SYNPO

Summary

SYNPO (synaptopodin, HGNC:30672) is a protein-coding gene on chromosome 5q33.1, encoding Synaptopodin (Q8N3V7). Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes.

Synaptopodin is an actin-associated protein that may play a role in actin-based cell shape and motility. The name synaptopodin derives from the protein’s associations with postsynaptic densities and dendritic spines and with renal podocytes (Mundel et al., 1997 [PubMed 9314539]).

Source: NCBI Gene 11346 — RefSeq curated summary.

At a glance

• Gene–disease (curated): focal segmental glomerulosclerosis (Limited, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 315 total
• MANE Select transcript: NM_007286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30672
Approved symbol	SYNPO
Name	synaptopodin
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1029, SYNPO1
Ensembl gene	ENSG00000171992
Ensembl biotype	protein_coding
OMIM	608155
Entrez	11346

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000307662, ENST00000394243, ENST00000518872, ENST00000519664, ENST00000522122, ENST00000866117, ENST00000866118, ENST00000866119, ENST00000952230

RefSeq mRNA: 4 — MANE Select: NM_007286 NM_001109974, NM_001166208, NM_001166209, NM_007286

CCDS: CCDS4308, CCDS54937, CCDS54938

Canonical transcript exons

ENST00000307662 — 3 exons

Exon	Start	End
ENSE00001145576	150640660	150640854
ENSE00001170768	150656404	150659207
ENSE00001170779	150647944	150650303

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.7701 / max 1062.4948, expressed in 1435 samples.

FANTOM5 promoters (28 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59473	21.5162	1192
59482	6.4202	1025
59483	1.6422	668
59480	1.2385	329
59507	0.8632	387
59474	0.8281	298
59494	0.7990	409
59506	0.6543	314
59472	0.6212	198
59493	0.5827	313

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.46	gold quality
apex of heart	UBERON:0002098	99.37	gold quality
descending thoracic aorta	UBERON:0002345	99.17	gold quality
gastrocnemius	UBERON:0001388	99.04	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.02	gold quality
thoracic aorta	UBERON:0001515	99.01	gold quality
ascending aorta	UBERON:0001496	99.00	gold quality
right coronary artery	UBERON:0001625	98.99	gold quality
right atrium auricular region	UBERON:0006631	98.96	gold quality
tendon of biceps brachii	UBERON:0008188	98.82	gold quality
heart left ventricle	UBERON:0002084	98.53	gold quality
cardiac atrium	UBERON:0002081	98.47	gold quality
aorta	UBERON:0000947	98.43	gold quality
cardiac ventricle	UBERON:0002082	98.39	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.29	gold quality
muscle of leg	UBERON:0001383	98.26	gold quality
coronary artery	UBERON:0001621	98.21	gold quality
left coronary artery	UBERON:0001626	98.15	gold quality
artery	UBERON:0001637	98.01	gold quality
popliteal artery	UBERON:0002250	98.01	gold quality
tibial artery	UBERON:0007610	98.01	gold quality
biceps brachii	UBERON:0001507	97.83	gold quality
heart	UBERON:0000948	97.73	gold quality
saphenous vein	UBERON:0007318	97.70	gold quality
left adrenal gland cortex	UBERON:0035825	97.24	gold quality
adrenal cortex	UBERON:0001235	97.19	gold quality
left adrenal gland	UBERON:0001234	97.18	gold quality
right adrenal gland	UBERON:0001233	97.17	gold quality
blood vessel layer	UBERON:0004797	97.07	gold quality
renal glomerulus	UBERON:0000074	97.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	16.63
E-ANND-3	yes	10.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR4

miRNA regulators (miRDB)

57 targeting SYNPO, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-548S	98.50	67.17	1213

Literature-anchored findings (GeneRIF, showing 19)

