ARHGAP9

Summary

ARHGAP9 (Rho GTPase activating protein 9, HGNC:14130) is a protein-coding gene on chromosome 12q13.3, encoding Rho GTPase-activating protein 9 (Q9BRR9). GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 64333 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 138 total
• MANE Select transcript: NM_032496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14130
Approved symbol	ARHGAP9
Name	Rho GTPase activating protein 9
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC1295, 10C
Ensembl gene	ENSG00000123329
Ensembl biotype	protein_coding
OMIM	610576
Entrez	64333

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 20 protein_coding, 9 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000393791, ENST00000393797, ENST00000424809, ENST00000430041, ENST00000546200, ENST00000546704, ENST00000547200, ENST00000547216, ENST00000548139, ENST00000548148, ENST00000549602, ENST00000550130, ENST00000550288, ENST00000550399, ENST00000550440, ENST00000550454, ENST00000551000, ENST00000551452, ENST00000551574, ENST00000552066, ENST00000552249, ENST00000552420, ENST00000552604, ENST00000552953, ENST00000906772, ENST00000906773, ENST00000906774, ENST00000906775, ENST00000906776, ENST00000948684, ENST00000948685

RefSeq mRNA: 11 — MANE Select: NM_032496 NM_001080156, NM_001080157, NM_001319850, NM_001319851, NM_001319852, NM_001367422, NM_001367423, NM_001367424, NM_001367425, NM_001367426, NM_032496

CCDS: CCDS44928, CCDS44929, CCDS81705, CCDS8941

Canonical transcript exons

ENST00000393791 — 18 exons

Exon	Start	End
ENSE00001516514	57472269	57472688
ENSE00002428299	57479730	57479866
ENSE00003479404	57476071	57476166
ENSE00003511799	57475291	57475398
ENSE00003529682	57477459	57477680
ENSE00003533520	57479091	57479424
ENSE00003544922	57474875	57474973
ENSE00003555039	57474423	57474476
ENSE00003570050	57474626	57474703
ENSE00003582835	57478540	57478757
ENSE00003589351	57475483	57475615
ENSE00003602645	57476590	57476651
ENSE00003619677	57477156	57477269
ENSE00003636996	57476364	57476454
ENSE00003655239	57473603	57473708
ENSE00003686668	57474042	57474176
ENSE00003692136	57475833	57475931
ENSE00003789348	57476871	57476963

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 99.43.

FANTOM5 (CAGE): breadth broad, TPM avg 11.5741 / max 437.9741, expressed in 589 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131686	3.0075	281
131687	2.8269	374
131699	2.1837	299
131701	1.1587	144
131688	0.6435	273
131690	0.5725	223
131703	0.2615	78
131689	0.1465	88
131691	0.1168	55
131698	0.1130	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.43	gold quality
blood	UBERON:0000178	99.26	gold quality
spleen	UBERON:0002106	98.73	gold quality
vermiform appendix	UBERON:0001154	98.26	gold quality
leukocyte	CL:0000738	98.00	gold quality
monocyte	CL:0000576	97.91	gold quality
lymph node	UBERON:0000029	97.77	gold quality
bone marrow	UBERON:0002371	97.25	gold quality
bone marrow cell	CL:0002092	96.96	gold quality
trabecular bone tissue	UBERON:0002483	96.71	gold quality
ileal mucosa	UBERON:0000331	96.48	gold quality
thymus	UBERON:0002370	95.45	gold quality
right lung	UBERON:0002167	94.24	gold quality
caecum	UBERON:0001153	94.09	gold quality
upper lobe of left lung	UBERON:0008952	93.85	gold quality
right testis	UBERON:0004534	93.22	gold quality
left testis	UBERON:0004533	93.20	gold quality
gall bladder	UBERON:0002110	93.06	gold quality
upper lobe of lung	UBERON:0008948	93.06	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.75	gold quality
testis	UBERON:0000473	90.97	gold quality
small intestine	UBERON:0002108	90.94	gold quality
mucosa of transverse colon	UBERON:0004991	90.11	gold quality
omental fat pad	UBERON:0010414	89.92	gold quality
peritoneum	UBERON:0002358	89.87	gold quality
decidua	UBERON:0002450	89.73	gold quality
superficial temporal artery	UBERON:0001614	89.61	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.55	gold quality
rectum	UBERON:0001052	89.43	gold quality
epithelium of nasopharynx	UBERON:0001951	89.31	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	42.22
E-MTAB-10287	yes	30.57
E-MTAB-6678	yes	30.00
E-ANND-3	yes	14.69
E-CURD-55	no	256.87
E-CURD-120	no	6.15
E-CURD-112	no	3.33

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting ARHGAP9, 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-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-887-5P	98.82	65.90	1347
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-8060	98.61	66.93	1187
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4781-3P	95.78	65.66	572

Literature-anchored findings (GeneRIF, showing 6)

• The Ala370Ser polymorphism in the ARHGAP9 gene is associated with coronary artery spasm. (PMID:19911011)
• The data clearly show that ARHGAP9/FOXJ2 inhibit cell migration and invasion during hepatocellular carcinoma development via inducing the transcription of CDH1. (PMID:30206221)
• The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia. (PMID:33579308)
• SOX4-induced upregulation of ARHGAP9 promotes the progression of acute myeloid leukemia. (PMID:34159626)
• GATA binding protein 5 (GATA5) induces Rho GTPase activating protein 9 (ARHGAP9) to inhibit the malignant process of lung adenocarcinoma cells. (PMID:35040754)
• ARHGAP9 inhibits colorectal cancer cell proliferation, invasion and EMT via targeting PI3K/AKT/mTOR signaling pathway. (PMID:35679685)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000013390
mus_musculus	Arhgap9	ENSMUSG00000040345
rattus_norvegicus	Arhgap9	ENSRNOG00000006946
drosophila_melanogaster	RhoGAP16F	FBGN0030893
caenorhabditis_elegans		WBGENE00008006

Paralogs (3): ARHGAP15 (ENSG00000075884), ARHGAP27 (ENSG00000159314), ARHGAP12 (ENSG00000165322)

Protein

Protein identifiers

Rho GTPase-activating protein 9 — Q9BRR9 (reviewed: Q9BRR9)

Alternative names: Rho-type GTPase-activating protein 9

All UniProt accessions (10): Q9BRR9, F8VQR0, F8VQY5, F8VR90, F8VSD0, F8VW89, F8W1N6, H0YI33, H0YI36, R4GN15

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Has a substantial GAP activity toward CDC42 and RAC1 and less toward RHOA. Has a role in regulating adhesion of hematopoietic cells to the extracellular matrix. Binds phosphoinositides, and has the highest affinity for phosphatidylinositol 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate.

Subunit / interactions. Interacts with FASLG.

Tissue specificity. Predominantly expressed in peripheral blood leukocytes, spleen, and thymus.

Domain organisation. A region including the PH domain and partially overlapping with the Rho-GAP domain mediates interaction with phosphoinositides.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9BRR9-1	1	yes
Q9BRR9-2	2
Q9BRR9-3	3
Q9BRR9-4	4
Q9BRR9-5	5

RefSeq proteins (11): NP_001073625, NP_001073626, NP_001306779, NP_001306780, NP_001306781, NP_001354351, NP_001354352, NP_001354353, NP_001354354, NP_001354355, NP_115885* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001202	WW_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035465	ARHGAP9_SH3	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR050729	Rho-GAP	Family

Pfam: PF00018, PF00169, PF00620

UniProt features (39 total): region of interest 6, compositionally biased region 6, strand 6, domain 4, splice variant 3, sequence variant 3, modified residue 2, mutagenesis site 2, sequence conflict 2, helix 2, chain 1, site 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2P0D	X-RAY DIFFRACTION	1.81
2P0H	X-RAY DIFFRACTION	1.9
2P0F	X-RAY DIFFRACTION	1.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRR9-F1	66.99	0.31

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): 578 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (2): 475, 500

Mutagenesis-validated functional residues (2):

Position	Phenotype
343	strongly reduced affinity for phosphoinositides.
399	reduced affinity for phosphoinositides.

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: 196 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, AACYNNNNTTCCS_UNKNOWN, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, MARSON_FOXP3_TARGETS_UP, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, HOWLIN_CITED1_TARGETS_1_UP, GOCC_SECRETORY_VESICLE, GOCC_VESICLE_LUMEN, STAT1_02, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, GOMF_PHOSPHATIDYLINOSITOL_PHOSPHATE_BINDING, GOMF_PHOSPHATIDYLINOSITOL_BINDING

GO Biological Process (3): small GTPase-mediated signal transduction (GO:0007264), regulation of small GTPase mediated signal transduction (GO:0051056), signal transduction (GO:0007165)

GO Molecular Function (4): GTPase activator activity (GO:0005096), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (5): extracellular region (GO:0005576), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), secretory granule lumen (GO:0034774)

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	3
binding	2
intracellular signaling cassette	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
anion binding	1
phosphatidylinositol phosphate binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
secretory granule	1
cytoplasmic vesicle lumen	1

Protein interactions and networks

STRING

1644 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP9	PLEK	P08567	698
ARHGAP9	PLEK2	Q9NYT0	690
ARHGAP9	NRSN1	Q8IZ57	630
ARHGAP9	CAMK2N1	Q7Z7J9	565
ARHGAP9	RAC2	P15153	543
ARHGAP9	COL4A1	P02462	543
ARHGAP9	NXPE1	Q8N323	531
ARHGAP9	CDC42	P21181	525
ARHGAP9	MAPK13	O15264	489
ARHGAP9	KHDRBS2	Q5VWX1	483
ARHGAP9	ARHGEF38	Q9NXL2	456
ARHGAP9	FASLG	P48023	453
ARHGAP9	ZNF831	Q5JPB2	443
ARHGAP9	NGEF	Q8N5V2	436
ARHGAP9	DAPP1	Q9UN19	432

IntAct

50 interactions, top by confidence:

A	B	Type	Score
GRB2	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
FHL2	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	GRB2	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	FHL2	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9		psi-mi:“MI:0915”(physical association)	0.560
	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
RUNX1T1	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	TSC22D4	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	ABI3	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	NME7	psi-mi:“MI:0915”(physical association)	0.560
SNRPC	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	GOLGA6A	psi-mi:“MI:0915”(physical association)	0.560
MRPL38	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.560
ARHGAP9	FASLG	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGAP9	MAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGAP9	MAPK14	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGAP9	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
RBPMS	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.370
ARHGAP9	TOMM40	psi-mi:“MI:0914”(association)	0.350
ARHGAP9	Mapk1	psi-mi:“MI:0914”(association)	0.350
	PIK3R2	psi-mi:“MI:0914”(association)	0.350
RUNX1T1	ARHGAP9	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP9	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
ARHGAP9	TSC22D4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (54): ARHGAP9 (Two-hybrid), ARHGAP9 (Two-hybrid), ARHGAP9 (Two-hybrid), ARHGAP9 (Two-hybrid), ARHGAP9 (Affinity Capture-MS), ARHGAP9 (Affinity Capture-MS), ARHGAP9 (Two-hybrid), ARHGAP9 (Two-hybrid), SNRPC (Two-hybrid), NME7 (Two-hybrid), GOLGA6A (Two-hybrid), TSC22D4 (Two-hybrid), CYSRT1 (Two-hybrid), GOLGA6L9 (Two-hybrid), MRPL38 (Two-hybrid)

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

1 interactions.

A	Effect	B	Mechanism
ARHGAP9	“down-regulates activity”	RAC1	“gtpase-activating protein”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	18
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2532 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57472687:CC:C	acceptor_gain	1.0000
12:57472688:CC:C	acceptor_gain	1.0000
12:57474473:CGCT:C	acceptor_gain	1.0000
12:57474620:TCTCA:T	donor_loss	1.0000
12:57474621:CTCAC:C	donor_loss	1.0000
12:57474622:TCAC:T	donor_loss	1.0000
12:57474623:CACC:C	donor_loss	1.0000
12:57474625:C:A	donor_loss	1.0000
12:57474704:CTGG:C	acceptor_loss	1.0000
12:57475287:TCA:T	donor_loss	1.0000
12:57475290:CCTCG:C	donor_loss	1.0000
12:57475308:T:TA	donor_gain	1.0000
12:57475399:C:CC	acceptor_gain	1.0000
12:57475481:A:AC	donor_gain	1.0000
12:57475482:C:CC	donor_gain	1.0000
12:57475633:C:CT	acceptor_gain	1.0000
12:57475639:G:T	acceptor_gain	1.0000
12:57475775:CCCCA:C	donor_gain	1.0000
12:57475782:C:CA	donor_gain	1.0000
12:57475808:C:A	donor_gain	1.0000
12:57475932:C:CC	acceptor_gain	1.0000
12:57475940:C:CT	acceptor_gain	1.0000
12:57476069:A:AC	donor_gain	1.0000
12:57476070:C:CC	donor_gain	1.0000
12:57476070:CGTG:C	donor_gain	1.0000
12:57476357:CA:C	donor_gain	1.0000
12:57476361:CA:C	donor_loss	1.0000
12:57476362:A:AC	donor_gain	1.0000
12:57476362:AC:A	donor_gain	1.0000
12:57476363:C:CC	donor_gain	1.0000

AlphaMissense

4673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57474963:G:C	F540L	0.999
12:57474963:G:T	F540L	0.999
12:57474965:A:G	F540L	0.999
12:57475903:A:G	L414P	0.999
12:57476445:C:A	W345C	0.999
12:57476445:C:G	W345C	0.999
12:57476447:A:G	W345R	0.999
12:57476447:A:T	W345R	0.999
12:57474646:A:G	L589P	0.998
12:57475868:A:G	W426R	0.998
12:57475868:A:T	W426R	0.998
12:57474147:A:G	W624R	0.997
12:57474147:A:T	W624R	0.997
12:57476451:C:A	K343N	0.997
12:57476451:C:G	K343N	0.997
12:57474110:A:G	L636P	0.996
12:57474112:C:A	K635N	0.996
12:57474112:C:G	K635N	0.996
12:57474643:C:G	R590P	0.996
12:57474646:A:T	L589H	0.996
12:57474655:A:T	V586D	0.996
12:57474964:A:G	F540S	0.996
12:57475331:T:A	R523S	0.996
12:57475331:T:G	R523S	0.996
12:57475900:A:G	L415P	0.996
12:57475906:A:G	F413S	0.996
12:57475930:A:T	I405N	0.996
12:57476129:A:T	L385Q	0.996
12:57476453:T:C	K343E	0.996
12:57479174:A:T	V78D	0.996

dbSNP variants (sampled 300 via entrez): RS1000032629 (12:57471809 T>C), RS1000034386 (12:57486118 G>T), RS1000100975 (12:57484443 C>A,T), RS1000295897 (12:57486439 T>A), RS1000489410 (12:57486354 C>G), RS1000647848 (12:57475727 C>A,T), RS1001360881 (12:57480097 C>T), RS1001413207 (12:57480295 T>G), RS1001435736 (12:57485736 A>G), RS1001597227 (12:57474131 A>G), RS1001805209 (12:57486062 C>A,G), RS1002213358 (12:57486456 GA>G), RS1002462651 (12:57475642 G>A,T), RS1002720012 (12:57472423 T>C,G), RS1002814196 (12:57472202 T>A,C)

Disease associations

OMIM: gene MIM:610576 | disease phenotypes: MIM:615486, MIM:616280, MIM:620323, MIM:303350

GenCC curated gene-disease

Mondo (4): severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (MONDO:0014206), Charcot-Marie-Tooth disease axonal type 2U (MONDO:0014566), autosomal recessive spastic paraplegia type 70 (MONDO:0018422), hereditary spastic paraplegia (MONDO:0019064)

Orphanet (4): Autosomal dominant Charcot-Marie-Tooth disease type 2U (Orphanet:397735), Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency (Orphanet:440427), Autosomal recessive spastic paraplegia type 70 (Orphanet:401835), Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002393_419	Monocyte count	5.000000e-12
GCST90002394_371	Monocyte percentage of white cells	5.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2228226	ARHGAP9, GLI1		0.00	0
rs2229300	ARHGAP9, GLI1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
diethyl maleate	increases expression	1
methylparaben	increases expression	1
butylparaben	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	increases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	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
thifluzamide	increases expression	1
abrine	increases expression	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Choline	affects expression	1
Cisplatin	affects expression	1
Nickel	increases expression	1
Ozone	affects expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT05514470	Not specified	WITHDRAWN	Impact of Mutations in Aminoacyl tRNA Synthetases on Protein Translation and Cellular Stress
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life