RASGRF1

Summary

RASGRF1 (Ras protein specific guanine nucleotide releasing factor 1, HGNC:9875) is a protein-coding gene on chromosome 15q25.1, encoding Ras-specific guanine nucleotide-releasing factor 1 (Q13972). Promotes the exchange of Ras-bound GDP by GTP.

The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) similar to the Saccharomyces cerevisiae CDC25 gene product. Functional analysis has demonstrated that this protein stimulates the dissociation of GDP from RAS protein. The studies of the similar gene in mouse suggested that the Ras-GEF activity of this protein in brain can be activated by Ca2+ influx, muscarinic receptors, and G protein beta-gamma subunit. Mouse studies also indicated that the Ras-GEF signaling pathway mediated by this protein may be important for long-term memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 5923 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 134 total
• Druggable target: yes
• MANE Select transcript: NM_001145648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9875
Approved symbol	RASGRF1
Name	Ras protein specific guanine nucleotide releasing factor 1
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	CDC25L, CDC25, GRF55, H-GRF55, GNRP, PP13187
Ensembl gene	ENSG00000058335
Ensembl biotype	protein_coding
OMIM	606600
Entrez	5923

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 TEC

ENST00000394745, ENST00000419573, ENST00000558480, ENST00000559926, ENST00000560286, ENST00000560334, ENST00000560943, ENST00000561112, ENST00000623620

RefSeq mRNA: 3 — MANE Select: NM_001145648 NM_001145648, NM_002891, NM_153815

CCDS: CCDS10309, CCDS42065, CCDS45320

Canonical transcript exons

ENST00000558480 — 27 exons

Exon	Start	End
ENSE00000942887	78971866	78971934
ENSE00001519423	79006186	79006434
ENSE00001665313	79064420	79064526
ENSE00002545241	79090223	79090780
ENSE00003460027	78985007	78985204
ENSE00003466435	78999743	78999913
ENSE00003492158	79035131	79035210
ENSE00003516548	79032123	79032316
ENSE00003539510	79003802	79004175
ENSE00003543038	78998096	78998208
ENSE00003555274	78995740	78995800
ENSE00003574051	78991691	78991794
ENSE00003576860	79058334	79058481
ENSE00003576908	79046746	79046999
ENSE00003585651	79015327	79015409
ENSE00003591163	78990189	78990273
ENSE00003595966	79027741	79027859
ENSE00003604505	79020041	79020104
ENSE00003604835	78973303	78973420
ENSE00003605898	79001662	79001787
ENSE00003618150	79025314	79025474
ENSE00003624090	79049496	79049588
ENSE00003638348	79017770	79017906
ENSE00003669499	78998719	78998825
ENSE00003672253	78980620	78980699
ENSE00003678504	79031400	79031509
ENSE00003900469	78959906	78962236

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 95.88.

FANTOM5 (CAGE): breadth broad, TPM avg 4.3131 / max 276.0691, expressed in 218 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151169	1.6558	127
151171	0.7115	105
151167	0.6075	94
151164	0.2820	61
207606	0.1713	77
151175	0.1600	73
151168	0.1232	60
151173	0.1095	62
151145	0.0961	25
151172	0.0930	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	95.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.53	gold quality
cerebellar hemisphere	UBERON:0002245	94.42	gold quality
cerebellar cortex	UBERON:0002129	94.28	gold quality
prefrontal cortex	UBERON:0000451	93.11	gold quality
cerebellum	UBERON:0002037	92.20	gold quality
spinal cord	UBERON:0002240	91.83	gold quality
right frontal lobe	UBERON:0002810	90.94	gold quality
frontal cortex	UBERON:0001870	88.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.99	gold quality
neocortex	UBERON:0001950	86.82	gold quality
cingulate cortex	UBERON:0003027	86.63	gold quality
anterior cingulate cortex	UBERON:0009835	86.49	gold quality
postcentral gyrus	UBERON:0002581	85.97	gold quality
islet of Langerhans	UBERON:0000006	85.74	gold quality
cerebral cortex	UBERON:0000956	84.78	gold quality
superior frontal gyrus	UBERON:0002661	82.92	gold quality
Ammon’s horn	UBERON:0001954	82.20	gold quality
hypothalamus	UBERON:0001898	81.39	gold quality
parietal lobe	UBERON:0001872	81.05	gold quality
Brodmann (1909) area 46	UBERON:0006483	80.61	gold quality
telencephalon	UBERON:0001893	80.45	gold quality
central nervous system	UBERON:0001017	79.84	gold quality
substantia nigra	UBERON:0002038	79.68	gold quality
corpus callosum	UBERON:0002336	79.50	gold quality
brain	UBERON:0000955	79.46	gold quality
cortical plate	UBERON:0005343	78.98	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.81	gold quality
primary visual cortex	UBERON:0002436	78.45	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CTNNB1, JUN

miRNA regulators (miRDB)