• interaction with tight junction protein MAGI-1 (PMID:12042308)
• Our data suggest dendritic spine accumulation of SYNPO critically depends on interaction with postsynaptic alpha-actinin and that SYNPO may regulate spine morphology, motility and function via its distinct modes of association with the actin cytoskeleton. (PMID:15659229)
• Discusses isoforms of mouse Synpo, two of which are consistent with those found in human. (PMID:15841212)
• Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary focal segmental glomerulosclerosis. (PMID:16564554)
• Synaptopodin, an actin-associated protein, as a novel regulator of RhoA signalling and cell migration in kidney podocytes. (PMID:16622418)
• We conclude that down-regulation of nephrin and synaptopodin is associated with proteinuria in women with preeclampsia. (PMID:17255128)
• Heterozygous mutations in the promoters of the ACTN4 and SYNPO genes are found in patients with idiopathic focal segmental glomerulosclerosis. (PMID:19666657)
• Podocyte BK(Ca) channels are regulated by synaptopodin, Rho, and actin microfilaments. (PMID:20630939)
• The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, alpha-actin4, and podocin were found to increase with the progression of diabetic nephropathy. (PMID:21655212)
• These results suggested that the SA is an important component of the molecular machinery controlling the calcium-dependent accumulation of AMPA-receptors (AMPA-R) at excitatory synapses. [review] (PMID:22217474)
• Shear stress induced actin binding proteins including SYNPO may play a critical role in endothelial wound healing. (PMID:24561195)
• This study identified and confirmed SYNPO protein changes within the postsynaptic density in schizophrenia (PMID:25048004)
• expression significantly down-regulated in presence of WT1 R458Q mutation (PMID:25145932)
• Case Report: immunohistologically detected synaptopodin upregulation in foamy podocytes in Fabry disease due to novel alpha-galactosidase A mutation. (PMID:25295576)
• SYNPO variants are involved in AMPA receptor trafficking and neuronal plasticity, which are associated with cognitive impairment and schizophrenia susceptibility. (PMID:26405221)
• Urine synaptopodin is associated with serum creatinine elevation in the patients with glomerulonephritis including diabetic kidney disease regardless of urine albumin excretion. We suggest that the urine synaptopodin level can predict glomerular damage independently of the urine albumin excretion. (PMID:27604800)
• The postsynaptic protein, synaptopodin (SYNPO) was significantly down-regulated in both dementia with Lewy bodies and Parkinson’s disease dementia subgroups, suggesting a defective synaptic transmission in the demented patients. (PMID:28800743)
• We show that recombinant human KIBRA WW2 domain is primarily disordered, binds SYNPO with relatively weak affinity and remains largely disordered in the complex. (PMID:31597702)
• Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin. (PMID:32398370)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000106873
mus_musculus	Synpo	ENSMUSG00000043079
rattus_norvegicus	Myoz3	ENSRNOG00000019181
drosophila_melanogaster	CG1674	FBGN0039897

Paralogs (2): SYNPO2L (ENSG00000166317), SYNPO2 (ENSG00000172403)

Protein

Protein identifiers

Synaptopodin — Q8N3V7 (reviewed: Q8N3V7)

All UniProt accessions (1): Q8N3V7

UniProt curated annotations — full annotation on UniProt →

Function. Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity.

Subunit / interactions. Interacts with BAIAP1. Interacts with actin. Interacts (via PPxY motifs) with WWC1 (via WW domains).

Subcellular location. Cytoplasm. Cytoskeleton. Cell junction. Tight junction. Perikaryon. Cell projection. Dendritic spine. Postsynaptic density. Synapse. Cytosol.

Tissue specificity. Expressed in cerebral cortex.

Post-translational modifications. O-glycosylated.

Similarity. Belongs to the synaptopodin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N3V7-1	1	yes
Q8N3V7-2	2
Q8N3V7-3	3

RefSeq proteins (4): NP_001103444, NP_001159680, NP_001159681, NP_009217* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR051976	Synaptopodin_domain	Family

UniProt features (56 total): modified residue 26, compositionally biased region 12, region of interest 7, sequence conflict 5, splice variant 2, short sequence motif 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3V7-F1	50.70	0.04

Functional residue map

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

Post-translational modifications (26): 140, 207, 263, 501, 525, 560, 580, 685, 702, 746, 754, 758, 779, 783, 833, 854, 1, 738, 784, 804 …

Glycosylation sites (1): 330

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 247 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, AP1_Q4_01, ONKEN_UVEAL_MELANOMA_UP, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION

GO Biological Process (3): positive regulation of actin filament bundle assembly (GO:0032233), regulation of stress fiber assembly (GO:0051492), spine apparatus assembly (GO:1905355)

GO Molecular Function (2): actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (18): stress fiber (GO:0001725), nucleus (GO:0005634), cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), postsynaptic density (GO:0014069), actin cytoskeleton (GO:0015629), Z disc (GO:0030018), dendritic spine (GO:0043197), perikaryon (GO:0043204), spine apparatus (GO:0097444), glutamatergic synapse (GO:0098978), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995), organelle (GO:0043226), synapse (GO:0045202), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
regulation of actin filament bundle assembly	2
cell junction	2
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
stress fiber assembly	1
regulation of actomyosin structure organization	1
organelle assembly	1
cytoskeletal protein binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular membrane-bounded organelle	1
cytoplasm	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
asymmetric synapse	1
postsynaptic specialization	1
cytoskeleton	1
I band	1
dendrite	1
neuron spine	1
postsynapse	1
neuronal cell body	1
endomembrane system	1
dendritic spine	1
membrane-bounded organelle	1
synapse	1
intracellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNPO	ACTN4	O43707	979
SYNPO	NPHS1	O60500	967
SYNPO	CD2AP	Q9Y5K6	962
SYNPO	NPHS2	Q9NP85	926
SYNPO	MAGI1	Q96QZ7	923
SYNPO	PODXL	O00592	921
SYNPO	WT1	P19544	843
SYNPO	TJP1	Q07157	832
SYNPO	DDN	O94850	723
SYNPO	PAX2	Q02962	719
SYNPO	SCEL	O95171	705
SYNPO	YWHAB	P31946	656
SYNPO	VCL	P18206	652
SYNPO	YIPF3	Q9GZM5	650
SYNPO	CYP26A1	O43174	648
SYNPO	SULF1	Q8IWU6	648

IntAct

56 interactions, top by confidence:

A	B	Type	Score
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
ACTN1	SYNPO	psi-mi:“MI:0915”(physical association)	0.560
SYNPO	SGF29	psi-mi:“MI:0915”(physical association)	0.560
SYNPO	CDC5L	psi-mi:“MI:0915”(physical association)	0.560
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
SYNPO	SCUBE2	psi-mi:“MI:0915”(physical association)	0.400
SYNPO	PCNA	psi-mi:“MI:0915”(physical association)	0.370
SYNPO	NUFIP2	psi-mi:“MI:0915”(physical association)	0.370
SYNPO	NONO	psi-mi:“MI:0915”(physical association)	0.370
SYNPO	LMO7	psi-mi:“MI:0914”(association)	0.350
OCRL	MYO1C	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
PRNP	SYNJ1	psi-mi:“MI:0914”(association)	0.350
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
SCARB2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VAMP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
GRB2	MYO1C	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
CCDC89	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FAM20B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (220): SYNPO (Affinity Capture-RNA), SYNPO (Affinity Capture-RNA), ACTB (Affinity Capture-MS), ACTN4 (Affinity Capture-MS), ACTN1 (Affinity Capture-MS), ADD3 (Affinity Capture-MS), AP2A1 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), APC (Affinity Capture-MS), CAMK2G (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), CD44 (Affinity Capture-MS), CD59 (Affinity Capture-MS), CFL1 (Affinity Capture-MS)

