RND3

Summary

RND3 (Rho family GTPase 3, HGNC:671) is a protein-coding gene on chromosome 2q23.3, encoding Rho-related GTP-binding protein RhoE (P61587). Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.

This gene encodes a protein which is a member of the small GTPase protein superfamily. The encoded protein binds only GTP but has no GTPase activity, and appears to act as a negative regulator of cytoskeletal organization leading to loss of adhesion. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 390 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_005168

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:671
Approved symbol	RND3
Name	Rho family GTPase 3
Location	2q23.3
Locus type	gene with protein product
Status	Approved
Aliases	RhoE, Rho8
Ensembl gene	ENSG00000115963
Ensembl biotype	protein_coding
OMIM	602924
Entrez	390

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263895, ENST00000375734, ENST00000409557, ENST00000439275, ENST00000454202, ENST00000466334, ENST00000472416, ENST00000473639, ENST00000497865, ENST00000868796, ENST00000914158, ENST00000914159

RefSeq mRNA: 2 — MANE Select: NM_005168 NM_001254738, NM_005168

CCDS: CCDS2190

Canonical transcript exons

ENST00000263895 — 6 exons

Exon	Start	End
ENSE00001034654	150487268	150487455
ENSE00001070099	150468195	150470238
ENSE00001905777	150487549	150487667
ENSE00003459456	150471627	150471761
ENSE00003550626	150486694	150486781
ENSE00003787877	150474875	150474984

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.8970 / max 2836.4539, expressed in 1563 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31098	95.3274	1563
31097	0.5153	147
31099	0.0543	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	99.41	gold quality
stromal cell of endometrium	CL:0002255	99.36	gold quality
tongue squamous epithelium	UBERON:0006919	98.82	gold quality
oral cavity	UBERON:0000167	98.55	gold quality
pharyngeal mucosa	UBERON:0000355	98.46	gold quality
esophagus squamous epithelium	UBERON:0006920	98.44	gold quality
urethra	UBERON:0000057	98.31	gold quality
mucosa of urinary bladder	UBERON:0001259	98.27	gold quality
cervix epithelium	UBERON:0004801	98.26	gold quality
squamous epithelium	UBERON:0006914	98.21	gold quality
ganglionic eminence	UBERON:0004023	98.19	gold quality
epithelium of esophagus	UBERON:0001976	98.17	gold quality
penis	UBERON:0000989	97.81	gold quality
mammary duct	UBERON:0001765	97.75	gold quality
cervix squamous epithelium	UBERON:0006922	97.64	gold quality
gingival epithelium	UBERON:0001949	97.63	gold quality
palpebral conjunctiva	UBERON:0001812	97.57	gold quality
epithelium of mammary gland	UBERON:0003244	97.52	gold quality
gingiva	UBERON:0001828	97.44	gold quality
mammalian vulva	UBERON:0000997	96.98	gold quality
adrenal tissue	UBERON:0018303	96.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.91	gold quality
calcaneal tendon	UBERON:0003701	96.87	gold quality
upper leg skin	UBERON:0004262	96.87	gold quality
cartilage tissue	UBERON:0002418	96.86	gold quality
decidua	UBERON:0002450	96.82	gold quality
saphenous vein	UBERON:0007318	96.69	gold quality
nipple	UBERON:0002030	96.68	gold quality
vena cava	UBERON:0004087	96.67	gold quality
parietal pleura	UBERON:0002400	96.47	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	1718.37
E-HCAD-56	yes	1084.59
E-CURD-11	yes	859.05
E-MTAB-10287	yes	445.06
E-MTAB-8142	yes	104.88
E-GEOD-135922	yes	54.62
E-HCAD-5	yes	22.53
E-HCAD-13	yes	12.80
E-MTAB-9388	yes	9.71
E-GEOD-81547	yes	9.18
E-CURD-112	yes	9.06
E-GEOD-93593	yes	8.88
E-GEOD-84465	yes	6.29
E-MTAB-10553	yes	5.25
E-MTAB-8894	no	1156.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, FOXD3, TLE5

miRNA regulators (miRDB)

111 targeting RND3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 40)

• Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers (PMID:11940653)
• RhoE is a tumor suppressor gene that is downregulated early in the development of prostate cancer (PMID:15754346)
• Rnd3/RhoE regulates the assembly of the apical junction complex and tight junction sealing when transfected to a rat tumor cell line. (PMID:15777789)
• The RND3 mRNA levels increased significantly after gestation in myometria. (PMID:16311049)
• RhoE plays an important role in the regulation of cell proliferation and survival and may be considered as an oncosupressor since it is capable to induce apoptosis in several tumor cell lines. (PMID:17182035)
• These results identify Rnd3 as a regulator of cross talk between the RAF/MEK/ERK and Rho/ROCK signaling pathways, and a key contributor to oncogene-mediated reorganization of the actin cytoskeleton and focal adhesions. (PMID:18045987)
• PDK1 competes directly with RhoE for binding to ROCK1. In the absence of PDK1, negative regulation by RhoE predominates, causing reduced acto-myosin contractility and motility. (PMID:18204440)
• Staphylococcal enterotoxin B-treated renal proximal tubule epithelial cells, show 32 differentially expressed transcripts; one of the down-regulated DETs matched the sequence for Rnd3, which normally inhibits Rho protein function. (PMID:18721871)
• Data show that RhoE integrates two processes essential for keratinocyte differentiation and stratification: regulation of proliferative status and integrin adhesion. (PMID:18923151)
• mutation of the RhoE effector region attenuates RhoE-mediated disruption of the actin cytoskeleton, indicating that RhoE exerts its inhibitory effects on ROCK-I through protein(s) binding to its effector region. (PMID:18946488)
• This study demonstrated that RhoE may promote the multidrug resistance phenotype of gastric cancer cells by decreasing the expression of Bax at posttranscriptional level, thus inhibiting vincristine-induced apoptosis. (PMID:19101510)
• Findings implicate Rnd3 as a major suppressor of RhoA-mediated actin cytoskeletal organization and in the acquisition of an invasive melanoma phenotype. (PMID:19244113)
• RhoE inhibits 4E-BP1 phosphorylation and eIF4E function impairing cap-dependent translation. (PMID:19850923)
• study demonstrates a novel role for mir-200b in cell cycle progression and identifies RND3 as a novel mir-200b target (PMID:20683643)
• RhoE expression in gastric cancer cells was regulated by histone deacetylation, but not by DNA methylation, at the epigenetic level. (PMID:21109974)
• Data show that the increased invasiveness of tumorigenic cells was associated with reduced expression of Rnd3. (PMID:21209796)
• Upregulation of FOXD3 expression following inhibition of B-RAF and MEK correlates with the downregulation of Rnd3, a Rho GTPase and inhibitor of RhoA-ROCK signaling. (PMID:21478267)
• Restoration of RND3 expression or RHOA knockdown attenuated the migratory ability of residual cells without affecting overall cell survival (PMID:21917148)
• This study identifies RhoE as a direct target for HIF-1 in gastric cancer cells. (PMID:22037464)
• the expression of miR-17 was negatively correlated with that of RND3 in colorectal cancer tissues and cells (PMID:22132820)
• expression of RhoE was significantly negatively associated with serum AFP (P = 0.013) and tumor grade (P = 0.016) (PMID:22213123)
• Rnd3 expression was significantly lower in invasive tumors with satellite nodules (PMID:22234932)
• The authors show that enteropathogenic Escherichia coli translocates EspH, which inactivates mammalian RhoGEFs and triggers cytotoxicity. (PMID:22251971)
• Results show that induction of RhoE by cAMP is mediated through protein kinase A (PKA) and promotes BeWo cell fusion but has no effect on functional differentiation. (PMID:22272352)
• role of the N-terminal region in signaling; Rnd1 and Rnd3 have a KERRA (Lys-Glu-Arg-Arg-Ala) sequence of amino acids in their N-terminus, which functions as the lipid raft-targeting determinant; the sequence mediates lipid raft targeting of p190 RhoGAP correlated with its activation (PMID:22357615)
• Loss of Rnd3 expression in keratinocytes results in altered colony morphology. (PMID:22454524)
• RhoE may play a driving role in the development and progression of ESCC, and targeting the RhoE may be an effective and feasible approach for treatment of ESCC. (PMID:22477709)
• frequently down-regulated in predominantly HBV-associated hepatocellular carcinomas (PMID:22829315)
• alteration of the malignant behavior of cancer cells by AES is related to RND3 regulation. (PMID:23546594)
• Study reports a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. (PMID:23622247)
• Rnd3 is a regulator of Notch1 signaling (PMID:23630292)
• Transfection of pre-miR-200c reduces RhoE expression. (PMID:23821457)
• a mechanism according to which proteasomal degradation of RhoE by Skp2 regulates its protein levels to control cellular proliferation. (PMID:24045951)
• CXCR4 might be a downstream effector for RhoE (PMID:24312338)
• RhoE may participate in human cancer progression and act as a candidate target of p53, and these findings also strongly suggest that RhoE may be a new candidate tumor suppressor and could serve as a potential target in the gene therapy of cancer. (PMID:24399089)
• define RhoE as a Notch1 target that is essential for recruitment of N1IC to promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling (PMID:24525741)
• MicroRNA-200b acts as a stimulant for the proliferation of HTFs by targeting p27/kip1 and RND3. (PMID:24667864)
• Rnd3 regulates lung cancer cell proliferation through notch signaling. (PMID:25372032)
• We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis. (PMID:26108681)
• the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome. (PMID:26132659)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnd3b	ENSDARG00000007396
danio_rerio	rnd3a	ENSDARG00000076799
mus_musculus	Rnd3	ENSMUSG00000017144
rattus_norvegicus	Rnd3	ENSRNOG00000004624