88 targeting RASGRF1, 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-3120-5P	100.00	65.56	965
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-5571-5P	99.49	66.99	1764

Literature-anchored findings (GeneRIF, showing 25)

• RasGRF family exchange factors, both endogenous and ectopically expressed, are present in the endoplasmic reticulum but not in the Golgi complex (PMID:14749369)
• Taken together our results demonstrate that U2AF35a is essential for HeLa cell division and suggest a novel role for both U2AF35 protein isoforms as regulators of alternative splicing of a specific subset of genes. (PMID:16855028)
• Vitamin K3 inhibitor H32 differentially inhibited growth of normal and liver tumor cells by preferentially inhibiting the actions of Cdc25 phosphatases (PMID:16969075)
• Rasgrf1 transgenic repeats serve at least two functions: first, to establish Rasgrf1 DNA methylation in the male germ line, and second, to resist global demethylation in the preimplantation embryo. (PMID:17030618)
• zoledronate induces DNA damage and S phase arrest, accompanied by activation of the ATM/Chk1/cdc25 pathway in a human osteosarcoma cell line (PMID:17611684)
• Enhanced expression and post-translational modification of RasGRF1 contributes to MMP-3 production in RA (PMID:19678938)
• Farnesylated or geranylgeranylated TC21 can be activated by RasGRF1 due to its pleckstrin homology 1 domain, by a mechanism independent of localization & of its ability to associate to membranes. (PMID:19692568)
• Single Nucleotide Polymorphisms in RASGRF1 is associated with refractive errors and myopia. (PMID:20835236)
• Demonstrate a role for RasGRF1/2 as negative regulators of Cdc42 activation, suppressing tumor cell movement, cytoskeletal dynamics and cell transformation. (PMID:21685891)
• RasGRF1 plays an important role in alveolar rhabdomyosarcoma pathogenesis (PMID:22752028)
• Aberrant methylation of RASGRF1 is associated with an epigenetic field defect and increased risk of gastric cancer. (PMID:22961779)
• Decreased expression of Ras-GRF1 could be involved in the pathogenesis of human temporal lobe epilepsy. (PMID:23200899)
• In this study, there was no association of the analyzed SNPs located in RASGRF1. GJD2, and ACTC1 with pathological myopia. (PMID:23834555)
• ZIC2 and RASGRF1 are susceptibility genes, not only for common myopia, but also for high myopia. (PMID:24150758)
• Rasgrf-1 is a novel GEF protein that has a role in BCR signaling and its overexpression further activates the Ras/Erk/MAPK pathway in CLL specimens. (PMID:24597981)
• CARD9 regulates H-Ras activation by linking Ras-GRF1 to H-Ras, which mediates Dectin-1-induced extracellular signal-regulated protein kinase (ERK) activation and proinflammatory responses when stimulated by their ligands. (PMID:25267792)
• Data show that microRNA miR-137 directly recognized the 3’-UTR (3’-untranslated region) of the RASGRF1 (Ras protein-specific guanine nucleotide-releasing factor 1) transcript and regulated RASGRF1 expression. (PMID:26440052)
• Impaired RASGRF1/ERK-mediated GM-CSF response characterizes CARD9 deficiency in French-Canadians. (PMID:26521038)
• Carriers of the rs8027411 G allele in the RASGRF1 gene may be at a lower risk of high myopia in Chinese and Japanese populations. (Meta-analysis) (PMID:26644762)
• Endoplasmic reticulum stress triggers a localized signaling module on the ER surface involving Nox4-dependent calcium mobilization, which directs local Ras activation through ER-associated, calcium-responsive RasGRF. (PMID:27856453)
• genetic variants in BICC1 and RASGRF1 are closely associated with high myopia, which appears to be a potential candidate for high myopia in Chinese Han population. (PMID:29044055)
• Low RASGRF1 expression due to hypermethylation is associated with Colorectal Cancer. (PMID:29530990)
• Our studies have shown that the heritability of myopia makes 66.4% in Lithuania. We detected significant associations between the combinations of GJD2 CC and RASGRF1 GT and odds ratio of developing myopia. (PMID:29793445)
• Benzothiazole amphiphiles promote RasGRF1-associated dendritic spine formation in human stem cell-derived neurons. (PMID:31943943)
• RASGRF1-rearranged Cutaneous Melanocytic Neoplasms With Spitzoid Cytomorphology: A Clinicopathologic and Genetic Study of 3 Cases. (PMID:34799483)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rasgrf1	ENSDARG00000073824
mus_musculus	Rasgrf1	ENSMUSG00000032356
rattus_norvegicus	Rasgrf1	ENSRNOG00000014025

