RAB11FIP1

Summary

RAB11FIP1 (RAB11 family interacting protein 1, HGNC:30265) is a protein-coding gene on chromosome 8p11.23, encoding Rab11 family-interacting protein 1 (Q6WKZ4). A Rab11 effector protein involved in the endosomal recycling process.

This gene encodes one of the Rab11-family interacting proteins (Rab11-FIPs), which play a role in the Rab-11 mediated recycling of vesicles. The encoded protein may be involved in endocytic sorting, trafficking of proteins including integrin subunits and epidermal growth factor receptor (EGFR), and transport between the recycling endosome and the trans-Golgi network. Alternative splicing results in multiple transcript variants. A pseudogene is described on the X chromosome.

Source: NCBI Gene 80223 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 214 total
• MANE Select transcript: NM_001002814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30265
Approved symbol	RAB11FIP1
Name	RAB11 family interacting protein 1
Location	8p11.23
Locus type	gene with protein product
Status	Approved
Aliases	RCP, FLJ22622, FLJ22524, Rab11-FIP1
Ensembl gene	ENSG00000156675
Ensembl biotype	protein_coding
OMIM	608737
Entrez	80223

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000287263, ENST00000330843, ENST00000522727, ENST00000522774, ENST00000523182, ENST00000524118, ENST00000882279, ENST00000966921, ENST00000966922

RefSeq mRNA: 2 — MANE Select: NM_001002814 NM_001002814, NM_025151

CCDS: CCDS34881, CCDS34882

Canonical transcript exons

ENST00000330843 — 6 exons

Exon	Start	End
ENSE00001236275	37874515	37875322
ENSE00001312334	37871278	37873179
ENSE00002104955	37899071	37899497
ENSE00002112214	37858618	37863113
ENSE00003499699	37870420	37870528
ENSE00003636778	37877109	37877551

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6572 / max 1145.3604, expressed in 1510 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92718	23.6572	1510

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	99.28	gold quality
lower lobe of lung	UBERON:0008949	97.91	gold quality
epithelium of esophagus	UBERON:0001976	97.87	gold quality
amniotic fluid	UBERON:0000173	96.94	gold quality
bronchial epithelial cell	CL:0002328	96.73	gold quality
oral cavity	UBERON:0000167	96.50	gold quality
islet of Langerhans	UBERON:0000006	96.49	gold quality
squamous epithelium	UBERON:0006914	96.29	gold quality
jejunal mucosa	UBERON:0000399	95.89	gold quality
ileal mucosa	UBERON:0000331	95.79	gold quality
colonic mucosa	UBERON:0000317	95.74	gold quality
tongue squamous epithelium	UBERON:0006919	95.60	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.55	gold quality
nasal cavity epithelium	UBERON:0005384	95.30	gold quality
epithelium of nasopharynx	UBERON:0001951	95.28	gold quality
pharyngeal mucosa	UBERON:0000355	95.13	gold quality
epithelium of bronchus	UBERON:0002031	95.07	gold quality
bronchus	UBERON:0002185	94.97	gold quality
rectum	UBERON:0001052	94.07	gold quality
cervix squamous epithelium	UBERON:0006922	93.97	gold quality
upper leg skin	UBERON:0004262	93.96	gold quality
duodenum	UBERON:0002114	93.92	gold quality
blood	UBERON:0000178	93.20	gold quality
palpebral conjunctiva	UBERON:0001812	93.04	gold quality
decidua	UBERON:0002450	93.03	gold quality
bone marrow	UBERON:0002371	92.91	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.40	gold quality
monocyte	CL:0000576	92.27	gold quality
trachea	UBERON:0003126	92.26	gold quality
lung	UBERON:0002048	92.24	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	54.32
E-HCAD-6	yes	44.85
E-MTAB-10287	yes	40.98
E-MTAB-9467	yes	22.37
E-CURD-122	yes	12.84
E-GEOD-135922	yes	10.40
E-GEOD-130148	yes	9.56
E-CURD-46	yes	9.46
E-MTAB-6678	yes	7.72
E-CURD-89	no	335.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

223 targeting RAB11FIP1, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230

Literature-anchored findings (GeneRIF, showing 36)

• Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein (PMID:11786538)
• Receptor cell surface expression and endocytosis experiments reveal that the small GTPase Rab11 protein is a determinant factor in controlling thromboxane A2 receptor beta isoform recycling back to the cell surface. (PMID:15134434)
• RCP functions primarily as a Rab11 binding protein that regulates protein sorting in tubular endosomes. (PMID:15181150)
• Rab11, rather than Rab4, mediates the intracellular localisation of RCP. (PMID:15280022)
• Acting as an intermediate between Rab4 and Rab11, RCP regulates membrane flux along the phagocytic pathway via recycling events. (PMID:15355514)
• once the Rab11/RCP-regulated cargo has been delivered from the endocytic recycling compartment to the plasma membrane, RCP is inactivated by calpain-mediated proteolysis (PMID:15769254)
• Rab11 and microtubules maintain the proper distribution of the subapical AQP2 storage compartment, and actin filaments regulate the trafficking of AQP2 from early endosomes to the storage compartment. (PMID:16049696)
• Results describe the endometrial expression of Rab coupling protein and its hormonal regulation. (PMID:16216915)
• identified eight alternatively spliced Rab11-FIP1 gene transcripts from human chromosome 8 (PMID:16920206)
• RCP provides a scaffold that promotes the physical association and coordinate trafficking of alpha5beta1 and EGFR1 and that this drives migration of tumor cells into three-dimensional matrices. (PMID:18838556)
• RCP is a human breast cancer-promoting gene with Ras-activating function. (PMID:19620787)
• FIP1/RCP binding to Golgin-97 is required for tethering and fusion of recycling endosome-derived retrograde transport vesicles to the trans-Golgi network. (PMID:20610657)
• An interaction with Rab11 is necessary for long-range targeting of beta1 integrins to the growth cone along axons and in neurons. (PMID:20810886)
• results suggest that Rab5 is involved in CB2 endocytosis and that internalized receptors are recycled via a Rab11 associated pathway rather than the rapid Rab4 associated pathway. (PMID:21640764)
• Rab11 is differentially phosphorylated by distinct PKC isoenzymes; this post-translational modification might be a regulatory mechanism of intracellular trafficking. (PMID:22188018)
• These findings suggest that Rab11-FIP1 proteins participate in spatially and temporally distinct steps of the recycling process along a complex and dynamic tubular network in which Rab11-FIPs occupy discrete domains (PMID:23283983)
• findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14 (PMID:23592992)
• rab11 effector protein FIP1 regulates adiponectin trafficking and secretion (PMID:24040321)
• Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the Drp1, which was regulated by the Rab11a effector protein FIP1/RCP. (PMID:24302731)
• We find that Rab14 indeed binds to RCP, albeit with reduced affinity relative to conventional Rab11-FIP and Rab25-FIP complexes. However, in vivo, Rab11 recruits RCP onto biological membranes. (PMID:26032412)
• GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. (PMID:26152716)
• REI/SH3BP5 protein family is conserved in evolution and is a group of new guanine nucleotide exchange factors for Rab11. (PMID:26745340)
• Rab11-FIP1A associates with and regulates trafficking at an early step in the process of membrane recycling (PMID:26790954)
• our findings indicate that FIP1C acts as a tumor suppressor in the context of ErbB2-positive breast cancer (PMID:26933086)
• Findings suggest that overexpression of micro ribonucleic acid-93 (miR-93) via targeting RAB11 family interacting protein (RAB11FIP1) as an early event plays an important role in oncogenesis of cervical cancer. MiR-93 and its target protein RAB11FIP1 may be potential therapeutic targets for cervical cancer and its precursors. (PMID:27279231)
• High RCP expression is associated with lung metastasis in ovarian cancer. (PMID:27524413)
• The article focuses on the latest advances regarding the mechanisms that ensure the compartmentalized regulation of Rab11 function through its interaction with phosphoinositides. (Review) (PMID:27658318)
• Phosphorylation of RCP at Ser(435) by Lemur tyrosine kinase-3 (LMTK3) and of EphA2 at Ser(897) by Akt are both necessary to promote Rab14-dependent (and Rab11-independent) trafficking of EphA2 which generates cell:cell repulsion events that drive tumour cells apart. (PMID:28294115)
• The findings thus define that delivery of recycling cargo toward the ERC requires spatial and sequential coupling of Rab11 activity with PtdIns(3)P turnover. (PMID:29915378)
• Mutant p53 Drives Cancer Metastasis via RCP-Mediated Hsp90alpha Secretion. (PMID:32640214)
• Zeb1 for RCP-induced oral cancer cell invasion and its suppression by resveratrol. (PMID:32728068)
• Thrombin-activated PAR1 membrane expression is regulated by Rab11a-RCP complex dissociation. (PMID:32860953)
• Rab11FIP1 maintains Rab35 at the intercellular bridge to promote actin removal and abscission. (PMID:34152390)
• Rab11-FIP1 and Rab11-FIP5 Regulate pIgR/pIgA Transcytosis through TRIM21-Mediated Polyubiquitination. (PMID:34638806)
• Rab11-FIP1C Is Dispensable for HIV-1 Replication in Primary CD4[+] T Cells, but Its Role Is Cell Type Dependent in Immortalized Human T-Cell Lines. (PMID:36354340)
• microRNA-205 represses breast cancer metastasis by perturbing the rab coupling protein [RCP]-mediated integrin beta1 recycling on the membrane. (PMID:37945815)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rab11fip1a	ENSDARG00000046124
mus_musculus	Rab11fip1	ENSMUSG00000031488
rattus_norvegicus	Rab11fip1	ENSRNOG00000058940
drosophila_melanogaster	Rip11	FBGN0027335
caenorhabditis_elegans		WBGENE00021456

Paralogs (2): RAB11FIP2 (ENSG00000107560), RAB11FIP5 (ENSG00000135631)

Protein

Protein identifiers

Rab11 family-interacting protein 1 — Q6WKZ4 (reviewed: Q6WKZ4)

Alternative names: Rab-coupling protein

All UniProt accessions (2): Q6WKZ4, E7EX40

UniProt curated annotations — full annotation on UniProt →

Function. A Rab11 effector protein involved in the endosomal recycling process. Also involved in controlling membrane trafficking along the phagocytic pathway and in phagocytosis. Interaction with RAB14 may function in the process of neurite formation.

Subunit / interactions. Interacts with RAB11A (GTP-bound form); the interaction induces RAB11FIP1 recruitment to membranes. Interacts with RAB14 (GTP-bound form). Homooligomer. Isoform 2 interacts with RAB4A, RAB11A, RAB11B and RAB25. According to PubMed:15280022, RAB4A binding to RAB11FIP1 is of very low affinity in vitro and in vivo.

Subcellular location. Recycling endosome. Cytoplasmic vesicle Cytoplasmic vesicle. Phagosome membrane.

Tissue specificity. Isoform 2 is expressed in brain, heart, testis, lung, spleen, ovary and small intestine.

Domain organisation. The FIP-RBD is involved in the interaction with Rab proteins.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6WKZ4-4	1, Rab11-FIP 1B	yes
Q6WKZ4-3	2, Rab11-FIP 1C
Q6WKZ4-1	3, Rab11-FIP 1A
Q6WKZ4-2	4, Rab11-FIP 1H, No Rab11-binding protein 2
Q6WKZ4-5	5

RefSeq proteins (2): NP_001002814, NP_079427 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR019018	Rab-bd_FIP-RBD	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037245	FIP-RBD_C_sf	Homologous_superfamily
IPR037789	FIP_classI	Family

Pfam: PF00168, PF09457

UniProt features (67 total): modified residue 19, compositionally biased region 13, sequence conflict 9, region of interest 7, splice variant 7, sequence variant 4, mutagenesis site 3, domain 2, helix 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4D0G	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6WKZ4-F1	47.19	0.10

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 (19): 184, 202, 206, 234, 300, 315, 339, 341, 343, 345, 356, 357, 382, 435, 477, 529, 545, 758, 1135

Mutagenesis-validated functional residues (3):

Position	Phenotype
1254	does not abolish the interaction with rab11a, homooligomerization and subcellular location. reduces the interaction with
1255	abolishes the interaction with rab11a, rab4a and rab14, homooligomerization and subcellular location.
1256	does not abolish the interaction with rab11a, homooligomerization and subcellular location. reduces the interaction with

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 278 (showing top): GGGACCA_MIR133A_MIR133B, PEREZ_TP63_TARGETS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING, PATIL_LIVER_CANCER, GTGCCTT_MIR506, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_EXOCYTOSIS, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (3): protein transport (GO:0015031), regulated exocytosis (GO:0045055), negative regulation of adiponectin secretion (GO:0070164)

GO Molecular Function (2): small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (7): cytosol (GO:0005829), phagocytic vesicle membrane (GO:0030670), recycling endosome (GO:0055037), cytoplasm (GO:0005737), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
transport	1
intracellular protein localization	1
establishment of protein localization	1
exocytosis	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
GTPase binding	1
binding	1
endocytic vesicle membrane	1
phagocytic vesicle	1
endosome	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1823 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAB11FIP1	RAB11A	P24410	987
RAB11FIP1	RAB25	P57735	974
RAB11FIP1	RAB4A	P20338	952
RAB11FIP1	RAB11FIP3	O75154	939
RAB11FIP1	RAB11FIP4	Q86YS3	932
RAB11FIP1	MYO5B	Q9ULV0	848
RAB11FIP1	ARF5	P26437	735
RAB11FIP1	RAB1A	P11476	633
RAB11FIP1	PLPBP	O94903	613
RAB11FIP1	ARF6	P26438	609
RAB11FIP1	EXOC7	Q9UPT5	584
RAB11FIP1	RAB14	P35287	565
RAB11FIP1	LETM2	Q2VYF4	543
RAB11FIP1	DDHD2	O94830	532
RAB11FIP1	ERLIN2	O94905	518

IntAct

94 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
RAB11A	EVI5	psi-mi:“MI:0914”(association)	0.800
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
RAB11FIP1	YWHAH	psi-mi:“MI:0914”(association)	0.740
KLC1	KIF5B	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CTBP2	ZNF217	psi-mi:“MI:0914”(association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
RAB11B	SH3BP5	psi-mi:“MI:0914”(association)	0.640
MMAB	DBT	psi-mi:“MI:0914”(association)	0.620
RAB11A	CHML	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
BAIAP2	WASL	psi-mi:“MI:0914”(association)	0.550
RAB11A	SH3BP5	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
RAB11FIP1	PASK	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RAB11A	LANCL1	psi-mi:“MI:2364”(proximity)	0.420
SEC24B	RAB11FIP1	psi-mi:“MI:0915”(physical association)	0.400
Rab11a	EVI5	psi-mi:“MI:0914”(association)	0.350

BioGRID (195): RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), ASAP1 (Affinity Capture-Western), RAB11FIP1 (Proximity Label-MS), RAB11FIP1 (Proximity Label-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS), RAB11FIP1 (Affinity Capture-MS)

ESM2 similar proteins: A2A995, A2ALU4, A4IGN8, A6NMK8, D3ZUI5, E1C2Q8, F1QGH6, O54931, O75128, O75363, O75410, O95425, P24275, P24588, P51827, Q1LWM5, Q1RMS0, Q1W617, Q3UHI0, Q3UMF0, Q3ZB98, Q499V8, Q53SF7, Q5JR59, Q5NBX1, Q5VWT5, Q5ZJ26, Q62394, Q66KC9, Q673G8, Q69ZL1, Q6GQV1, Q6INC4, Q6QZN6, Q6WKZ4, Q6Y685, Q7TP36, Q7TS75, Q80YN3, Q8BI29

Diamond homologs: C9J798, G3XA57, O43374, O95294, P41823, Q3B7T9, Q6DN14, Q6PFQ7, Q6WKZ4, Q7L804, Q8R361, Q9BXF6, Q9D620, Q9SKA3, Q9ZVT9, Q4KUS2, Q62768, Q62769, Q62770, Q8K0T7, Q8NB66, Q9UPW8, Q9Z1N9, O35681, P41885

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MARK2	“up-regulates quantity”	RAB11FIP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
Activation of BAD and translocation to mitochondria	7	78.4×	3e-10
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	69.2×	5e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	69.2×	5e-10
Activation of BH3-only proteins	7	51.1×	4e-09
RHO GTPases activate PKNs	7	32.7×	1e-07
Intrinsic Pathway for Apoptosis	7	30.1×	2e-07
FOXO-mediated transcription	5	24.7×	4e-05
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	18.2×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	22.1×	1e-03
intracellular protein localization	9	11.3×	8e-05
protein autophosphorylation	6	10.5×	5e-03
positive regulation of ERK1 and ERK2 cascade	7	7.2×	7e-03
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	6.6×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	178
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1302 predictions. Top by Δscore:

Variant	Effect	Δscore
8:37862956:T:TA	donor_gain	1.0000
8:37870415:CATA:C	donor_loss	1.0000
8:37870416:ATAC:A	donor_loss	1.0000
8:37870418:A:C	donor_loss	1.0000
8:37870419:C:G	donor_loss	1.0000
8:37870529:C:CC	acceptor_gain	1.0000
8:37875318:CATGA:C	acceptor_gain	1.0000
8:37875319:ATGA:A	acceptor_gain	1.0000
8:37875320:TGA:T	acceptor_gain	1.0000
8:37875323:C:CC	acceptor_gain	1.0000
8:37875324:T:C	acceptor_gain	1.0000
8:37875325:T:C	acceptor_gain	1.0000
8:37875325:T:TC	acceptor_gain	1.0000
8:37877104:CTCA:C	donor_loss	1.0000
8:37877105:TCA:T	donor_loss	1.0000
8:37877106:CACC:C	donor_loss	1.0000
8:37877107:A:AC	donor_gain	1.0000
8:37877107:A:T	donor_loss	1.0000
8:37877107:AC:A	donor_gain	1.0000
8:37877107:ACCAT:A	donor_gain	1.0000
8:37877108:C:CA	donor_gain	1.0000
8:37877108:CC:C	donor_gain	1.0000
8:37877108:CCAT:C	donor_gain	1.0000
8:37877108:CCATC:C	donor_gain	1.0000
8:37899066:CTCA:C	donor_gain	1.0000
8:37899069:A:AC	donor_gain	1.0000
8:37899069:ACTG:A	donor_gain	1.0000
8:37899070:C:CG	donor_gain	1.0000
8:37899070:CTG:C	donor_gain	1.0000
8:37899070:CTGC:C	donor_gain	1.0000

AlphaMissense

8351 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:37862974:A:G	L1258P	1.000
8:37899244:C:A	W66C	1.000
8:37899244:C:G	W66C	1.000
8:37899246:A:G	W66R	1.000
8:37899246:A:T	W66R	1.000
8:37862971:A:G	L1259P	0.999
8:37862995:A:G	L1251P	0.999
8:37863058:A:G	L1230P	0.999
8:37877480:A:G	F148S	0.999
8:37877492:A:T	V144D	0.999
8:37877498:A:T	I142N	0.999
8:37877505:C:G	G140R	0.999
8:37877505:C:T	G140R	0.999
8:37877540:A:G	L128S	0.999
8:37899128:C:T	G105D	0.999
8:37899129:C:G	G105R	0.999
8:37899133:G:C	F103L	0.999
8:37899133:G:T	F103L	0.999
8:37899134:A:G	F103S	0.999
8:37899135:A:G	F103L	0.999
8:37899140:T:A	D101V	0.999
8:37899173:A:G	L90P	0.999
8:37899227:A:G	F72S	0.999
8:37899245:C:G	W66S	0.999
8:37899318:A:C	Y42D	0.999
8:37862962:A:T	V1262D	0.998
8:37863049:A:G	L1233P	0.998
8:37877504:C:A	G140V	0.998
8:37877504:C:T	G140E	0.998
8:37877540:A:C	L128W	0.998

dbSNP variants (sampled 300 via entrez): RS1000112202 (8:37878097 G>A,C), RS1000196590 (8:37898883 G>A,C,T), RS1000295767 (8:37877904 G>A,C), RS1000472151 (8:37861422 A>G), RS1000572142 (8:37861156 G>A), RS1000646840 (8:37896585 T>C), RS1000651405 (8:37899658 G>A,T), RS1000761431 (8:37899563 A>C,G,T), RS1000872124 (8:37890706 C>T), RS1000892933 (8:37866110 C>A,G,T), RS1000932782 (8:37872512 C>T), RS1000998571 (8:37859673 G>A,C), RS1001198966 (8:37900637 C>T), RS1001347322 (8:37888693 G>C), RS1001454580 (8:37868859 C>T)

Disease associations

OMIM: gene MIM:608737 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002115_11	Axial length	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Valproic Acid	increases expression, affects expression	4
Estradiol	decreases expression, increases expression	3
Smoke	decreases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
methylmercuric chloride	increases expression	2
bisphenol A	increases reaction, decreases expression, affects binding	2
trichostatin A	affects expression, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Doxorubicin	decreases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
ethylbenzene	increases methylation, affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

Clinical trials (associated diseases)

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