ARHGAP45

Summary

ARHGAP45 (Rho GTPase activating protein 45, HGNC:17102) is a protein-coding gene on chromosome 19p13.3, encoding Rho GTPase-activating protein 45 (Q92619). Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading.

Predicted to enable GTPase activator activity. Predicted to be involved in negative regulation of small GTPase mediated signal transduction. Located in cytosol and plasma membrane.

Source: NCBI Gene 23526 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_012292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17102
Approved symbol	ARHGAP45
Name	Rho GTPase activating protein 45
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0223, HA-1
Ensembl gene	ENSG00000180448
Ensembl biotype	protein_coding
OMIM	601155
Entrez	23526

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000313093, ENST00000539243, ENST00000543365, ENST00000586033, ENST00000586378, ENST00000586866, ENST00000586937, ENST00000587186, ENST00000587602, ENST00000590214, ENST00000590512, ENST00000590577, ENST00000591169, ENST00000591293, ENST00000592297, ENST00000592335, ENST00000885658, ENST00000885659, ENST00000885660, ENST00000885661, ENST00000885662, ENST00000964187

RefSeq mRNA: 5 — MANE Select: NM_012292 NM_001258328, NM_001282334, NM_001282335, NM_001321232, NM_012292

CCDS: CCDS32863, CCDS58637, CCDS74242, CCDS74243, CCDS82263

Canonical transcript exons

ENST00000313093 — 23 exons

Exon	Start	End
ENSE00001250874	1080464	1080547
ENSE00001250882	1080255	1080379
ENSE00001250974	1068414	1068744
ENSE00001250989	1067167	1067495
ENSE00001330045	1085660	1086628
ENSE00003471537	1080682	1080786
ENSE00003475652	1081550	1081738
ENSE00003485716	1074343	1074407
ENSE00003505564	1074104	1074241
ENSE00003515056	1073948	1074014
ENSE00003523230	1084238	1084346
ENSE00003547614	1073674	1073746
ENSE00003569054	1083143	1083353
ENSE00003574654	1074799	1074879
ENSE00003574967	1073149	1073292
ENSE00003601725	1082840	1083066
ENSE00003614606	1073506	1073590
ENSE00003629447	1079928	1080118
ENSE00003642387	1077857	1078045
ENSE00003645393	1079703	1079840
ENSE00003663850	1080892	1081064
ENSE00003671714	1081824	1081961
ENSE00003692791	1074614	1074724

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1650 / max 731.0665, expressed in 1208 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172856	8.2535	870
172858	7.9795	726
172854	2.7818	480
172857	1.1899	323
172864	1.0143	149
172870	0.9431	256
172869	0.5094	108
172859	0.3776	160
172868	0.3005	140
172855	0.2341	134

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.07	gold quality
blood	UBERON:0000178	98.47	gold quality
spleen	UBERON:0002106	97.70	gold quality
oocyte	CL:0000023	97.65	gold quality
secondary oocyte	CL:0000655	97.60	gold quality
leukocyte	CL:0000738	97.36	gold quality
monocyte	CL:0000576	97.28	gold quality
mononuclear cell	CL:0000842	97.27	gold quality
lymph node	UBERON:0000029	95.91	gold quality
thymus	UBERON:0002370	94.56	gold quality
vermiform appendix	UBERON:0001154	94.55	gold quality
bone marrow cell	CL:0002092	94.27	gold quality
mucosa of transverse colon	UBERON:0004991	94.00	gold quality
right lung	UBERON:0002167	93.83	gold quality
upper lobe of left lung	UBERON:0008952	93.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.49	gold quality
upper lobe of lung	UBERON:0008948	92.39	gold quality
periodontal ligament	UBERON:0008266	92.36	gold quality
caecum	UBERON:0001153	92.22	gold quality
bone marrow	UBERON:0002371	92.07	gold quality
small intestine	UBERON:0002108	90.53	gold quality
trabecular bone tissue	UBERON:0002483	90.25	gold quality
bone element	UBERON:0001474	90.24	gold quality
transverse colon	UBERON:0001157	88.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	87.88	gold quality
tonsil	UBERON:0002372	87.82	gold quality
sural nerve	UBERON:0015488	87.56	gold quality
ileal mucosa	UBERON:0000331	87.49	gold quality
epithelium of nasopharynx	UBERON:0001951	87.18	gold quality
omental fat pad	UBERON:0010414	86.93	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.30
E-CURD-97	no	681.39
E-CURD-112	no	3.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

65 targeting ARHGAP45, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-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-22-3P	99.93	68.13	917
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311

Literature-anchored findings (GeneRIF, showing 14)

• The intensity of the tetramer-staining of the HA-1/HA-2-specific cytotoxic T cells strongly correlates with their capability to recognize mHag positive target cells. (PMID:11920221)
• HA-1-specific CTLs restricted by nonself HLA-A2 molecules can be generated in an HLA-A2-mismatched setting. (PMID:12091347)
• In bone marrow transplant recipients and their genetically HLA-identical siblings, the presence of different alleles of two minor histocompatibility antigen genes is studied. (PMID:15350465)
• Pre-existing HA-1-specific T cells are observed in cord blood samples. Both circulating and ex vivo-generated HA-1-specific T cells show specific and hematopoietic restricted lysis of HLA-A2+/HA-1+ target cells, including leukemic cells. (PMID:15498856)
• the incidence of the HA-1 168His allele is significantly lower in Sjogren’s syndrome patients than in controls (PMID:15593299)
• There was no difference in acute rejection rates between the HA-1-matched and -mismatched groups in kidney transplantation. (PMID:17580157)
• targeting mHags encoded not only by HMHA1, whose aberrant expression in solid tumors has been reported, but also BCL2A1 may bring about beneficial selective graft-versus-tumor effects (PMID:18414982)
• study examined antigenic presentation & T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1(H) versus HA-1(R)) in the HMHA1 gene; results define the molecular mechanisms governing immunogenicity of HA-1 (PMID:19234124)
• the information on allele and genotype frequencies of HA-1 and HA-2 in a Taiwanese population (PMID:20509834)
• study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells (PMID:24086303)
• Placental HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. (PMID:26095815)
• HMHA1 significantly promotes melanoma cells proliferation, invasion and migration, and prevents cell apoptosis. (PMID:28939173)
• ArhGAP45 acts as a Rac-GAP contributing to the balance between formation and disruption of endothelial junctions, which is required for the dynamic regulation of vascular permeability. (PMID:29174013)
• Hypoxia- and Postirradiation reoxygenation-induced HMHA1/ARHGAP45 expression contributes to cancer cell invasion in a HIF-dependent manner. (PMID:38740970)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap45a	ENSDARG00000052496
danio_rerio	arhgap45b	ENSDARG00000062049
danio_rerio	arhgap45b	ENSDARG00000095174
mus_musculus	Arhgap45	ENSMUSG00000035697
rattus_norvegicus	Arhgap45	ENSRNOG00000013220
caenorhabditis_elegans		WBGENE00014051

Paralogs (2): GMIP (ENSG00000089639), ARHGAP29 (ENSG00000137962)

Protein

Protein identifiers

Rho GTPase-activating protein 45 — Q92619 (reviewed: Q92619)

All UniProt accessions (8): A0A087X1A3, Q92619, F5H1R4, K7EM55, K7EM85, K7EQA4, K7ES92, K7ES98

UniProt curated annotations — full annotation on UniProt →

Function. Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity. Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL.

Subunit / interactions. HA-1 forms a complex with MHC class I HLA-A*0201.

Subcellular location. Cytoplasm. Cell projection. Ruffle membrane.

Tissue specificity. Expressed on cells of the hematopoietic lineage. Detected in dendritic cells and epidermal Langerhans cells. Expressed in peripheral blood mononuclear cells, in all leukemia/lymphoma cell lines. Detected also in some solid tumors and tissues such as cancerous and non-cancerous tissue.

Domain organisation. Rho-GAP domain is able to regulate RhoGTPase activity, actin cytoskeleton and cell spreading. However N-terminally BAR domain plays an autoinhibitory role.

Polymorphism. The HA-1H allele is presented on the cell surface and recognized by CTL, whereas the HA-1R allele is poorly represented by HLA-A and non-immunogenic, although HA-1R allelic frequency is the highest.

Miscellaneous. Infusion of lymphocyte from mHag HA-1-negative donors results in a durable remission in mHag HA-1-positive patients with leukemia or multiple myeloma.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92619-1	1	yes
Q92619-2	2

RefSeq proteins (5): NP_001245257, NP_001269263, NP_001269264, NP_001308161, NP_036424* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001060	FCH_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR046349	C1-like_sf	Homologous_superfamily
IPR051025	RhoGAP	Family
IPR054713	GMIP/FCHO2-like_FCH	Domain
IPR057028	RHG29_45_N	Domain

Pfam: PF00620, PF22699, PF24235

UniProt features (34 total): modified residue 13, sequence variant 5, region of interest 4, coiled-coil region 2, compositionally biased region 2, domain 2, chain 1, peptide 1, site 1, splice variant 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3D25	X-RAY DIFFRACTION	1.3
3FT3	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92619-F1	67.96	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 797 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (13): 23, 25, 73, 93, 99, 569, 578, 592, 619, 949, 1027, 1030, 1032

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle

MSigDB gene sets: 311 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GNF2_CASP8, MODULE_255, GOCC_SECRETORY_GRANULE, CMYB_01, SP3_Q3, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, MODULE_317, RACCACAR_AML_Q6, GOCC_RUFFLE, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (3): signal transduction (GO:0007165), regulation of small GTPase mediated signal transduction (GO:0051056), negative regulation of small GTPase mediated signal transduction (GO:0051058)

GO Molecular Function (4): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), ruffle membrane (GO:0032587), secretory granule lumen (GO:0034774), azurophil granule lumen (GO:0035578), cytoplasm (GO:0005737), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RHO GTPase cycle	3
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
small GTPase-mediated signal transduction	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of intracellular signal transduction	1
regulation of small GTPase mediated signal transduction	1
negative regulation of intracellular signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
secretory granule	1
cytoplasmic vesicle lumen	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP45	ABCA7	Q8IZY2	866
ARHGAP45	MYO1G	B0I1T2	692
ARHGAP45	HLA-A	P01891	681
ARHGAP45	POLR2E	P19388	525
ARHGAP45	SBNO2	Q9Y2G9	497
ARHGAP45	FAM174C	Q9BVV8	482
ARHGAP45	PUM3	Q15397	470
ARHGAP45	R3HDM4	Q96D70	445
ARHGAP45	KRT35	Q92764	430
ARHGAP45	RBIS	Q8N0T1	409
ARHGAP45	UBASH3A	P57075	402
ARHGAP45	TMEM259	Q4ZIN3	401
ARHGAP45	CCDC200	A0A1B0GVQ3	400
ARHGAP45	FCHSD1	Q86WN1	397
ARHGAP45	HMHB1	O97980	396

IntAct

49 interactions, top by confidence:

A	B	Type	Score
ARHGAP45	RAC1	psi-mi:“MI:0403”(colocalization)	0.570
ARHGAP45	RAC1	psi-mi:“MI:0915”(physical association)	0.570
RAC1	ARHGAP45	psi-mi:“MI:0407”(direct interaction)	0.570
ARHGAP45	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP45	TP53BP2	psi-mi:“MI:0915”(physical association)	0.560
PDE4DIP	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
TP53BP2	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP45	ZUP1	psi-mi:“MI:0915”(physical association)	0.560
PIBF1	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP45	GMIP	psi-mi:“MI:0915”(physical association)	0.560
RINT1	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP45	PPP1R13B	psi-mi:“MI:0915”(physical association)	0.560
TRIM50	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
BICD2	ARHGAP45	psi-mi:“MI:0915”(physical association)	0.560
PATJ	PLEKHG5	psi-mi:“MI:0914”(association)	0.350
PATJ	LIN7A	psi-mi:“MI:0914”(association)	0.350
PALS1	MPDZ	psi-mi:“MI:0914”(association)	0.350
PALS1	POLR3A	psi-mi:“MI:0914”(association)	0.350
MAPK1	SEC16A	psi-mi:“MI:0914”(association)	0.350
ARHGAP45	CDC42	psi-mi:“MI:0403”(colocalization)	0.270
RHOA	ARHGAP45	psi-mi:“MI:0403”(colocalization)	0.270
ARHGAP45	ZUP1	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP45	PIBF1	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP45	GMIP	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP45	GOLGA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): HMHA1 (Affinity Capture-MS), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), HMHA1 (Two-hybrid), BICD2 (Two-hybrid), HMHA1 (Affinity Capture-MS), HMHA1 (Affinity Capture-RNA), HMHA1 (Proximity Label-MS), HMHA1 (Affinity Capture-RNA), HMHA1 (Affinity Capture-MS)

ESM2 similar proteins: A2AB59, B1AK53, B2DD29, D3YZU1, D3ZG83, O09039, O14976, O54967, O75427, P80192, P98171, Q02779, Q17R13, Q3TBD2, Q3U1V8, Q3UHC7, Q4ACU6, Q4LDD4, Q5DU25, Q5JU85, Q5RB40, Q5RJI5, Q5TCX8, Q5U2X5, Q5VWQ8, Q61097, Q61210, Q66HA1, Q66L42, Q6TLK4, Q6ZUM4, Q80XI6, Q86VW2, Q8IVT5, Q8R0S2, Q8R5F8, Q8R5G7, Q8TDC3, Q8TE68, Q8WWN8

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	8
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

3183 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1068708:GGCCT:G	donor_gain	1.0000
19:1068726:G:GT	donor_gain	1.0000
19:1068798:G:GT	donor_gain	1.0000
19:1068799:G:T	donor_gain	1.0000
19:1073144:A:AG	acceptor_gain	1.0000
19:1073145:G:GG	acceptor_gain	1.0000
19:1073146:CA:C	acceptor_loss	1.0000
19:1073147:A:T	acceptor_loss	1.0000
19:1073289:AAAG:A	donor_loss	1.0000
19:1073290:AAG:A	donor_loss	1.0000
19:1073501:CCCA:C	acceptor_loss	1.0000
19:1073502:CCA:C	acceptor_loss	1.0000
19:1073503:CAG:C	acceptor_loss	1.0000
19:1073504:A:AG	acceptor_gain	1.0000
19:1073504:AG:A	acceptor_loss	1.0000
19:1073505:G:GT	acceptor_gain	1.0000
19:1073505:GC:G	acceptor_gain	1.0000
19:1073505:GCC:G	acceptor_gain	1.0000
19:1073505:GCCT:G	acceptor_gain	1.0000
19:1073505:GCCTT:G	acceptor_gain	1.0000
19:1073587:GCAC:G	donor_gain	1.0000
19:1073589:ACGTG:A	donor_loss	1.0000
19:1073590:CGTG:C	donor_loss	1.0000
19:1073591:G:GA	donor_loss	1.0000
19:1073591:G:GG	donor_gain	1.0000
19:1073600:G:GT	donor_gain	1.0000
19:1073673:GAGT:G	acceptor_gain	1.0000
19:1073943:TACA:T	acceptor_loss	1.0000
19:1073945:C:G	acceptor_gain	1.0000
19:1073945:CA:C	acceptor_loss	1.0000

AlphaMissense

7376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:1080981:C:G	H703D	1.000
19:1081014:T:C	C714R	1.000
19:1081056:T:C	C728R	1.000
19:1081565:C:G	H736D	1.000
19:1083172:T:C	M925T	1.000
19:1077876:T:C	L402P	0.999
19:1079712:G:C	A462P	0.999
19:1079724:T:G	Y466D	0.999
19:1079745:G:C	A473P	0.999
19:1079820:A:C	S498R	0.999
19:1079822:C:A	S498R	0.999
19:1079822:C:G	S498R	0.999
19:1080973:C:A	A700D	0.999
19:1080981:C:A	H703N	0.999
19:1080983:C:A	H703Q	0.999
19:1080983:C:G	H703Q	0.999
19:1081014:T:A	C714S	0.999
19:1081015:G:C	C714S	0.999
19:1081036:T:A	V721D	0.999
19:1081038:T:G	Y722D	0.999
19:1081041:T:C	F723L	0.999
19:1081042:T:C	F723S	0.999
19:1081043:C:A	F723L	0.999
19:1081043:C:G	F723L	0.999
19:1081047:G:C	G725R	0.999
19:1081056:T:A	C728S	0.999
19:1081057:G:C	C728S	0.999
19:1081058:T:G	C728W	0.999
19:1081550:T:C	C731R	0.999
19:1081565:C:A	H736N	0.999

dbSNP variants (sampled 300 via entrez): RS1000018092 (19:1086523 G>A), RS1000043948 (19:1065936 C>A,G,T), RS1000063154 (19:1083786 G>A), RS1000160944 (19:1076274 C>A,T), RS1000212991 (19:1076127 C>A), RS1000376215 (19:1074977 T>G), RS1000499663 (19:1075469 T>G), RS1000682403 (19:1071101 C>A,T), RS1000932449 (19:1078213 G>A), RS1001180910 (19:1075442 A>G), RS1001254584 (19:1075105 C>T), RS1001267275 (19:1086112 G>A,C), RS1001337602 (19:1078380 T>C,G), RS1001368463 (19:1079556 C>A,T), RS1001436637 (19:1078182 C>A,T)

Disease associations

OMIM: gene MIM:601155 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST001729_23	Crohn’s disease	8.000000e-22
GCST001963_1	Alzheimer’s disease (late onset)	2.000000e-09
GCST004599_139	Mean platelet volume	1.000000e-12
GCST004606_39	Eosinophil count	4.000000e-12
GCST004617_130	Eosinophil percentage of granulocytes	1.000000e-11
GCST004623_89	Neutrophil percentage of granulocytes	5.000000e-10
GCST004624_21	Sum eosinophil basophil counts	7.000000e-11
GCST004627_180	Lymphocyte count	3.000000e-21
GCST004632_13	Lymphocyte percentage of white cells	2.000000e-11
GCST004633_125	Neutrophil percentage of white cells	2.000000e-12
GCST006135_14	Cortical amyloid beta load	7.000000e-06
GCST006135_9	Cortical amyloid beta load	6.000000e-07
GCST006585_854	Blood protein levels	1.000000e-06
GCST008570_6	Composite immunoglobulin trait (IgA x IgG/IgM)	2.000000e-07
GCST90002381_561	Eosinophil count	8.000000e-34
GCST90002382_496	Eosinophil percentage of white cells	2.000000e-28
GCST90002385_301	High light scatter reticulocyte count	3.000000e-11
GCST90002386_100	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002388_522	Lymphocyte count	9.000000e-41
GCST90002389_255	Lymphocyte percentage of white cells	2.000000e-28
GCST90002395_296	Mean platelet volume	2.000000e-22
GCST90002395_297	Mean platelet volume	3.000000e-12
GCST90002399_212	Neutrophil percentage of white cells	2.000000e-26
GCST90002406_524	Reticulocyte fraction of red cells	2.000000e-10
GCST90002407_172	White blood cell count	3.000000e-12

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007707	cerebral amyloid deposition measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases methylation	3
Valproic Acid	increases methylation, affects expression, increases expression	3
bisphenol A	decreases expression, increases methylation, affects cotreatment, decreases methylation	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
muconaldehyde	increases expression	1
tamibarotene	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
brinzolamide	affects expression	1
entinostat	increases 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	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Temozolomide	increases expression	1
Decitabine	increases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

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