ARHGAP24

Summary

ARHGAP24 (Rho GTPase activating protein 24, HGNC:25361) is a protein-coding gene on chromosome 4q21.23-q21.3, encoding Rho GTPase-activating protein 24 (Q8N264). Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization.

This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 83478 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial idiopathic steroid-resistant nephrotic syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 63
• Clinical variants (ClinVar): 343 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 17
• MANE Select transcript: NM_001025616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25361
Approved symbol	ARHGAP24
Name	Rho GTPase activating protein 24
Location	4q21.23-q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564B1162, FLJ33877, FilGAP
Ensembl gene	ENSG00000138639
Ensembl biotype	protein_coding
OMIM	610586
Entrez	83478

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000264343, ENST00000395183, ENST00000395184, ENST00000502537, ENST00000503917, ENST00000503995, ENST00000505856, ENST00000506421, ENST00000509300, ENST00000509709, ENST00000512201, ENST00000514229

RefSeq mRNA: 5 — MANE Select: NM_001025616 NM_001025616, NM_001042669, NM_001287805, NM_001346093, NM_031305

CCDS: CCDS34025, CCDS3611, CCDS43246

Canonical transcript exons

ENST00000395184 — 10 exons

Exon	Start	End
ENSE00000801107	85994583	85995657
ENSE00001076708	85977570	85977691
ENSE00001319149	86000479	86002666
ENSE00001520832	85475150	85475559
ENSE00003511482	85942066	85942273
ENSE00003548085	85923648	85923770
ENSE00003567717	85974888	85974961
ENSE00003648420	85570522	85570721
ENSE00003665268	85721885	85721972
ENSE00003787086	85972036	85972168

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.8503 / max 388.1038, expressed in 1533 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48636	3.6409	1000
48637	2.5793	905
48640	2.5608	480
48651	1.8840	528
48650	1.6999	605
48639	0.7674	356
48641	0.4972	196
48661	0.3311	122
48652	0.2593	108
48635	0.2548	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal medulla	UBERON:0000362	97.95	gold quality
pons	UBERON:0000988	93.17	gold quality
metanephros cortex	UBERON:0010533	92.87	gold quality
adult mammalian kidney	UBERON:0000082	92.69	gold quality
parotid gland	UBERON:0001831	91.27	gold quality
kidney	UBERON:0002113	90.95	gold quality
sural nerve	UBERON:0015488	90.87	gold quality
pylorus	UBERON:0001166	90.66	gold quality
colonic epithelium	UBERON:0000397	90.42	gold quality
vena cava	UBERON:0004087	90.24	gold quality
cardia of stomach	UBERON:0001162	89.21	gold quality
calcaneal tendon	UBERON:0003701	88.54	gold quality
right coronary artery	UBERON:0001625	88.49	gold quality
visceral pleura	UBERON:0002401	88.47	gold quality
substantia nigra pars compacta	UBERON:0001965	87.95	gold quality
right lung	UBERON:0002167	87.63	gold quality
cortex of kidney	UBERON:0001225	87.45	gold quality
right atrium auricular region	UBERON:0006631	87.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.21	gold quality
tibial nerve	UBERON:0001323	87.14	gold quality
adrenal tissue	UBERON:0018303	87.05	gold quality
stromal cell of endometrium	CL:0002255	87.03	gold quality
body of pancreas	UBERON:0001150	86.96	gold quality
monocyte	CL:0000576	86.63	gold quality
tonsil	UBERON:0002372	86.63	gold quality
pleura	UBERON:0000977	86.59	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.58	silver quality
bone marrow	UBERON:0002371	86.49	gold quality
parietal pleura	UBERON:0002400	86.49	gold quality
mononuclear cell	CL:0000842	86.30	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	4058.04
E-HCAD-30	yes	4035.92
E-HCAD-35	yes	3123.92
E-GEOD-180759	yes	2967.88
E-HCAD-25	yes	2117.08
E-HCAD-1	yes	109.53
E-CURD-122	yes	103.37
E-CURD-88	yes	56.35
E-HCAD-4	yes	47.64
E-CURD-46	yes	34.04
E-HCAD-10	yes	27.44
E-ANND-3	yes	20.38
E-CURD-135	no	1102.79
E-MTAB-6386	no	236.66

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting ARHGAP24, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
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-4789-5P	99.98	70.76	2721
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683

Literature-anchored findings (GeneRIF, showing 24)

• p73, a vascular cell-specific GTPase-activating protein, is an important modulator of angiogenesis (PMID:15302923)
• propose that RC-GAP72 affects cellular morphology by targeting activated Cdc42 and Rac1 GTPases to specific subcellular sites, triggering local morphological changes (PMID:15611138)
• FilGAP plays a role in protecting cells against force-induced apoptosis. (PMID:19144823)
• Point mutagenesis revealed that disruption of the FLNa-FilGAP interface perturbs cell spreading. FilGAP does not bind FLNa homologs FLNb or FLNc establishing the importance of this interaction to the human FLNa mutations (PMID:19293932)
• Polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants. (PMID:21823009)
• sequencing of the ARHGAP24 gene in patients with focal segmental glomerulosclerosis (FSGS) identified a mutation that impaired its Rac1-GAP activity and was associated with disease in a family with FSGS (PMID:21911940)
• Consistent with structural predictions, strain increases beta-integrin binding to FLNA, whereas it causes FilGAP to dissociate from FLNA, providing a direct and specific molecular basis for cellular mechanotransduction (PMID:21926999)
• Data indicate that phosphorylation of FilGAP by ROCK appears to promote amoeboid morphology. (PMID:23097497)
• FilGAP may function as a mediator of the regulation of Rac by Arf6. (PMID:24526684)
• FilGAP may contribute to change in cell motility of B-lymphocytes and in addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular follicular lymphoma. (PMID:25641953)
• study suggests that Arf6 and phosphorylation of FilGAP may regulate FilGAP, and phosphorylation of Ser-402 may play a role in the regulation of cell spreading on fibronectin (PMID:26359494)
• Src family tyrosine kinase signaling may regulate FilGAP through association with RBM10 (PMID:26751795)
• Study identified FilGAP as a negative regulator of lymphocyte polarization and migration and shows that FilGAP may suppress lamellae formation at the front of migrating lymphocyte. (PMID:27130700)
• this study clearly provided evidence that FilGAP, as well as IDH1 status, may be useful for predicting the behavior of astrocytomas. In addition, the FilGAP/Rac1 axis may serve as an important regulator of tumor progression in GBMs, probably through alteration of cell morphology. (PMID:27790861)
• ARHGAP24 may regulate pseudopod formation downstream of activated ARF6 in MDA-MB-231 human breast carcinoma cells. (PMID:28870903)
• MicroRNA-590-5p regulates cell viability, apoptosis, migration and invasion of renal cell carcinoma cell lines through targeting ARHGAP24 (PMID:29019371)
• ARHGAP24 can suppress the development of MDA-MB-231 cells via the STAT3 signaling pathway, and sorafenib inhibits cell viability, migration, invasion, and STAT3 activation in MDA-MB-231 cells through ARHGAP24. (PMID:30499465)
• Results showed that ARHGAP24 expression was downregulated in lung cancer tissues and cell lines. (PMID:30599132)
• AGAP1 regulates subcellular localization of FilGAP and control cancer cell invasion. (PMID:31785816)
• study showed that HOTAIRM1 suppressed ovarian cancer progression through derepression of ARHGAP24 by sponging miR-106a-5p (PMID:31935390)
• FilGAP, a GAP protein for Rac, regulates front-rear polarity and tumor cell migration through the ECM. (PMID:33710706)
• ARHGAP24 represses beta-catenin transactivation-induced invasiveness in hepatocellular carcinoma mainly by acting as a GTPase-independent scaffold. (PMID:36168627)
• FilGAP regulates tumor growth in Glioma through the regulation of mTORC1 and mTORC2. (PMID:38065968)
• Exosome-transmitted circular RNA circ-LMO7 facilitates the progression of osteosarcoma by regulating miR-21-5p/ARHGAP24 axis. (PMID:38742566)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arhgap24	ENSDARG00000100973
mus_musculus	Arhgap24	ENSMUSG00000057315
rattus_norvegicus	Arhgap24	ENSRNOG00000056944