Paralogs (24): RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGEF1C (ENSG00000146090), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ras-specific guanine nucleotide-releasing factor 1 — Q13972 (reviewed: Q13972)

Alternative names: Guanine nucleotide-releasing protein, Ras-specific nucleotide exchange factor CDC25

All UniProt accessions (1): Q13972

UniProt curated annotations — full annotation on UniProt →

Function. Promotes the exchange of Ras-bound GDP by GTP.

Subunit / interactions. Homooligomer and heterooligomer with RASGRF2. Interacts with USP8, thereby regulating its stability.

Post-translational modifications. Phosphorylated by PLK2, leading to ubiquitination and degradation by the proteasome. Ubiquitinated and degraded following phosphorylation by PLK2. Phosphorylated by SRC and LCK. Phosphorylation by LCK increases its capacity to stimulate the GDP/GTP exchange on Ras, whereas its phosphorylation by SRC does not seem to have an effect on stimulation activity.

Domain organisation. The DH (DBL-homology) domain mediates interaction with RASGRF2.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13972-1	1	yes
Q13972-2	2
Q13972-3	3

RefSeq proteins (3): NP_001139120, NP_002882, NP_722522 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily

Pfam: PF00169, PF00617, PF00618, PF00621

UniProt features (22 total): domain 6, modified residue 5, splice variant 3, sequence conflict 3, compositionally biased region 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13972-F1	72.89	0.30

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 (5): 577, 626, 758, 779, 800

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-442982	Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 194 (showing top): GOBP_MEMORY, MODY_HIPPOCAMPUS_POSTNATAL, BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_NEURONAL_SYNAPTIC_PLASTICITY, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEUROGENESIS, MEF2_02, STOSSI_RESPONSE_TO_ESTRADIOL, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (15): signal transduction (GO:0007165), Ras protein signal transduction (GO:0007265), long-term memory (GO:0007616), neuron projection development (GO:0031175), response to endoplasmic reticulum stress (GO:0034976), positive regulation of Rac protein signal transduction (GO:0035022), negative regulation of MAPK cascade (GO:0043409), positive regulation of MAPK cascade (GO:0043410), type B pancreatic cell proliferation (GO:0044342), regulation of Ras protein signal transduction (GO:0046578), positive regulation of Ras protein signal transduction (GO:0046579), regulation of synaptic plasticity (GO:0048167), regulation of neuronal synaptic plasticity (GO:0048168), small GTPase-mediated signal transduction (GO:0007264), intracellular signal transduction (GO:0035556)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), glutamate receptor binding (GO:0035254)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), growth cone (GO:0030426), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of small GTPase mediated signal transduction	2
MAPK cascade	2
regulation of MAPK cascade	2
Ras protein signal transduction	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
small GTPase-mediated signal transduction	1
memory	1
neuron development	1
plasma membrane bounded cell projection organization	1
cellular response to stress	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
negative regulation of intracellular signal transduction	1
positive regulation of intracellular signal transduction	1
epithelial cell proliferation	1
regulation of small GTPase mediated signal transduction	1
regulation of Ras protein signal transduction	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
regulation of synaptic plasticity	1
intracellular signaling cassette	1
intracellular anatomical structure	1
signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
signaling receptor binding	1
cytoplasm	1
cellular anatomical structure	1
membrane	1
cell periphery	1
site of polarized growth	1
distal axon	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASGRF1	HRAS	P01112	937
RASGRF1	GRIN2B	Q13224	935
RASGRF1	MCF2	P10911	649
RASGRF1	RABIF	P47224	644
RASGRF1	SNRPN	P14648	613
RASGRF1	NTRK1	P04629	609
RASGRF1	IGF2R	P11717	600
RASGRF1	DLK1	P15803	591
RASGRF1	CARD9	Q9H257	583
RASGRF1	CALM1	P02593	582
RASGRF1	CALML3	P27482	582
RASGRF1	CALML5	Q9NZT1	582
RASGRF1	CALML6	Q8TD86	571
RASGRF1	CALML4	Q96GE6	571
RASGRF1	ZDBF2	Q9HCK1	571

