AVIL

Summary

AVIL (advillin, HGNC:14188) is a protein-coding gene on chromosome 12q14.1, encoding Advillin (O75366). Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling.

The protein encoded by this gene is a member of the gelsolin/villin family of actin regulatory proteins. This protein has structural similarity to villin. It binds actin and may play a role in the development of neuronal cells that form ganglia.

Source: NCBI Gene 10677 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 21 (Limited, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 208 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_006576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14188
Approved symbol	AVIL
Name	advillin
Location	12q14.1
Locus type	gene with protein product
Status	Approved
Aliases	p92, FLJ12386, ADVIL, DOC6
Ensembl gene	ENSG00000135407
Ensembl biotype	protein_coding
OMIM	613397
Entrez	10677

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 retained_intron, 2 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000257861, ENST00000546952, ENST00000548843, ENST00000549548, ENST00000549753, ENST00000549851, ENST00000549994, ENST00000550083, ENST00000550537, ENST00000551248

RefSeq mRNA: 1 — MANE Select: NM_006576 NM_006576

CCDS: CCDS8959

Canonical transcript exons

ENST00000549994 — 20 exons

Exon	Start	End
ENSE00002325475	57818629	57818734
ENSE00002350239	57815975	57816059
ENSE00003479367	57808395	57808548
ENSE00003489440	57810349	57810551
ENSE00003494054	57810816	57810926
ENSE00003506264	57813227	57813423
ENSE00003507397	57806360	57806539
ENSE00003532761	57799795	57799920
ENSE00003533252	57803247	57803391
ENSE00003537299	57808194	57808294
ENSE00003552564	57814152	57814226
ENSE00003573039	57809597	57809695
ENSE00003573463	57801144	57801212
ENSE00003582021	57811019	57811127
ENSE00003627734	57807590	57807727
ENSE00003649447	57802160	57802348
ENSE00003666778	57809812	57809890
ENSE00003670479	57807331	57807489
ENSE00003682280	57803524	57803669
ENSE00003928055	57797380	57797995

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0563 / max 29.8107, expressed in 18 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131762	0.0363	16
131763	0.0200	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	96.59	gold quality
cerebellar hemisphere	UBERON:0002245	91.06	gold quality
gastrocnemius	UBERON:0001388	90.95	gold quality
cerebellar cortex	UBERON:0002129	90.89	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.75	gold quality
muscle of leg	UBERON:0001383	90.55	gold quality
trigeminal ganglion	UBERON:0001675	90.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.79	gold quality
mucosa of transverse colon	UBERON:0004991	89.03	gold quality
cerebellum	UBERON:0002037	88.17	gold quality
right adrenal gland	UBERON:0001233	87.39	gold quality
right uterine tube	UBERON:0001302	86.16	gold quality
right lobe of thyroid gland	UBERON:0001119	86.06	gold quality
muscle organ	UBERON:0001630	85.78	gold quality
skeletal muscle organ	UBERON:0014892	85.78	gold quality
body of pancreas	UBERON:0001150	84.99	gold quality
left lobe of thyroid gland	UBERON:0001120	84.95	gold quality
left adrenal gland	UBERON:0001234	84.92	gold quality
right adrenal gland cortex	UBERON:0035827	84.69	gold quality
right lobe of liver	UBERON:0001114	84.34	gold quality
left adrenal gland cortex	UBERON:0035825	84.16	gold quality
metanephros cortex	UBERON:0010533	84.06	gold quality
thyroid gland	UBERON:0002046	83.86	gold quality
adenohypophysis	UBERON:0002196	83.52	gold quality
transverse colon	UBERON:0001157	83.45	gold quality
apex of heart	UBERON:0002098	83.34	gold quality
tendon of biceps brachii	UBERON:0008188	83.33	silver quality
descending thoracic aorta	UBERON:0002345	83.22	gold quality
adrenal gland	UBERON:0002369	83.20	gold quality
lower esophagus mucosa	UBERON:0035834	82.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	1211.74
E-MTAB-8410	yes	5.36
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting AVIL, 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-4692	100.00	67.32	2066
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-1206	99.30	69.32	1016

Literature-anchored findings (GeneRIF, showing 6)

• NMR structure of the C-terminal headpiece subdomains of advillin. Evaluation of F-actin-binding requirements. (PMID:15096633)
• Predicting the effect of a point mutation on a protein fold: the villin and advillin headpieces and their Pro62Ala mutants. (PMID:18022635)
• podocyte migration rate was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. (PMID:29058690)
• A cytoskeleton regulator AVIL drives tumorigenesis in glioblastoma. (PMID:32651364)
• Targeting AVIL, a New Cytoskeleton Regulator in Glioblastoma. (PMID:34948433)
• The Potential for Targeting AVIL and Other Actin-Binding Proteins in Rhabdomyosarcoma. (PMID:37762498)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	avil	ENSDARG00000059342
mus_musculus	Avil	ENSMUSG00000025432
rattus_norvegicus	Avil	ENSRNOG00000050419
drosophila_melanogaster	Gel	FBGN0010225
caenorhabditis_elegans		WBGENE00010593