ESM2 similar proteins: A2A7S8, A2AI08, A5D7K1, B0BN13, O54931, O75128, Q13796, Q2NL68, Q32LQ1, Q3U2K0, Q499V8, Q4KMQ1, Q5JTD0, Q5JXC2, Q5NBX1, Q5RBH3, Q5SW24, Q5SX79, Q5T0Z8, Q5XHX2, Q68DK7, Q6P9J5, Q6PDH0, Q6PDM1, Q6PFX7, Q7TN08, Q7TT28, Q7Z591, Q86WR7, Q8BG26, Q8BI29, Q8BRV5, Q8C5R2, Q8CC35, Q8CCJ4, Q8IVT2, Q8IY92, Q8K124, Q8N3V7, Q8N7J2

Diamond homologs: A1ZA47, A2ALK8, A2ALU4, D4A702, E9Q9W7, O00151, O70209, O70400, O75112, O88382, P36202, P50479, P52944, P70271, Q13796, Q1W617, Q3SX40, Q3SYZ8, Q3T005, Q3T0C8, Q3TJD7, Q53GG5, Q5E9E1, Q5F488, Q5RBI7, Q5TCQ9, Q62920, Q66HS7, Q679P3, Q6GLJ6, Q6INU3, Q6P7E4, Q6QGC0, Q86UL8, Q8CC35, Q8CI51, Q8N3V7, Q8TEU7, Q8TF72, Q91YE8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	218
Likely benign	54
Benign	20

Top pathogenic / likely-pathogenic (0)

SpliceAI

262 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150640840:G:GT	donor_gain	1.0000
5:150640850:GCAGA:G	donor_gain	1.0000
5:150640853:GA:G	donor_gain	1.0000
5:150640855:G:GG	donor_gain	1.0000
5:150647942:A:AG	acceptor_gain	1.0000
5:150647942:AGC:A	acceptor_gain	1.0000
5:150647943:G:GA	acceptor_gain	1.0000
5:150647943:GCG:G	acceptor_gain	1.0000
5:150647943:GCGT:G	acceptor_gain	1.0000
5:150647943:GCGTT:G	acceptor_gain	1.0000
5:150640825:G:T	donor_gain	0.9900
5:150640841:G:T	donor_gain	0.9900
5:150640859:G:GG	donor_gain	0.9900
5:150640864:A:G	donor_gain	0.9900
5:150647939:T:TA	acceptor_gain	0.9900
5:150647939:TGTA:T	acceptor_loss	0.9900
5:150647940:GTA:G	acceptor_loss	0.9900
5:150647941:TA:T	acceptor_loss	0.9900
5:150647943:GC:G	acceptor_gain	0.9900
5:150640825:G:GT	donor_gain	0.9800
5:150640851:CAGA:C	donor_gain	0.9800
5:150640854:AG:A	donor_loss	0.9800
5:150640855:G:T	donor_loss	0.9800
5:150640857:GA:G	donor_gain	0.9800
5:150640858:AGT:A	donor_loss	0.9800
5:150656398:CCCCA:C	acceptor_loss	0.9800
5:150656399:CCCAG:C	acceptor_loss	0.9800
5:150656400:CCAG:C	acceptor_loss	0.9800
5:150656401:CAGGA:C	acceptor_loss	0.9800
5:150656402:A:AG	acceptor_gain	0.9800

AlphaMissense

5746 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150649734:C:A	R731S	1.000
5:150649416:T:C	F625L	0.999
5:150649418:T:A	F625L	0.999
5:150649418:T:G	F625L	0.999
5:150649459:T:C	L639S	0.999
5:150649462:T:C	L640P	0.999
5:150649468:T:C	L642P	0.999
5:150649723:T:C	L727P	0.999
5:150649735:G:C	R731P	0.999
5:150648364:T:C	L274P	0.998
5:150649417:T:C	F625S	0.998
5:150649459:T:G	L639W	0.998
5:150649713:G:A	G724R	0.998
5:150649713:G:C	G724R	0.998
5:150649725:T:G	Y728D	0.998
5:150649732:G:C	R730P	0.998
5:150649734:C:G	R731G	0.998
5:150649830:T:A	W763R	0.998
5:150649830:T:C	W763R	0.998
5:150650271:T:C	F910L	0.998
5:150650273:C:A	F910L	0.998
5:150650273:C:G	F910L	0.998
5:150649422:T:C	F627L	0.997
5:150649424:C:A	F627L	0.997
5:150649424:C:G	F627L	0.997
5:150649708:G:A	G722E	0.997
5:150649714:G:A	G724E	0.997
5:150649731:C:A	R730S	0.997
5:150649744:G:C	R734P	0.997
5:150649417:T:G	F625C	0.996

dbSNP variants (sampled 300 via entrez): RS1000014144 (5:150640309 G>T), RS1000021113 (5:150591243 C>A,T), RS1000147253 (5:150599068 C>A,T), RS1000162677 (5:150618049 G>A), RS1000176017 (5:150634170 G>A,C), RS1000249793 (5:150593571 C>G), RS1000285299 (5:150640008 C>A), RS1000298214 (5:150652045 G>A), RS1000310228 (5:150612466 T>G), RS1000434567 (5:150646852 C>G), RS1000439796 (5:150604150 G>A), RS1000444057 (5:150618245 T>G), RS1000452558 (5:150658902 C>T), RS1000455516 (5:150588064 A>G), RS1000524911 (5:150646909 T>C)

Disease associations

OMIM: gene MIM:608155 | disease phenotypes: MIM:616032

GenCC curated gene-disease

Disease	Classification	Inheritance
focal segmental glomerulosclerosis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
focal segmental glomerulosclerosis	Limited	AD

Mondo (3): nephrotic syndrome (MONDO:0005377), focal segmental glomerulosclerosis 8 (MONDO:0014462), focal segmental glomerulosclerosis (MONDO:0100313)

Orphanet (1): Hereditary steroid-resistant nephrotic syndrome (Orphanet:656)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06
GCST007934_3	Medication use (anti-inflammatory and antirheumatic products, non-steroids)	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009935	Non-steroidal anti-inflammatory and antirheumatic product use measurement

MeSH disease descriptors (2)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	3
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	increases expression, decreases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression, decreases expression	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Tobacco Smoke Pollution	decreases expression	2
FR900359	affects phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	affects expression	1
sulforaphane	decreases expression, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
aflatoxin B2	increases methylation	1
cupric chloride	decreases expression	1
coumarin	increases phosphorylation	1
perfluorodecanoic acid	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
polyhexamethyleneguanidine	affects 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	1
clothianidin	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

173 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
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
NCT01164098	PHASE3	TERMINATED	Rituximab to Prevent Recurrence of Proteinuria
NCT02683889	PHASE3	COMPLETED	Use of Acthar in Patients With FSGS That Will be Undergoing Renal Transplantation
NCT03298698	PHASE3	UNKNOWN	Efficacy of Rituximab in Comparison to Continued Corticosteroid Treatment in Idiopathic Nephrotic Syndrome
NCT03493685	PHASE3	COMPLETED	Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
NCT05183646	PHASE3	RECRUITING	A Study of the Efficacy and Safety of DMX-200 in Patients With FSGS Who Are Receiving an ARB
NCT07220083	PHASE3	RECRUITING	A Study to Find Out if BI 764198 Helps Adults and Adolescents With a Kidney Condition Called Focal Segmental Glomerulosclerosis (FSGS)
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)
NCT00550342	PHASE2	WITHDRAWN	Rituximab Treatment of Focal Segmental Glomerulosclerosis
NCT00814255	PHASE2	COMPLETED	Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
NCT01613118	PHASE2	COMPLETED	Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis