RAB11FIP3

Summary

RAB11FIP3 (RAB11 family interacting protein 3, HGNC:17224) is a protein-coding gene on chromosome 16p13.3, encoding Rab11 family-interacting protein 3 (O75154). Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery.

Proteins of the large Rab GTPase family (see RAB1A; MIM 179508) have regulatory roles in the formation, targeting, and fusion of intracellular transport vesicles. RAB11FIP3 is one of many proteins that interact with and regulate Rab GTPases (Hales et al., 2001 [PubMed 11495908]).

Source: NCBI Gene 9727 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 166 total
• MANE Select transcript: NM_014700

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17224
Approved symbol	RAB11FIP3
Name	RAB11 family interacting protein 3
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0665, Rab11-FIP3, eferin
Ensembl gene	ENSG00000090565
Ensembl biotype	protein_coding
OMIM	608738
Entrez	9727

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 20 protein_coding, 5 retained_intron

ENST00000262305, ENST00000412256, ENST00000434585, ENST00000449879, ENST00000450428, ENST00000452814, ENST00000461009, ENST00000464263, ENST00000483002, ENST00000487899, ENST00000495663, ENST00000918302, ENST00000918303, ENST00000918304, ENST00000941638, ENST00000941639, ENST00000941640, ENST00000941641, ENST00000941642, ENST00000941643, ENST00000941644, ENST00000941645, ENST00000941646, ENST00000941647, ENST00000941648

RefSeq mRNA: 3 — MANE Select: NM_014700 NM_001142272, NM_001370401, NM_014700

CCDS: CCDS32351, CCDS92071

Canonical transcript exons

ENST00000262305 — 14 exons

Exon	Start	End
ENSE00000664289	520122	520277
ENSE00000664290	519754	519891
ENSE00000664307	488851	489000
ENSE00001142674	520459	520599
ENSE00001246789	503004	503097
ENSE00001246797	496824	496859
ENSE00001745300	471295	471389
ENSE00001769445	461404	461497
ENSE00001886439	520726	523011
ENSE00002222336	425649	426720
ENSE00003498823	518943	519024
ENSE00003516291	482525	482736
ENSE00003573218	505524	505627
ENSE00003684218	510660	510800

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.6983 / max 207.3187, expressed in 1799 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151919	29.3199	1798
151920	1.0640	542
151923	0.1383	12
151927	0.1124	28
151922	0.0347	11
151928	0.0175	9
151925	0.0068	2
151924	0.0047	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.31	gold quality
pancreatic ductal cell	CL:0002079	97.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.48	gold quality
adult mammalian kidney	UBERON:0000082	97.45	gold quality
sural nerve	UBERON:0015488	97.24	gold quality
renal medulla	UBERON:0000362	97.21	gold quality
cerebellar hemisphere	UBERON:0002245	97.20	gold quality
cortex of kidney	UBERON:0001225	97.16	gold quality
cerebellar cortex	UBERON:0002129	97.10	gold quality
visceral pleura	UBERON:0002401	96.96	gold quality
cerebellum	UBERON:0002037	96.92	gold quality
metanephros cortex	UBERON:0010533	96.92	gold quality
right frontal lobe	UBERON:0002810	96.52	gold quality
anterior cingulate cortex	UBERON:0009835	95.83	gold quality
body of pancreas	UBERON:0001150	95.78	gold quality
adult organism	UBERON:0007023	95.78	gold quality
pituitary gland	UBERON:0000007	95.62	gold quality
kidney	UBERON:0002113	95.58	gold quality
adenohypophysis	UBERON:0002196	95.30	gold quality
parietal pleura	UBERON:0002400	95.29	gold quality
primary visual cortex	UBERON:0002436	95.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.08	gold quality
lower esophagus	UBERON:0013473	95.07	gold quality
ascending aorta	UBERON:0001496	94.82	gold quality
thoracic aorta	UBERON:0001515	94.81	gold quality
left ovary	UBERON:0002119	94.72	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.70	gold quality
right coronary artery	UBERON:0001625	94.68	gold quality
right testis	UBERON:0004534	94.68	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	2210.90
E-CURD-119	yes	2182.16
E-ANND-3	yes	6.06
E-GEOD-124858	no	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting RAB11FIP3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-656-3P	100.00	72.15	2788
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4279	99.19	66.70	2437

Literature-anchored findings (GeneRIF, showing 12)

• Rab11-FIP3 localises to a Rab11-positive pericentrosomal compartment during interphase and to the cleavage furrow during cytokinesis (PMID:15158446)
• FIP-3 and RAB11 protein complex regulates recycling endosomes targeting to the cleavage furrow during late cytokinesis. (PMID:15601896)
• Results describe the distinct C-terminal binding regions of FIP3 and FIP4 for Rab11 and ARF5/ARF6, and the crystal structure of Rab11 in complex with the Rab11-binding domain (RBD) of FIP3. (PMID:17030804)
• Necessary for the structural integrity of the pericentrosomal endosomal recycling compartment. (PMID:17394487)
• FIP3 is a scaffolding protein that, in addition to regulating endosome targeting to the cleavage furrow, also is required for Arf6 recruitment to the midbody during late telophase. (PMID:17628206)
• Rab11-FIP3 is a Rab11-binding protein that regulates breast cancer cell motility by modulating the actin cytoskeleton.(325-41) (PMID:19327867)
• FIP3 was identified as the first membrane-associated interacting-partner for DLIC-2. (PMID:20214888)
• CART1 might be a cytoplasmic, testis-specific derepressor of RAR (PMID:20736163)
• Rab11-FIP3 coordinates the interactions of ASAP1 and Rab11a with Rabin8. (PMID:25673879)
• Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation (PMID:27154205)
• RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor. (PMID:28215104)
• IKZF4/NONO-RAB11FIP3 axis promotes immune evasion in gastric cancer via facilitating PD-L1 endosome recycling. (PMID:38211652)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab11fip3	ENSDARG00000016490
mus_musculus	Rab11fip3	ENSMUSG00000037098
rattus_norvegicus	Nme4	ENSRNOG00000032152
drosophila_melanogaster	nuf	FBGN0013718
caenorhabditis_elegans		WBGENE00018869

Paralogs (1): RAB11FIP4 (ENSG00000131242)

Protein

Protein identifiers

Rab11 family-interacting protein 3 — O75154 (reviewed: O75154)

Alternative names: Arfophilin-1, EF hands-containing Rab-interacting protein, MU-MB-17.148

All UniProt accessions (5): O75154, A0A0A0MSV1, F6X994, H0Y7F9, X6RFI8

UniProt curated annotations — full annotation on UniProt →

Function. Downstream effector molecule for Rab11 GTPase which is involved in endocytic trafficking, cytokinesis and intracellular ciliogenesis by participating in membrane delivery. Recruited by Rab11 to endosomes where it links Rab11 to dynein motor complex. The functional Rab11-RAB11FIP3-dynein complex regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endocytic recycling compartment (ERC) during interphase of cell cycle. Facilitates the interaction between dynein and dynactin and activates dynein processivity. Binding with ASAP1 is needed to regulate the pericentrosomal localization of recycling endosomes. The Rab11-RAB11FIP3 complex is also implicated in the transport during telophase of vesicles derived from recycling endosomes to the cleavage furrow via centrosome-anchored microtubules, where the vesicles function to deliver membrane during late cytokinesis and abscission. The recruitment of Rab11-RAB11FIP3-containing endosomes to the cleavage furrow and tethering to the midbody is co-mediated by RAB11FIP3 interaction with ARF6-exocyst and RACGAP1-MKLP1 tethering complexes. Also involved in the Rab11-Rabin8-Rab8 ciliogenesis cascade by facilitating the orderly assembly of a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which directs preciliary vesicle trafficking to mother centriole and ciliogenesis initiation. Also promotes the activity of Rab11 and ASAP1 in the ARF4-dependent Golgi-to-cilia transport of the sensory receptor rhodopsin. Competes with WDR44 for binding to Rab11, which controls intracellular ciliogenesis pathway. May play a role in breast cancer cell motility by regulating actin cytoskeleton.

Subunit / interactions. Homodimer. Interacts with RAB11A; the interaction is direct and is required for the recruitment to endosomes. Interacts with RAB11B. Forms a ternary complex with RAB11A and dynein intermediate chain DYNC1LI1; RAB11FIP3 links RAB11A to dynein and the interaction regulates endocytic trafficking. Interacts with dynein intermediate chain and dynactin (DCTN1); the interaction activates dynein processivity. Interacts with ARF6 and EXOC7; the interaction serves for recruitment and tethering of recycling endosomes-derived vesicles to the cleavage furrow/midbody. Interacts with RACGAP1/MgcRacGAP; the interaction occurs at late telophase and is required for recruitment and tethering of recycling endosomes-derived vesicles to the cleavage furrow/midbody. Forms a complex with RAB11A and Rabin8/RAB3IP, probably a heterohexamer with two of each protein subunit, where RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking. Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport. Interacts with RAB11FIP4. Interacts with RAB25.

Subcellular location. Endosome membrane. Recycling endosome membrane. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Cleavage furrow. Midbody. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network membrane.

Post-translational modifications. Phosphorylated at Ser-102 by CDK1 during metaphase, and dephosphorylated as cells enter telophase.

Domain organisation. The RBD-FIP domain mediates the interaction with Rab11 (RAB11A or RAB11B).

Isoforms (3)

UniProt ID	Names	Canonical?
O75154-1	1	yes
O75154-2	2
O75154-3	3

RefSeq proteins (3): NP_001135744, NP_001357330, NP_055515* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR019018	Rab-bd_FIP-RBD	Domain
IPR037245	FIP-RBD_C_sf	Homologous_superfamily
IPR051977	Rab11-interacting_regulator	Family
IPR057316	Rab11-FIP3/4_dom	Domain

Pfam: PF09457, PF13499, PF25450

UniProt features (40 total): modified residue 8, binding site 7, compositionally biased region 5, mutagenesis site 5, region of interest 4, domain 3, splice variant 3, helix 3, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2D7C	X-RAY DIFFRACTION	1.75
2HV8	X-RAY DIFFRACTION	1.86
4UJ3	X-RAY DIFFRACTION	3
4UJ4	X-RAY DIFFRACTION	4.2
4D0M	X-RAY DIFFRACTION	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75154-F1	67.32	0.35

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 (7): 215; 217; 219; 226; 247; 249; 258

Post-translational modifications (8): 52, 102, 281, 348, 488, 538, 647, 648

Mutagenesis-validated functional residues (5):

Position	Phenotype
737	abolishes rab11-binding.
738	abolishes rab11-binding. capable of binding to dync1li1. impaired trafficking towards the pericentrosomal endosomal recy
739	abolishes rab11-binding.
746	abolishes rab11-binding.
747	abolishes rab11-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5620916	VxPx cargo-targeting to cilium

MSigDB gene sets: 206 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_MITOTIC_CYTOKINESIS, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, BENPORATH_ES_WITH_H3K27ME3, YAGI_AML_WITH_INV_16_TRANSLOCATION, PEREZ_TP63_TARGETS, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CYTOKINETIC_PROCESS

GO Biological Process (19): vesicle-mediated transport (GO:0016192), endocytic recycling (GO:0032456), regulation of cytokinesis (GO:0032465), Golgi to plasma membrane protein transport (GO:0043001), positive regulation of cilium assembly (GO:0045724), cell division (GO:0051301), regulation of vesicle-mediated transport (GO:0060627), obsolete early endosome to recycling endosome transport (GO:0061502), protein localization to cilium (GO:0061512), negative regulation of adiponectin secretion (GO:0070164), regulation of cilium assembly (GO:1902017), obsolete regulation of early endosome to recycling endosome transport (GO:1902954), positive regulation of mitotic cytokinetic process (GO:1903438), regulation of protein localization to centrosome (GO:1904779), protein localization to cleavage furrow (GO:1905345), regulation of endocytic recycling (GO:2001135), mitotic cytokinesis (GO:0000281), obsolete vesicle docking involved in exocytosis (GO:0006904), microtubule-based movement (GO:0007018)

GO Molecular Function (9): calcium ion binding (GO:0005509), protein-macromolecule adaptor activity (GO:0030674), small GTPase binding (GO:0031267), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), dynein light intermediate chain binding (GO:0051959), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (26): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), endosome (GO:0005768), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), endocytic vesicle (GO:0030139), midbody (GO:0030496), endocytic vesicle membrane (GO:0030666), cleavage furrow (GO:0032154), trans-Golgi network membrane (GO:0032588), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), intercellular bridge (GO:0045171), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), postsynaptic recycling endosome membrane (GO:0098944), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), endosome membrane (GO:0010008), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), bounding membrane of organelle (GO:0098588)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cargo trafficking to the periciliary membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein binding	3
cellular process	2
cilium assembly	2
binding	2
bounding membrane of organelle	2
cytoplasm	2
cytoplasmic vesicle	2
microtubule organizing center	2
transport	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
Golgi to plasma membrane transport	1
protein transport	1
establishment of protein localization to plasma membrane	1
protein localization to plasma membrane	1
positive regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
positive regulation of organelle assembly	1
vesicle-mediated transport	1
regulation of cellular process	1
regulation of transport	1
protein localization to organelle	1
negative regulation of hormone secretion	1
negative regulation of protein secretion	1
negative regulation of multicellular organismal process	1
adiponectin secretion	1
regulation of adiponectin secretion	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
mitotic cytokinetic process	1
regulation of mitotic cytokinetic process	1
positive regulation of mitotic cytokinesis	1
regulation of protein localization	1
protein localization to centrosome	1
protein localization to membrane	1
protein localization to cell division site	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB11FIP3	RAB11A	P24410	997
RAB11FIP3	RAB11FIP2	Q7L804	966
RAB11FIP3	ARF6	P26438	960
RAB11FIP3	RAB11FIP1	Q6WKZ4	939
RAB11FIP3	RAB11FIP5	Q9BXF6	931
RAB11FIP3	ASAP1	Q9ULH1	869
RAB11FIP3	ARF5	P26437	866
RAB11FIP3	RAB25	P57735	857
RAB11FIP3	RAB3IP	Q96QF0	794
RAB11FIP3	EXOC7	Q9UPT5	788
RAB11FIP3	DYNC1LI1	Q9Y6G9	755
RAB11FIP3	HOOK3	Q86VS8	746
RAB11FIP3	BICD2	Q8TD16	731
RAB11FIP3	BICDL1	Q6ZP65	730
RAB11FIP3	RAB4A	P20338	684

IntAct

15 interactions, top by confidence:

A	B	Type	Score
RAB11FIP3	RACGAP1	psi-mi:“MI:0407”(direct interaction)	0.650
RAB11FIP3	RACGAP1	psi-mi:“MI:0915”(physical association)	0.650
RACGAP1	RAB11FIP3	psi-mi:“MI:0407”(direct interaction)	0.650
RACGAP1	RAB11FIP3	psi-mi:“MI:0403”(colocalization)	0.650
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
RAB11A	RAB11FIP3	psi-mi:“MI:0407”(direct interaction)	0.440
TBC1D14	RAB11FIP3	psi-mi:“MI:0915”(physical association)	0.400
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
RAB11FIP4	RAB11FIP3	psi-mi:“MI:0914”(association)	0.350
RAB11FIP3	KIF23	psi-mi:“MI:0914”(association)	0.350
RAB11FIP3	RAB11FIP5	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (38): RAB11FIP3 (Affinity Capture-Western), ASAP1 (Affinity Capture-Western), RAB11FIP3 (Affinity Capture-Western), RAB11FIP3 (Affinity Capture-Western), RAB11FIP3 (Affinity Capture-Western), RAB11FIP3 (Affinity Capture-Western), ASAP1 (Reconstituted Complex), ARF5 (Reconstituted Complex), ARF6 (Reconstituted Complex), RAB11A (Reconstituted Complex), RAB11FIP3 (FRET), RAB11FIP3 (Affinity Capture-MS), RAB11FIP3 (Affinity Capture-RNA), RAB11FIP3 (Affinity Capture-MS), RAB11FIP3 (Two-hybrid)

ESM2 similar proteins: A0JMK8, A0JNH6, A0JNT9, A1A5D9, A6NC98, A6NGB0, A7YWC8, A9QT41, B1MTG4, B3EX63, B7ZNG0, F6XLV1, H7BZ55, O15049, O75154, P0CF95, P58660, Q0V9T6, Q2KJ21, Q2M1P5, Q2TAC2, Q3LUD3, Q3TMW1, Q3UMT1, Q4QRL3, Q5ND29, Q5TZA2, Q60952, Q6NSJ2, Q6NZW0, Q6PGZ0, Q6PHN1, Q6QZQ4, Q6ZP65, Q7TMK6, Q8BP01, Q8C7U1, Q8CB62, Q8CHW5, Q8CJ40

Diamond homologs: A4IIE8, B3DGU2, O75154, Q3LGD4, Q7T005, Q86YS3, Q8BQP8, Q8CHD8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK1	“up-regulates quantity”	RAB11FIP3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	132
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

4105 predictions. Top by Δscore:

Variant	Effect	Δscore
16:429104:C:G	donor_gain	1.0000
16:482520:CCTA:C	acceptor_loss	1.0000
16:482521:CTA:C	acceptor_loss	1.0000
16:482522:TA:T	acceptor_loss	1.0000
16:482523:A:AG	acceptor_gain	1.0000
16:482524:G:GA	acceptor_gain	1.0000
16:482524:GGCC:G	acceptor_gain	1.0000
16:488845:TTGCA:T	acceptor_loss	1.0000
16:488846:TGCA:T	acceptor_loss	1.0000
16:488847:GCAG:G	acceptor_loss	1.0000
16:488848:CAGG:C	acceptor_loss	1.0000
16:488849:A:AG	acceptor_gain	1.0000
16:488849:A:G	acceptor_loss	1.0000
16:488849:AG:A	acceptor_gain	1.0000
16:488850:G:GA	acceptor_gain	1.0000
16:488850:GG:G	acceptor_gain	1.0000
16:488850:GGC:G	acceptor_gain	1.0000
16:488850:GGCC:G	acceptor_gain	1.0000
16:488850:GGCCT:G	acceptor_gain	1.0000
16:488996:CCCAG:C	donor_loss	1.0000
16:488997:CCAG:C	donor_loss	1.0000
16:488999:AGGT:A	donor_loss	1.0000
16:489000:GGT:G	donor_loss	1.0000
16:489001:GTAAT:G	donor_loss	1.0000
16:489002:T:G	donor_loss	1.0000
16:502999:TGTA:T	acceptor_loss	1.0000
16:503000:GTAG:G	acceptor_loss	1.0000
16:503001:TA:T	acceptor_loss	1.0000
16:503002:A:AC	acceptor_loss	1.0000
16:503096:AGG:A	donor_loss	1.0000

AlphaMissense

4952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:520135:T:C	L625P	1.000
16:520147:T:C	L629P	1.000
16:520156:T:C	L632P	1.000
16:520270:T:C	L670P	1.000
16:520472:T:C	L677P	1.000
16:520493:T:C	L684P	1.000
16:520514:T:C	L691P	1.000
16:520727:T:C	L720P	1.000
16:520769:T:C	L734P	1.000
16:520798:G:C	A744P	1.000
16:520802:T:A	I745N	1.000
16:520826:T:A	L753Q	1.000
16:520826:T:C	L753P	1.000
16:426671:T:A	V222D	0.999
16:426698:C:A	A231D	0.999
16:482588:T:C	F323L	0.999
16:482590:C:A	F323L	0.999
16:482590:C:G	F323L	0.999
16:510683:T:C	L508P	0.999
16:520123:T:C	L621P	0.999
16:520138:G:C	R626P	0.999
16:520249:T:C	L663P	0.999
16:520502:A:C	Q687P	0.999
16:520505:T:C	I688T	0.999
16:520505:T:G	I688S	0.999
16:520508:T:A	I689N	0.999
16:520516:A:C	S692R	0.999
16:520518:C:A	S692R	0.999
16:520518:C:G	S692R	0.999
16:520520:T:A	I693N	0.999

dbSNP variants (sampled 300 via entrez): RS1000025470 (16:438530 C>T), RS1000040992 (16:438881 G>A,C), RS1000059005 (16:433297 C>G,T), RS1000088616 (16:515776 G>A,C), RS1000091388 (16:450874 C>A,G,T), RS1000120201 (16:480102 C>T), RS1000141280 (16:443773 C>G), RS1000159926 (16:492732 C>T), RS1000178828 (16:489502 G>T), RS1000231298 (16:489756 C>G), RS1000236970 (16:502341 C>A,G), RS1000267217 (16:446686 A>G), RS1000315659 (16:463004 T>C), RS1000345663 (16:497077 G>A,T), RS1000359219 (16:490631 A>G)

Disease associations

OMIM: gene MIM:608738 | disease phenotypes: MIM:600669, MIM:617027

GenCC curated gene-disease

Mondo (2): idiopathic generalized epilepsy (MONDO:0005579), hyperaldosteronism, familial, type IV (MONDO:0014875)

Orphanet (1): Familial hyperaldosteronism type IV (Orphanet:642671)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004603_238	Platelet count	9.000000e-13
GCST004616_65	Platelet distribution width	5.000000e-10
GCST005174_43	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	8.000000e-06
GCST006979_950	Heel bone mineral density	3.000000e-11
GCST90002390_643	Mean corpuscular hemoglobin	2.000000e-15
GCST90002392_488	Mean corpuscular volume	8.000000e-12
GCST90002395_183	Mean platelet volume	2.000000e-09
GCST90002400_165	Plateletcrit	6.000000e-23
GCST90002401_105	Platelet distribution width	1.000000e-26
GCST90002402_173	Platelet count	2.000000e-32

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0004723	coronary artery calcification
EFO:0009270	heel bone mineral density
EFO:0004527	mean corpuscular hemoglobin
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression, affects methylation	3
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	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
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	decreases expression	1
Demecolcine	increases expression	1
Malathion	increases expression	1
Methyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT06908356	PHASE2	RECRUITING	An Open Label Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adults With Focal Onset or Tonic-Clonic Seizures
NCT06425159	PHASE2/PHASE3	TERMINATED	A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT01311440	Not specified	COMPLETED	Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
NCT01432821	Not specified	COMPLETED	Blinking and Yawning in Epilepsy: The Role of Dopamine
NCT03368469	Not specified	WITHDRAWN	Transcranial Direct Current Stimulation (tDCS) in Children and Adolescents With Epilepsy and Depression
NCT03457961	Not specified	UNKNOWN	Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT04252846	Not specified	COMPLETED	A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy
NCT04965571	Not specified	COMPLETED	Clinical Features and Outcome of Wilson’s Disease With Generalized Epilepsy in Chinese Patients
NCT05374928	Not specified	ACTIVE_NOT_RECRUITING	Human Epilepsy Project 3
NCT05530109	Not specified	TERMINATED	Study of Attentional Disorders in Patients Suffering From Idiopathic Generalized Epilepsy.
NCT06388174	Not specified	RECRUITING	Idiopathic Generalized Epilepsy Syndromes
NCT06797791	Not specified	COMPLETED	Assessment of Multifocal Continuous Theta Burst Transcranial Magnetic Stimulation (cTBS) Effects in Generalized Epilepsy Patients.