RIC8A

Summary

RIC8A (RIC8 guanine nucleotide exchange factor A, HGNC:29550) is a protein-coding gene on chromosome 11p15.5, encoding Chaperone Ric-8A (Q9NPQ8). Chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ.

Predicted to enable G-protein alpha-subunit binding activity; GTPase regulator activity; and protein folding chaperone. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including basement membrane organization; gastrulation; and visual learning. Predicted to be located in cell cortex and membrane. Predicted to be active in cytoplasm and plasma membrane.

Source: NCBI Gene 60626 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 100 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001286134

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29550
Approved symbol	RIC8A
Name	RIC8 guanine nucleotide exchange factor A
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	synembryn, synembryn-A
Ensembl gene	ENSG00000177963
Ensembl biotype	protein_coding
OMIM	609146
Entrez	60626

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 20 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000325207, ENST00000524854, ENST00000526104, ENST00000526557, ENST00000526982, ENST00000527039, ENST00000527468, ENST00000527696, ENST00000527728, ENST00000528357, ENST00000529275, ENST00000530149, ENST00000530889, ENST00000531541, ENST00000532241, ENST00000532373, ENST00000626818, ENST00000853235, ENST00000853236, ENST00000853237, ENST00000853238, ENST00000853239, ENST00000853240, ENST00000853241, ENST00000853242, ENST00000941737, ENST00000941738

RefSeq mRNA: 4 — MANE Select: NM_001286134 NM_001286134, NM_001386941, NM_001386942, NM_021932

CCDS: CCDS65982, CCDS7690

Canonical transcript exons

ENST00000526104 — 10 exons

Exon	Start	End
ENSE00001267210	212837	212981
ENSE00001267216	213299	213418
ENSE00001267226	212416	212511
ENSE00001267253	209271	209318
ENSE00001267721	214230	215113
ENSE00002155049	212615	212759
ENSE00002164162	207708	208938
ENSE00003465532	210571	210662
ENSE00003616220	209407	210000
ENSE00003671287	211199	211349

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5569 / max 282.6214, expressed in 1820 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112143	15.9139	1808
112145	11.7785	1792
112146	8.0124	1764
112142	0.4965	247
112144	0.3557	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.45	gold quality
ventricular zone	UBERON:0003053	95.79	gold quality
granulocyte	CL:0000094	95.19	gold quality
ganglionic eminence	UBERON:0004023	95.12	gold quality
lower esophagus	UBERON:0013473	95.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.08	gold quality
smooth muscle tissue	UBERON:0001135	94.95	gold quality
gall bladder	UBERON:0002110	94.75	gold quality
cortical plate	UBERON:0005343	94.75	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.64	gold quality
adenohypophysis	UBERON:0002196	94.63	gold quality
prefrontal cortex	UBERON:0000451	94.61	gold quality
right coronary artery	UBERON:0001625	94.61	gold quality
decidua	UBERON:0002450	94.58	gold quality
left uterine tube	UBERON:0001303	94.44	gold quality
apex of heart	UBERON:0002098	94.43	gold quality
thoracic aorta	UBERON:0001515	94.36	gold quality
ascending aorta	UBERON:0001496	94.34	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.34	gold quality
endocervix	UBERON:0000458	94.33	gold quality
ectocervix	UBERON:0012249	94.25	gold quality
islet of Langerhans	UBERON:0000006	94.23	gold quality
upper lobe of left lung	UBERON:0008952	94.22	gold quality
lower esophagus mucosa	UBERON:0035834	94.17	gold quality
body of uterus	UBERON:0009853	94.13	gold quality
aorta	UBERON:0000947	94.12	gold quality
pituitary gland	UBERON:0000007	94.02	gold quality
left coronary artery	UBERON:0001626	94.02	gold quality
left testis	UBERON:0004533	94.01	gold quality
popliteal artery	UBERON:0002250	94.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting RIC8A, 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-4455	100.00	65.48	1587
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-4536-5P	98.47	64.39	657
HSA-MIR-376B-5P	98.46	66.40	606
HSA-MIR-376C-5P	98.46	66.64	589

Literature-anchored findings (GeneRIF, showing 12)

• Ric-8A signaling leads to assembly of a cortical signaling complex that functions to orient the mitotic spindle. (PMID:20479129)
• Ric-8A is critical for growth factor receptor-induced actin cytoskeletal reorganization (PMID:21771786)
• RGS14 can form complexes with GPCRs in cells that are dependent on Galpha(i/o) and these RGS14.Galpha(i1).GPCR complexes may be substrates for other signaling partners such as Ric-8A (PMID:21880739)
• NCAM180 regulates Ric8A membrane localization and potentiates beta-adrenergic response (PMID:22384181)
• The ubiquitination of Galphai2 and Galphaq is suppressed by expression of Ric-8A. The suppression likely requires Ric-8A interaction with these Galpha proteins; the C-terminal truncation of Galphaq and Galphai2 completely abrogates their interaction with Ric-8A. (PMID:23665327)
• Ric-8A co-localized with Vps34 at the midbody. (PMID:24466196)
• Human NCS-1 and Ric8a reproduce the binding and maintain the structural requirements at these key positions. Drosophila Ric8a and Galphas regulate synapse number and neurotransmitter release, and both are functionally linked to Frq2. (PMID:25074811)
• Results confirmed that Ric-8A can directly bind to AGS3S but failed to facilitate Galpha(i)-induced suppression of adenylyl cyclase, suggesting that it may not serve as a guanine exchange factor for AGS3/Galpha(i/o)-GDP complex in a cellular environment. (PMID:25480567)
• These results indicate that dual phosphorylation represents a critical form of conserved Ric-8 regulation and demonstrate that Ric-8 proteins are needed for effective Galpha signaling. (PMID:29844055)
• Structures of Galpha Proteins in Complex with Their Chaperone Reveal Quality Control Mechanisms. (PMID:32126208)
• circPDE4B prevents articular cartilage degeneration and promotes repair by acting as a scaffold for RIC8A and MID1. (PMID:34039624)
• Neomorphic Galphao mutations gain interaction with Ric8 proteins in GNAO1 encephalopathies. (PMID:38874642)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ric8a	ENSDARG00000007247
mus_musculus	Ric8a	ENSMUSG00000025485
rattus_norvegicus	Ric8a	ENSRNOG00000013256
drosophila_melanogaster	ric8a	FBGN0028292
caenorhabditis_elegans		WBGENE00004367

Paralogs (1): RIC8B (ENSG00000111785)

Protein

Protein identifiers

Chaperone Ric-8A — Q9NPQ8 (reviewed: Q9NPQ8)

Alternative names: Synembryn-A

All UniProt accessions (8): E9PI04, E9PLE5, E9PMP0, E9PSI0, Q9NPQ8, H0YC88, H0YE35, H0YEN0

UniProt curated annotations — full annotation on UniProt →

Function. Chaperone that specifically binds and folds nascent G alpha proteins prior to G protein heterotrimer formation, promoting their stability and activity: folds GNAI1, GNAO1, GNA13 and GNAQ. Does not fold G(s) G-alpha proteins GNAS nor GNAL. Also acts as a guanine nucleotide exchange factor (GEF) for G alpha proteins by stimulating exchange of bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein (GNAI1), possibly leading to release G(i)-alpha-GTP and NuMA proteins from the NuMA-GPSM2-G(i)-alpha-GDP complex. Also acts as an activator for G(q)-alpha (GNAQ) protein by enhancing the G(q)-coupled receptor-mediated ERK activation.

Subunit / interactions. Interacts with GDP-bound G alpha proteins GNAI1, GNAO1 and GNAQ, and with GNA13 with lower affinity. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma. Interacts (via C-terminus) with RGS14; the interaction stimulates the dissociation of the complex between RGS14 and the active GTP-bound form of GNAI1. Interacts with NCS1; interaction is favored in the absence of Ca(2+) and myristoylation of NCS1 is not required.

Subcellular location. Cytoplasm. Cell cortex.

Post-translational modifications. Phosphorylated at Ser-436 and Thr-441 by CK2, stabilizing its interface with G alpha proteins.

Similarity. Belongs to the synembryn family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NPQ8-1	1	yes
Q9NPQ8-2	2
Q9NPQ8-3	3
Q9NPQ8-4	4

RefSeq proteins (4): NP_001273063, NP_001373870, NP_001373871, NP_068751 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008376	Chaperone_Ric-8_A/B	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR019318	Gua_nucleotide_exch_fac_Ric8	Family

Pfam: PF10165

UniProt features (13 total): modified residue 7, splice variant 3, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPQ8-F1	90.37	0.73

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 (7): 436, 441, 443, 502, 523, 524, 528

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 140 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ASSOCIATIVE_LEARNING, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_CELL_CELL_ADHESION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_PROTEIN_MATURATION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT

GO Biological Process (11): in utero embryonic development (GO:0001701), vasculature development (GO:0001944), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), visual learning (GO:0008542), cell migration involved in gastrulation (GO:0042074), cell-cell adhesion involved in gastrulation (GO:0070586), basement membrane organization (GO:0071711), protein folding (GO:0006457), gastrulation (GO:0007369), response to light stimulus (GO:0009416)

GO Molecular Function (4): G-protein alpha-subunit binding (GO:0001965), guanyl-nucleotide exchange factor activity (GO:0005085), protein folding chaperone (GO:0044183), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell cortex (GO:0005938), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gastrulation	2
cellular anatomical structure	2
cell periphery	2
chordate embryonic development	1
system development	1
circulatory system development	1
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
visual behavior	1
associative learning	1
ameboidal-type cell migration	1
cell-cell adhesion	1
extracellular matrix organization	1
cellular process	1
protein maturation	1
ectoderm formation	1
endoderm formation	1
mesoderm formation	1
embryonic morphogenesis	1
response to radiation	1
protein binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
molecular_function	1
protein folding	1
binding	1
intracellular anatomical structure	1
membrane	1
cytoplasm	1

Protein interactions and networks

STRING

1230 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RIC8A	GNAQ	P50148	899
RIC8A	RABIF	P47224	871
RIC8A	GNAI3	P08754	807
RIC8A	GNA13	Q14344	797
RIC8A	GNAO1	P09471	786
RIC8A	GNAL	P38405	677
RIC8A	TMTC1	Q8IUR5	671
RIC8A	GNAI1	P04898	642
RIC8A	NCS1	P36610	642
RIC8A	GNAS	Q5JWF2	641
RIC8A	PCP2	Q8IVA1	639
RIC8A	RGS7	P49802	629
RIC8A	RGS19	P49795	622
RIC8A	CIMAP1A	Q96PU9	616
RIC8A	GNAI2	P04899	609

IntAct

62 interactions, top by confidence:

A	B	Type	Score
UBQLN1	RIC8A	psi-mi:“MI:0915”(physical association)	0.750
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
RIC8A	EFEMP1	psi-mi:“MI:0915”(physical association)	0.550
EFEMP1	RIC8A	psi-mi:“MI:0915”(physical association)	0.550
RIC8A	GNAI1	psi-mi:“MI:0915”(physical association)	0.550
GNAI1	GNAT3	psi-mi:“MI:0914”(association)	0.530
RIC8A	VAPB	psi-mi:“MI:0914”(association)	0.530
GNAZ	MTHFR	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
GNAO1	RIC8A	psi-mi:“MI:0915”(physical association)	0.500
espJ	RIC8A	psi-mi:“MI:0915”(physical association)	0.370
RIC8A	espJ	psi-mi:“MI:0915”(physical association)	0.370
RABAC1	RIC8A	psi-mi:“MI:0915”(physical association)	0.370
SDCBP	RIC8A	psi-mi:“MI:0915”(physical association)	0.370
NUTM1	RIC8A	psi-mi:“MI:0915”(physical association)	0.370
XPO1	RIC8A	psi-mi:“MI:0915”(physical association)	0.370
Cct4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
ANG	DDX39A	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (144): RIC8A (Two-hybrid), RIC8A (Two-hybrid), RIC8A (Two-hybrid), RIC8A (Two-hybrid), RIC8A (Two-hybrid), NUTM1 (Two-hybrid), RIC8A (Two-hybrid), RIC8A (Affinity Capture-MS), RIC8A (Affinity Capture-MS), RIC8A (Affinity Capture-MS), RIC8A (Two-hybrid), RIC8A (Affinity Capture-MS), RIC8A (Affinity Capture-MS), RIC8A (Two-hybrid), RIC8A (Affinity Capture-MS)

ESM2 similar proteins: A1ZBY1, A2BFL2, A6H639, A8HMZ4, B1WBW4, C0LLJ0, E7FBU4, F4I735, O00329, P21541, Q28205, Q2KI89, Q3TIR3, Q45TX8, Q4R720, Q53R41, Q5E9J8, Q5R8F5, Q5RAG3, Q5ZKK3, Q5ZL77, Q64282, Q642H7, Q68F70, Q68F79, Q6DI86, Q6DRJ9, Q6NU09, Q6P4W7, Q6P5U7, Q6WRX3, Q7Z7L7, Q80XE1, Q80ZG0, Q80ZG1, Q80ZJ6, Q8BTZ4, Q8BYA0, Q8CIM8, Q8IWX7

Diamond homologs: Q29IC2, Q3TIR3, Q45TX8, Q4R720, Q5E9J8, Q5R8F5, Q5ZL77, Q61A92, Q642H7, Q6DRJ9, Q6P4W7, Q80XE1, Q80ZG0, Q80ZG1, Q9NPQ8, Q9NVN3, Q9W358, Q9GSX9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 66 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
ADP signalling through P2Y purinoceptor 12	5	52.8×	4e-06
ADORA2B mediated anti-inflammatory cytokines production	6	32.4×	4e-06
GPER1 signaling	6	31.7×	4e-06
G alpha (z) signalling events	6	29.8×	4e-06
Extra-nuclear estrogen signaling	5	18.1×	4e-04
G alpha (s) signalling events	7	10.9×	2e-04
G alpha (i) signalling events	9	7.5×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	7	42.9×	1e-07
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	6	23.9×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	86
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
981209	GRCh37/hg19 11p15.5-15.4(chr11:210300-8664358)x3	Pathogenic

SpliceAI

1671 predictions. Top by Δscore:

Variant	Effect	Δscore
11:208935:GGAG:G	donor_gain	1.0000
11:208936:G:GT	donor_gain	1.0000
11:208936:GAG:G	donor_gain	1.0000
11:208939:G:GG	donor_gain	1.0000
11:208939:GTA:G	donor_loss	1.0000
11:209997:CGAGG:C	donor_loss	1.0000
11:209999:AGGTG:A	donor_loss	1.0000
11:210001:G:A	donor_loss	1.0000
11:210002:T:A	donor_loss	1.0000
11:210564:T:A	acceptor_gain	1.0000
11:210565:G:A	acceptor_gain	1.0000
11:210567:TCAG:T	acceptor_loss	1.0000
11:210568:CAG:C	acceptor_loss	1.0000
11:210570:GGAA:G	acceptor_gain	1.0000
11:210660:CGGGT:C	donor_loss	1.0000
11:210661:GG:G	donor_gain	1.0000
11:210662:GG:G	donor_gain	1.0000
11:210662:GGT:G	donor_loss	1.0000
11:210663:G:GG	donor_gain	1.0000
11:210663:GTGAG:G	donor_loss	1.0000
11:210664:T:A	donor_loss	1.0000
11:211197:A:AG	acceptor_gain	1.0000
11:211198:G:GC	acceptor_gain	1.0000
11:211198:GC:G	acceptor_gain	1.0000
11:211198:GCC:G	acceptor_gain	1.0000
11:211198:GCCAC:G	acceptor_gain	1.0000
11:211258:T:TA	acceptor_gain	1.0000
11:211345:ACAAG:A	donor_loss	1.0000
11:211346:CAAGG:C	donor_loss	1.0000
11:211347:AAGG:A	donor_loss	1.0000

AlphaMissense

3466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:212861:G:A	G412D	0.999
11:212867:G:A	G414E	0.999
11:212873:C:A	A416D	0.999
11:212876:C:A	A417D	0.999
11:213316:G:A	G458E	0.999
11:212649:C:A	P367H	0.998
11:212682:T:A	V378D	0.998
11:212860:G:C	G412R	0.998
11:212861:G:T	G412V	0.998
11:212866:G:T	G414W	0.998
11:212867:G:T	G414V	0.998
11:212871:T:A	N415K	0.998
11:212871:T:G	N415K	0.998
11:213381:G:C	A480P	0.998
11:213391:T:C	L483P	0.998
11:209959:T:C	F229L	0.997
11:209961:C:A	F229L	0.997
11:209961:C:G	F229L	0.997
11:212749:C:G	C400W	0.997
11:212860:G:T	G412C	0.997
11:212866:G:A	G414R	0.997
11:212866:G:C	G414R	0.997
11:212872:G:C	A416P	0.997
11:212879:G:A	G418D	0.997
11:212885:T:A	L420Q	0.997
11:212885:T:C	L420P	0.997
11:213315:G:A	G458R	0.997
11:213315:G:C	G458R	0.997
11:209779:T:C	F169L	0.996
11:209781:C:A	F169L	0.996

dbSNP variants (sampled 300 via entrez): RS1000026443 (11:209151 G>A), RS1000072392 (11:214932 G>A,C), RS1000121608 (11:210790 G>A), RS1000463030 (11:208998 G>A,C,T), RS1000586469 (11:206898 A>G), RS1000980696 (11:207795 A>C), RS1001013272 (11:206637 T>G), RS1001101899 (11:213952 A>G), RS1001246578 (11:211718 A>G), RS1001299706 (11:210196 G>A,C), RS1001532011 (11:213787 CAAAA>C,CAA,CAAA,CAAAAA), RS1001870999 (11:205754 AACAACTCTGCCAG>A), RS1001915740 (11:211648 C>G,T), RS1002019134 (11:206392 G>A,T), RS1002136498 (11:212377 G>C)

Disease associations

OMIM: gene MIM:609146 | disease phenotypes: MIM:180860

GenCC curated gene-disease

Mondo (1): Silver-Russell syndrome 1 (MONDO:0020796)

Orphanet (1): Silver-Russell syndrome (Orphanet:813)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001027_3	Uterine fibroids	4.000000e-12
GCST002186_8	Platelet count	5.000000e-12
GCST005870_1	Meningioma	1.000000e-08
GCST005992_32	Mean corpuscular hemoglobin concentration	3.000000e-12
GCST009158_1	Uterine fibroids	2.000000e-14
GCST009822_3	Gynecologic disease	4.000000e-17
GCST009823_2	Gynecologic disease (multivariate analysis)	8.000000e-16
GCST009824_5	Gynecologic disease	3.000000e-16
GCST009833_2	Uterine fibroids (MTAG)	4.000000e-17
GCST009834_36	Uterine fibroids	1.000000e-21
GCST009963_12	Cataracts (operation)	5.000000e-08
GCST012013_11	Cataracts	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296100 (PROTEIN COMPLEX)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol F	increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
bisphenol AF	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzene	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Benztropine	affects cotreatment, increases expression	1
Caffeine	increases phosphorylation	1
Cannabidiol	decreases expression	1
Clozapine	decreases expression	1
Cuprizone	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4145364	Binding	Inhibition of human NCS1 and V5-tagged Ric8a interaction expressed in HEK293 cells at 20 uM after 24 hrs by Western blot analysis relative to control	Deciphering the Inhibition of the Neuronal Calcium Sensor 1 and the Guanine Exchange Factor Ric8a with a Small Phenothiazine Molecule for the Rational Generation of Therapeutic Synapse Function Regulators. — J Med Chem

Clinical trials (associated diseases)

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