RHOU

Summary

RHOU (ras homolog family member U, HGNC:17794) is a protein-coding gene on chromosome 1q42.13, encoding Rho-related GTP-binding protein RhoU (Q7L0Q8). Binds to and activates protein kinase PAK1.

This gene encodes a member of the Rho family of GTPases. This protein can activate PAK1 and JNK1, and can induce filopodium formation and stress fiber dissolution. It may also mediate the effects of WNT1 signaling in the regulation of cell morphology, cytoskeletal organization, and cell proliferation. A non-coding transcript variant of this gene results from naturally occurring read-through transcription between this locus and the neighboring DUSP5P (dual specificity phosphatase 5 pseudogene) locus.

Source: NCBI Gene 58480 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_021205

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17794
Approved symbol	RHOU
Name	ras homolog family member U
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Aliases	WRCH-1, DJ646B12.2, FLJ10616, WRCH1, CDC42L1, hG28K, fJ646B12.2
Ensembl gene	ENSG00000116574
Ensembl biotype	protein_coding
OMIM	606366
Entrez	58480

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000366691

RefSeq mRNA: 1 — MANE Select: NM_021205 NM_021205

CCDS: CCDS1575

Canonical transcript exons

ENST00000366691 — 3 exons

Exon	Start	End
ENSE00000792996	228737673	228737731
ENSE00001442329	228743285	228746664
ENSE00001442330	228735479	228736004

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8038 / max 480.2515, expressed in 1156 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8965	16.3832	1084
8964	1.8130	786
8963	0.2599	133
8966	0.1678	76
201985	0.1149	43
8967	0.0650	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	95.89	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.45	gold quality
duodenum	UBERON:0002114	94.51	gold quality
adrenal tissue	UBERON:0018303	93.65	gold quality
gall bladder	UBERON:0002110	93.52	gold quality
endometrium	UBERON:0001295	93.42	gold quality
descending thoracic aorta	UBERON:0002345	92.70	gold quality
Ammon’s horn	UBERON:0001954	92.65	gold quality
putamen	UBERON:0001874	92.37	gold quality
substantia nigra	UBERON:0002038	92.20	gold quality
amygdala	UBERON:0001876	91.87	gold quality
temporal lobe	UBERON:0001871	91.83	gold quality
placenta	UBERON:0001987	91.27	gold quality
fallopian tube	UBERON:0003889	90.60	gold quality
right ovary	UBERON:0002118	90.54	gold quality
mucosa of stomach	UBERON:0001199	90.23	gold quality
omental fat pad	UBERON:0010414	90.12	gold quality
gastrocnemius	UBERON:0001388	90.10	gold quality
left uterine tube	UBERON:0001303	90.07	gold quality
caudate nucleus	UBERON:0001873	89.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.45	gold quality
thoracic aorta	UBERON:0001515	89.44	gold quality
muscle of leg	UBERON:0001383	89.22	gold quality
ascending aorta	UBERON:0001496	89.16	gold quality
primary visual cortex	UBERON:0002436	89.15	gold quality
ovary	UBERON:0000992	88.43	gold quality
rectum	UBERON:0001052	88.43	gold quality
body of stomach	UBERON:0001161	88.37	gold quality
left ovary	UBERON:0002119	88.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.06	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	10.64
E-ANND-3	no	0.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

127 targeting RHOU, 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-574-5P	100.00	66.01	989
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-659-3P	99.85	70.69	1620

Literature-anchored findings (GeneRIF, showing 20)