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RASGRF1	PALM	psi-mi:“MI:0915”(physical association)	0.400
PLK1	RASGRF1	psi-mi:“MI:0915”(physical association)	0.400
TP53	RASGRF1	psi-mi:“MI:0915”(physical association)	0.400
RASGRF1	GRK2	psi-mi:“MI:0915”(physical association)	0.370
CEBPA	RASGRF1	psi-mi:“MI:0915”(physical association)	0.370
RASGRF1	SNRNP70	psi-mi:“MI:0915”(physical association)	0.370
RASGRF1	EHD4	psi-mi:“MI:0915”(physical association)	0.370
	RASGRF1	psi-mi:“MI:0915”(physical association)	0.000
RASGRF1	MDM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): RASGRF1 (Biochemical Activity), RASGRF1 (Biochemical Activity), RASGRF1 (Reconstituted Complex), YWHAB (Reconstituted Complex), RASGRF1 (Two-hybrid), MARK3 (Affinity Capture-Western), RASGRF1 (Affinity Capture-Western), RASGRF1 (Proximity Label-MS), RASGRF1 (Two-hybrid), RASGRF1 (Affinity Capture-Western), RASGRF1 (Reconstituted Complex), GRIN2B (Reconstituted Complex), RASGRF1 (Affinity Capture-MS), RASGRF1 (Cross-Linking-MS (XL-MS)), RASGRF1 (Two-hybrid)

ESM2 similar proteins: A1Z7A6, A2CEA7, A8JQ65, B3M301, B3P8A3, B4I4Y1, B4NBP4, B4QSF0, B4R0A5, G5EBZ8, G5EEW9, G5EFD2, G5EFI8, O14827, O43150, O97902, P27671, P28818, P34400, P49809, P70392, Q13972, Q19857, Q1AAU6, Q21653, Q5W7F2, Q6NRL1, Q7SIG6, Q8BXK8, Q8MLZ5, Q8VHH5, Q94071, Q95RG8, Q96P47, Q99JE4, Q9C6C3, Q9FIT8, Q9P246, Q9QWY8, Q9SMX5

Diamond homologs: A2AR50, A2CEA7, B0M0P8, B0UXH6, F1M386, F1MSG6, F1PBJ0, O14827, P27671, P28818, P70392, Q03385, Q03386, Q07889, Q07890, Q12967, Q13905, Q13972, Q3MIN7, Q3UYI5, Q4R7W3, Q54FF3, Q54PQ4, Q54TK8, Q552M5, Q55GH9, Q5JS13, Q5ZJK0, Q60695, Q86G47, Q86X27, Q8CHG7, Q8IS14, Q8IS15, Q8IS16, Q8IS18, Q8IS20, Q8IS21, Q8SSQ0, Q8SSW7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CHEK2	down-regulates	RASGRF1	phosphorylation
SRC	“down-regulates activity”	RASGRF1	phosphorylation
PRKACA	up-regulates	RASGRF1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	101
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

4186 predictions. Top by Δscore:

Variant	Effect	Δscore
15:78971860:GCTTA:G	donor_loss	1.0000
15:78971861:CTTA:C	donor_loss	1.0000
15:78971862:TTAC:T	donor_loss	1.0000
15:78971863:TACCT:T	donor_loss	1.0000
15:78971930:GATAT:G	acceptor_gain	1.0000
15:78971931:ATAT:A	acceptor_gain	1.0000
15:78971931:ATATC:A	acceptor_loss	1.0000
15:78971932:TAT:T	acceptor_gain	1.0000
15:78971933:AT:A	acceptor_gain	1.0000
15:78971933:ATC:A	acceptor_loss	1.0000
15:78971934:TCT:T	acceptor_loss	1.0000
15:78971935:C:CC	acceptor_gain	1.0000
15:78971935:CT:C	acceptor_loss	1.0000
15:78971936:T:A	acceptor_loss	1.0000
15:78972583:T:TA	donor_gain	1.0000
15:78972588:AGCG:A	donor_gain	1.0000
15:78973305:T:TA	donor_gain	1.0000
15:78973311:T:C	donor_gain	1.0000
15:78973392:CCAGG:C	acceptor_gain	1.0000
15:78973393:C:T	acceptor_gain	1.0000
15:78973393:CAGG:C	acceptor_gain	1.0000
15:78973394:A:T	acceptor_gain	1.0000
15:78973418:CAACT:C	acceptor_gain	1.0000
15:78973422:T:C	acceptor_gain	1.0000
15:78985212:CCGA:C	acceptor_gain	1.0000
15:78985213:C:T	acceptor_gain	1.0000
15:78985213:CGA:C	acceptor_gain	1.0000
15:78985214:G:T	acceptor_gain	1.0000
15:78985215:A:AC	acceptor_gain	1.0000
15:78985215:A:C	acceptor_gain	1.0000

AlphaMissense

8338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:78971909:C:G	R1229P	1.000
15:78971918:C:G	R1226P	1.000
15:78971928:G:C	H1223D	1.000
15:78973303:C:A	M1220I	1.000
15:78973303:C:G	M1220I	1.000
15:78973303:C:T	M1220I	1.000
15:78973304:A:C	M1220R	1.000
15:78973304:A:G	M1220T	1.000
15:78973304:A:T	M1220K	1.000
15:78973306:C:A	R1219S	1.000
15:78973306:C:G	R1219S	1.000
15:78973307:C:A	R1219M	1.000
15:78973307:C:G	R1219T	1.000
15:78973312:C:A	K1217N	1.000
15:78973312:C:G	K1217N	1.000
15:78973314:T:C	K1217E	1.000
15:78973318:G:C	F1215L	1.000
15:78973318:G:T	F1215L	1.000
15:78973319:A:C	F1215C	1.000
15:78973319:A:G	F1215S	1.000
15:78973320:A:G	F1215L	1.000
15:78973321:G:C	N1214K	1.000
15:78973321:G:T	N1214K	1.000
15:78973325:A:T	V1213D	1.000
15:78973366:G:C	F1199L	1.000
15:78973366:G:T	F1199L	1.000
15:78973367:A:G	F1199S	1.000
15:78973368:A:G	F1199L	1.000
15:78973373:A:G	L1197P	1.000
15:78973376:T:A	D1196V	1.000

dbSNP variants (sampled 300 via entrez): RS1000010048 (15:79030120 A>C,T), RS1000028525 (15:79084745 T>G), RS1000037714 (15:79045265 G>A), RS1000043730 (15:79092463 T>A,C), RS1000091146 (15:79053736 G>A), RS1000097894 (15:79053234 C>T), RS1000108850 (15:78982208 G>T), RS1000113435 (15:79024019 T>A), RS1000118338 (15:78979140 A>G), RS1000180813 (15:78994838 C>T), RS1000188225 (15:79050649 A>C), RS1000196962 (15:78988284 C>T), RS1000199447 (15:78971650 T>C), RS1000264285 (15:79090595 G>A,C,T), RS1000313704 (15:78984296 G>C)

Disease associations

OMIM: gene MIM:606600 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000451_7	RR interval (heart rate)	2.000000e-06
GCST000794_1	Refractive error	2.000000e-09
GCST001858_18	Refractive error	4.000000e-11
GCST002104_24	Bronchopulmonary dysplasia	6.000000e-06
GCST003455_34	Spherical equivalent (joint analysis main effects and education interaction)	4.000000e-08
GCST003455_35	Spherical equivalent (joint analysis main effects and education interaction)	5.000000e-06
GCST003997_36	Myopia	4.000000e-18
GCST005830_47	Hand grip strength	4.000000e-08
GCST006291_137	Spherical equivalent or myopia (age of diagnosis)	2.000000e-24
GCST010002_101	Refractive error	8.000000e-84
GCST010988_208	Adult body size	1.000000e-12
GCST010994_8	High myopia	7.000000e-10
GCST011569_7	Pancreatic beta-cell glucose sensitivity	6.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004831	RR interval
EFO:0004784	self reported educational attainment
EFO:0006941	grip strength measurement
EFO:0004847	age at onset
EFO:0006842	diabetes mellitus biomarker

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5468 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Estradiol	affects expression, affects cotreatment, decreases expression, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Aflatoxin B1	decreases methylation, increases expression, increases methylation	2
bisphenol A	affects cotreatment, decreases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
terbufos	increases methylation	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Fonofos	increases methylation	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	decreases methylation	1
Naled	affects expression	1
Ouabain	decreases expression	1
Parathion	increases methylation	1
Pesticides	decreases methylation	1
Silicon Dioxide	decreases expression	1
Tamoxifen	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vanadates	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001806	Binding	Inhibition of Cdc25	Sesquiterpenoid metabolites with antiplasmodial activity from a Caribbean gorgonian coral, Eunicea sp. — J Nat Prod

Clinical trials (associated diseases)

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