IQGAP2

Summary

IQGAP2 (IQ motif containing GTPase activating protein 2, HGNC:6111) is a protein-coding gene on chromosome 5q13.3, encoding Ras GTPase-activating-like protein IQGAP2 (Q13576). Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity.

This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10788 — RefSeq curated summary.

At a glance

• GWAS associations: 55
• Clinical variants (ClinVar): 269 total
• MANE Select transcript: NM_006633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6111
Approved symbol	IQGAP2
Name	IQ motif containing GTPase activating protein 2
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000145703
Ensembl biotype	protein_coding
OMIM	605401
Entrez	10788

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 protein_coding, 6 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000274364, ENST00000379730, ENST00000396234, ENST00000502745, ENST00000504254, ENST00000504477, ENST00000504558, ENST00000504815, ENST00000508410, ENST00000509074, ENST00000509741, ENST00000512256, ENST00000512383, ENST00000513534, ENST00000514001, ENST00000514350, ENST00000514579, ENST00000515505, ENST00000685113, ENST00000685564, ENST00000692467

RefSeq mRNA: 4 — MANE Select: NM_006633 NM_001285460, NM_001285461, NM_001285462, NM_006633

CCDS: CCDS34188, CCDS68897, CCDS68898, CCDS75262

Canonical transcript exons

ENST00000274364 — 36 exons

Exon	Start	End
ENSE00000971750	76637034	76637176
ENSE00000971751	76640933	76641103
ENSE00000971752	76652750	76652833
ENSE00000971753	76654200	76654271
ENSE00000971754	76654934	76655003
ENSE00000971760	76673952	76674036
ENSE00000971761	76674477	76674709
ENSE00000971762	76677218	76677350
ENSE00001082592	76611020	76611183
ENSE00001278087	76707200	76708132
ENSE00001377392	76403285	76403591
ENSE00002431609	76665026	76665175
ENSE00002454433	76668681	76668844
ENSE00003468251	76683776	76683917
ENSE00003493997	76695454	76695666
ENSE00003494484	76693355	76693442
ENSE00003527433	76658459	76658667
ENSE00003527460	76683115	76683217
ENSE00003528789	76631859	76632026
ENSE00003539915	76673449	76673589
ENSE00003542725	76702482	76702590
ENSE00003586403	76461570	76461669
ENSE00003600428	76701076	76701213
ENSE00003600585	76562396	76562552
ENSE00003604884	76627410	76627500
ENSE00003607071	76671759	76671983
ENSE00003626796	76697987	76698147
ENSE00003716297	76590408	76590586
ENSE00003720932	76592838	76592925
ENSE00003721272	76588906	76588973
ENSE00003729247	76600812	76600972
ENSE00003731397	76597439	76597602
ENSE00003736681	76575693	76575769
ENSE00003737145	76570580	76570657
ENSE00003753942	76589615	76589728
ENSE00003754520	76606179	76606303

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7383 / max 1249.4840, expressed in 930 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57107	5.1450	721
57109	4.8687	651
57106	4.2893	771
57104	3.1061	347
57105	0.6242	201
57110	0.4370	218
57108	0.3483	188
57103	0.3001	154
57125	0.1056	45
57102	0.1032	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.65	gold quality
ventricular zone	UBERON:0003053	98.32	gold quality
renal glomerulus	UBERON:0000074	97.46	gold quality
metanephric glomerulus	UBERON:0004736	97.40	gold quality
secondary oocyte	CL:0000655	97.09	gold quality
liver	UBERON:0002107	96.83	gold quality
right lobe of liver	UBERON:0001114	96.70	gold quality
oocyte	CL:0000023	96.69	gold quality
duodenum	UBERON:0002114	96.56	gold quality
parotid gland	UBERON:0001831	96.21	gold quality
monocyte	CL:0000576	95.83	gold quality
mononuclear cell	CL:0000842	95.76	gold quality
kidney epithelium	UBERON:0004819	95.73	gold quality
leukocyte	CL:0000738	95.72	gold quality
colonic mucosa	UBERON:0000317	95.63	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.43	gold quality
mucosa of transverse colon	UBERON:0004991	94.76	gold quality
seminal vesicle	UBERON:0000998	93.91	gold quality
pigmented layer of retina	UBERON:0001782	93.82	gold quality
retina	UBERON:0000966	93.79	gold quality
bone marrow cell	CL:0002092	93.59	gold quality
nephron tubule	UBERON:0001231	93.54	gold quality
granulocyte	CL:0000094	93.43	gold quality
ganglionic eminence	UBERON:0004023	93.39	gold quality
body of pancreas	UBERON:0001150	93.37	gold quality
placenta	UBERON:0001987	93.12	gold quality
left testis	UBERON:0004533	92.83	gold quality
bone marrow	UBERON:0002371	92.69	gold quality
right testis	UBERON:0004534	92.47	gold quality
rectum	UBERON:0001052	92.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	171.39
E-HCAD-6	yes	40.74
E-CURD-119	yes	32.66
E-GEOD-135922	yes	21.69
E-HCAD-10	yes	17.51
E-GEOD-137537	yes	16.29
E-HCAD-1	yes	11.03
E-CURD-114	yes	10.41
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting IQGAP2, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4789-5P	99.98	70.76	2721

Literature-anchored findings (GeneRIF, showing 22)

• The gene for the putative rac1/cdc42 effector protein IQGAP2 was found in the PAR gene cluster at 5q13, flanked by PAR1 & encompassing PAR3. It functions as a GTP-dependent effector protein in thrombin-induced platelet cytoskeletal reorganization. (PMID:12515716)
• silencing of IQGAP2 by promoter methylation may contribute to gastric cancer development. (PMID:17957782)
• The top-ranked SNP, rs457717 for association with age-related hearing impairment(P-value 3.55 x 10(-7)), was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). (PMID:20068591)
• increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. (PMID:20977743)
• The first IQ-motifs from IQGAP2 and IQGAP3 form transient interactions with calmodulin in the absence of calcium. (PMID:21299499)
• observations strongly indicate that IQGAP2 is a surveillance type of tumour suppressor for prostate cancer (PMID:22406297)
• Low IQGAP2 expression was associated with hepatocellular carcinoma. (PMID:24998570)
• 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)
• Data show that IQ motif-containing GTPase-activating protein 2 (IQGAP2) expression is altered in colitis. (PMID:26047140)
• we identified IQGAP2 as a human and zebrafish podocyte gene product that is downregulated in microarray data sets from kidney biopsies of human patients with focal segmental glomerulosclerosis and minimal change nephrotic syndrome. (PMID:26154927)
• IQGAP2 TagSNP rs457717 (A/G) was not associated with Age-Related Hearing impairment in Han male Chinese population. (PMID:26187738)
• Thus, these data identified IQGAP2 as a novel tumor suppressor for ovarian cancer to inhibit cell invasion through regulating Wnt/b-catenin signaling, and provided a new biomarker and potential therapeutic strategy for this disease. (PMID:26549344)
• The most frequently identified and connected to preterm birth genes in the exome library were IGF1, ATM and IQGAP2. (PMID:27163930)
• The structural basis for Cdc42-induced dimerization of IQGAP1 and IQGAP2 has been uncovered. (PMID:27524202)
• IQGAP2 expression correlated positively with survivability, on the contrary, IQGAP3 expression levels correlated inversely with survivability (PMID:29073199)
• Data suggest that CDC42 binding to Ex-domain of IQGAP2 releases Ex-domain at C-terminal region of GRD2 domain, facilitating IQGAP2 dimerization; this promotes allosteric changes in ras GTPase-activating protein binding site providing binding site for second CDC42; RAC1 binds only to apo-IQGAP2. (IQGAP2 = IQ motif containing GTPase activating protein-2; CDC42 = GTP-binding protein CDC42; RAC1 = Rac family small GTPase-1) (PMID:29358323)
• IQGAP2 Inhibits Migration and Invasion of Gastric Cancer Cells via Elevating SHIP2 Phosphatase Activity. (PMID:32183047)
• Circular RNA sequencing indicates circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers of primary Sjogren’s syndrome. (PMID:32250392)
• Reduced IQGAP2 expression promotes EMT and inhibits apoptosis by modulating the MEK-ERK and p38 signaling in breast cancer irrespective of ER status. (PMID:33846302)
• IQGAP2 acts as an independent prognostic factor and is related to immunosuppression in DLBCL. (PMID:34034707)
• Upregulation of IQGAP2 by EBV transactivator Rta and its influence on EBV life cycle. (PMID:37504571)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Iqgap2	ENSMUSG00000021676
rattus_norvegicus	Iqgap2	ENSRNOG00000025406
caenorhabditis_elegans	pes-7	WBGENE00003980

Paralogs (2): IQGAP1 (ENSG00000140575), IQGAP3 (ENSG00000183856)

Protein

Protein identifiers

Ras GTPase-activating-like protein IQGAP2 — Q13576 (reviewed: Q13576)

All UniProt accessions (8): A0A8I5KRM2, D6R939, Q13576, D6R999, D6RDK8, E9PDT6, F5H7S7, H0YA28

UniProt curated annotations — full annotation on UniProt →

Function. Binds to activated CDC42 and RAC1 but does not seem to stimulate their GTPase activity. Associates with calmodulin.

Tissue specificity. Isoform 2 expression is enhanced in testis.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13576-1	1	yes
Q13576-2	2
Q13576-3	3

RefSeq proteins (4): NP_001272389, NP_001272390, NP_001272391, NP_006624* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000048	IQ_motif_EF-hand-BS	Binding_site
IPR000593	IQGAP_helical	Domain
IPR001202	WW_dom	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 (85 total): helix 30, modified residue 14, sequence variant 13, strand 10, domain 6, splice variant 4, sequence conflict 4, turn 3, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3IEZ	X-RAY DIFFRACTION	1.5
4EZA	X-RAY DIFFRACTION	1.5
5CJP	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13576-F1	78.16	0.19

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 (14): 599, 685, 716, 782, 881, 1002, 1269, 1271, 1279, 1358, 1461, 16, 356, 595

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-5626467	RHO GTPases activate IQGAPs
R-HSA-6798695	Neutrophil degranulation
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
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: 420 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_MITOTIC_CYTOKINESIS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MODULE_45, GOCC_CELL_SURFACE, AREB6_01, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, CHANDRAN_METASTASIS_DN, GOBP_CYTOKINETIC_PROCESS, HERNANDEZ_ABERRANT_MITOSIS_BY_DOCETACEL_2NM_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GTGCCTT_MIR506

GO Biological Process (6): signal transduction (GO:0007165), regulation of actin cytoskeleton organization (GO:0032956), Arp2/3 complex-mediated actin nucleation (GO:0034314), thrombin-activated receptor signaling pathway (GO:0070493), mitotic actomyosin contractile ring assembly actin filament organization (GO:1903479), regulation of GTPase activity (GO:0043087)

GO Molecular Function (9): actin binding (GO:0003779), GTPase inhibitor activity (GO:0005095), GTPase activator activity (GO:0005096), calmodulin binding (GO:0005516), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), small GTPase binding (GO:0031267), actin filament binding (GO:0051015), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (15): cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), plasma membrane (GO:0005886), microvillus (GO:0005902), cell cortex (GO:0005938), cell surface (GO:0009986), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), filopodium (GO:0030175), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062), membrane (GO:0016020), cell leading edge (GO:0031252), plasma membrane bounded cell projection (GO:0120025)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
RHO GTPase cycle	3
Signaling by Rho GTPases	2
RHO GTPase Effectors	1
Innate Immune System	1
Immune System	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	5
GTPase activity	3
GTPase regulator activity	2
protein-containing complex binding	2
cytoplasm	2
cell periphery	2
actin-based cell projection	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
actin nucleation	1
G protein-coupled receptor signaling pathway	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
cytoskeletal protein binding	1
enzyme inhibitor activity	1
enzyme activator activity	1
protein binding	1
anion binding	1
phosphatidylinositol phosphate binding	1
GTPase binding	1
actin binding	1
binding	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
actin filament bundle	1
cytoskeleton	1
cell leading edge	1
plasma membrane bounded cell projection	1
secretory granule	1
cytoplasmic vesicle membrane	1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IQGAP2	CALM1	P02593	914
IQGAP2	AKAP11	Q9UKA4	890
IQGAP2	CALML3	P27482	889
IQGAP2	CALML5	Q9NZT1	889
IQGAP2	CALML6	Q8TD86	879
IQGAP2	CALML4	Q96GE6	879
IQGAP2	CDC42	P21181	847
IQGAP2	GRM7	Q14831	738
IQGAP2	CLIP1	P30622	568
IQGAP2	AKT1	P31749	517
IQGAP2	A0A590UK56	A0A590UK56	487
IQGAP2	SCARB1	Q8WTV0	465
IQGAP2	EIF2S3	P41091	464
IQGAP2	SCARB2	Q14108	455
IQGAP2	MAPK3	P27361	454

IntAct

99 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
RABIF	RAB3A	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IQGAP2	CDC42	psi-mi:“MI:0407”(direct interaction)	0.690
RAC1	COX6C	psi-mi:“MI:0914”(association)	0.640
MYL6	MYH9	psi-mi:“MI:0914”(association)	0.640
SDF4	GTPBP6	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
	AP3D1	psi-mi:“MI:0914”(association)	0.460
	MYL12B	psi-mi:“MI:0914”(association)	0.460
RAC1	IQGAP2	psi-mi:“MI:0407”(direct interaction)	0.440
IQGAP2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
IQGAP2		psi-mi:“MI:0915”(physical association)	0.370
STK4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
MYC	ILVBL	psi-mi:“MI:0914”(association)	0.350
GOLM1	RAB19	psi-mi:“MI:0914”(association)	0.350
BCL2L14		psi-mi:“MI:0914”(association)	0.350
CD74		psi-mi:“MI:0914”(association)	0.350
MAP3K14	IKBKG	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
SUCLA2	GTPBP10	psi-mi:“MI:0914”(association)	0.350
MAGEA1	ANKHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (158): IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Co-fractionation), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), IQGAP2 (Affinity Capture-MS), VCP (Affinity Capture-Western)

ESM2 similar proteins: A0JNC0, A1A5Q0, A2VE39, A4IHS2, D2HRF1, E1BTG2, O08808, O14730, O35226, O60870, O95801, P28289, P42898, P49813, P70566, P70567, Q0VC48, Q13576, Q1JQD4, Q1RMT7, Q2M146, Q3UQ44, Q58DA0, Q5BLF0, Q5EA11, Q5I598, Q5R981, Q5U2Z5, Q60HE5, Q6GNS3, Q6P2Z6, Q6P5Q4, Q6TH47, Q7T0W1, Q7ZXX9, Q803R5, Q8K339, Q8N1G2, Q8R3H9, Q8R424

Diamond homologs: O14188, P46940, Q12280, Q13576, Q3UQ44, Q86VI3, Q9JKF1, Q10201, Q5AH02, P14318, Q08873, Q24799, Q55GV9, Q54K32, O00899

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AKAP11	“up-regulates activity”	IQGAP2	binding
PKA	“up-regulates activity”	IQGAP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 122 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	7	48.2×	4e-08
RHO GTPases activate CIT	5	38.0×	5e-05
RHO GTPases activate PKNs	5	20.1×	7e-04
TAK1-dependent IKK and NF-kappa-B activation	5	19.0×	8e-04
Interleukin-1 family signaling	5	17.2×	9e-04
Toll Like Receptor 10 (TLR10) Cascade	5	13.6×	1e-03
Toll Like Receptor 5 (TLR5) Cascade	5	13.6×	1e-03
MyD88 cascade initiated on plasma membrane	5	12.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	209
Likely benign	10
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

7847 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76403588:GGCT:G	donor_gain	1.0000
5:76403589:GCTG:G	donor_gain	1.0000
5:76403592:G:GG	donor_gain	1.0000
5:76461562:A:AG	acceptor_gain	1.0000
5:76461563:T:G	acceptor_gain	1.0000
5:76461567:TAGCT:T	acceptor_loss	1.0000
5:76461568:A:AG	acceptor_gain	1.0000
5:76461568:AGCT:A	acceptor_loss	1.0000
5:76461569:G:GG	acceptor_gain	1.0000
5:76461569:GC:G	acceptor_gain	1.0000
5:76461569:GCT:G	acceptor_gain	1.0000
5:76461569:GCTA:G	acceptor_gain	1.0000
5:76461569:GCTAT:G	acceptor_gain	1.0000
5:76461667:AAGG:A	donor_loss	1.0000
5:76461668:AGG:A	donor_loss	1.0000
5:76461670:G:GG	donor_gain	1.0000
5:76461671:T:A	donor_loss	1.0000
5:76562390:CTTTA:C	acceptor_loss	1.0000
5:76562394:AGGT:A	acceptor_gain	1.0000
5:76562394:AGGTG:A	acceptor_gain	1.0000
5:76562395:GGT:G	acceptor_gain	1.0000
5:76562395:GGTG:G	acceptor_gain	1.0000
5:76562395:GGTGG:G	acceptor_gain	1.0000
5:76562549:TAAG:T	donor_loss	1.0000
5:76562550:AAGG:A	donor_loss	1.0000
5:76562551:AG:A	donor_loss	1.0000
5:76562552:GGTA:G	donor_loss	1.0000
5:76562553:GTAA:G	donor_loss	1.0000
5:76562554:T:A	donor_loss	1.0000
5:76575691:A:AG	acceptor_gain	1.0000

AlphaMissense

10411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76461618:G:C	R32T	1.000
5:76461618:G:T	R32M	1.000
5:76461619:G:C	R32S	1.000
5:76461619:G:T	R32S	1.000
5:76461633:C:A	A37D	1.000
5:76461641:T:C	Y40H	1.000
5:76461641:T:G	Y40D	1.000
5:76461642:A:G	Y40C	1.000
5:76461645:T:C	L41P	1.000
5:76461647:T:C	C42R	1.000
5:76461648:G:A	C42Y	1.000
5:76461649:C:G	C42W	1.000
5:76461650:C:G	H43D	1.000
5:76461662:G:C	A47P	1.000
5:76461663:C:A	A47D	1.000
5:76562397:T:A	W50R	1.000
5:76562397:T:C	W50R	1.000
5:76562398:G:C	W50S	1.000
5:76562399:G:C	W50C	1.000
5:76562399:G:T	W50C	1.000
5:76562455:T:C	L69P	1.000
5:76562458:G:C	R70P	1.000
5:76562462:T:A	N71K	1.000
5:76562462:T:G	N71K	1.000
5:76562463:G:A	G72R	1.000
5:76562463:G:C	G72R	1.000
5:76562464:G:A	G72E	1.000
5:76562464:G:T	G72V	1.000
5:76570595:T:C	F107L	1.000
5:76570596:T:C	F107S	1.000

dbSNP variants (sampled 300 via entrez): RS1000002766 (5:76589962 C>T), RS1000012932 (5:76446807 C>A,T), RS1000029455 (5:76597090 G>C), RS1000032028 (5:76414261 T>C), RS1000035611 (5:76585267 C>T), RS1000044129 (5:76445068 T>C), RS1000046535 (5:76675369 G>A), RS1000060554 (5:76581015 T>C), RS1000062401 (5:76633043 T>G), RS1000071039 (5:76504491 C>G,T), RS1000084857 (5:76459612 G>C), RS1000096548 (5:76451257 C>G,T), RS1000119274 (5:76645070 A>G), RS1000139197 (5:76603671 C>T), RS1000140785 (5:76648044 C>T)

Disease associations

OMIM: gene MIM:605401 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST000566_2	Hearing impairment	4.000000e-07
GCST001859_53	Thiazide-induced adverse metabolic effects in hypertensive patients	5.000000e-06
GCST003815_49	Late-onset Alzheimer’s disease	8.000000e-06
GCST004068_72	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	9.000000e-07
GCST004599_26	Mean platelet volume	1.000000e-16
GCST004599_27	Mean platelet volume	2.000000e-18
GCST004599_28	Mean platelet volume	1.000000e-34
GCST004599_29	Mean platelet volume	5.000000e-54
GCST004599_30	Mean platelet volume	1.000000e-204
GCST004603_1	Platelet count	2.000000e-10
GCST004603_2	Platelet count	7.000000e-56
GCST004611_77	High light scatter reticulocyte count	2.000000e-16
GCST004616_6	Platelet distribution width	2.000000e-13
GCST004619_183	Reticulocyte fraction of red cells	1.000000e-17
GCST004622_179	Reticulocyte count	4.000000e-09
GCST004622_180	Reticulocyte count	2.000000e-20
GCST005959_1	Waist-to-hip ratio adjusted for BMI x sex interaction	6.000000e-06
GCST008755_1	Phenylephrine infusion rate during anesthesia	2.000000e-07
GCST009267_8	Dental caries (decayed, missing and filled teeth)	1.000000e-06
GCST009268_10	Dental caries (decayed, missing and filled tooth surfaces)	2.000000e-06
GCST010242_227	HDL cholesterol levels	9.000000e-09
GCST012231_228	A body shape index	4.000000e-09
GCST90002385_288	High light scatter reticulocyte count	1.000000e-11
GCST90002385_339	High light scatter reticulocyte count	1.000000e-16
GCST90002385_340	High light scatter reticulocyte count	6.000000e-21
GCST90002385_341	High light scatter reticulocyte count	2.000000e-45
GCST90002386_34	High light scatter reticulocyte percentage of red cells	2.000000e-16
GCST90002386_35	High light scatter reticulocyte percentage of red cells	6.000000e-17
GCST90002386_36	High light scatter reticulocyte percentage of red cells	1.000000e-38
GCST90002390_131	Mean corpuscular hemoglobin	7.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0004309	platelet count
EFO:0007986	reticulocyte count
EFO:0007984	platelet component distribution width
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit
EFO:0004305	erythrocyte count
EFO:0007874	gut microbiome measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	8
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression, affects methylation	4
Aflatoxin B1	increases methylation, affects expression, decreases expression, decreases methylation	4
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, decreases methylation	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
FR900359	decreases phosphorylation	1
tungsten carbide	affects binding, decreases expression	1
urushiol	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
periodate-oxidized adenosine	affects expression	1
aflatoxin B2	decreases methylation, increases methylation	1
nickel sulfate	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
enzalutamide	decreases expression	1

Cellosaurus cell lines

5 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line, 1 finite cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6WY	GM29309	Induced pluripotent stem cell	Male
CVCL_SS79	HAP1 IQGAP2 (-) 1	Cancer cell line	Male
CVCL_UT83	GM27241	Transformed cell line	Male
CVCL_XP83	HAP1 IQGAP2 (-) 2	Cancer cell line	Male
CVCL_YE54	GM27461	Finite cell line	Male

Clinical trials (associated diseases)

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