• Down regulation of WRCH1 by estradiol in breast cancer and altered expression of WRCH1 is associated with other cancers (PMID:11894124)
• G28K cDNA encodes a protein of 258 amino acids with homology to the cell division cycle 42/G25K protein; this gene is located at 1q42.11-q42.3; G28K was abundantly expressed in the stomach and the small intestine (PMID:14731133)
• These data suggest that Wrch-1 regulates cell migration by multiple mechanisms: on the one hand Wrch-1 controls focal adhesions by regulating myosin light chain and on the other hand Wrch-1 stimulates the activation of Akt and JNK. (PMID:17504809)
• Wrch-1-induced morphological and growth transformation may occur in part through Par6-mediated disruption of tight junction and actin organization. (PMID:19064640)
• As an essential actor of osteoclast differentiation, the atypical RhoGTPase Wrch1/RhoU could be an interesting target for the development of novel antiresorptive drugs. (PMID:19135548)
• Studies revealed a requirement for serum-stimulated tyrosine phosphorylation of Wrch1 at residue Y254 within its C-terminal membrane targeting domain, mediated by the nonreceptor tyrosine kinase Src. (PMID:20547754)
• data suggest a unique regulatory mechanism by which RhoU interaction with SH3 adaptor proteins might serve to integrate growth factor receptor signaling with RhoU activatio (PMID:21508312)
• A screen for Wrch-1 binding-partners identified the novel RhoGAP protein, ARHGAP30, as a Wrch-1 interactor. (PMID:21565175)
• results indicate that NOTCH1 mutation stimulates T-cell acute lymphoblastic leukaemia cell migration through RhoU upregulation that could contribute to the leukaemia cell dissemination (PMID:22349824)
• multiple upstream signals may converge on Wrch1 directly through its SH3 domain-binding properties (PMID:23183748)
• Data indicate that upregulated miR-126 upon coxsackievirus B3 (CVB3) infection targets SPRED1, LRP6, and WRCH1 genes, mediating cross-talk between ERK1/2 and Wnt/beta-catenin pathways, and thus promoting viral replication. (PMID:23811937)
• This review addresses the developmental roles of 2 GTPases of the Rho family, RhoV/Chp and RhoU/Wrch. (PMID:26555387)
• PAK4 and RhoU cooperate to drive adhesion turnover and promote cell migration. (PMID:26598620)
• These results unravel a role for RhoU not only in regulating the migratory features of malignant plasma cells, but also in controlling cell cycle progression. (PMID:29440639)
• RHOU expression is reduced in human colorectal tumour samples. RhoU knockdown in human DLD-1 colon cancer cells also elicits a higher growth index and reduces cell apoptosis. (PMID:30834544)
• These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs, and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment. (PMID:31601299)
• Lipogenic signalling modulates prostate cancer cell adhesion and migration via modification of Rho GTPases. (PMID:32139877)
• LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability. (PMID:36221055)
• RhoU forms homo-oligomers to regulate cellular responses. (PMID:38180080)
• SUMOylation of annexin A6 retards cell migration and tumor growth by suppressing RHOU/AKT1-involved EMT in hepatocellular carcinoma. (PMID:38566133)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhoua	ENSDARG00000019709
mus_musculus	Rhou	ENSMUSG00000039960
rattus_norvegicus	Rhou	ENSRNOG00000062578

Paralogs (22): RHOBTB2 (ENSG00000008853), RHOA (ENSG00000067560), CDC42 (ENSG00000070831), RHOBTB1 (ENSG00000072422), RHOV (ENSG00000104140), RND2 (ENSG00000108830), RND3 (ENSG00000115963), 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 RhoU — Q7L0Q8 (reviewed: Q7L0Q8)

Alternative names: CDC42-like GTPase 1, GTP-binding protein-like 1, Rho GTPase-like protein ARHU, Ryu GTPase, Wnt-1 responsive Cdc42 homolog 1

All UniProt accessions (1): Q7L0Q8

UniProt curated annotations — full annotation on UniProt →

Function. Binds to and activates protein kinase PAK1. Plays a role in the regulation of cell morphology, cytoskeletal organization and focal adhesion assembly during cell migration. Also stimulates quiescent cells to reenter the cell cycle. Has no detectable GTPase activity but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound.

Subunit / interactions. Interacts with PAK1. Interacts with PAK3. Interacts with ARHGAP30 in a GTP-independent manner. In its GTP-loaded conformation, interacts with ARHGAP31. Interacts with PTK2B/PYK2. Interacts with PAK4; the interaction is PAK4 kinase activity-independent and protects RHOU from ubiquitination.

Subcellular location. Cell membrane. Golgi apparatus membrane. Cell junction. Focal adhesion. Cell projection. Podosome.

Tissue specificity. Ubiquitously expressed in all tissues examined. Expressed at high levels in the stomach, small intestine, brain, skeletal muscle and placenta.

Post-translational modifications. Ubiquitinated. ‘Lys-48’-linked ubiquitination at Lys-177 and Lys-248 by the ECS(RAB40A) complex leading to its degradation. Tyrosine phosphorylated by SRC in response to PTK2B/PYK2 activation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q7L0Q8-1	1	yes
Q7L0Q8-2	2

RefSeq proteins (1): NP_067028* (*=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

Pfam: PF00071

UniProt features (44 total): mutagenesis site 11, strand 8, helix 8, binding site 3, splice variant 2, compositionally biased region 2, sequence conflict 2, turn 2, cross-link 2, chain 1, region of interest 1, sequence variant 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2Q3H	X-RAY DIFFRACTION	1.73

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L0Q8-F1	79.99	0.60

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): 56–63; 103–107; 161–164

Post-translational modifications (3): 256, 177, 248

Mutagenesis-validated functional residues (11):

Position	Phenotype
63	loss of gtp-binding and localization to focal adhesions. no effect on arhgap30-binding.
80	no effect on arhgap30-binding.
81	loss of binding to pak3; when associated with a-83 and c-86.
83	loss of binding to pak3; when associated with s-81 and c-86.
83	loss of arhgap30-binding.
86	loss of pak3-binding; when associated with s-81 and a-83. no effect on arhgap30-binding.
107	constitutively active. results in increased rates of stress fiber dissolution and cell migration. no effect on arhgap30-
177	decreased ubiquitination.
248	decreased ubiquitination.
255	no effect on subcellular location.
256	loss of subcellular location to plasma and intracellular membranes.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9013420	RHOU GTPase cycle

MSigDB gene sets: 223 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MODULE_418, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_PROTEIN_TARGETING, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GTGCCTT_MIR506

GO Biological Process (13): G1/S transition of mitotic cell cycle (GO:0000082), endocytosis (GO:0006897), cytoskeleton organization (GO:0007010), actin filament organization (GO:0007015), signal transduction (GO:0007165), regulation of cell shape (GO:0008360), Rac protein signal transduction (GO:0016601), establishment of cell polarity (GO:0030010), regulation of small GTPase mediated signal transduction (GO:0051056), positive regulation of focal adhesion disassembly (GO:0120183), obsolete positive regulation of protein targeting to mitochondrion (GO:1903955), small GTPase-mediated signal transduction (GO:0007264), actin cytoskeleton organization (GO:0030036)

GO Molecular Function (8): GTPase activity (GO:0003924), guanyl-nucleotide exchange factor activity (GO:0005085), GTP binding (GO:0005525), protein kinase binding (GO:0019901), protein-macromolecule adaptor activity (GO:0030674), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): Golgi membrane (GO:0000139), podosome (GO:0002102), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), endosome membrane (GO:0010008), Golgi apparatus (GO:0005794), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by Interleukins	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
small GTPase-mediated signal transduction	2
bounding membrane of organelle	2
cytoplasm	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
organelle organization	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of cell morphogenesis	1
regulation of biological quality	1
establishment or maintenance of cell polarity	1
regulation of intracellular signal transduction	1
focal adhesion disassembly	1
regulation of focal adhesion disassembly	1
positive regulation of cell-substrate junction organization	1
intracellular signaling cassette	1
cytoskeleton organization	1
actin filament-based process	1
ribonucleoside triphosphate phosphatase activity	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
kinase binding	1
protein binding	1
molecular adaptor activity	1
cation binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

3305 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHOU	PAK4	O96013	854
RHOU	WNT1	P04628	669
RHOU	ARHGAP30	Q7Z6I6	599
RHOU	NCK2	O43639	551
RHOU	NCK1	P16333	544
RHOU	GRB2	P29354	529
RHOU	CCN4	O95388	524
RHOU	CTNNB1	P35222	516
RHOU	FN1	P02751	478
RHOU	MAPK8	P45983	474
RHOU	RHOBTB3	O94955	469
RHOU	GALNTL5	Q7Z4T8	453
RHOU	RYK	P34925	451
RHOU	ABI2	Q9NYB9	435
RHOU	RHOA	P06749	433

IntAct

41 interactions, top by confidence:

A	B	Type	Score
RHOU	NCK2	psi-mi:“MI:0915”(physical association)	0.790
NCK2	RHOU	psi-mi:“MI:0403”(colocalization)	0.790
NCK2	RHOU	psi-mi:“MI:0915”(physical association)	0.790
NCK2	RHOU	psi-mi:“MI:0407”(direct interaction)	0.790
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
PAK1	RHOU	psi-mi:“MI:0915”(physical association)	0.590
RHOU	PTK2B	psi-mi:“MI:0915”(physical association)	0.580
PTK2B	RHOU	psi-mi:“MI:0915”(physical association)	0.580
GRB2	RHOU	psi-mi:“MI:0915”(physical association)	0.520
RHOU	GRB2	psi-mi:“MI:0915”(physical association)	0.520
ARHGAP30	RHOU	psi-mi:“MI:0915”(physical association)	0.510
ARHGAP30	RHOU	psi-mi:“MI:0915”(physical association)	0.460
ARHGAP30	RHOU	psi-mi:“MI:0403”(colocalization)	0.460
	RHOU	psi-mi:“MI:0407”(direct interaction)	0.440
PTK2	RHOU	psi-mi:“MI:0915”(physical association)	0.400
Arhgap31	RHOU	psi-mi:“MI:0915”(physical association)	0.400
RHOU	NCK1	psi-mi:“MI:0915”(physical association)	0.400
PLCG1	RHOU	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (528): RHOU (Affinity Capture-Western), RHOU (Reconstituted Complex), ZFAND2B (Reconstituted Complex), PLEK (Reconstituted Complex), CTCF (Reconstituted Complex), POT1 (Reconstituted Complex), ERF (Reconstituted Complex), RALBP1 (Reconstituted Complex), MARCKS (Reconstituted Complex), ERO1L (Reconstituted Complex), ZNF177 (Reconstituted Complex), RPS15A (Reconstituted Complex), ZNF625 (Reconstituted Complex), DMRT2 (Reconstituted Complex), CPNE3 (Reconstituted Complex)

ESM2 similar proteins: A0FGR8, A1DZY4, A5D7J5, O35141, O35929, O75628, O75808, O94103, P01114, P01115, P0C0E4, P27040, P35739, P55040, P55041, P55043, P63032, P63033, P70268, Q00993, Q06AU5, Q13637, Q17QI8, Q3UFB7, Q496Y0, Q5R541, Q63433, Q67VP4, Q6IMB1, Q6P0U3, Q6T310, Q7L0Q8, Q7YS69, Q864R5, Q8HXH0, Q8IYK8, Q8J212, Q8QFP8, Q8VDU1, Q8VEL9

Diamond homologs: A0A286QZ36, A5D7J5, C4YDI6, O04369, O76321, O82480, O82481, O88931, O94103, O96390, P01122, P08134, P0CY33, P15153, P17081, P19073, P24406, P34144, P34145, P34146, P34147, P34148, P34149, P34150, P40792, P40793, P48148, P48554, P60763, P60764, P60766, P60952, P60953, P61585, P61586, P61589, P62998, P62999, P63000, P63001

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRC	“down-regulates activity”	RHOU	phosphorylation
has-mir-126-3p	“down-regulates quantity by repression”	RHOU	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 30 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
RHOU GTPase cycle	8	89.1×	3e-12
VEGFA-VEGFR2 Pathway	5	27.9×	3e-05
SLC-mediated transmembrane transport	6	14.2×	7e-05
Transport of small molecules	6	6.0×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	5	44.2×	1e-05
cell migration	6	13.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

701 predictions. Top by Δscore:

Variant	Effect	Δscore
1:228736556:GCT:G	donor_gain	1.0000
1:228737670:A:AG	acceptor_gain	1.0000
1:228737670:AAGC:A	acceptor_gain	1.0000
1:228737671:A:AG	acceptor_gain	1.0000
1:228737671:AGC:A	acceptor_gain	1.0000
1:228737672:G:GA	acceptor_gain	1.0000
1:228737672:GCG:G	acceptor_gain	1.0000
1:228736004:GGTGA:G	donor_loss	0.9900
1:228736005:G:GG	donor_gain	0.9900
1:228736005:GTG:G	donor_loss	0.9900
1:228736006:T:G	donor_loss	0.9900
1:228736580:GA:G	donor_gain	0.9900
1:228736582:G:GG	donor_gain	0.9900
1:228737670:AAGCG:A	acceptor_gain	0.9900
1:228737672:GC:G	acceptor_gain	0.9900
1:228737672:GCGGT:G	acceptor_gain	0.9900
1:228737667:TTTAA:T	acceptor_loss	0.9800
1:228737668:TTAA:T	acceptor_loss	0.9800
1:228737669:TAA:T	acceptor_loss	0.9800
1:228737670:AAG:A	acceptor_loss	0.9800
1:228737671:A:AT	acceptor_loss	0.9800
1:228737672:G:GT	acceptor_loss	0.9800
1:228737673:C:CA	acceptor_gain	0.9800
1:228737728:ACAGG:A	donor_loss	0.9800
1:228737729:CAGGT:C	donor_loss	0.9800
1:228737730:AGG:A	donor_loss	0.9800
1:228737731:GGTC:G	donor_loss	0.9800
1:228737732:G:GA	donor_loss	0.9800
1:228737733:T:G	donor_loss	0.9800
1:228737734:CAGTA:C	donor_loss	0.9800

AlphaMissense

1674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:228735908:G:C	G56R	1.000
1:228735923:G:C	G61R	1.000
1:228735924:G:A	G61D	1.000
1:228735924:G:T	G61V	1.000
1:228735930:C:T	T63M	1.000
1:228735936:T:C	L65P	1.000
1:228735947:T:G	Y69D	1.000
1:228737717:G:C	D103H	1.000
1:228737718:A:C	D103A	1.000
1:228737718:A:G	D103G	1.000
1:228737718:A:T	D103V	1.000
1:228737719:C:A	D103E	1.000
1:228737719:C:G	D103E	1.000
1:228743344:C:G	C127W	1.000
1:228743390:T:A	W143R	1.000
1:228743390:T:C	W143R	1.000
1:228743392:G:C	W143C	1.000
1:228743392:G:T	W143C	1.000
1:228743439:T:A	V159D	1.000
1:228743442:G:A	G160E	1.000
1:228743454:A:G	D164G	1.000
1:228743457:T:C	L165P	1.000
1:228743606:T:C	F215L	1.000
1:228743608:T:A	F215L	1.000
1:228743608:T:G	F215L	1.000
1:228743616:C:A	A218D	1.000
1:228735908:G:A	G56S	0.999
1:228735908:G:T	G56C	0.999
1:228735909:G:A	G56D	0.999
1:228735909:G:T	G56V	0.999

dbSNP variants (sampled 300 via entrez): RS1000014968 (1:228733755 T>C), RS1000032588 (1:228690720 C>T), RS1000070948 (1:228684367 T>C,G), RS1000094259 (1:228647265 T>A,G), RS1000136955 (1:228674276 A>G), RS1000172244 (1:228733599 A>C), RS1000190489 (1:228658741 G>A,T), RS1000192943 (1:228653582 G>A,C), RS1000216557 (1:228714251 T>A,C), RS1000242902 (1:228703175 C>T), RS1000269363 (1:228671482 C>T), RS1000271577 (1:228714749 T>C), RS1000290876 (1:228720531 C>T), RS1000351955 (1:228713952 G>A), RS1000375624 (1:228665323 A>C)

Disease associations

OMIM: gene MIM:606366 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000249_2	Basal cell carcinoma	6.000000e-12
GCST000797_1	Endometriosis	5.000000e-06
GCST001599_8	Aging	5.000000e-06
GCST001786_27	Dental caries	5.000000e-07
GCST001786_7	Dental caries	4.000000e-06
GCST001809_4	Type 2 diabetes	2.000000e-06
GCST002331_4	Basal cell carcinoma	2.000000e-13
GCST002842_2	Basal cell carcinoma	8.000000e-14
GCST002927_14	Mercury levels	4.000000e-08
GCST003726_12	Basal cell carcinoma	1.000000e-14
GCST003803_3	Response to antidepressants in depression	1.000000e-06
GCST004146_30	Chronic lymphocytic leukemia	1.000000e-10
GCST005896_77	Non-melanoma skin cancer	8.000000e-22
GCST010676_2	Leukoderma in response to rhododendrol	8.000000e-06
GCST90013410_32	Basal cell carcinoma	1.000000e-71

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0009260	non-melanoma skin carcinoma

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, increases expression, affects cotreatment	8
trichostatin A	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance	3
Tretinoin	increases expression	3
bisphenol A	increases expression, increases methylation, decreases expression	2
Estradiol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Progesterone	increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
enzalutamide	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Irinotecan	increases expression	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1

Clinical trials (associated diseases)

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