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RHOU (ENSG00000116574), RHOQ (ENSG00000119729), RHOJ (ENSG00000126785), RHOT1 (ENSG00000126858), RAC2 (ENSG00000128340), RAC1 (ENSG00000136238), RHOF (ENSG00000139725), RHOT2 (ENSG00000140983), RHOB (ENSG00000143878), RHOC (ENSG00000155366), RHOBTB3 (ENSG00000164292), RHOH (ENSG00000168421), RAC3 (ENSG00000169750), RND1 (ENSG00000172602), RHOD (ENSG00000173156), RHOG (ENSG00000177105)

Protein

Protein identifiers

Rho-related GTP-binding protein RhoE — P61587 (reviewed: P61587)

Alternative names: Protein MemB, Rho family GTPase 3, Rho-related GTP-binding protein Rho8, Rnd3

All UniProt accessions (3): P61587, E9PFH1, Q53RZ3

UniProt curated annotations — full annotation on UniProt →

Function. Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.

Subunit / interactions. Binds ROCK1. Interacts with UBXD5.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the small GTPase superfamily. Rho family.

RefSeq proteins (2): NP_001241667, NP_005159* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR003578	Small_GTPase_Rho	Family
IPR005225	Small_GTP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041843	RhoE	Family

Pfam: PF00071

UniProt features (26 total): helix 9, strand 6, turn 3, binding site 3, chain 1, propeptide 1, short sequence motif 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8B2K	X-RAY DIFFRACTION	1.4
8BFC	X-RAY DIFFRACTION	1.4
7OBC	X-RAY DIFFRACTION	1.9
1M7B	X-RAY DIFFRACTION	2
7OBD	X-RAY DIFFRACTION	2
4BG6	X-RAY DIFFRACTION	2.3
2V55	X-RAY DIFFRACTION	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61587-F1	81.58	0.69

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 (3): 30–37; 77–81; 135–138

Post-translational modifications (2): 241, 241

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9696264	RND3 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 323 (showing top): WENDT_COHESIN_TARGETS_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_52, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, TGACCTY_ERR1_Q2, GHO_ATF5_TARGETS_DN, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, MODULE_66, MODULE_118

GO Biological Process (6): actin filament organization (GO:0007015), cell adhesion (GO:0007155), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), actin cytoskeleton organization (GO:0030036), regulation of actin cytoskeleton organization (GO:0032956)

GO Molecular Function (5): GTPase activity (GO:0003924), GTP binding (GO:0005525), protein kinase binding (GO:0019901), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): Golgi membrane (GO:0000139), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
actin cytoskeleton organization	2
cellular process	2
cytoplasm	2
cellular anatomical structure	2
supramolecular fiber organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
cytoskeleton organization	1
actin filament-based process	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
cell-substrate junction	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

36 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
PLXNB1	RND3	psi-mi:“MI:0915”(physical association)	0.680
RND3	PLXNB1	psi-mi:“MI:0407”(direct interaction)	0.680
RND3	YWHAZ	psi-mi:“MI:0407”(direct interaction)	0.650
YWHAZ	RND3	psi-mi:“MI:0407”(direct interaction)	0.650
YWHAB	RND3	psi-mi:“MI:0407”(direct interaction)	0.590
RND3	YWHAB	psi-mi:“MI:0407”(direct interaction)	0.590
RND3	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.560
PLEKHG5	RND3	psi-mi:“MI:0915”(physical association)	0.560
RND3	CPLANE2	psi-mi:“MI:0915”(physical association)	0.560
RND3	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
RND3	ANGPT1	psi-mi:“MI:0915”(physical association)	0.400
EEA1	RND3	psi-mi:“MI:0915”(physical association)	0.400
SFN	RND3	psi-mi:“MI:0915”(physical association)	0.400
CFTR	RND3	psi-mi:“MI:0915”(physical association)	0.370
RND3	PLEKHG5	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (288): NOTCH1 (Affinity Capture-Western), RBPJ (Affinity Capture-Western), MAML1 (Affinity Capture-Western), RND3 (Affinity Capture-Western), RND3 (Affinity Capture-Western), RND3 (Affinity Capture-Western), RND3 (Affinity Capture-Western), RND3 (Affinity Capture-MS), RND3 (Two-hybrid), ARHGAP5 (Affinity Capture-Western), ARHGAP5 (Reconstituted Complex), ROCK1 (Reconstituted Complex), CIT (Two-hybrid), RND3 (Reconstituted Complex), RSG1 (Two-hybrid)

ESM2 similar proteins: D3Z8L7, E2RQ15, O00212, O13928, O77683, P06781, P10833, P35278, P46629, P51146, P51147, P51148, P52198, P57735, P61017, P61018, P61587, P61588, P97348, Q06AU6, Q0PD08, Q15669, Q1RMR4, Q23862, Q2HJ68, Q2HJG3, Q32NQ0, Q3SZA1, Q3ZC27, Q58DS9, Q58DW6, Q5R7L7, Q5R9F4, Q6SA80, Q86YS6, Q874R1, Q8BLR7, Q8BYP3, Q91ZR1, Q96AX2

Diamond homologs: A8HME3, O77683, P52198, P61587, P61588, Q381A3, Q4R4K5, Q567Y6, Q5E9J4, Q5FVJ7, Q5M8K8, Q5R9F4, Q6SA80, Q9DAI2, Q9H7X7, Q9QYM5, A0A286QZ36, C4YDI6, O00212, O42825, O76321, O88931, O96390, P01122, P06780, P08134, P0CY33, P15153, P17081, P19073, P22122, P24406, P34144, P34145, P34146, P34148, P34149, P34150, P40792, P40793

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ROCK1	up-regulates	RND3	phosphorylation
PRKCA	“down-regulates activity”	RND3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

566 predictions. Top by Δscore:

Variant	Effect	Δscore
2:150471625:A:AC	donor_gain	1.0000
2:150471625:A:C	donor_loss	1.0000
2:150471626:C:CC	donor_gain	1.0000
2:150471626:C:CG	donor_loss	1.0000
2:150471757:TTCCA:T	acceptor_gain	1.0000
2:150471758:TCCA:T	acceptor_gain	1.0000
2:150471759:CCA:C	acceptor_gain	1.0000
2:150471759:CCAC:C	acceptor_gain	1.0000
2:150471760:CA:C	acceptor_gain	1.0000
2:150471760:CAC:C	acceptor_gain	1.0000
2:150471762:C:CC	acceptor_gain	1.0000
2:150471764:A:AC	acceptor_gain	1.0000
2:150471764:A:C	acceptor_gain	1.0000
2:150474981:GAAC:G	acceptor_gain	1.0000
2:150474982:AAC:A	acceptor_gain	1.0000
2:150474982:AACCT:A	acceptor_loss	1.0000
2:150474983:AC:A	acceptor_gain	1.0000
2:150474984:CC:C	acceptor_gain	1.0000
2:150474984:CCT:C	acceptor_loss	1.0000
2:150474985:C:CC	acceptor_gain	1.0000
2:150474985:CTGA:C	acceptor_loss	1.0000
2:150474986:T:A	acceptor_loss	1.0000
2:150487263:CTCA:C	donor_loss	1.0000
2:150487264:TCACC:T	donor_loss	1.0000
2:150487265:CA:C	donor_loss	1.0000
2:150487266:A:T	donor_loss	1.0000
2:150487267:C:A	donor_loss	1.0000
2:150487267:CCT:C	donor_gain	1.0000
2:150470235:CCCC:C	acceptor_gain	0.9900
2:150470236:CCC:C	acceptor_gain	0.9900

AlphaMissense

1614 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:150470165:A:T	V186D	1.000
2:150470238:C:A	G162W	1.000
2:150471705:G:C	C135W	1.000
2:150471709:C:T	G134D	1.000
2:150471712:A:T	V133D	1.000
2:150471738:A:C	F124L	1.000
2:150471738:A:T	F124L	1.000
2:150471740:A:G	F124L	1.000
2:150471759:C:A	W117C	1.000
2:150471759:C:G	W117C	1.000
2:150471761:A:G	W117R	1.000
2:150471761:A:T	W117R	1.000
2:150474920:G:C	C101W	1.000
2:150474921:C:T	C101Y	1.000
2:150474922:A:G	C101R	1.000
2:150474927:A:G	L99P	1.000
2:150474954:A:G	L90P	1.000
2:150474954:A:T	L90H	1.000
2:150474961:G:T	R88S	1.000
2:150474963:A:T	V87D	1.000
2:150486694:C:G	G80R	1.000
2:150486701:G:C	D77E	1.000
2:150486701:G:T	D77E	1.000
2:150486702:T:A	D77V	1.000
2:150486702:T:C	D77G	1.000
2:150486702:T:G	D77A	1.000
2:150486703:C:A	D77Y	1.000
2:150486703:C:G	D77H	1.000
2:150486703:C:T	D77N	1.000
2:150486706:A:G	W76R	1.000

dbSNP variants (sampled 300 via entrez): RS1000043471 (2:150472125 G>A), RS1000158259 (2:150472174 T>C), RS1000221682 (2:150478627 C>A), RS1000267152 (2:150478870 G>A), RS1000329829 (2:150483798 T>C), RS1000420166 (2:150470773 C>A,T), RS1000477426 (2:150476558 G>A), RS1000594760 (2:150476227 T>C), RS1000717978 (2:150482783 T>C), RS1000800519 (2:150484070 T>C), RS1000994998 (2:150474143 C>T), RS1001048722 (2:150473881 T>A,C,G), RS1001372329 (2:150469628 A>G), RS1001449439 (2:150483401 A>G,T), RS1001454405 (2:150472997 C>T)

Disease associations

OMIM: gene MIM:602924 | 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
GCST001369_2	Type 2 diabetes	7.000000e-09
GCST001894_3	Endometriosis	6.000000e-08
GCST005651_3	Urinary metabolite levels in chronic kidney disease	4.000000e-08
GCST006531_1	Esophageal adenocarcinoma x gastroesophageal reflux disease interaction	2.000000e-07
GCST008039_21	Platelet count	4.000000e-08
GCST010168_2	Neonatal total 25-hydroxyvitamin D levels (fetal genetic effect)	2.000000e-06
GCST010656_2	Arterial stiffness (brachial-ankle pulse wave velocity)	1.000000e-07
GCST011494_13	Daytime nap	4.000000e-10
GCST012490_161	Femur bone mineral density x serum urate levels interaction	3.000000e-11
GCST90002385_449	High light scatter reticulocyte count	1.000000e-12
GCST90002386_263	High light scatter reticulocyte percentage of red cells	1.000000e-14
GCST90002387_268	Immature fraction of reticulocytes	8.000000e-12
GCST90002406_58	Reticulocyte fraction of red cells	1.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004309	platelet count
EFO:0004517	arterial stiffness measurement
EFO:0007828	daytime rest measurement
EFO:0004531	urate measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
sodium arsenite	affects methylation, decreases expression, increases expression	6
Acetaminophen	increases expression, decreases expression	4
Cadmium	increases expression	4
Particulate Matter	decreases expression, increases abundance, affects cotreatment, affects expression, increases reaction	4
bisphenol A	decreases expression, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	decreases expression, affects cotreatment, increases expression	3
Benzo(a)pyrene	increases expression, affects expression, affects methylation	3
Tobacco Smoke Pollution	affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression, increases methylation	3
Aflatoxin B1	decreases methylation, increases expression, affects expression	3
Cadmium Chloride	increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression	2
monomethylarsonous acid	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Vehicle Emissions	affects expression, increases reaction, decreases expression, increases abundance	2
Cannabidiol	increases expression, affects cotreatment	2
Estradiol	decreases expression, decreases reaction, increases expression	2
Formaldehyde	increases expression	2
Mustard Gas	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
Glupearl 19S	increases expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1

Clinical trials (associated diseases)

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