Paralogs (2): ARHGAP22 (ENSG00000128805), ARHGAP25 (ENSG00000163219)

Protein

Protein identifiers

Rho GTPase-activating protein 24 — Q8N264 (reviewed: Q8N264)

Alternative names: Filamin-A-associated RhoGAP, RAC1- and CDC42-specific GTPase-activating protein of 72 kDa, Rho-type GTPase-activating protein 24, RhoGAP of 73 kDa, Sarcoma antigen NY-SAR-88, p73RhoGAP

All UniProt accessions (4): Q8N264, D6RBC2, D6RCP5, D6RHH1

UniProt curated annotations — full annotation on UniProt →

Function. Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis.

Subunit / interactions. Interacts with FLNA.

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Adherens junction. Focal adhesion. Cell projection.

Tissue specificity. Isoform 1 is widely expressed with a higher level in kidney. Isoform 2 is mainly expressed in endothelial cells.

Post-translational modifications. Phosphorylated by ROCK, leading to activate the RacGAP activity.

Domain organisation. The coiled coil domain mediates the interaction with FLNA leading to its recruitment to lamellae.

Induction. Up-regulated during capillary tube formation in umbilical vein endothelial cells.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8N264-1	1	yes
Q8N264-2	2
Q8N264-3	3
Q8N264-4	4
Q8N264-5	5

RefSeq proteins (5): NP_001020787, NP_001036134, NP_001274734, NP_001333022, NP_112595 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR051025	RhoGAP	Family

Pfam: PF00169, PF00620

UniProt features (36 total): modified residue 9, splice variant 8, compositionally biased region 6, region of interest 3, sequence conflict 3, domain 2, mutagenesis site 2, chain 1, site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N264-F1	66.68	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): 175 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (9): 369, 391, 396, 398, 402, 413, 415, 437, 452

Mutagenesis-validated functional residues (2):

Position	Phenotype
175	loss of function.
175	does not abolish the effect on actin stress fibers but moderates its capability to induce membrane protrusions.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 316 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_RUFFLE_ASSEMBLY, AP4_Q6, TGACCTY_ERR1_Q2, HNF1_Q6, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (7): angiogenesis (GO:0001525), signal transduction (GO:0007165), cell differentiation (GO:0030154), negative regulation of Rac protein signal transduction (GO:0035021), wound healing, spreading of epidermal cells (GO:0035313), negative regulation of ruffle assembly (GO:1900028), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (2): GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (6): cytoskeleton (GO:0005856), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell projection (GO:0042995), cytoplasm (GO:0005737), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	3

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental process	1
Rac protein signal transduction	1
regulation of Rac protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
wound healing, spreading of cells	1
ruffle assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of ruffle assembly	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membraneless organelle	1
cell-cell junction	1
cell-substrate junction	1
intracellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGAP24	FLNA	P21333	985
ARHGAP24	SCN10A	Q9Y5Y9	740
ARHGAP24	CAV2	P51636	678
ARHGAP24	RHOA	P06749	652
ARHGAP24	CDC42	P21181	629
ARHGAP24	ARHGDIA	P52565	622
ARHGAP24	INF2	Q27J81	618
ARHGAP24	TBX5	Q99593	599
ARHGAP24	NPHS2	Q9NP85	545
ARHGAP24	ROCK1	Q13464	535
ARHGAP24	PECAM1	P16284	531
ARHGAP24	CAV1	Q03135	524
ARHGAP24	KANK2	Q63ZY3	524
ARHGAP24	SCN5A	Q14524	523
ARHGAP24	NPHS1	O60500	517
ARHGAP24	ACTN1	P12814	517

IntAct

17 interactions, top by confidence:

A	B	Type	Score
ARHGAP24	FLNA	psi-mi:“MI:0915”(physical association)	0.640
FLNA	ARHGAP24	psi-mi:“MI:0915”(physical association)	0.640
ARHGAP24	FLNA	psi-mi:“MI:0403”(colocalization)	0.640
	RAC1	psi-mi:“MI:0915”(physical association)	0.610
ARHGAP24	Rock1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
CDC42	ARHGAP24	psi-mi:“MI:0915”(physical association)	0.400
ARHGAP24	HTT	psi-mi:“MI:0915”(physical association)	0.370
HTT	ARHGAP24	psi-mi:“MI:0915”(physical association)	0.370
ARHGAP32	SEC61B	psi-mi:“MI:0914”(association)	0.350
SRGAP3	NKTR	psi-mi:“MI:0914”(association)	0.350
PIP	RBM47	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (495): SRGAP3 (Affinity Capture-Western), ARHGAP32 (Affinity Capture-Western), ACAT1 (Affinity Capture-MS), CKB (Affinity Capture-MS), DDB1 (Affinity Capture-MS), DEK (Affinity Capture-MS), DLD (Affinity Capture-MS), DPY30 (Affinity Capture-MS), HSPE1 (Affinity Capture-MS), LDHA (Affinity Capture-MS), MIB1 (Affinity Capture-MS), NACA (Affinity Capture-MS), NME2 (Affinity Capture-MS), PFN1 (Affinity Capture-MS), PNN (Affinity Capture-MS)

ESM2 similar proteins: A2AR50, B0UXH6, D3ZAZ5, D4AB98, F1M386, F1MSG6, F1PBJ0, F7EL49, O60343, O75044, O97790, P0CE43, P42331, Q00IB7, Q13905, Q14155, Q15678, Q28CB1, Q4R7W3, Q58DL5, Q5JS13, Q5U2Z7, Q5ZJK0, Q60695, Q60949, Q62130, Q62136, Q6INE5, Q6INP9, Q6P112, Q6P549, Q7Z6B7, Q80TI1, Q86TI0, Q86X27, Q8BYJ6, Q8BYW1, Q8C4V1, Q8CHG7, Q8IV61

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

12 interactions.

A	Effect	B	Mechanism
ROCK1	up-regulates	ARHGAP24	phosphorylation
ROCK1	“up-regulates activity”	ARHGAP24	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	165
Likely benign	86
Benign	57

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
146118	GRCh38/hg38 4q21.23-21.3(chr4:84577519-86077547)x3	Pathogenic
2685118	GRCh37/hg19 4q21.23-21.3(chr4:85721709-86937764)x1	Pathogenic
3062786	GRCh37/hg19 4q21.23(chr4:85821886-86397283)x1	Likely pathogenic

SpliceAI

5243 predictions. Top by Δscore:

Variant	Effect	Δscore
4:85604218:T:G	acceptor_gain	1.0000
4:85647371:T:TA	acceptor_gain	1.0000
4:85659243:A:T	donor_gain	1.0000
4:85721879:TCACA:T	acceptor_loss	1.0000
4:85721881:ACAG:A	acceptor_gain	1.0000
4:85721883:A:AG	acceptor_gain	1.0000
4:85721883:AG:A	acceptor_gain	1.0000
4:85721884:G:GG	acceptor_gain	1.0000
4:85721884:GG:G	acceptor_gain	1.0000
4:85721884:GGGT:G	acceptor_gain	1.0000
4:85721884:GGGTA:G	acceptor_gain	1.0000
4:85721947:G:T	donor_gain	1.0000
4:85721971:AGG:A	donor_loss	1.0000
4:85721972:GGT:G	donor_loss	1.0000
4:85721973:G:GC	donor_loss	1.0000
4:85721974:T:G	donor_loss	1.0000
4:85741692:G:GT	donor_gain	1.0000
4:85855082:T:TA	donor_gain	1.0000
4:85855083:A:AA	donor_gain	1.0000
4:85923642:TCACA:T	acceptor_loss	1.0000
4:85923645:CA:C	acceptor_loss	1.0000
4:85923646:A:AG	acceptor_gain	1.0000
4:85923647:G:GG	acceptor_gain	1.0000
4:85923647:G:GT	acceptor_loss	1.0000
4:85923647:GGA:G	acceptor_gain	1.0000
4:85923767:GGAG:G	donor_gain	1.0000
4:85923768:GAG:G	donor_gain	1.0000
4:85923768:GAGG:G	donor_gain	1.0000
4:85923771:G:GG	donor_gain	1.0000
4:85923771:G:T	donor_loss	1.0000

AlphaMissense

5038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:85570612:G:A	G24E	1.000
4:85570618:T:C	L26P	1.000
4:85570623:A:G	K28E	1.000
4:85570625:G:C	K28N	1.000
4:85570625:G:T	K28N	1.000
4:85570647:T:A	W36R	1.000
4:85570647:T:C	W36R	1.000
4:85570656:C:A	R39S	1.000
4:85570657:G:C	R39P	1.000
4:85570662:T:C	F41L	1.000
4:85570663:T:C	F41S	1.000
4:85570664:T:A	F41L	1.000
4:85570664:T:G	F41L	1.000
4:85570669:T:C	L43P	1.000
4:85570684:T:C	L48P	1.000
4:85570689:T:G	Y50D	1.000
4:85721958:T:C	F85S	1.000
4:85923693:T:C	L105P	1.000
4:85923725:T:A	W116R	1.000
4:85923725:T:C	W116R	1.000
4:85923727:G:C	W116C	1.000
4:85923727:G:T	W116C	1.000
4:85942071:T:C	F133L	1.000
4:85942072:T:C	F133S	1.000
4:85942072:T:G	F133C	1.000
4:85942073:T:A	F133L	1.000
4:85942073:T:G	F133L	1.000
4:85942132:C:A	P153Q	1.000
4:85942132:C:G	P153R	1.000
4:85942149:T:C	C159R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000304 (4:85551353 C>A), RS1000001060 (4:85729355 C>A), RS10000107 (4:85891267 G>A,C,T), RS1000012327 (4:85782078 T>C), RS1000015520 (4:85782759 G>A,T), RS1000021742 (4:85923217 T>C), RS1000024262 (4:85598545 C>T), RS1000024447 (4:85967531 G>A,C), RS1000024584 (4:85738308 C>T), RS10000253 (4:85891598 C>T), RS1000031720 (4:85653702 C>T), RS1000031739 (4:85922975 C>A,T), RS1000032519 (4:85631339 C>T), RS1000033453 (4:85899911 C>T), RS1000041546 (4:85594713 T>C)

Disease associations

OMIM: gene MIM:610586 | disease phenotypes: MIM:189800, MIM:603278

GenCC curated gene-disease

Disease	Classification	Inheritance
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant
inherited focal segmental glomerulosclerosis	Limited	Autosomal dominant

Mondo (6): focal segmental glomerulosclerosis (MONDO:0100313), preeclampsia (MONDO:0005081), focal segmental glomerulosclerosis 1 (MONDO:0011303), nephrotic syndrome (MONDO:0005377), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006), inherited focal segmental glomerulosclerosis (MONDO:0005363)

Orphanet (3): Preeclampsia (Orphanet:275555), Hereditary steroid-resistant nephrotic syndrome (Orphanet:656), OBSOLETE: Familial idiopathic steroid-resistant nephrotic syndrome with focal segmental hyalinosis (Orphanet:93213)

