IQGAP3

Summary

IQGAP3 (IQ motif containing GTPase activating protein 3, HGNC:20669) is a protein-coding gene on chromosome 1q22, encoding Ras GTPase-activating-like protein IQGAP3 (Q86VI3).

Enables calmodulin binding activity and myosin VI light chain binding activity. Predicted to be involved in mitotic actomyosin contractile ring assembly actin filament organization. Predicted to act upstream of or within several processes, including G1/S transition of mitotic cell cycle; intracellular signaling cassette; and regulation of macromolecule metabolic process. Predicted to be located in cytosol. Predicted to be active in cell cortex.

Source: NCBI Gene 128239 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary peripheral neuropathy (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 341 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_178229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20669
Approved symbol	IQGAP3
Name	IQ motif containing GTPase activating protein 3
Location	1q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183856
Ensembl biotype	protein_coding
OMIM	621092
Entrez	128239

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361170, ENST00000476565, ENST00000491900, ENST00000498755, ENST00000862862

RefSeq mRNA: 1 — MANE Select: NM_178229 NM_178229

CCDS: CCDS1144

Canonical transcript exons

ENST00000361170 — 38 exons

Exon	Start	End
ENSE00001291041	156531160	156531247
ENSE00001293544	156533773	156533875
ENSE00001295447	156544389	156544472
ENSE00001295555	156528916	156529082
ENSE00001295575	156551974	156552095
ENSE00001295781	156539838	156539990
ENSE00001296544	156563553	156563666
ENSE00001299296	156564615	156564691
ENSE00001299587	156550261	156550351
ENSE00001300366	156560934	156561021
ENSE00001302118	156562587	156562665
ENSE00001302500	156537181	156537321
ENSE00001302769	156538809	156539033
ENSE00001303128	156543981	156544050
ENSE00001303512	156527952	156528060
ENSE00001305775	156548348	156548487
ENSE00001309642	156569376	156569463
ENSE00001310143	156534009	156534141
ENSE00001315225	156525405	156526599
ENSE00001316750	156544152	156544223
ENSE00001317236	156530105	156530317
ENSE00001317286	156551705	156551868
ENSE00001317834	156532980	156533106
ENSE00001318049	156566027	156566104
ENSE00001319291	156548073	156548243
ENSE00001319511	156554235	156554392
ENSE00001321610	156563134	156563312
ENSE00001322518	156556533	156556693
ENSE00001324099	156548581	156548748
ENSE00001325253	156540708	156540916
ENSE00001325355	156528509	156528610
ENSE00001325360	156561838	156562001
ENSE00001327648	156534501	156534733
ENSE00001435349	156535163	156535247
ENSE00001690199	156539374	156539537
ENSE00001706904	156563757	156563824
ENSE00001814775	156572493	156572565
ENSE00003521128	156566390	156566546

Expression profiles

Bgee: expression breadth ubiquitous, 180 present calls, max score 92.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.8049 / max 195.7712, expressed in 1195 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15146	5.9958	1160
15147	0.4230	267
15148	0.3467	224
15145	0.0170	3
15142	0.0082	3
15143	0.0077	1
15144	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.74	gold quality
oocyte	CL:0000023	90.05	gold quality
secondary oocyte	CL:0000655	89.29	gold quality
ventricular zone	UBERON:0003053	88.99	gold quality
ileal mucosa	UBERON:0000331	88.65	gold quality
sperm	CL:0000019	87.28	gold quality
stromal cell of endometrium	CL:0002255	81.00	gold quality
ganglionic eminence	UBERON:0004023	80.75	gold quality
mucosa of transverse colon	UBERON:0004991	79.48	gold quality
lower esophagus mucosa	UBERON:0035834	78.59	gold quality
cartilage tissue	UBERON:0002418	77.90	gold quality
rectum	UBERON:0001052	76.01	gold quality
duodenum	UBERON:0002114	75.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.96	gold quality
bone marrow cell	CL:0002092	74.94	gold quality
esophagus mucosa	UBERON:0002469	74.61	gold quality
tibialis anterior	UBERON:0001385	73.46	silver quality
amniotic fluid	UBERON:0000173	73.32	gold quality
trabecular bone tissue	UBERON:0002483	73.32	silver quality
heart right ventricle	UBERON:0002080	72.74	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.10	gold quality
nasal cavity epithelium	UBERON:0005384	71.83	gold quality
superficial temporal artery	UBERON:0001614	71.80	gold quality
biceps brachii	UBERON:0001507	70.70	gold quality
colonic epithelium	UBERON:0000397	70.50	gold quality
esophagus squamous epithelium	UBERON:0006920	70.03	gold quality
gingiva	UBERON:0001828	69.60	silver quality
vermiform appendix	UBERON:0001154	69.53	gold quality
right testis	UBERON:0004534	68.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7051	yes	826.72
E-MTAB-7037	yes	116.50
E-ANND-3	yes	5.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

76 targeting IQGAP3, 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-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3191-3P	99.45	63.94	356
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-544B	99.18	67.41	1632

Literature-anchored findings (GeneRIF, showing 22)

• The first IQ-motifs from IQGAP2 and IQGAP3 form transient interactions with calmodulin in the absence of calcium. (PMID:21299499)
• IQGAP3 may contribute to the pathogenesis of lung cancer by modulating EGFR-ERK signaling (PMID:24849319)
• Mammalian IQGAP proteins may play a role in cytokinesis by regulating the localization of key cytokinesis regulatory proteins to the contractile apparatus during mitosis. (PMID:25229330)
• IQGAP1, IQGAP2, and IQGAP3 have diverse roles in vertebrate physiology, operating in the kidney, nervous system, cardiovascular system, pancreas, and lung. (Review) (PMID:25722290)
• IQGAP3 may be a potential therapeutic target in human breast cancer. (PMID:28281966)
• IQGAP3 functions as an important regulator of metastasis and epithelial-to-mesenchymal transition by constitutively activating the TGF-beta signaling pathway in Hepatocellular carcinoma. (PMID:28810875)
• IQGAP2 expression correlated positively with survivability, on the contrary, IQGAP3 expression levels correlated inversely with survivability (PMID:29073199)
• These results suggest that IQGAP3 plays an important role in gastric cancer stem cells (CSCs). The location of IQGAP3 on the cell membrane makes it a potential therapeutic target for gastric cancer (GC). (PMID:29131081)
• Both IQGAP3/BMP4 and IQGAP3/FAM107A ratios in ucfDNA were significantly higher in patients with BC than in those with hematuria. (PMID:30446454)
• Data found that the IQGAP3/BMP4 ratio in urinary cell-free DNA (ucfDNA) was significantly associated with recurrence-free survival (RFS) and progression-free survival (PFS) in non-muscle-invasive bladder cancer (NMIBC) patients suggesting that the IQGAP3/BMP4 ratio in ucfDNA may be an important independent factor for NMIBC prognosis. (PMID:31088707)
• IQGAP3 was upregulated in colorectal cancer at the tissue level and cellular level. Based on immunohistochemistry results of the tissue microarrays, authors demonstrated that higher expression of IQGAP3 was associated with higher tumor node metastasis stage (P = 0.005), higher incidence of lymph node metastasis (P = 0.004), and shorter overall survival (P = 0.022). (PMID:31544570)
• IQGAP3 may be a potential target gene for Kaempferol in the treatment of breast cancer. (PMID:31605603)
• Enhancement of Migration and Invasion of Gastric Cancer Cells by IQGAP3. (PMID:32824461)
• IQGAP3 interacts with Rad17 to recruit the Mre11-Rad50-Nbs1 complex and contributes to radioresistance in lung cancer. (PMID:32896617)
• IQGAP3, a YAP Target, Is Required for Proper Cell-Cycle Progression and Genome Stability. (PMID:34183451)
• CDC42 Regulates Cell Proliferation and Apoptosis in Bladder Cancer via the IQGAP3-Mediated Ras/ERK Pathway. (PMID:35412170)
• Comprehensive Multiomics Analysis Identified IQGAP3 as a Potential Prognostic Marker in Pan-Cancer. (PMID:36164370)
• IQGAP3 in clear cell renal cell carcinoma contributes to drug resistance and genome stability. (PMID:36275458)
• IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms. (PMID:36681115)
• Identification and validation of non-coding RNA-mediated high expression of IQGAP3 in poor prognosis of lung adenocarcinoma. (PMID:38282143)
• Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma. (PMID:38470497)
• IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases. (PMID:38674130)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	iqgap3	ENSDARG00000098650
mus_musculus	Iqgap3	ENSMUSG00000028068
rattus_norvegicus	Iqgap3	ENSRNOG00000027894
caenorhabditis_elegans	pes-7	WBGENE00003980

Paralogs (2): IQGAP1 (ENSG00000140575), IQGAP2 (ENSG00000145703)

Protein

Protein identifiers

Ras GTPase-activating-like protein IQGAP3 — Q86VI3 (reviewed: Q86VI3)

All UniProt accessions (2): Q86VI3, F2Z2E2

RefSeq proteins (1): NP_839943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR000593	IQGAP_helical	Domain
IPR001715	CH_dom	Domain
IPR001936	RasGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR023152	RasGAP_CS	Conserved_site
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00307, PF00612, PF00616, PF03836

UniProt features (30 total): sequence variant 7, strand 7, domain 6, helix 4, modified residue 3, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3ISU	X-RAY DIFFRACTION	1.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VI3-F1	79.89	0.21

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 (3): 162, 539, 1424

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 242 (showing top): GOBP_MITOTIC_CYTOKINESIS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_MAMMARY_GLAND_EPITHELIAL_CELL_PROLIFERATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MAMMARY_GLAND_EPITHELIUM_DEVELOPMENT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOMF_GTPASE_BINDING, KONG_E2F3_TARGETS, GOBP_CYTOKINETIC_PROCESS, SHEPARD_BMYB_MORPHOLINO_DN, GOLDRATH_ANTIGEN_RESPONSE, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, WATANABE_COLON_CANCER_MSI_VS_MSS_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1

GO Biological Process (12): G1/S transition of mitotic cell cycle (GO:0000082), Ras protein signal transduction (GO:0007265), regulation of cell size (GO:0008361), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), mammary gland epithelial cell proliferation (GO:0033598), positive regulation of mammary gland epithelial cell proliferation (GO:0033601), positive regulation of MAPK cascade (GO:0043410), ERK1 and ERK2 cascade (GO:0070371), mitotic actomyosin contractile ring assembly actin filament organization (GO:1903479), regulation of GTPase activity (GO:0043087)

GO Molecular Function (6): GTPase activator activity (GO:0005096), calmodulin binding (GO:0005516), small GTPase binding (GO:0031267), actin filament binding (GO:0051015), myosin VI light chain binding (GO:0070856), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), cell-cell junction (GO:0005911), cell cortex (GO:0005938), lateral plasma membrane (GO:0016328), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHO GTPase cycle	7
Signaling by Rho GTPases	2
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
regulation of gene expression	2
MAPK cascade	2
GTPase activity	2
cytoplasm	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G1/S phase transition	1
small GTPase-mediated signal transduction	1
regulation of cellular component size	1
macromolecule biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
epithelial cell proliferation	1
mammary gland epithelium development	1
mammary gland epithelial cell proliferation	1
regulation of mammary gland epithelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
mitotic cell cycle process	1
mitotic actomyosin contractile ring assembly	1
actomyosin contractile ring assembly actin filament organization	1
regulation of hydrolase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein binding	1
GTPase binding	1
actin binding	1
protein-containing complex binding	1
myosin light chain binding	1
myosin VI binding	1
binding	1
anchoring junction	1
cell periphery	1
plasma membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQGAP3	CALML3	P27482	593
IQGAP3	CALML5	Q9NZT1	593
IQGAP3	CALML4	Q96GE6	560
IQGAP3	CALML6	Q8TD86	559
IQGAP3	AKAP11	Q9UKA4	545
IQGAP3	RABGAP1	Q9Y3P9	505
IQGAP3	CDC42	P21181	496
IQGAP3	NIPAL2	Q9H841	474
IQGAP3	LGR4	Q9BXB1	464
IQGAP3	RASA1	P20936	461
IQGAP3	PTBP3	O95758	446
IQGAP3	TTC24	A2A3L6	440
IQGAP3	SRGAP1	Q7Z6B7	436
IQGAP3	TM2D1	Q9BX74	429
IQGAP3	CAMK2N1	Q7Z7J9	413

IntAct

152 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
RAC1	COX6C	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
DMWD	IQGAP3	psi-mi:“MI:0915”(physical association)	0.560
	IQGAP3	psi-mi:“MI:0915”(physical association)	0.560
FGFR3	IQGAP3	psi-mi:“MI:0915”(physical association)	0.560
IQGAP3	GSN	psi-mi:“MI:0915”(physical association)	0.560
KLF11	IQGAP3	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	IQGAP3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (184): IQGAP3 (Two-hybrid), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IST1 (Co-fractionation), MYH2 (Co-fractionation), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS)

ESM2 similar proteins: A2VE45, A4IFF3, A4IHU6, A6H739, A6QQ71, A6QR40, A8E7I5, D3ZQF4, E9Q6P5, F6PHZ6, O75344, O95801, Q0HA38, Q0P5H9, Q1JQC5, Q32KL4, Q499U2, Q4G069, Q5BK48, Q5EA11, Q5R8E4, Q60864, Q66H45, Q66HA5, Q68G30, Q6P1N0, Q6P5E6, Q6P5P3, Q7Z4L5, Q7ZU45, Q810A3, Q86VI3, Q86WT1, Q8BYZ7, Q8K1A6, Q8N0Z6, Q8N4P2, Q8N5M4, Q8R0H9, Q8R307

Diamond homologs: O14188, P46940, Q12280, Q13576, Q3UQ44, Q86VI3, Q9JKF1, Q10201, Q5AH02, P14318, Q08873, Q24799, Q55GV9, Q54K32

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 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
RHO GTPases activate PAKs	5	25.6×	8e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	7	10.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	249
Likely benign	40
Benign	13

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
617477	LMNA-NTRK1 fusion	Pathogenic
694497	NM_178229.5(IQGAP3):c.3422+6T>A	Likely pathogenic

SpliceAI

5896 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156526598:TC:T	acceptor_gain	1.0000
1:156526599:CC:C	acceptor_gain	1.0000
1:156528913:TA:T	donor_loss	1.0000
1:156528914:A:AC	donor_gain	1.0000
1:156528914:ACT:A	donor_loss	1.0000
1:156528915:C:CT	donor_gain	1.0000
1:156530101:TTAC:T	donor_loss	1.0000
1:156530103:A:C	donor_loss	1.0000
1:156530104:C:CT	donor_loss	1.0000
1:156530314:CTTC:C	acceptor_gain	1.0000
1:156530318:C:CA	acceptor_loss	1.0000
1:156530319:T:A	acceptor_loss	1.0000
1:156531154:ACT:A	donor_loss	1.0000
1:156531156:TCA:T	donor_loss	1.0000
1:156531158:A:AC	donor_gain	1.0000
1:156531159:C:CA	donor_gain	1.0000
1:156531159:CTTG:C	donor_gain	1.0000
1:156531243:TGGTG:T	acceptor_gain	1.0000
1:156531246:TG:T	acceptor_gain	1.0000
1:156531248:C:CC	acceptor_gain	1.0000
1:156532976:CCAC:C	donor_loss	1.0000
1:156532976:CCACC:C	donor_gain	1.0000
1:156532977:CACCT:C	donor_loss	1.0000
1:156532978:A:AC	donor_gain	1.0000
1:156532978:A:C	donor_loss	1.0000
1:156532979:C:CC	donor_gain	1.0000
1:156532979:C:CG	donor_loss	1.0000
1:156532979:CCT:C	donor_gain	1.0000
1:156533103:TCAC:T	acceptor_gain	1.0000
1:156533104:CAC:C	acceptor_gain	1.0000

AlphaMissense

10648 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156566072:G:C	N105K	0.998
1:156566072:G:T	N105K	0.998
1:156566545:A:G	W43R	0.998
1:156566545:A:T	W43R	0.998
1:156566087:G:C	F100L	0.997
1:156566087:G:T	F100L	0.997
1:156566089:A:G	F100L	0.997
1:156569383:C:G	A40P	0.997
1:156569391:A:G	L37P	0.997
1:156526595:A:G	L1596P	0.996
1:156528557:A:G	L1542P	0.996
1:156564621:G:T	A144D	0.996
1:156566086:G:T	R101S	0.996
1:156528566:G:T	A1539D	0.995
1:156563605:G:C	F189L	0.995
1:156563605:G:T	F189L	0.995
1:156563607:A:G	F189L	0.995
1:156564618:A:G	L145P	0.995
1:156564650:G:C	N134K	0.995
1:156564650:G:T	N134K	0.995
1:156566062:A:G	W109R	0.995
1:156566062:A:T	W109R	0.995
1:156566478:C:T	G65E	0.995
1:156566487:A:G	L62P	0.995
1:156526523:A:G	L1620P	0.994
1:156564664:A:C	Y130D	0.994
1:156566543:C:A	W43C	0.994
1:156566543:C:G	W43C	0.994
1:156569400:A:G	L34P	0.994
1:156526538:A:T	V1615D	0.993

dbSNP variants (sampled 300 via entrez): RS1000024878 (1:156538926 A>G), RS1000222596 (1:156560234 G>A,T), RS1000224720 (1:156560556 T>C), RS1000255627 (1:156560233 G>A), RS1000294317 (1:156526870 T>C), RS1000339357 (1:156573219 G>T), RS1000344407 (1:156551566 C>G,T), RS1000449253 (1:156567215 T>A), RS1000570642 (1:156567429 C>T), RS1000588052 (1:156545349 T>G), RS1000693170 (1:156549553 T>G), RS1000779702 (1:156530901 T>C), RS1000799758 (1:156551378 G>A), RS1000873112 (1:156572653 G>A), RS1000896310 (1:156525255 G>A,C)

Disease associations

OMIM: gene MIM:621092 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary peripheral neuropathy	Limited	Autosomal dominant

Mondo (2): congenital fibrosarcoma (MONDO:0004557), hereditary peripheral neuropathy (MONDO:0020127)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006014_2	Creatine kinase levels	6.000000e-11
GCST010988_257	Adult body size	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	4
bisphenol A	decreases expression, decreases reaction, increases abundance	2
Acetaminophen	decreases expression, increases expression	2
Doxorubicin	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
ginger extract	increases abundance, decreases expression, decreases reaction	1
dicrotophos	increases expression	1
propionaldehyde	decreases expression	1
tetrahydropalmatine	decreases expression	1
arsenite	affects binding, decreases reaction	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
phenethyl isothiocyanate	decreases expression	1
polyhexamethyleneguanidine	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Leflunomide	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Benzophenoneidum	increases expression	1
Caffeine	decreases phosphorylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1UY	HyCyte U2OS KO-hIQGAP3	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03834961	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia
NCT03278093	Not specified	UNKNOWN	Effect of Orthoses and Underfoot Vibration on Balance in Neuropathy
NCT03899792	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
NCT05236257	Not specified	COMPLETED	A Study Called EPI VITRAKVI to Compare Treatment Results in Patients With Infantile Fibrosarcoma (IFS), a Type of Connective Soft Tissue Cancer, Who Received a Treatment Called Larotrectinib From a Study Called SCOUT With Patient Data From an External Database