Paralogs (7): SCIN (ENSG00000006747), CAPG (ENSG00000042493), VIL1 (ENSG00000127831), VILL (ENSG00000136059), GSN (ENSG00000148180), FLII (ENSG00000177731), SVIL (ENSG00000197321)

Protein

Protein identifiers

Advillin — O75366 (reviewed: O75366)

Alternative names: p92

All UniProt accessions (3): O75366, F8VNY0, F8VVU1

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling. May have a unique function in the morphogenesis of neuronal cells which form ganglia. Required for SREC1-mediated regulation of neurite-like outgrowth. Plays a role in regenerative sensory axon outgrowth and remodeling processes after peripheral injury in neonates. Involved in the formation of long fine actin-containing filopodia-like structures in fibroblast. Plays a role in ciliogenesis. In podocytes, controls lamellipodia formation through the regulation of EGF-induced diacylglycerol generation by PLCE1 and ARP2/3 complex assembly.

Subunit / interactions. Associates (via C-terminus) with F-actin. Interacts with SCARF1. Interacts with PLCE1. Interacts with ACTR2 and ACTR3; associates with the ARP2/3 complex.

Subcellular location. Cytoplasm. Cytoskeleton. Cell projection. Lamellipodium. Cell junction. Focal adhesion. Neuron projection. Axon.

Tissue specificity. Most highly expressed in the small intestine and colonic lining. Weaker expression also detected in the thymus, prostate, testes and uterus. Expressed in podocytes (at protein level).

Disease relevance. Nephrotic syndrome 21 (NPHS21) [MIM:618594] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS21 is an autosomal recessive, rapidly progressive, steroid-resistant form characterized by onset of kidney dysfunction in the first year of life. Some patients may have variable extra-renal manifestations. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the villin/gelsolin family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75366-1	1	yes
O75366-2	2

RefSeq proteins (1): NP_006567* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003128	Villin_headpiece	Domain
IPR007122	Villin/Gelsolin	Family
IPR007123	Gelsolin-like_dom	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR036180	Gelsolin-like_dom_sf	Homologous_superfamily
IPR036886	Villin_headpiece_dom_sf	Homologous_superfamily

Pfam: PF00626, PF02209

UniProt features (25 total): repeat 6, sequence variant 4, region of interest 3, helix 3, binding site 2, modified residue 2, chain 1, splice variant 1, mutagenesis site 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1UND	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75366-F1	79.82	0.24

Functional residue map

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

Ligand- & substrate-binding residues (2): 109–116; 135–143

Post-translational modifications (2): 85, 758

Mutagenesis-validated functional residues (1):

Position	Phenotype
62	reduces interaction with f-actin.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, PEREZ_TP63_TARGETS, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BARBED_END_ACTIN_FILAMENT_CAPPING, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (13): actin filament organization (GO:0007015), nervous system development (GO:0007399), actin polymerization or depolymerization (GO:0008154), positive regulation of lamellipodium assembly (GO:0010592), positive regulation of neuron projection development (GO:0010976), actin filament severing (GO:0051014), barbed-end actin filament capping (GO:0051016), cilium assembly (GO:0060271), regulation of diacylglycerol biosynthetic process (GO:1900480), cytoskeleton organization (GO:0007010), positive regulation of cellular component biogenesis (GO:0044089), actin filament capping (GO:0051693), positive regulation of lamellipodium organization (GO:1902745)

GO Molecular Function (5): actin binding (GO:0003779), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), actin filament binding (GO:0051015), Arp2/3 complex binding (GO:0071933), protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), actin filament (GO:0005884), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), axon (GO:0030424), cell projection (GO:0042995), neuron projection (GO:0043005), cytoskeleton (GO:0005856), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cell projection organization	2
protein-containing complex binding	2
cellular anatomical structure	2
plasma membrane bounded cell projection	2
actin cytoskeleton organization	1
supramolecular fiber organization	1
system development	1
actin filament organization	1
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
regulation of neuron projection development	1
neuron projection development	1
actin filament-based process	1
actin filament capping	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
diacylglycerol biosynthetic process	1
regulation of lipid biosynthetic process	1
organelle organization	1
cellular component biogenesis	1
regulation of cellular component biogenesis	1
positive regulation of cellular process	1
negative regulation of actin filament depolymerization	1
negative regulation of actin filament polymerization	1
lamellipodium organization	1
regulation of lamellipodium organization	1
cytoskeletal protein binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
actin binding	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AVIL	ACTR3	P32391	876
AVIL	ALPP	P05187	672
AVIL	ADH1A	P07327	588
AVIL	SCN10A	Q9Y5Y9	576
AVIL	SCN9A	Q15858	478
AVIL	TRPV1	Q8NER1	473
AVIL	SH2D7	A6NKC9	458
AVIL	EEF1AKMT3	Q96AZ1	447
AVIL	TRPM5	Q9NZQ8	446
AVIL	TRPA1	O75762	426
AVIL	ALMS1	Q8TCU4	410
AVIL	ACTR2	P61160	405
AVIL	CALCA	P01258	392
AVIL	PIEZO2	Q9H5I5	389
AVIL	YBX3	P16989	388

