ICAM3

Summary

ICAM3 (intercellular adhesion molecule 3, HGNC:5346) is a protein-coding gene on chromosome 19p13.2, encoding Intercellular adhesion molecule 3 (P32942). Cell adhesion molecule that functions as a receptor ligand of the signaling receptor ITGAL:ITGB2/LFA-1 (lymphocyte-function associated (LFA) molecule 1) ensuring apoptotic neutrophil phagocytosis by macrophages.

The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 3385 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 98 total
• Druggable target: yes
• MANE Select transcript: NM_002162

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5346
Approved symbol	ICAM3
Name	intercellular adhesion molecule 3
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	CDW50, ICAM-R, CD50
Ensembl gene	ENSG00000076662
Ensembl biotype	protein_coding
OMIM	146631
Entrez	3385

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding_CDS_not_defined, 3 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

ENST00000160262, ENST00000585439, ENST00000587992, ENST00000589249, ENST00000589261, ENST00000589580, ENST00000589900, ENST00000590569, ENST00000592439, ENST00000592945, ENST00000706691, ENST00000706692, ENST00000706693, ENST00000912542

RefSeq mRNA: 7 — MANE Select: NM_002162 NM_001320605, NM_001320606, NM_001320608, NM_001395374, NM_001395375, NM_001395376, NM_002162

CCDS: CCDS12235

Canonical transcript exons

ENST00000160262 — 7 exons

Exon	Start	End
ENSE00000676168	10335066	10335353
ENSE00000676169	10335671	10335976
ENSE00002767860	10333776	10334059
ENSE00003519005	10338682	10338948
ENSE00003598713	10339539	10339624
ENSE00003611651	10334160	10334408
ENSE00003996606	10334528	10334782

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.6331 / max 1463.7834, expressed in 1632 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179115	19.0789	411
179116	4.0998	348
179112	3.9025	1268
179113	0.4324	61
179114	0.1196	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.14	gold quality
granulocyte	CL:0000094	99.02	gold quality
leukocyte	CL:0000738	97.98	gold quality
monocyte	CL:0000576	97.93	gold quality
mononuclear cell	CL:0000842	97.88	gold quality
bone marrow cell	CL:0002092	97.82	gold quality
bone marrow	UBERON:0002371	97.72	gold quality
trabecular bone tissue	UBERON:0002483	96.59	gold quality
periodontal ligament	UBERON:0008266	96.50	gold quality
spleen	UBERON:0002106	95.99	gold quality
lymph node	UBERON:0000029	94.21	gold quality
right lobe of liver	UBERON:0001114	93.69	gold quality
vermiform appendix	UBERON:0001154	93.22	gold quality
mucosa of transverse colon	UBERON:0004991	90.30	gold quality
epithelium of nasopharynx	UBERON:0001951	89.70	gold quality
liver	UBERON:0002107	89.19	gold quality
tonsil	UBERON:0002372	88.48	gold quality
palpebral conjunctiva	UBERON:0001812	88.09	gold quality
caecum	UBERON:0001153	87.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.84	gold quality
superficial temporal artery	UBERON:0001614	87.66	gold quality
parotid gland	UBERON:0001831	86.61	gold quality
apex of heart	UBERON:0002098	86.42	gold quality
ileal mucosa	UBERON:0000331	86.20	gold quality
right lung	UBERON:0002167	86.17	gold quality
colonic mucosa	UBERON:0000317	85.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.25	gold quality
stromal cell of endometrium	CL:0002255	85.10	gold quality
thymus	UBERON:0002370	84.45	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	286.96
E-MTAB-9067	yes	32.45
E-MTAB-10287	yes	31.11
E-MTAB-8410	yes	30.48
E-HCAD-11	yes	27.66
E-HCAD-10	yes	25.44
E-GEOD-135922	yes	24.73
E-MTAB-6701	yes	20.68
E-ANND-3	yes	14.01
E-MTAB-9801	yes	9.53
E-MTAB-10042	yes	7.78
E-MTAB-7606	no	1828.66
E-GEOD-76312	no	342.95
E-MTAB-7381	no	136.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX3

Literature-anchored findings (GeneRIF, showing 40)

• A novel serine-rich motif in the intercellular adhesion molecule 3 is critical for its ezrin/radixin/moesin-directed subcellular targeting (PMID:11784723)
• identification of DC-SIGN binding sites (PMID:11799126)
• interactions with DC-SIGN does not promote DC-SIGN mediated HIV-1 transmission (PMID:12021323)
• Expression of DC-SIGN and its ligand, ICAM-3, is found in substantial amounts only in RA synovium, suggesting that their interaction is implicated in the additional activation of synovial macrophages that leads to the production of EMMPRIN and MMP-1. (PMID:12571844)
• the expression of ICAM-1 might involve both p38 MAPK and NF-kappaB activities, whereas the regulation of CD11b, CD18, and ICAM-3 expressions might be mediated through p38 MAPK but not NF-kappaB. (PMID:12600815)
• ICAM-3 is highly expressed on the surface of human eosinophils and has a role in the downregulation of GM-CSF production. (PMID:12743567)
• Relationship of intercellular adhesion molecule-3 and hepatocyte growth factor with amyloidosis A in chronic renal-failure patients. There was a higher density of intercellular adhesion molecule-3-positive cells in the patients with amyloidosis A. (PMID:14704632)
• ICAM-3 is expressed on human bone marrow endothelial cells and controls endothelial integrity via reactive oxygen species-dependent signaling. (PMID:14726630)
• soluble DC-SIGN bound to gp120-Fc more than 100- and 50-fold better than ICAM-2-Fc and ICAM-3-Fc, respectively. Binding sites are described. (PMID:14970226)
• acts as a costimulating molecule to increase HIV-1 transcription and viral replication, a process allowing productive infection of quiescent CD4+ T lymphocytes. (PMID:15163761)
• Expression of ICAM-3 can be used as a valuable biomarker to predict the radiation resistance in cervical cancer that occurs during radiotherapy. (PMID:15880373)
• the hybrid domain of integrin alphaL beta2 has different requirements of affinity states for ICAM-1 and ICAM-3 binding (PMID:15958383)
• The results suggest that ICAM-3 assists in the interaction of granulocytes with DC-SIGN of dendritic cells. (PMID:17145745)
• Patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels and lower total white blood cell counts. (PMID:17570115)
• talin induced an intermediate affinity alphaLbeta2 that adhered constitutively to its ligand intercellular adhesion molecule ICAM-1 but not ICAM-3. (PMID:17591777)
• Here we demonstrate that leukocyte function-associated antigen 1 (LFA-1), intercellular adhesion molecule 1 (ICAM-1), and ICAM-3 are enriched at the VS and that inhibition of these interactions influences conjugate formation and reduces VS assembly. (PMID:17913807)
• This is the first case of CD20 positive mycosis fungoides involving a lymph node to be reported in the literature. (PMID:18261116)
• extended alpha(L)beta(2) with an open headpiece is required for ICAM-3 adhesion (PMID:18354203)
• Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma. (PMID:19225705)
• no significant risk association was found for SARS infection for the ICAM-3 Asp143Gly SNP. (PMID:19801714)
• ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB (PMID:19956847)
• CCR1 antagonist, BX471, did not significantly alter ICAM-3 expression in relapsing-remitting multiple sclerosis patients. (PMID:20086017)
• Single nucleotide polymorphisms in ICAM3 gene is associated with lymphoma. (PMID:21239057)
• induction of morphological polarization in primary T lymphocytes and Jurkat cells enhances Kidins220/ARMS colocalization with ICAM-3 (PMID:21381019)
• the cross-talk between neutrophils and NK cells is mediated by ICAM-3 and CD11d/CD18, respectively. (PMID:21712539)
• ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes. (PMID:22117198)
• the molecular basis of allergen-induced Th2 cell polarization (PMID:22205703)
• analysis of activated apoptotic cells induce dendritic cell maturation via engagement of Toll-like receptor 4 (TLR4), dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN), and beta2 integrins (PMID:22396536)
• Results indicate that the ICAM-3 gene promoter is negatively regulated by RUNX3. (PMID:22479382)
• Intercellular adhesion molecule (ICAM)-3 mRNA is upregulated in non-adherent endothelial forming cells. (PMID:23144795)
• ICAM3 acts as recognition receptors in the phagocytosis portals of macrophages for engulfment of apoptotic neutrophils. (PMID:23775590)
• this data clearly indicate that ICAM-3 promotes drug resistance via inhibition of apoptosis. (PMID:24177012)
• with larger patient groups and preferably detailed histopathological and clinical evaluations, are needed to explain the severity of ICAM-1, ICAM-2, and ICAM-3 molecules in Barrett’s esophagus (PMID:24474251)
• Increased expression of PECAM-1, ICAM-3, and VCAM-1 in colonic biopsies from patients with inflammatory bowel disease (IBD) in clinical remission is associated with subsequent flares; this suggests that increases in the expression of these proteins may be early events that lead to flares in patients with IBD (PMID:27552332)
• we identify a potential CSC regulator and suggest a novel mechanism by which ICAM3 governs cancer cell stemness and inflammation. (PMID:29477378)
• Lewis-antigen-containing ICAM-2/3 on Jurkat leukemia cells interact with DC-SIGN to regulate DC functions. (PMID:29671117)
• exploration of the underlying mechanism demonstrated that ICAM3 not only binds to LFA-1 with its extracellular domain and structure protein ERM but also to lamellipodia with its intracellular domain which causes a tension that pulls cells apart (metastasis). (PMID:29729315)
• Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine. (PMID:32013031)
• Vascular injury biomarkers and stroke risk: A population-based study. (PMID:32371447)
• Association of Circulating ICAM3 Concentrations with Severity and Short-term Outcomes of Acute Ischemic Stroke. (PMID:33999358)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	icam3	ENSDARG00000076144
danio_rerio	sc:d0202	ENSDARG00000078180
danio_rerio	si:ch211-66e2.3	ENSDARG00000078824
danio_rerio	si:ch73-208g10.1	ENSDARG00000079808
danio_rerio	si:ch211-66e2.5	ENSDARG00000091579
danio_rerio	si:ch211-74m13.1	ENSDARG00000094952
danio_rerio		ENSDARG00000095312

Paralogs (4): ICAM1 (ENSG00000090339), ICAM4 (ENSG00000105371), ICAM5 (ENSG00000105376), ICAM2 (ENSG00000108622)

Protein

Protein identifiers

Intercellular adhesion molecule 3 — P32942 (reviewed: P32942)

Alternative names: CDw50, ICAM-R

All UniProt accessions (4): P32942, A0A9L9PXS1, A0A9L9PXU5, K7EMH0

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion molecule that functions as a receptor ligand of the signaling receptor ITGAL:ITGB2/LFA-1 (lymphocyte-function associated (LFA) molecule 1) ensuring apoptotic neutrophil phagocytosis by macrophages. Is also a ligand for integrin ITGAD/ITGB2. Ligand of CD209 on dendritic cells (DC) through an integrin-independent mechanism that requires Ca(2+) and that forms a first contact between DC and resting T cell, facilitating the downstream DC-T cell clustering process and DC-induced proliferation of resting T Cells.

Subunit / interactions. Interacts (via cytoplasmic tail) with MSN/moesin.

Subcellular location. Cell membrane.

Tissue specificity. Constitutively expressed only on resting leukocytes. No expressed on resting or cytokine-activated endothelial cells.

Post-translational modifications. N-glycosylated; glycans consist of a mixture of tri- and tetra-antennary complex-type chains and high-mannose chains.

Similarity. Belongs to the immunoglobulin superfamily. ICAM family.

RefSeq proteins (7): NP_001307534, NP_001307535, NP_001307537, NP_001382303, NP_001382304, NP_001382305, NP_002153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR003987	ICAM_VCAM_N	Domain
IPR003988	ICAM	Domain
IPR007110	Ig-like_dom	Domain
IPR013768	ICAM_N	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR047012	ICAM_VCAM	Family
IPR048679	ICAM1_3_5_D2	Domain

Pfam: PF03921, PF21146

UniProt features (44 total): glycosylation site 15, strand 7, disulfide bond 6, domain 5, sequence variant 4, topological domain 2, signal peptide 1, chain 1, binding site 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1T0P	X-RAY DIFFRACTION	1.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32942-F1	87.08	0.75

Functional residue map

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

Ligand- & substrate-binding residues (1): 66

Disulfide bonds (6): 53–96, 57–100, 139–190, 241–294, 336–375, 423–462

Glycosylation sites (15): 52, 84, 87, 101, 110, 134, 206, 264, 295, 308, 320, 363, 389, 453, 457

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083	Integrin cell surface interactions
R-HSA-5621575	CD209 (DC-SIGN) signaling

MSigDB gene sets: 179 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_45, MODULE_64, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_16, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, GOBP_CELL_CELL_ADHESION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_LEUKOCYTE_PROLIFERATION, KESHELAVA_MULTIPLE_DRUG_RESISTANCE

GO Biological Process (8): phagocytosis (GO:0006909), immune response (GO:0006955), cell adhesion (GO:0007155), leukocyte cell-cell adhesion (GO:0007159), integrin-mediated signaling pathway (GO:0007229), immature T cell proliferation (GO:0033079), cell-cell adhesion mediated by integrin (GO:0033631), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): signaling receptor binding (GO:0005102), integrin binding (GO:0005178), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Adaptive Immune System	1
Extracellular matrix organization	1
C-type lectin receptors (CLRs)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
signaling receptor binding	2
endocytosis	1
immune system process	1
response to stimulus	1
cellular process	1
cell surface receptor signaling pathway	1
T cell proliferation	1
cell adhesion mediated by integrin	1
cell adhesion	1
protein binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
signal transduction	1
signaling receptor activator activity	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ICAM3	CD209	Q9NNX6	999
ICAM3	ITGB2	P05107	992
ICAM3	CLEC4M	Q9H2X3	992
ICAM3	ITGAL	P20701	987
ICAM3	ITIH4	Q14624	793
ICAM3	VCAM1	P19320	778
ICAM3	ERVW-1	Q9UQF0	747
ICAM3	CD4	P01730	701
ICAM3	ICAM1	P05362	643
ICAM3	MSN	P26038	632
ICAM3	ICAM2	P13598	630
ICAM3	ITGAM	P11215	626
ICAM3	CXCR4	P30991	619
ICAM3	CLEC7A	Q9BXN2	604
ICAM3	PECAM1	P16284	600

IntAct

42 interactions, top by confidence:

A	B	Type	Score
ICAM3	BRICD5	psi-mi:“MI:0915”(physical association)	0.560
TSPO	ICAM3	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	NINJ2	psi-mi:“MI:0915”(physical association)	0.560
CLDN4	ICAM3	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	ICAM3	psi-mi:“MI:0915”(physical association)	0.560
SFTPC	ICAM3	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	SEC22A	psi-mi:“MI:0915”(physical association)	0.560
ZNF431	TYRP1	psi-mi:“MI:0914”(association)	0.530
ITGAL	ICAM3	psi-mi:“MI:0407”(direct interaction)	0.440
CD209	ICAM3	psi-mi:“MI:0407”(direct interaction)	0.440
CLEC4M	ICAM3	psi-mi:“MI:0407”(direct interaction)	0.440
ICAM3	TMEM192	psi-mi:“MI:0915”(physical association)	0.400
ICAM3	PICALM	psi-mi:“MI:0915”(physical association)	0.400
ICAM3	E6	psi-mi:“MI:0915”(physical association)	0.370
ICAM3	TMEM192	psi-mi:“MI:0914”(association)	0.350
BRICD5	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
TSPO	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
EDDM3B	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
NINJ2	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
CLDN4	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
CLDN19	ICAM3	psi-mi:“MI:0915”(physical association)	0.000
SEC22A	ICAM3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (30): ICAM3 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), FUT8 (Affinity Capture-MS), TSPO (Two-hybrid), SEC22A (Two-hybrid), CLDN19 (Two-hybrid), SMCO4 (Two-hybrid), SFTPC (Two-hybrid), NINJ2 (Two-hybrid), EDDM3B (Two-hybrid), BRICD5 (Two-hybrid), CLDN4 (Two-hybrid), SMIM1 (Two-hybrid), ICAM3 (Reconstituted Complex), MSN (Affinity Capture-Western)

ESM2 similar proteins: A6NMB1, A7LCJ3, G1T7E7, G1TR84, M3XWH1, O15389, O43699, O70540, P04217, P05362, P0DP72, P13597, P20138, P32942, P33729, Q00238, Q08ET2, Q14773, Q28125, Q28730, Q28806, Q2KJF1, Q5NKT8, Q5NKU6, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q62230, Q64JA4, Q6DN72, Q7L513, Q80ZE3, Q91Y57, Q920A9, Q920G3, Q92154, Q95132, Q95LH0, Q96A28

Diamond homologs: P05362, P13597, P13598, P32942, P33729, P35330, Q00238, Q14773, Q28125, Q28730, Q28806, Q5NKT8, Q5NKU6, Q5NKV1, Q5NKV2, Q5NKV4, Q5NKV6, Q5NKV9, Q60625, Q95132, Q9UMF0, Q290N5, O95727, P04921, Q00609, Q149L7, Q1WIM1, Q1WIM2, Q1WIM3, Q5RD64, Q66KX2, Q6AYP5, Q6DJ83, Q6XFR6, Q78HU7, Q7ZXX1, Q8BLQ9, Q8N126, Q8N3J6, Q8NFZ8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCQ	“up-regulates activity”	ICAM3	phosphorylation
ICAM3	“up-regulates activity”	“AD/b2 integrin”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	7
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1458 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10334055:CCCAG:C	acceptor_gain	1.0000
19:10334056:CCAG:C	acceptor_gain	1.0000
19:10334056:CCAGC:C	acceptor_gain	1.0000
19:10334057:CAG:C	acceptor_gain	1.0000
19:10334057:CAGC:C	acceptor_gain	1.0000
19:10334060:C:CC	acceptor_gain	1.0000
19:10334527:CA:C	donor_gain	1.0000
19:10335064:A:AC	donor_gain	1.0000
19:10335065:C:CC	donor_gain	1.0000
19:10335974:GCC:G	acceptor_gain	1.0000
19:10335975:CC:C	acceptor_gain	1.0000
19:10335975:CCC:C	acceptor_gain	1.0000
19:10335975:CCCT:C	acceptor_loss	1.0000
19:10335976:CC:C	acceptor_gain	1.0000
19:10335977:C:CC	acceptor_gain	1.0000
19:10335977:C:T	acceptor_gain	1.0000
19:10338680:A:AC	donor_gain	1.0000
19:10338681:C:CT	donor_gain	1.0000
19:10338681:CTGTA:C	donor_gain	1.0000
19:10334058:AG:A	acceptor_gain	0.9900
19:10334059:GCTG:G	acceptor_loss	0.9900
19:10334060:C:T	acceptor_loss	0.9900
19:10334061:T:G	acceptor_loss	0.9900
19:10334062:G:C	acceptor_gain	0.9900
19:10334062:G:GC	acceptor_gain	0.9900
19:10334158:AC:A	donor_gain	0.9900
19:10334159:CC:C	donor_gain	0.9900
19:10334522:A:AC	donor_gain	0.9900
19:10334523:C:CC	donor_gain	0.9900
19:10334526:A:AC	donor_gain	0.9900

AlphaMissense

3515 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10334216:C:G	C462S	0.993
19:10334217:A:T	C462S	0.993
19:10334333:C:G	C423S	0.990
19:10334334:A:T	C423S	0.990
19:10334362:C:A	W413C	0.990
19:10334362:C:G	W413C	0.990
19:10334297:C:G	C435S	0.986
19:10334298:A:T	C435S	0.986
19:10334334:A:G	C423R	0.980
19:10334217:A:G	C462R	0.979
19:10334381:C:G	C407S	0.978
19:10334382:A:T	C407S	0.978
19:10334298:A:G	C435R	0.977
19:10334223:A:C	Y460D	0.974
19:10338776:G:C	F83L	0.973
19:10338776:G:T	F83L	0.973
19:10338778:A:G	F83L	0.973
19:10334322:C:A	G427C	0.972
19:10334382:A:G	C407R	0.970
19:10335904:C:G	C139S	0.970
19:10335905:A:T	C139S	0.970
19:10334596:C:G	C375S	0.967
19:10334597:A:T	C375S	0.967
19:10334322:C:G	G427R	0.966
19:10334215:G:C	C462W	0.965
19:10334364:A:G	W413R	0.964
19:10334364:A:T	W413R	0.964
19:10334596:C:T	C375Y	0.964
19:10334321:C:A	G427V	0.962
19:10334595:G:C	C375W	0.961

dbSNP variants (sampled 300 via entrez): RS1000033187 (19:10338127 G>A), RS1000639468 (19:10333737 TG>T), RS1000818991 (19:10337382 A>C), RS1000850149 (19:10335514 G>A,C), RS1001900897 (19:10340875 C>T), RS1002015689 (19:10340286 G>C), RS1004227720 (19:10336885 G>A), RS1004323985 (19:10337064 C>A,T), RS1006324266 (19:10340182 G>A), RS1006586277 (19:10341163 A>G), RS1006656742 (19:10341558 C>G,T), RS1006806669 (19:10333824 A>G), RS1007048795 (19:10334858 C>G), RS1008311173 (19:10336062 C>T), RS1008722660 (19:10333803 C>A)

Disease associations

OMIM: gene MIM:146631 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000879_7	Crohn’s disease	1.000000e-12
GCST003620_8	Systemic lupus erythematosus or rheumatoid arthritis	3.000000e-08
GCST004131_88	Inflammatory bowel disease	2.000000e-11
GCST004132_111	Crohn’s disease	3.000000e-13
GCST005568_15	Rheumatoid arthritis (ACPA-positive)	2.000000e-14
GCST005569_38	Rheumatoid arthritis	3.000000e-13

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712862 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	7
Tretinoin	increases expression, increases reaction	4
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
doxifluridine	increases response to substance	1
avobenzone	increases expression	1
tamibarotene	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
S 1 (combination)	increases response to substance	1
GW 1929	affects localization, decreases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
beta-hydroxy simvastatin acid	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
Aripiprazole	affects cotreatment, decreases expression	1
Rosiglitazone	affects localization, decreases reaction	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1

Clinical trials (associated diseases)

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