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000969	Edema
HP:0001945	Fever
HP:0001967	Diffuse mesangial sclerosis
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002586	Peritonitis
HP:0003073	Hypoalbuminemia
HP:0003774	Stage 5 chronic kidney disease
HP:0011947	Respiratory tract infection
HP:0012579	Minimal change glomerulonephritis
HP:0012622	Chronic kidney disease
HP:0031504	Foamy urine
HP:0100539	Periorbital edema

GWAS associations

63 associations (top):

Study	Trait	p-value
GCST000561_1	Electrocardiographic traits	3.000000e-17
GCST000562_3	PR interval	6.000000e-20
GCST001735_6	PR interval	3.000000e-09
GCST001762_580	Obesity-related traits	5.000000e-06
GCST002456_4	PR segment duration	1.000000e-14
GCST002875_52	Diisocyanate-induced asthma	1.000000e-06
GCST002875_7	Diisocyanate-induced asthma	1.000000e-06
GCST003272_1	Systolic blood pressure	5.000000e-17
GCST004212_15	Height	4.000000e-08
GCST004775_21	Pulse pressure	4.000000e-10
GCST004776_17	Systolic blood pressure	7.000000e-10
GCST005080_7	PR interval	6.000000e-11
GCST005171_39	QT interval	2.000000e-06
GCST006039_6	Peanut allergy	2.000000e-06
GCST006188_25	Systolic blood pressure (cigarette smoking interaction)	2.000000e-17
GCST006259_47	Systolic blood pressure	2.000000e-09
GCST006288_206	Heel bone mineral density	5.000000e-11
GCST006288_523	Heel bone mineral density	1.000000e-11
GCST006633_9	Initial alcohol sensitivity	7.000000e-06
GCST006979_438	Heel bone mineral density	2.000000e-32
GCST006988_64	Blond vs. brown/black hair color	1.000000e-13
GCST007000_1	Logical memory (delayed recall) in mild cognitive impairment	3.000000e-08
GCST007045_4	PR interval	3.000000e-61
GCST007096_91	Pulse pressure	6.000000e-08
GCST007099_77	Systolic blood pressure	4.000000e-07
GCST007226_9	PR interval	6.000000e-21
GCST007267_267	Systolic blood pressure	4.000000e-13
GCST007269_96	Pulse pressure	5.000000e-12
GCST009870_10	Calcific aortic valve stenosis	1.000000e-06
GCST010152_11	Neuroblastoma or malignant cutaneous melanoma	1.000000e-07

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004730	hormone measurement
EFO:0005095	PR segment
EFO:0006995	response to diisocyanate
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004682	QT interval
EFO:0007017	peanut allergy measurement
EFO:0006527	smoking status measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0004874	memory performance
EFO:0000266	aortic stenosis
EFO:0008328	chronotype measurement
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D011225	Pre-Eclampsia	C12.050.703.395.249
C538457	Segmental glomerulosclerosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	6
Cisplatin	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	affects methylation, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
belinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression, decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
mirdametinib	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01129557	PHASE4	TERMINATED	Aldosterone Breakthrough During Diovan, Tekturna, and Combination Therapy in Patients With Proteinuric Kidney Disease
NCT02399462	PHASE4	WITHDRAWN	Acthar for Treatment of Post-transplant FSGS
NCT02585804	PHASE4	COMPLETED	Treating to Reduce Albuminuria and Normalize Hemodynamic Function in Focal ScLerosis With dApagliflozin Trial Effects
NCT02633046	PHASE4	COMPLETED	Acthar for Treatment-Resistant or Treatment-Intolerant Proteinuria
NCT07219121	PHASE4	RECRUITING	Sparsentan in Posttransplant Immunoglobulin A Nephropathy or Focal Segmental Glomerulosclerosis
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia