ARL6IP5

Summary

ARL6IP5 (ARF like GTPase 6 interacting protein 5, HGNC:16937) is a protein-coding gene on chromosome 3p14.1, encoding PRA1 family protein 3 (O75915). Regulates intracellular concentrations of taurine and glutamate.

Expression of this gene is affected by vitamin A. The encoded protein of this gene may be associated with the cytoskeleton. A similar protein in rats may play a role in the regulation of cell differentiation. The rat protein binds and inhibits the cell membrane glutamate transporter EAAC1. The expression of the rat gene is upregulated by retinoic acid, which results in a specific reduction in EAAC1-mediated glutamate transport.

Source: NCBI Gene 10550 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 38 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_006407

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16937
Approved symbol	ARL6IP5
Name	ARF like GTPase 6 interacting protein 5
Location	3p14.1
Locus type	gene with protein product
Status	Approved
Aliases	PRAF3, JWA, GTRAP3-18, DERP11, HSPC127, Yip6b
Ensembl gene	ENSG00000144746
Ensembl biotype	protein_coding
OMIM	605709
Entrez	10550

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000273258, ENST00000470936, ENST00000478935, ENST00000484921, ENST00000485444, ENST00000889982, ENST00000941226, ENST00000941227

RefSeq mRNA: 1 — MANE Select: NM_006407 NM_006407

CCDS: CCDS2912

Canonical transcript exons

ENST00000273258 — 3 exons

Exon	Start	End
ENSE00001679658	69084937	69085223
ENSE00002422723	69104464	69106092
ENSE00003645828	69101839	69102056

Expression profiles

Bgee: expression breadth ubiquitous, 307 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 131.3630 / max 1722.4337, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37225	107.5210	1814
37223	16.0130	1600
37224	7.1018	1388
37222	0.7273	374

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.45	gold quality
visceral pleura	UBERON:0002401	99.39	gold quality
pleura	UBERON:0000977	99.36	gold quality
parietal pleura	UBERON:0002400	99.34	gold quality
heart right ventricle	UBERON:0002080	99.33	gold quality
superficial temporal artery	UBERON:0001614	99.31	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.29	gold quality
hair follicle	UBERON:0002073	99.27	gold quality
substantia nigra pars compacta	UBERON:0001965	99.21	gold quality
synovial joint	UBERON:0002217	99.20	gold quality
biceps brachii	UBERON:0001507	99.19	gold quality
epithelium of mammary gland	UBERON:0003244	99.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.18	gold quality
parotid gland	UBERON:0001831	99.17	gold quality
mammary duct	UBERON:0001765	99.16	gold quality
pons	UBERON:0000988	99.15	gold quality
skin of hip	UBERON:0001554	99.13	gold quality
caput epididymis	UBERON:0004358	99.10	gold quality
lateral globus pallidus	UBERON:0002476	99.09	gold quality
myocardium	UBERON:0002349	99.08	gold quality
epithelial cell of pancreas	CL:0000083	99.04	gold quality
decidua	UBERON:0002450	99.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.01	gold quality
calcaneal tendon	UBERON:0003701	99.00	gold quality
periodontal ligament	UBERON:0008266	98.99	gold quality
epididymis	UBERON:0001301	98.98	gold quality
esophagus squamous epithelium	UBERON:0006920	98.98	gold quality
trabecular bone tissue	UBERON:0002483	98.97	gold quality
cauda epididymis	UBERON:0004360	98.97	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-31	yes	23.43
E-MTAB-8410	yes	23.36
E-GEOD-81608	yes	16.16
E-CURD-112	yes	15.11
E-MTAB-8142	yes	12.19
E-CURD-114	yes	11.74
E-MTAB-10042	yes	9.87
E-GEOD-135922	yes	7.05
E-MTAB-7606	no	1363.95
E-GEOD-75367	no	1256.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ING4

miRNA regulators (miRDB)

80 targeting ARL6IP5, 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-5692A	100.00	74.40	6850
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
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-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548BB-3P	99.86	70.58	4354

Literature-anchored findings (GeneRIF, showing 37)

• highly conserved protein and genomic organization amongst vertebrates (PMID:12119102)
• protein expression is upregulated by methyl-beta-cyclodextrin and not by retinoic acid (PMID:12562531)
• Rsults suggest that JWA can be regulated by oxidative stress and is actively involved in the signal pathways of oxidative stress in the cells. (PMID:15864752)
• Data show that the JWA -76G–>C variant genotype may play an important role in transcription regulation of JWA gene and in the susceptibility to bladder cancer. (PMID:16331563)
• JWA may function as a lineage-restricted gene during differentiation along the monocyte/macrophage-like or granulocytic pathway (PMID:16430862)
• all-trans retinoic acid up-regulates JWA expression by stimulating the transcriptional activity of JWA gene promoter (PMID:16468075)
• This paper deals primarily with PRAF2, but comparisons with PRAF3 are also provided. (PMID:16481131)
• all-trans retinoic acid increased JWA gene expression in human pulmonary artery smooth muscle cells. (PMID:16638297)
• The JWA determined might function as a potential effective environmental responsive gene and actively participated in the process of B (a) P exposure associated with intracellular signal pathways of DNA damage and repair (PMID:16640902)
• JWA participates in the signal pathways of H2O2 induced oxidative stress in K562 cells (PMID:16766476)
• The effects of All Trans Retinoic Acid in regulating cellular proliferation and apoptosis may be mediated in part by JWA expression. (PMID:16922813)
• JWA regulated-tumor cellular migration might involve MAPK cascades activation and F-actin cytoskeleton rearrangement mechanisms. (PMID:17336041)
• Three novel functional genetic poly- morphisms of JWA gene, -76C, 454A, and 723G, appear to contribute to the etiology of bladder cancer (PMID:17479401)
• Single nucleotide polymorphisms of JWA were associated with enhanced risk of gastric cancer and esophageal squamous cell carcinoma in a Chinese population. (PMID:17479402)
• The potentially functional genetic polymorphism 454CA of the JWA gene appears to contribute to the risk of multiple kinds of leukemia in a south Chinese population. (PMID:17479403)
• These results show GTRAP3-18 to negatively and dominantly regulate cellular GSH content via interaction with EAAC1 at the plasma membrane. (PMID:17646425)
• Expression of GTRAP3-18 delays the ER exit of EAAC1, as well as other members of the excitatory amino acid transporter family. (PMID:18167356)
• JWA night play an important role in neoplastic transformation of HBE cells through regulation of p53 expression. (PMID:19080375)
• The gene polymorphisms at site 76 and GG/CT haploid type of JWA gene were associated with hypertension in workers exposed to high temperature. (PMID:22357531)
• PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC. (PMID:22433565)
• JWA and XRCC1 protein levels were downregulated in gastric cancer lesions compared with adjacent noncancerous tissues;JWA and XRCC1 protein expressions in tumor are candidate prognostic markers and predictive factors for benefit from adjuvant platinum-based chemotherapy in resectable gastric carcinoma (PMID:22452940)
• This review gives an overview of EAAC1-mediated GSH synthesis, and its regulatory mechanisms by GTRAP3-18 in the brain, and a potential approach against neurodegeneration. (PMID:23109897)
• data demonstrate that JWA plays a crucial role in HCC progression and suggest JWA may be a potential prognostic biomarker and therapeutic target for HCC. (PMID:23169062)
• A combined effect of p53 with JWA as efficient prognostic indicators was found for the first time. (PMID:23285001)
• JWA plays an important role in the occurrence and progress of human esophageal squamous cell carcinoma (ESCC) and that high expression level of JWA may predict a favorable prognosis in ESCC patients. (PMID:23461062)
• A significant negative correlation between JWA and ILK in melanoma biopsies. (PMID:24064223)
• Loss of JWA expression was strongly correlated with increased gastric cancer angiogenesis. (PMID:24072772)
• JWA has an important role in ING4-regulated melanoma angiogenesis, and ING4/JWA/ILK are promising prognostic markers and may be used as anti-angiogenic therapeutic targets for melanoma. (PMID:24157826)
• JWA reverses cisplatin resistance via the CK2-XRCC1 pathway in human gastric cancer cells. (PMID:25476899)
• the JWA gene may regulate human breast cancer cells through the MAPK signaling pathway using different types of regulation. (PMID:25586271)
• JWA and topoisomerase II alpha regulate each other in tumor cells arrested in G2/M. (PMID:26046674)
• our results demonstrate that JWA is a novel negative regulator of HER2 expression…in HER2-positive gastric cancer cells (PMID:27167206)
• Protective effect of JWA against paraquat neurotoxicity involves regulation of the MEK/PI3K-Nrf2 axis. (PMID:28428137)
• increased RNF185 expression facilitated GC cell migration in vitro and promoted GC metastasis in vivo by downregulating JWA expression. (PMID:29481911)
• These data demonstrated that JWA suppressed the migration/invasion of breast carcinoma cells by downregulating the expression of CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in patients with breast cancer. (PMID:29658570)
• Correlation between JWA gene polymorphism and acute lymphoblastic leukemia. (PMID:31726816)
• ARL6IP5 reduces cisplatin-resistance by suppressing DNA repair and promoting apoptosis pathways in ovarian carcinoma. (PMID:35293383)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl6ip5b	ENSDARG00000016238
danio_rerio	arl6ip5a	ENSDARG00000077044
mus_musculus	Arl6ip5	ENSMUSG00000035199
rattus_norvegicus	Arl6ip5	ENSRNOG00000006818
drosophila_melanogaster	Jwa	FBGN0032704
caenorhabditis_elegans		WBGENE00017070

Paralogs (1): PRAF2 (ENSG00000243279)

Protein

Protein identifiers

PRA1 family protein 3 — O75915 (reviewed: O75915)

Alternative names: ADP-ribosylation factor-like protein 6-interacting protein 5, Cytoskeleton-related vitamin A-responsive protein, Dermal papilla-derived protein 11, GTRAP3-18, Glutamate transporter EAAC1-interacting protein, JM5, Prenylated Rab acceptor protein 2, Protein JWa, Putative MAPK-activating protein PM27

All UniProt accessions (4): O75915, C9JQU6, F8WF33, F8WF90

UniProt curated annotations — full annotation on UniProt →

Function. Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. Plays a role in the retention of SLC1A1/EAAC1 in the endoplasmic reticulum.

Subunit / interactions. Homodimer. Heterodimer with ARL6IP1. Forms multimers. Interacts with ARL6. Interacts with prenylated RAB1A and RAB3A. Interacts with SLC1A1/EAAC1. Interacts with RTN2 (via first transmembrane domain). Does not interact with VAMP1, VAMP2 or VAMP3.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane. Cytoplasm. Cytoskeleton.

Induction. By methyl-beta-cyclodextrin. Up-regulated upon induced differentiation and in heat stress.

Similarity. Belongs to the PRA1 family.

RefSeq proteins (1): NP_006398* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004895	Prenylated_rab_accept_PRA1	Family

Pfam: PF03208

UniProt features (12 total): transmembrane region 4, topological domain 3, region of interest 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75915-F1	89.91	0.64

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 (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-210500	Glutamate Neurotransmitter Release Cycle

MSigDB gene sets: 265 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, CAGCTG_AP4_Q5, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE

GO Biological Process (13): negative regulation of L-glutamate import across plasma membrane (GO:0002037), glutathione metabolic process (GO:0006749), learning or memory (GO:0007611), intrinsic apoptotic signaling pathway in response to oxidative stress (GO:0008631), negative regulation of mitochondrial membrane potential (GO:0010917), protein transport (GO:0015031), L-glutamate transmembrane transport (GO:0015813), positive regulation of stress-activated MAPK cascade (GO:0032874), cellular response to oxidative stress (GO:0034599), positive regulation of apoptotic process (GO:0043065), negative regulation of transport (GO:0051051), protein localization to plasma membrane (GO:0072659), L-glutamate import across plasma membrane (GO:0098712)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), membrane (GO:0016020), presynaptic cytosol (GO:0099523), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter release cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
cellular anatomical structure	2
regulation of L-glutamate import across plasma membrane	1
negative regulation of organic acid transport	1
negative regulation of transmembrane transport	1
negative regulation of amino acid transport	1
L-glutamate import across plasma membrane	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
behavior	1
cognition	1
intrinsic apoptotic signaling pathway	1
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
intracellular protein localization	1
establishment of protein localization	1
L-glutamate import	1
L-alpha-amino acid transmembrane transport	1
regulation of stress-activated MAPK cascade	1
positive regulation of MAPK cascade	1
stress-activated MAPK cascade	1
positive regulation of stress-activated protein kinase signaling cascade	1
response to oxidative stress	1
cellular response to chemical stress	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
negative regulation of biological process	1
regulation of transport	1
protein localization to membrane	1
protein localization to cell periphery	1
L-glutamate transmembrane transport	1
amino acid import across plasma membrane	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL6IP5	SLC1A1	P43005	939
ARL6IP5	RABAC1	Q9UI14	772
ARL6IP5	COPS7A	Q9UBW8	581
ARL6IP5	GHITM	Q9H3K2	571
ARL6IP5	UBA3	Q8TBC4	570
ARL6IP5	ARL6	Q9H0F7	555
ARL6IP5	MINDY3	Q9H8M7	541
ARL6IP5	TMEM45A	Q9NWC5	540
ARL6IP5	SOD1	P00441	514
ARL6IP5	ARL6IP1	Q15041	503
ARL6IP5	BCL2	P10415	455
ARL6IP5	TMEM9	Q9P0T7	431
ARL6IP5	DYNLT2B	Q8WW35	421
ARL6IP5	XRCC1	P18887	417
ARL6IP5	PPIB	P23284	415

IntAct

147 interactions, top by confidence:

A	B	Type	Score
ESYT1	ESYT2	psi-mi:“MI:0914”(association)	0.770
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FPR2	ARL6IP5	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
PRAF2	ARL6IP5	psi-mi:“MI:0915”(physical association)	0.620
ARL6IP5	PRAF2	psi-mi:“MI:0915”(physical association)	0.620
PRAF2	ARL6IP5	psi-mi:“MI:0403”(colocalization)	0.620
RNF185	ARL6IP5	psi-mi:“MI:0915”(physical association)	0.560
MIEF1	ARL6IP5	psi-mi:“MI:0915”(physical association)	0.560
ARL6IP5	MIEF1	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
S1PR2	PALM3	psi-mi:“MI:0914”(association)	0.530
GYPB	TCAF2	psi-mi:“MI:0914”(association)	0.530
TSPAN11	IGLL5	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
HTR3E	ARL6IP5	psi-mi:“MI:0914”(association)	0.530
FAM241A	NRP1	psi-mi:“MI:0914”(association)	0.530
FAM241A	SPTLC2	psi-mi:“MI:0914”(association)	0.530

BioGRID (289): RNF185 (Two-hybrid), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS)

ESM2 similar proteins: B0S4Q1, B9EN89, O43462, O54862, O75915, Q0III2, Q0IIK4, Q15041, Q1LZE6, Q28H54, Q3SWT5, Q4G019, Q4KLV1, Q4R4R4, Q502G2, Q56P28, Q5BJC1, Q5E978, Q5E9M1, Q5NV96, Q5R454, Q5R4X8, Q5RAC8, Q5ZLL0, Q66H21, Q66J05, Q66J44, Q68EQ9, Q6AXM5, Q6DFT6, Q6GPZ5, Q6IFY7, Q6INE8, Q7ZYQ3, Q80TA1, Q8BGS7, Q8C025, Q8CHX6, Q8LEQ4, Q8NFR3

Diamond homologs: O60831, O75915, Q2KHX3, Q4R4I9, Q4R4R4, Q56P28, Q5E9M1, Q5F433, Q5R4X8, Q8R5J9, Q9ES40, Q9JIG8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
Defective CFTR causes cystic fibrosis	5	12.5×	2e-03
Class A/1 (Rhodopsin-like receptors)	11	9.3×	1e-05
GPCR ligand binding	10	7.3×	1e-04
ABC-family protein mediated transport	5	6.9×	8e-03
Anchoring of the basal body to the plasma membrane	5	6.4×	1e-02
Signaling by GPCR	11	5.0×	8e-04
G alpha (i) signalling events	11	4.9×	8e-04
GPCR downstream signalling	9	4.4×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	9	8.4×	4e-04
chemotaxis	7	7.6×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	30
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4682578	GRCh37/hg19 3p14.1-12.2(chr3:67967190-80941234)x1	Pathogenic
562781	GRCh37/hg19 3p14.1-12.3(chr3:66133719-75076440)x1	Pathogenic
151504	GRCh38/hg38 3p14.1-12.3(chr3:68328980-76764319)x3	Likely pathogenic

SpliceAI

527 predictions. Top by Δscore:

Variant	Effect	Δscore
3:69085194:G:GA	donor_gain	1.0000
3:69085219:GTGGG:G	donor_gain	1.0000
3:69085220:TGGG:T	donor_gain	1.0000
3:69085221:GGG:G	donor_gain	1.0000
3:69085221:GGGG:G	donor_gain	1.0000
3:69085222:GG:G	donor_gain	1.0000
3:69085222:GGG:G	donor_gain	1.0000
3:69085222:GGGT:G	donor_loss	1.0000
3:69085223:GG:G	donor_gain	1.0000
3:69085223:GGT:G	donor_loss	1.0000
3:69101830:A:AG	acceptor_gain	1.0000
3:69101831:T:G	acceptor_gain	1.0000
3:69101832:A:AG	acceptor_gain	1.0000
3:69101835:TCAGG:T	acceptor_loss	1.0000
3:69101836:CAGGT:C	acceptor_loss	1.0000
3:69101837:A:AG	acceptor_gain	1.0000
3:69101837:AG:A	acceptor_gain	1.0000
3:69101838:G:GA	acceptor_gain	1.0000
3:69101838:GG:G	acceptor_gain	1.0000
3:69101838:GGT:G	acceptor_gain	1.0000
3:69101838:GGTTT:G	acceptor_gain	1.0000
3:69102052:GCTGT:G	donor_gain	1.0000
3:69102053:CTGT:C	donor_gain	1.0000
3:69102053:CTGTG:C	donor_loss	1.0000
3:69102054:TGTGT:T	donor_loss	1.0000
3:69102055:GT:G	donor_gain	1.0000
3:69102055:GTGTA:G	donor_loss	1.0000
3:69102057:G:C	donor_loss	1.0000
3:69102057:G:GG	donor_gain	1.0000
3:69102058:T:G	donor_loss	1.0000

AlphaMissense

1256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:69104488:G:C	R140T	1.000
3:69085141:T:A	W32R	0.999
3:69085141:T:C	W32R	0.999
3:69085150:C:A	R35S	0.999
3:69085164:C:A	N39K	0.999
3:69085164:C:G	N39K	0.999
3:69085166:T:C	L40P	0.999
3:69085185:C:A	N46K	0.999
3:69085185:C:G	N46K	0.999
3:69101987:A:C	S109R	0.999
3:69101989:C:A	S109R	0.999
3:69101989:C:G	S109R	0.999
3:69102048:C:G	P129R	0.999
3:69104478:G:C	A137P	0.999
3:69104479:C:A	A137E	0.999
3:69104488:G:T	R140I	0.999
3:69104489:A:C	R140S	0.999
3:69104489:A:T	R140S	0.999
3:69085072:C:A	R9S	0.998
3:69085109:T:C	F21S	0.998
3:69085150:C:G	R35G	0.998
3:69085151:G:C	R35P	0.998
3:69085179:G:C	Q44H	0.998
3:69085179:G:T	Q44H	0.998
3:69085181:C:T	T45I	0.998
3:69085186:T:C	Y47H	0.998
3:69085222:G:A	G59R	0.998
3:69085222:G:C	G59R	0.998
3:69102035:G:C	G125R	0.998
3:69102036:G:A	G125D	0.998

dbSNP variants (sampled 300 via entrez): RS1000100629 (3:69095410 A>G), RS1000113822 (3:69095563 C>G), RS1000126139 (3:69091679 G>T), RS1000233848 (3:69094987 C>T), RS1000547972 (3:69095739 C>G), RS1000864847 (3:69087605 A>C,G,T), RS1000921496 (3:69103059 T>C), RS1000939657 (3:69088000 C>G,T), RS1000969513 (3:69083872 T>C), RS1001043718 (3:69100676 G>A), RS1001060528 (3:69090155 G>C), RS1001205103 (3:69100655 C>T), RS1001286305 (3:69094702 C>A), RS1001515670 (3:69093823 C>T), RS1001870016 (3:69085941 T>G)

Disease associations

OMIM: gene MIM:605709 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008971_47	Urate levels	5.000000e-08
GCST008972_157	Urate levels	5.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases reaction, increases expression, affects expression, affects cotreatment, affects reaction (+2 more)	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	decreases expression, increases expression	4
Air Pollutants	increases abundance, decreases expression, affects expression	4
Arsenic Trioxide	increases reaction, increases phosphorylation, increases expression, increases cleavage, increases activity (+4 more)	3
Acetaminophen	decreases expression	2
Cisplatin	affects cotreatment, affects response to substance, affects expression	2
Estradiol	affects expression, decreases expression	2
Tetradecanoylphorbol Acetate	decreases reaction, increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Cyclosporine	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
phoxim	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
kojic acid	increases expression	1
hydroxyhydroquinone	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
CD 437	affects expression	1
chloropicrin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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