FMNL2

Summary

FMNL2 (formin like 2, HGNC:18267) is a protein-coding gene on chromosome 2q23.3, encoding Formin-like protein 2 (Q96PY5). Plays a role in the regulation of cell morphology and cytoskeletal organization.

This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined.

Source: NCBI Gene 114793 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inflammatory bowel disease (Limited, GenCC)
• GWAS associations: 19
• Clinical variants (ClinVar): 161 total — 1 likely-pathogenic
• MANE Select transcript: NM_052905

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18267
Approved symbol	FMNL2
Name	formin like 2
Location	2q23.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1902
Ensembl gene	ENSG00000157827
Ensembl biotype	protein_coding
OMIM	616285
Entrez	114793

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000288670, ENST00000475377, ENST00000492942, ENST00000497192, ENST00000850951, ENST00000850952, ENST00000850953, ENST00000869108, ENST00000939795, ENST00000939796

RefSeq mRNA: 1 — MANE Select: NM_052905 NM_052905

CCDS: CCDS46429

Canonical transcript exons

ENST00000288670 — 26 exons

Exon	Start	End
ENSE00001165972	152637573	152637674
ENSE00001467951	152636427	152636590
ENSE00001578740	152335174	152335720
ENSE00001580926	152521943	152522026
ENSE00001585885	152542739	152542819
ENSE00001611045	152617091	152617192
ENSE00001614972	152578888	152578964
ENSE00001652296	152629656	152629724
ENSE00001664787	152632008	152632137
ENSE00001670992	152639958	152640056
ENSE00001685682	152628299	152628533
ENSE00001689314	152549021	152549097
ENSE00001703629	152611495	152611605
ENSE00001708712	152619509	152619718
ENSE00001738552	152607339	152607413
ENSE00001754463	152640791	152640914
ENSE00001764485	152560883	152561035
ENSE00001768452	152629825	152629905
ENSE00001771013	152626525	152626727
ENSE00001786397	152614851	152615000
ENSE00001786604	152575136	152575244
ENSE00001794876	152558740	152558823
ENSE00001799899	152618846	152619158
ENSE00003480875	152580956	152581049
ENSE00003603430	152625438	152625562
ENSE00004282909	152647796	152649826

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0705 / max 1302.5797, expressed in 1633 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23074	25.9629	1583
23073	4.6677	1285
23075	1.0874	468
23098	0.3434	112
23090	0.0090	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
inferior vagus X ganglion	UBERON:0005363	99.61	gold quality
corpus callosum	UBERON:0002336	99.58	gold quality
subthalamic nucleus	UBERON:0001906	99.57	gold quality
lateral globus pallidus	UBERON:0002476	99.49	gold quality
medulla oblongata	UBERON:0001896	99.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.43	gold quality
superior vestibular nucleus	UBERON:0007227	99.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.26	gold quality
ventral tegmental area	UBERON:0002691	99.23	gold quality
globus pallidus	UBERON:0001875	99.19	gold quality
substantia nigra pars compacta	UBERON:0001965	99.18	gold quality
medial globus pallidus	UBERON:0002477	99.10	gold quality
pons	UBERON:0000988	99.04	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.80	gold quality
spinal cord	UBERON:0002240	98.76	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.63	gold quality
trigeminal ganglion	UBERON:0001675	98.58	gold quality
endothelial cell	CL:0000115	98.45	gold quality
midbrain	UBERON:0001891	98.18	gold quality
substantia nigra	UBERON:0002038	98.04	gold quality
parietal lobe	UBERON:0001872	97.96	gold quality
occipital lobe	UBERON:0002021	97.83	gold quality
postcentral gyrus	UBERON:0002581	97.82	gold quality
dorsal root ganglion	UBERON:0000044	97.62	gold quality
entorhinal cortex	UBERON:0002728	97.54	gold quality
primary visual cortex	UBERON:0002436	97.49	gold quality
Ammon’s horn	UBERON:0001954	97.39	gold quality
cortical plate	UBERON:0005343	97.18	gold quality
superior frontal gyrus	UBERON:0002661	97.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	5740.69
E-HCAD-25	yes	3034.92
E-HCAD-35	yes	86.58
E-ANND-3	yes	11.84
E-CURD-114	yes	7.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HMGA1, NFKB, NFKBIA, PAX6

miRNA regulators (miRDB)

174 targeting FMNL2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
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-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 29)

• FMNL2 may play an important role in the metastasis of CRC and may be a useful marker for metastasis of CRC. (PMID:18665374)
• a novel regulatory and functional interaction between RhoC and FMNL2 for modulating cell shape and invasiveness and provide mechanistic insight into RhoC-specific signalling events. (PMID:20101212)
• Findings identify a novel EMT and tumor promoting function for FMNL2, which is involved in TGF-beta-induced EMT and colorectal carcinoma cell invasion via Smad3 effectors, or in collaboration with MAPK/MEK pathway. (PMID:21071512)
• formin-like 2 expression correlated positively with tumor differentiation (P = .046) and vascular invasion (P = .008). Patients whose tumors had lower formin-like 2 expression had shorter overall survival times (PMID:21496865)
• FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia. (PMID:22608513)
• Protein N-myristoylation plays critical roles in the cellular morphological changes induced by FMNL2 and FMNL3. (PMID:22790947)
• miR-137, induced by its upstream transcription factor HMGA1, can suppress colorectal cancer cell invasion and metastasis by targeting FMNL2. (PMID:23201162)
• The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia. (PMID:25963737)
• Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2. (PMID:25963818)
• MiR-34a was down-regulated in colorectal cancer cells and inversely correlated with FMNL2 and E2F5 expressions. Our study suggests that miR-34a is an important tumor suppressor of CRC progression by targeting FMNL2 and E2F5. (PMID:26103003)
• These data establish a role for FMNL2 in the regulation of beta1-integrin and provide a mechanistic understanding of the function of FMNL2 in cancer invasiveness. (PMID:26256210)
• miR-206 functioned as a tumor suppressor in the progression of colorectal cancer(CRC) by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC. (PMID:26515696)
• Capping protein and FMNL2 functionally coregulate filament barbed-end assembly. (PMID:26564775)
• FMNL2 is likely to be generally required in melanoma cells for invasion. (PMID:27578625)
• Our data proved that RMRP acted as an oncogene LncRNA to promote the expression of KRAS, FMNL2 and SOX9 by inhibiting miR-206 expression in lung cancer. These data suggested that RMRP might serve as a therapeutic target in lung adenocarcinoma (PMID:27906963)
• Data demonstrate that the FMNL2/COMMD10/p65 NF kappaB axis acts as a critical regulator in the maintenance of metastatic phenotypes in colorectal cancer. (PMID:28817833)
• Data indicate that the interaction of cortactin and formin-like 2 (FMNL2) could promote the invadopodia formation and matrix degradation. (PMID:29374558)
• FMNL2 knockout cells were characterized by impaired filopodia formation similar to depletion of the Rho GTPase Cdc42. (PMID:29579104)
• Findings reveal that the aberrant activation of FMNL2 promotes the pathogenesis of adenomyosis through inducing the EMT process. (PMID:31175924)
• MicroRNA-22 targets FMNL2 to inhibit melanoma progression via the regulation of the Wnt/beta-catenin signaling pathway and epithelial-mesenchymal transition. (PMID:31298385)
• Results demonstrated that N-myristoylation-dependent phosphorylation in FMNL2 occurs at a single Ser residue at position 171, which is a Ser residue conserved between FMNL2 and FMNL3, corresponding to Ser-174 in FMNL3 (PMID:31751425)
• CircHIPK3 promotes colorectal cancer cells proliferation and metastasis via modulating of miR-1207-5p/FMNL2 signal. (PMID:32046858)
• FMNL2 regulates dynamics of fascin in filopodia. (PMID:32294157)
• Characterization of a L136P mutation in Formin-like 2 (FMNL2) from a patient with chronic inflammatory bowel disease. (PMID:34043722)
• FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer’s disease. (PMID:35608697)
• Formin-Like 2 Is a Potential Biomarker of Poor Prognosis in Nasopharyngeal Carcinoma. (PMID:35772391)
• LINC00839 promotes malignancy of liver cancer via binding FMNL2 under hypoxia. (PMID:36335129)
• Spatiotemporal Regulation of FMNL2 by N-Terminal Myristoylation and C-Terminal Phosphorylation Drives Rapid Filopodia Formation. (PMID:36979484)
• [Effect of miR-22 Targeting FMNL2 on Cell Migration and Apoptosis in Childhood Acute Myeloid Leukemia]. (PMID:38071036)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fmnl2a	ENSDARG00000012586
mus_musculus	Fmnl2	ENSMUSG00000036053
rattus_norvegicus	Fmnl2	ENSRNOG00000055567
caenorhabditis_elegans		WBGENE00018976
caenorhabditis_elegans		WBGENE00019030
caenorhabditis_elegans	sydn-1	WBGENE00021473

Paralogs (18): DAAM1 (ENSG00000100592), FNBP4 (ENSG00000109920), DIAPH1 (ENSG00000131504), FHOD3 (ENSG00000134775), FHOD1 (ENSG00000135723), FHDC1 (ENSG00000137460), DIAPH3 (ENSG00000139734), DAAM2 (ENSG00000146122), DIAPH2 (ENSG00000147202), FMN2 (ENSG00000155816), FMNL3 (ENSG00000161791), FMNL1 (ENSG00000184922), FAM47A (ENSG00000185448), SHTN1 (ENSG00000187164), FAM47B (ENSG00000189132), FAM47C (ENSG00000198173), INF2 (ENSG00000203485), GRID2IP (ENSG00000215045)

Protein

Protein identifiers

Formin-like protein 2 — Q96PY5 (reviewed: Q96PY5)

Alternative names: Formin homology 2 domain-containing protein 2

All UniProt accessions (2): C9IZY8, Q96PY5

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics.

Subcellular location. Cytoplasm.

Domain organisation. The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments.

Similarity. Belongs to the formin homology family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96PY5-1	1	yes
Q96PY5-3	2

RefSeq proteins (1): NP_443137* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010472	FH3_dom	Domain
IPR010473	GTPase-bd	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR014767	DAD_dom	Domain
IPR014768	GBD/FH3_dom	Domain
IPR015425	FH2_Formin	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR042201	FH2_Formin_sf	Homologous_superfamily
IPR043592	FMNL_animal	Family

Pfam: PF02181, PF06367, PF06371

UniProt features (42 total): helix 21, compositionally biased region 4, sequence conflict 3, domain 3, sequence variant 2, turn 2, initiator methionine 1, chain 1, modified residue 1, lipid moiety-binding region 1, splice variant 1, strand 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4YC7	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PY5-F1	77.31	0.43

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): 188, 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5663220	RHO GTPases Activate Formins
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle

MSigDB gene sets: 235 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8_TCELL_UP, RNGTGGGC_UNKNOWN, GCM_MAP4K4, AAGCAAT_MIR137, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOMF_GTPASE_BINDING, GTGCCTT_MIR506, CATTTCA_MIR203, FOSTER_TOLERANT_MACROPHAGE_UP, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, ZIC1_01, DODD_NASOPHARYNGEAL_CARCINOMA_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, GOMF_ACTIN_BINDING

GO Biological Process (7): cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), cell migration (GO:0016477), regulation of cell morphogenesis (GO:0022604), cortical actin cytoskeleton organization (GO:0030866), cellular component organization (GO:0016043), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (4): small GTPase binding (GO:0031267), cadherin binding (GO:0045296), actin filament binding (GO:0051015), actin binding (GO:0003779)

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	2
RHO GTPase Effectors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell motility	1
cell morphogenesis	1
regulation of anatomical structure morphogenesis	1
actin cytoskeleton organization	1
cortical cytoskeleton organization	1
cellular component organization or biogenesis	1
cytoskeleton organization	1
actin filament-based process	1
GTPase binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FMNL2	RHOC	P08134	898
FMNL2	BAG4	O95429	697
FMNL2	ARL6IP6	Q8N6S5	646
FMNL2	PFN4	Q8NHR9	622
FMNL2	PFN3	P60673	607
FMNL2	E2F5	Q15329	601
FMNL2	PFN1	P07737	591
FMNL2	WBP4	O75554	582
FMNL2	FNBP4	Q8N3X1	575
FMNL2	ITCH	Q96J02	560
FMNL2	PRPF40A	O75400	556
FMNL2	SRGAP2	O75044	465
FMNL2	FNBP1	Q96RU3	465
FMNL2	ANKRD52	Q8NB46	462
FMNL2	MBNL3	Q9NUK0	461

IntAct

41 interactions, top by confidence:

A	B	Type	Score
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
UNC119	PDE8A	psi-mi:“MI:0914”(association)	0.530
CD44	PDPK1	psi-mi:“MI:0914”(association)	0.530
FMNL2	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
FMNL2		psi-mi:“MI:0915”(physical association)	0.370
FMNL2	PRPF40A	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
ANK2	IGKV2-40	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
ARRDC3	ESYT2	psi-mi:“MI:0914”(association)	0.350
ACTG1	ENAH	psi-mi:“MI:0914”(association)	0.350
PFN1	WASL	psi-mi:“MI:0914”(association)	0.350
FMNL2	A2ML1	psi-mi:“MI:0914”(association)	0.350
FMNL3	UBXN7	psi-mi:“MI:0914”(association)	0.350
FMNL2	PLPBP	psi-mi:“MI:0914”(association)	0.350
RPS19	ZNF316	psi-mi:“MI:0914”(association)	0.350
TMED2		psi-mi:“MI:0914”(association)	0.350
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
CTNNA1	MYO1G	psi-mi:“MI:0914”(association)	0.350
ATF3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CASP3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CTNNA1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
FOS	MYO1G	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (208): FMNL2 (Two-hybrid), FMNL2 (Affinity Capture-MS), FMNL2 (Affinity Capture-MS), FMNL2 (Proximity Label-MS), FMNL2 (Affinity Capture-MS), FMNL2 (Affinity Capture-MS), FMNL2 (Affinity Capture-MS), FMNL2 (Proximity Label-MS), FMNL2 (Affinity Capture-RNA), FMNL2 (Affinity Capture-MS), FMNL2 (Two-hybrid), FMNL2 (Two-hybrid), FMNL2 (Two-hybrid), FMNL2 (Two-hybrid), FMNL2 (Two-hybrid)

ESM2 similar proteins: A0A1D5P556, A0A3Q1LSX9, A2A5R2, A2APV2, B0DOB5, B2RQE8, D3ZYR1, D4A631, F1LVW7, F1M775, F4IUX6, G3X9K3, O08808, O46382, O60308, O60610, O75674, O95466, Q07139, Q0IHV1, Q0JRZ9, Q3UQN2, Q4S6U8, Q5MIZ7, Q5R807, Q5SP90, Q6DFT3, Q6IN85, Q6INN7, Q6NTV6, Q6NXC0, Q6P2K6, Q6ZPF4, Q7TSU1, Q7ZX60, Q801Q7, Q80U19, Q86T65, Q8BPM0, Q8IVF7

Diamond homologs: A0A3Q1LSX9, A2APV2, O23373, O95466, Q0D5P3, Q69MT2, Q6H7U3, Q6NTV6, Q6NXC0, Q6ZPF4, Q8IVF7, Q96PY5, Q9JL26, Q9VUC6, Q0D519, Q0GNC1, Q27J81, Q6MWG9, Q94B77, A0A1D5P556, A2XUA1, A2YVG8, A3AB67, B0DOB5, F1LVW7, O04532, O22824, O48682, P0C5K5, Q0DLG0, Q10Q99, Q24120, Q54PI9, Q5TJ56, Q6ZKB2, Q7XUV2, Q7XWS7, Q80U19, Q84ZL0, Q8BPM0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates activity”	FMNL2	phosphorylation
FMNL2	“up-regulates activity”	PLK1	binding
PRKCA	“up-regulates activity”	FMNL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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.

GO biological processes:

GO term	Partners	Fold	FDR
endocytosis	6	13.0×	2e-03
cell migration	7	9.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	114
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
997783	NM_052905.4(FMNL2):c.407T>C (p.Leu136Pro)	Likely pathogenic

SpliceAI

6580 predictions. Top by Δscore:

Variant	Effect	Δscore
2:152335716:TGCTG:T	donor_gain	1.0000
2:152335717:GCTG:G	donor_gain	1.0000
2:152335717:GCTGG:G	donor_gain	1.0000
2:152335720:GGTA:G	donor_loss	1.0000
2:152335722:T:G	donor_loss	1.0000
2:152521937:A:AG	acceptor_gain	1.0000
2:152522023:TCAG:T	donor_loss	1.0000
2:152522024:CAG:C	donor_loss	1.0000
2:152522025:AGGTA:A	donor_loss	1.0000
2:152522026:GGTAA:G	donor_loss	1.0000
2:152522027:GTAAG:G	donor_loss	1.0000
2:152522028:T:A	donor_loss	1.0000
2:152558736:ACAG:A	acceptor_loss	1.0000
2:152558738:A:AG	acceptor_gain	1.0000
2:152558738:AGAT:A	acceptor_gain	1.0000
2:152558738:AGATG:A	acceptor_gain	1.0000
2:152558739:G:GC	acceptor_loss	1.0000
2:152558739:G:GG	acceptor_gain	1.0000
2:152558739:GAT:G	acceptor_gain	1.0000
2:152558739:GATG:G	acceptor_gain	1.0000
2:152558739:GATGG:G	acceptor_gain	1.0000
2:152558819:GTAAC:G	donor_gain	1.0000
2:152558820:TAAC:T	donor_gain	1.0000
2:152558822:ACG:A	donor_loss	1.0000
2:152558823:CGTA:C	donor_loss	1.0000
2:152558824:G:GG	donor_gain	1.0000
2:152558824:GTAA:G	donor_loss	1.0000
2:152558825:T:A	donor_loss	1.0000
2:152558826:A:AG	donor_loss	1.0000
2:152560877:TTTTA:T	acceptor_gain	1.0000

AlphaMissense

7209 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004689 (2:152476450 C>T), RS1000005390 (2:152606007 T>G), RS1000012199 (2:152346026 T>A), RS1000017496 (2:152555161 A>G), RS1000024772 (2:152387408 G>A), RS1000045503 (2:152609646 T>C), RS1000051973 (2:152461021 T>C), RS1000069732 (2:152431579 T>C), RS1000070526 (2:152475912 C>T), RS1000088096 (2:152596334 A>G), RS1000091158 (2:152385828 G>A,T), RS1000106635 (2:152557081 A>G), RS1000113358 (2:152470433 C>T), RS1000127381 (2:152474558 C>T), RS1000128773 (2:152354310 G>A)

Disease associations

OMIM: gene MIM:616285 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inflammatory bowel disease	Limited	Autosomal dominant

Mondo (2): Crohn disease (MONDO:0005011), inflammatory bowel disease (MONDO:0005265)

Orphanet (1): NON RARE IN EUROPE: Crohn disease (Orphanet:206)

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST003832_5	Asthma (childhood onset)	3.000000e-06
GCST005170_55	Intraocular pressure	5.000000e-13
GCST005580_214	Intraocular pressure	1.000000e-22
GCST005580_225	Intraocular pressure	5.000000e-19
GCST006065_35	Glaucoma (primary open-angle)	2.000000e-11
GCST006394_48	Intraocular pressure	1.000000e-25
GCST006395_2	Glaucoma	3.000000e-07
GCST006412_3	Intraocular pressure	7.000000e-25
GCST006979_40	Heel bone mineral density	3.000000e-13
GCST007157_1	Corneal astigmatism	6.000000e-07
GCST007159_2	Corneal astigmatism	3.000000e-07
GCST007160_9	Refractive astigmatism	7.000000e-06
GCST009723_22	Vertical cup-disc ratio (adjusted for vertical disc diameter)	4.000000e-09
GCST009725_10	Intraocular pressure	4.000000e-26
GCST011438_3	Glaucoma (primary open-angle)	3.000000e-08
GCST011439_20	Glaucoma (primary open-angle)	4.000000e-09
GCST90002388_299	Lymphocyte count	3.000000e-10
GCST90002407_69	White blood cell count	2.000000e-12
GCST90011770_38	Glaucoma (primary open-angle)	3.000000e-37

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density
EFO:1002040	Corneal astigmatism
EFO:0006939	cup-to-disc ratio measurement
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003424	Crohn Disease	C06.405.205.731.500; C06.405.469.432.500
D015212	Inflammatory Bowel Diseases	C06.405.205.731; C06.405.469.432

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression, affects expression	3
Cyclosporine	decreases expression, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
Acetaminophen	affects expression, increases expression	2
Cisplatin	decreases expression, increases expression	2
Estradiol	affects expression, increases expression	2
Aflatoxin B1	decreases methylation, increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
mirdametinib	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00205062	PHASE4	TERMINATED	Positron Emission Tomography (PET)-Computed Tomography (CT) in Inflammatory Bowel Disease (IBD)
NCT00567593	PHASE4	COMPLETED	Gene Regulation by Thiazolidinediones
NCT00746395	PHASE4	COMPLETED	Randomized, Placebo-controlled Trial of Lubiprostone as a Preparation for Capsule Endoscopy
NCT01034358	PHASE4	COMPLETED	Immune Response to the Human Papillomavirus Vaccine in Young Women With Inflammatory Bowel Disease
NCT01056913	PHASE4	COMPLETED	NITI CAR27 (ColonRing) Compression Anastomosis in Colorectal Surgery
NCT01067547	PHASE4	COMPLETED	A Trial of Iron Replacement in Patients With Iron Deficiency.
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01908283	PHASE4	COMPLETED	Induction of Immunity Against Streptococcus Pneumoniae in Adults With Inflammatory Bowel Disease
NCT01934088	PHASE4	COMPLETED	Satisfaction With Nurse Administered Propofol Sedation vs. Midazolam With Fentanyl Sedation for Endoscopy
NCT02162862	PHASE4	COMPLETED	Treating Disrupted Sleep in Individuals With Inflammatory Bowel Disease
NCT02248337	PHASE4	COMPLETED	Low Volume Colon Preparation for IBD
NCT02281799	PHASE4	WITHDRAWN	Thiopurine Induced Pancreatitis in IBD Patients
NCT02392286	PHASE4	TERMINATED	Corticosteroid Dosage for Crohn’s Disease Flare
NCT02437591	PHASE4	COMPLETED	Study to Evaluate the Pharmacokinetics of Fidaxomicin in Inflammatory Bowel Disease (IBD) Subjects With Clostridium Difficile Infection (CDI)
NCT02453776	PHASE4	COMPLETED	Precision Dosing of Infliximab Versus Conventional Dosing of Infliximab
NCT02461758	PHASE4	COMPLETED	Trial of High Dose vs. Standard Dose Influenza Vaccine in Inflammatory Bowel Disease Patients
NCT02566889	PHASE4	TERMINATED	An Efficacy and Safety Study of Infliximab Dose Escalation in Pediatric Participants With Inflammatory Bowel Disease
NCT02774057	PHASE4	UNKNOWN	Trial of Captafer® vs. Oral Iron Sulfate in the Treatment of Iron Deficiency Anemia in Patients With IBD
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT02946203	PHASE4	COMPLETED	Comparison of VoLumen and Breeza Oral Contrast Agents in Pediatric Patients
NCT02994836	PHASE4	COMPLETED	GIS-SUSANTI-TNF-2015 (Anti-TNF Discontinuation )
NCT03220841	PHASE4	UNKNOWN	Stricture Definition and Treatment (STRIDENT) Drug Therapy Study
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03466983	PHASE4	COMPLETED	A Trial Comparing the Incidence of Hypophosphatemia in Relation to Treatment With Iron Isomaltoside and Ferric Carboxymaltose in Subjects With Iron Deficiency Anaemia Due to Inflammatory Bowel Disease
NCT03591770	PHASE4	TERMINATED	Shingrix Vaccine in Patients With Moderate to Severe Ulcerative Colitis on Tofacitinib
NCT03629379	PHASE4	COMPLETED	Response to Ustekinumab for Anti-tnf Induced Psoriasiform Skin Lesions
NCT03723447	PHASE4	COMPLETED	Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)
NCT03798691	PHASE4	COMPLETED	Immunogenicity of Herpes Zoster Subunit Vaccine in Inflammatory Bowel Disease Patients Treated With Vedolizumab
NCT03860012	PHASE4	UNKNOWN	Folic Acid in Pediatric Inflammatory Bowel Disease
NCT03885713	PHASE4	COMPLETED	Identification of Predictive Biomarkers for Response to Biologic Therapies and Tofacitinib in Inflammatory Bowel Disease
NCT03917303	PHASE4	RECRUITING	Control Crohn Safe Trial
NCT04045782	PHASE4	COMPLETED	Evaluation of the Safety and Effectiveness of Switching From Humira® to Imraldi® in Flanders
NCT04304950	PHASE4	COMPLETED	Chronotherapy in Inflammatory Bowel Disease
NCT04626947	PHASE4	TERMINATED	Prevention of Recurrent Clostridium Difficile Infection (CDI) in Patients With Inflammatory Bowel Disease (IBD).
NCT04646187	PHASE4	ENROLLING_BY_INVITATION	De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04982172	PHASE4	COMPLETED	Model-informed Dose De-escalation of Infliximab in Patients With Inflammatory Bowel Diseases
NCT05180175	PHASE4	COMPLETED	The Nordic IBD Treatment Strategy Trial
NCT05280405	PHASE4	UNKNOWN	Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study