673

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	F11R	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	8	51.9×	6e-10
Unblocking of NMDA receptors, glutamate binding and activation	5	30.9×	3e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	30.9×	3e-05
Long-term potentiation	5	27.0×	5e-05
Assembly and cell surface presentation of NMDA receptors	7	20.2×	8e-06
Neurexins and neuroligins	8	17.9×	3e-06
Protein-protein interactions at synapses	5	15.1×	6e-04
RHOQ GTPase cycle	5	10.3×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	45.8×	7e-12
protein localization to synapse	6	36.2×	3e-06
receptor clustering	7	34.4×	4e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	23.4×	4e-05
exocytosis	8	9.6×	2e-04
cell-cell adhesion	10	8.0×	7e-05
chemical synaptic transmission	9	5.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2103 predictions. Top by Δscore:

Variant	Effect	Δscore
1:160998794:C:CT	donor_gain	1.0000
1:160998795:T:TT	donor_gain	1.0000
1:160998903:CTCC:C	acceptor_gain	1.0000
1:160998907:C:CA	acceptor_loss	1.0000
1:160998907:C:CC	acceptor_gain	1.0000
1:160999035:ATACT:A	donor_loss	1.0000
1:160999036:TACT:T	donor_loss	1.0000
1:160999037:ACTC:A	donor_loss	1.0000
1:160999039:TCA:T	donor_loss	1.0000
1:160999040:CA:C	donor_loss	1.0000
1:160999041:A:AC	donor_gain	1.0000
1:160999041:ACTT:A	donor_gain	1.0000
1:160999042:C:CT	donor_gain	1.0000
1:160999042:CTT:C	donor_gain	1.0000
1:160999042:CTTC:C	donor_gain	1.0000
1:160999042:CTTCA:C	donor_gain	1.0000
1:160999088:AGTCC:A	acceptor_loss	1.0000
1:160999092:CTGT:C	acceptor_loss	1.0000
1:160999634:A:AC	donor_gain	1.0000
1:160999635:C:CC	donor_gain	1.0000
1:160999635:CTTA:C	donor_gain	1.0000
1:160999636:TTA:T	donor_loss	1.0000
1:160999637:TA:T	donor_loss	1.0000
1:160999638:A:AC	donor_gain	1.0000
1:160999638:ACTGT:A	donor_gain	1.0000
1:160999639:C:CA	donor_gain	1.0000
1:160999639:CT:C	donor_gain	1.0000
1:160999639:CTG:C	donor_gain	1.0000
1:160999639:CTGT:C	donor_gain	1.0000
1:160999639:CTGTC:C	donor_gain	1.0000

AlphaMissense

1924 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161000239:C:A	W166C	1.000
1:161000239:C:G	W166C	1.000
1:160999935:C:G	C212S	0.999
1:160999936:A:G	C212R	0.999
1:160999936:A:T	C212S	0.999
1:160999941:T:C	Y210C	0.999
1:160999942:A:C	Y210D	0.999
1:161000147:A:G	L197P	0.999
1:161000241:A:G	W166R	0.999
1:161000241:A:T	W166R	0.999
1:161000280:A:G	C153R	0.999
1:161000700:A:C	Y107D	0.999
1:161001075:C:A	W62C	0.999
1:161001075:C:G	W62C	0.999
1:161001076:C:G	W62S	0.999
1:161001077:A:G	W62R	0.999
1:161001077:A:T	W62R	0.999
1:160999941:T:G	Y210S	0.998
1:161000278:G:C	C153W	0.998
1:161000279:C:G	C153S	0.998
1:161000280:A:T	C153S	0.998
1:161000285:A:G	L151P	0.998
1:161000693:C:G	C109S	0.998
1:161000694:A:G	C109R	0.998
1:161000694:A:T	C109S	0.998
1:161000706:C:A	G105W	0.998
1:160999934:A:C	C212W	0.997
1:160999935:C:T	C212Y	0.997
1:161000240:C:G	W166S	0.997
1:161000692:A:C	C109W	0.997

dbSNP variants (sampled 300 via entrez): RS1000000886 (1:160996798 A>G), RS1000271902 (1:161001051 G>C), RS1000311212 (1:161009817 T>C), RS1000371594 (1:161013540 C>G,T), RS1000394039 (1:161003527 T>A), RS1000585398 (1:161015988 G>C), RS1000589921 (1:161006334 G>A), RS1000740506 (1:161007558 G>A,C,T), RS1000761585 (1:161008324 T>A), RS1000799328 (1:161011812 T>G), RS1000917590 (1:161018784 C>T), RS1000979144 (1:161000036 T>A), RS1000992417 (1:161015003 G>A), RS1001076289 (1:161021172 G>A), RS1001195066 (1:161017227 C>A,T)

Disease associations

OMIM: gene MIM:605721 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001725_36	Inflammatory bowel disease	7.000000e-09
GCST003542_114	Night sleep phenotypes	7.000000e-06
GCST003542_135	Night sleep phenotypes	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	5
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	2
Fulvestrant	decreases reaction, increases expression, decreases methylation	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Doxorubicin	decreases expression, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tretinoin	increases expression	2
Cyclosporine	increases expression, affects expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
tributyltin	decreases expression	1
quercitrin	affects expression	1
trichostatin A	affects expression	1
sulforaphane	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ochratoxin A	increases expression	1
cupric chloride	decreases expression	1
4-cresol	decreases expression	1
nivalenol	decreases expression	1
dibenzo(a,l)pyrene	decreases expression	1
estradiol 3-benzoate	decreases reaction, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SM70	HAP1 F11R (-) 1	Cancer cell line	Male
CVCL_XN61	HAP1 F11R (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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