IntAct

7 interactions, top by confidence:

A	B	Type	Score
AVIL	VIL1	psi-mi:“MI:0914”(association)	0.530
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
AVIL	DCTN6	psi-mi:“MI:0914”(association)	0.350
RBSN	LMX1B	psi-mi:“MI:0914”(association)	0.350
SP4	AVIL	psi-mi:“MI:0914”(association)	0.350

BioGRID (56): AVIL (Affinity Capture-MS), DDX11 (Affinity Capture-MS), DUS3L (Affinity Capture-MS), FIGNL1 (Affinity Capture-MS), SCYL1 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), VIL1 (Affinity Capture-MS), TMOD2 (Affinity Capture-MS), RICTOR (Affinity Capture-MS), RIPK4 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), MCM8 (Affinity Capture-MS), THUMPD3 (Affinity Capture-MS), BRIP1 (Affinity Capture-MS), MYO5C (Affinity Capture-MS)

ESM2 similar proteins: A0A6B9KZ40, A8XV95, B3DJT0, B8ATT7, B8AY58, D3ZGS3, F8WK50, O61270, O65570, O75366, O81643, O81644, O88398, O89040, P10733, P16885, P19686, P24452, P34268, P36418, P40121, Q01968, Q02108, Q07171, Q0DKN3, Q0J716, Q0JAD9, Q21253, Q23989, Q24020, Q24800, Q27319, Q2KHZ2, Q4ZHS0, Q5R6Y0, Q67U26, Q69ZS7, Q6AXM7, Q6AYC4, Q6GM14

Diamond homologs: A0A6B9KZ40, A8XV95, B8ATT7, F8WK50, O15195, O61270, O65570, O75366, O81643, O81644, O81645, O88398, O93510, P02640, P06396, P09327, P10733, P13020, P14885, P20305, P24452, P34268, P40121, Q07171, Q0J716, Q0JAD9, Q10L71, Q13045, Q21253, Q24020, Q24800, Q27319, Q28046, Q28372, Q29261, Q29297, Q3SX14, Q3SZP7, Q5ZIV9, Q60604

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	151
Likely benign	19
Benign	17

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
684648	NM_006576.4(AVIL):c.1273C>A (p.Leu425Met)	Pathogenic
684649	NM_006576.4(AVIL):c.1337G>A (p.Arg446His)	Pathogenic
1810257	NM_006576.4(AVIL):c.595C>T (p.Arg199Ter)	Likely pathogenic
4845723	NM_006576.4(AVIL):c.505A>T (p.Lys169Ter)	Likely pathogenic
684650	NM_006576.4(AVIL):c.404G>A (p.Arg135Gln)	Likely pathogenic

SpliceAI

3473 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57801142:A:AC	donor_gain	1.0000
12:57801143:C:CC	donor_gain	1.0000
12:57801143:CAG:C	donor_gain	1.0000
12:57801209:CTGC:C	acceptor_gain	1.0000
12:57801213:C:CC	acceptor_gain	1.0000
12:57802159:CA:C	donor_gain	1.0000
12:57802214:AAAC:A	donor_gain	1.0000
12:57802214:AAACC:A	donor_gain	1.0000
12:57802226:A:AC	donor_gain	1.0000
12:57802227:A:C	donor_gain	1.0000
12:57803242:CTTAC:C	donor_loss	1.0000
12:57803243:TTACC:T	donor_loss	1.0000
12:57803244:TACC:T	donor_loss	1.0000
12:57803245:A:T	donor_loss	1.0000
12:57803246:C:CA	donor_loss	1.0000
12:57803667:CCC:C	acceptor_gain	1.0000
12:57803668:CC:C	acceptor_gain	1.0000
12:57803668:CCC:C	acceptor_gain	1.0000
12:57803669:CC:C	acceptor_gain	1.0000
12:57806357:TA:T	donor_loss	1.0000
12:57806358:AC:A	donor_loss	1.0000
12:57806535:CCACC:C	acceptor_gain	1.0000
12:57806536:CACCC:C	acceptor_gain	1.0000
12:57806538:CC:C	acceptor_gain	1.0000
12:57806539:CC:C	acceptor_gain	1.0000
12:57807348:T:TA	donor_gain	1.0000
12:57807349:C:A	donor_gain	1.0000
12:57808189:CTTA:C	donor_loss	1.0000
12:57808191:TACC:T	donor_loss	1.0000
12:57808192:A:AC	donor_gain	1.0000

AlphaMissense

1031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57813381:A:G	W62R	0.997
12:57813381:A:T	W62R	0.997
12:57813374:C:A	G64V	0.994
12:57813284:C:G	R94P	0.993
12:57813320:A:G	L82P	0.993
12:57813374:C:T	G64E	0.993
12:57813379:C:A	W62C	0.992
12:57813379:C:G	W62C	0.992
12:57814167:G:C	C42W	0.992
12:57813375:C:A	G64W	0.991
12:57813380:C:G	W62S	0.990
12:57815986:A:G	W19R	0.990
12:57815986:A:T	W19R	0.990
12:57811056:A:G	L137P	0.983
12:57813375:C:G	G64R	0.983
12:57813375:C:T	G64R	0.983
12:57813381:A:C	W62G	0.983
12:57811059:A:G	L136P	0.981
12:57813254:A:G	F104S	0.979
12:57813287:T:G	H93P	0.979
12:57813387:G:C	H60D	0.978
12:57813341:G:T	A75E	0.977
12:57813265:C:A	E100D	0.976
12:57813265:C:G	E100D	0.976
12:57814156:A:G	L46P	0.976
12:57814168:C:T	C42Y	0.976
12:57814169:A:G	C42R	0.976
12:57813241:G:C	F108L	0.975
12:57813241:G:T	F108L	0.975
12:57813243:A:G	F108L	0.975

dbSNP variants (sampled 300 via entrez): RS1000011333 (12:57803668 C>A,T), RS1000093708 (12:57807573 G>A,C), RS1000374331 (12:57813396 G>A), RS1000396709 (12:57818421 C>G,T), RS1000613742 (12:57802147 T>C), RS1000680389 (12:57800361 C>G), RS1000766300 (12:57818222 A>G), RS1000830151 (12:57813803 C>G), RS1000898397 (12:57801664 C>A), RS1000903425 (12:57814047 C>A,G,T), RS1001032806 (12:57819486 G>A), RS1001079019 (12:57808311 G>A), RS1001476649 (12:57812924 A>G), RS1001509758 (12:57807016 G>A,C), RS1001688445 (12:57799032 A>G)

Disease associations

OMIM: gene MIM:613397 | disease phenotypes: MIM:610505, MIM:618594

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 21	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nephrotic syndrome, type 21	Limited	AR

Mondo (4): fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (MONDO:0012512), nephrotic syndrome, type 21 (MONDO:0032826), nephrotic syndrome (MONDO:0005377), steroid-resistant nephrotic syndrome (MONDO:0044765)

Orphanet (1): Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 (Orphanet:168566)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
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:0012588	Steroid-resistant nephrotic syndrome
HP:0012622	Chronic kidney disease
HP:0031266	Podocyte foot process effacement
HP:0031504	Foamy urine
HP:0100539	Periorbital edema

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010703_209	Brain morphology (MOSTest)	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C566467	Combined Oxidative Phosphorylation Deficiency 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Gelsolin/villin cytoskeleton proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound A [PMID: 41604465]	Binding	5.22	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
sodium bichromate	increases expression	1
ochratoxin A	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
pentanal	decreases expression	1
2-palmitoylglycerol	increases expression	1
quinocetone	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	increases expression, affects binding	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	decreases expression	1
Methapyrilene	decreases methylation	1
Naphthoquinones	increases expression	1
Nickel	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT03408405	PHASE4	WITHDRAWN	ACTHAR Gel for Drug REsistant Nephrotic Syndrome in Children
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02394106	PHASE2	TERMINATED	Ofatumumab in Children With Drug Resistant Idiopathic Nephrotic Syndrome
NCT02394119	PHASE2	COMPLETED	Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT02966717	PHASE2	UNKNOWN	Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
NCT03004001	PHASE2	TERMINATED	Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
NCT03949855	PHASE2	RECRUITING	Belimumab With Rituximab for Primary Membranous Nephropathy
NCT05599815	PHASE2	WITHDRAWN	Part 1 - A Clinical Trial in Patients With Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome
NCT05704400	PHASE2	UNKNOWN	Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome