KIRREL2

Summary

KIRREL2 (kirre like nephrin family adhesion molecule 2, HGNC:18816) is a protein-coding gene on chromosome 19q13.12, encoding Kin of IRRE-like protein 2 (Q6UWL6). May regulate basal insulin secretion.

This gene encodes a type I transmembrane protein and member of the immunoglobulin superfamily of cell adhesion molecules. The encoded protein localizes to adherens junctions in pancreatic beta cells and regulates insulin secretion. Autoantibodies against the encoded protein have been detected in serum from patients with type 1 diabetes. This gene may also play a role in glomerular development and decreased expression of this gene has been observed in human glomerular diseases. This gene and the related opposite-strand gene nephrin (GeneID: 527362) are regulated by a bidirectional promoter.

Source: NCBI Gene 84063 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 280 total — 10 pathogenic, 12 likely-pathogenic
• MANE Select transcript: NM_199180

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18816
Approved symbol	KIRREL2
Name	kirre like nephrin family adhesion molecule 2
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	NLG1, NEPH3, FILTRIN, DKFZp564A1164, MGC15718
Ensembl gene	ENSG00000126259
Ensembl biotype	protein_coding
OMIM	607762
Entrez	84063

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000262625, ENST00000347900, ENST00000360202, ENST00000586102, ENST00000592409, ENST00000906487, ENST00000929449, ENST00000929450, ENST00000929451

RefSeq mRNA: 5 — MANE Select: NM_199180 NM_001329530, NM_001363667, NM_032123, NM_199179, NM_199180

CCDS: CCDS12479, CCDS12480, CCDS12481, CCDS86753

Canonical transcript exons

ENST00000360202 — 15 exons

Exon	Start	End
ENSE00000862879	35858408	35858557
ENSE00000862880	35858704	35858864
ENSE00001269744	35864648	35864713
ENSE00001269748	35862927	35863036
ENSE00001269837	35859481	35859631
ENSE00001331424	35862493	35862597
ENSE00001331427	35861805	35862024
ENSE00001331429	35861541	35861641
ENSE00001331431	35861122	35861254
ENSE00001331432	35860909	35861036
ENSE00001331434	35860519	35860667
ENSE00001331436	35860297	35860402
ENSE00001331442	35857345	35857494
ENSE00002846010	35856911	35857180
ENSE00002965158	35866157	35867136

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 94.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5741 / max 51.1810, expressed in 181 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175409	0.5180	178
175408	0.0561	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	94.81	gold quality
pancreas	UBERON:0001264	87.82	gold quality
left ventricle myocardium	UBERON:0006566	83.68	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.58	gold quality
islet of Langerhans	UBERON:0000006	77.65	gold quality
myocardium	UBERON:0002349	77.12	gold quality
kidney epithelium	UBERON:0004819	75.93	gold quality
nasal cavity epithelium	UBERON:0005384	69.89	gold quality
ventricular zone	UBERON:0003053	69.62	gold quality
sperm	CL:0000019	69.42	gold quality
vastus lateralis	UBERON:0001379	68.43	gold quality
quadriceps femoris	UBERON:0001377	67.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.33	gold quality
ganglionic eminence	UBERON:0004023	65.73	gold quality
pigmented layer of retina	UBERON:0001782	65.19	gold quality
retina	UBERON:0000966	65.18	gold quality
vena cava	UBERON:0004087	64.23	silver quality
prefrontal cortex	UBERON:0000451	63.77	gold quality
cerebellar vermis	UBERON:0004720	63.74	gold quality
epithelial cell of pancreas	CL:0000083	63.62	gold quality
cortical plate	UBERON:0005343	62.15	gold quality
superficial temporal artery	UBERON:0001614	61.31	gold quality
lateral globus pallidus	UBERON:0002476	60.98	silver quality
germinal epithelium of ovary	UBERON:0001304	59.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	59.24	gold quality
pancreatic ductal cell	CL:0002079	59.11	silver quality
buccal mucosa cell	CL:0002336	58.55	gold quality
lymph node	UBERON:0000029	58.45	gold quality
frontal cortex	UBERON:0001870	57.56	gold quality
gingival epithelium	UBERON:0001949	57.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, SP1, WT1

miRNA regulators (miRDB)

36 targeting KIRREL2, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-7850-5P	98.12	67.28	1111
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3691-3P	97.90	65.97	791
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-924	97.78	66.21	681
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-647	97.73	67.79	927
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-3187-3P	97.38	65.80	904

Literature-anchored findings (GeneRIF, showing 8)

• Filtrin is a novel protein with substantial homology to nephrin. It is a transmembrane protein of the immunoglobulin superfamily (apparent molecular weight 107 kDa) and most prominently expressed in the pancreas, lymph nodes as well as kidney glomerulus. (PMID:12504092)
• Identification of Filtrin as a member of nephrin-like proteins. (PMID:12504092)
• KIRREL2 protein is a beta-cell-expressed Ig domain protein and may be involved in pancreas development or beta cell function (PMID:12837264)
• Filtrin can act as autoantigen, and autoantibodies against these can be detected in patients with type 1 diabetes. (PMID:16741999)
• NF-kappaB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. (PMID:19703278)
• Transcription of nephrin-Neph3 gene pair is synergistically activated by WT1 and NF-kappaB and silenced by DNA methylation. (PMID:21980157)
• summarize the current knowledge of the functions of nephrin and Neph-family proteins and transcription factors and agents that control nephrin and Neph3 gene expression. (PMID:24219158)
• SNP V353M confers high risk of renal failure in primary hematuric glomerulopathies and predisposition to microalbuminuria in the general population (PMID:28334007)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	kirrel3l	ENSDARG00000104665
mus_musculus	Kirrel2	ENSMUSG00000036915
rattus_norvegicus	Kirrel2	ENSRNOG00000020864
drosophila_melanogaster	ed	FBGN0000547
drosophila_melanogaster	rst	FBGN0003285
drosophila_melanogaster	kirre	FBGN0028369
drosophila_melanogaster	fred	FBGN0051774
caenorhabditis_elegans		WBGENE00006365
caenorhabditis_elegans		WBGENE00018215

Paralogs (3): KIRREL3 (ENSG00000149571), NPHS1 (ENSG00000161270), KIRREL1 (ENSG00000183853)

Protein

Protein identifiers

Kin of IRRE-like protein 2 — Q6UWL6 (reviewed: Q6UWL6)

Alternative names: Kin of irregular chiasm-like protein 2, Nephrin-like protein 3

All UniProt accessions (5): A0A0A0MQV3, A0A0A0MRC1, Q6UWL6, K7EJS8, V9GXZ7

UniProt curated annotations — full annotation on UniProt →

Function. May regulate basal insulin secretion.

Subunit / interactions. Homodimer. Interacts with NPHS2/podocin (via the C-terminus). Interacts with NPHS1 (via the Ig-like domains). Interacts with FYN.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in beta-cells of the pancreatic islets.

Post-translational modifications. N-glycosylated. The extracellular domain is cleaved leading to the generation of a soluble fragment and a membrane-bound C-terminal fragment, which is further cleaved by gamma-secretase.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6UWL6-1	1	yes
Q6UWL6-2	2, Kirrel2a
Q6UWL6-3	3, Kirrel2b
Q6UWL6-5	5, Kirrel2c

RefSeq proteins (5): NP_001316459, NP_001350596, NP_115499, NP_954648, NP_954649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051275	Cell_adhesion_signaling	Family

Pfam: PF07679, PF08205, PF13927

UniProt features (44 total): sequence conflict 7, disulfide bond 5, splice variant 5, sequence variant 5, domain 5, modified residue 4, glycosylation site 3, region of interest 2, compositionally biased region 2, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UWL6-F1	75.30	0.52

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 (4): 571, 603, 604, 661

Disulfide bonds (5): 45–103, 146–204, 248–291, 333–375, 419–485

Glycosylation sites (3): 143, 301, 484

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-373753	Nephrin family interactions
R-HSA-1500931	Cell-Cell communication

MSigDB gene sets: 73 (showing top): GCANCTGNY_MYOD_Q6, AP4_Q6, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, GOCC_MICROTUBULE_ORGANIZING_CENTER, EFC_Q6, GOBP_CELL_CELL_ADHESION, NF1_Q6_01, GOCC_CENTROSOME, TGACATY_UNKNOWN, GATA1_04, GATA1_03, YY1_01, PTF1BETA_Q6, IK3_01

GO Biological Process (2): cell adhesion (GO:0007155), cell-cell adhesion (GO:0098609)

GO Molecular Function (3): identical protein binding (GO:0042802), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), membrane (GO:0016020), slit diaphragm (GO:0036057)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular process	1
cell adhesion	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
cellular anatomical structure	1
filtration diaphragm	1

Protein interactions and networks

STRING

926 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIRREL2	NPHS2	Q9NP85	922
KIRREL2	PDZK1	Q5T2W1	818
KIRREL2	NPHS1	O60500	742
KIRREL2	ITK	Q08881	717
KIRREL2	EFNA5	P52803	645
KIRREL2	CNGA2	Q16280	589
KIRREL2	GRB2	P29354	549
KIRREL2	EPHA5	P54756	536
KIRREL2	SKOR2	Q2VWA4	536
KIRREL2	PTF1A	Q7RTS3	522
KIRREL2	EFNA4	P52798	502
KIRREL2	NLGN1	Q8N2Q7	486
KIRREL2	ADCY3	O60266	478
KIRREL2	FAT1	Q14517	463
KIRREL2	EFNA2	O43921	456

IntAct

124 interactions, top by confidence:

A	B	Type	Score
KIRREL2	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
KIRREL2	FHL3	psi-mi:“MI:0915”(physical association)	0.560
PSMA3	KIRREL2	psi-mi:“MI:0915”(physical association)	0.560
MAST2	KIRREL2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	KIRREL2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
PDZD2	KIRREL2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL2	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (27): KIRREL2 (Two-hybrid), KIRREL2 (Two-hybrid), CPS1 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), PIGS (Affinity Capture-MS), LEPREL2 (Affinity Capture-MS), AURKA (Affinity Capture-MS), MANBA (Affinity Capture-MS), VHL (Affinity Capture-MS), VHL (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), CPS1 (Affinity Capture-MS), AURKA (Affinity Capture-MS), MANBA (Affinity Capture-MS)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A0A0R4IGV4, A2ASQ1, A2VEC9, A4IFW2, A6QNY1, A8WQH2, B0V2N1, C0HL13, D4A1J9, D4ABX8, F1NWE3, G5EG78, O00468, O15146, O15230, O88277, O94898, P02469, P05548, P07942, P0C7J6, P11047, P14090, P23468, P25304, P53767, P98073, P98160, P98163, P98164, P98167, Q05793, Q08ET2, Q13332, Q13753, Q16363, Q16787, Q19319, Q19981, Q1ENI8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	47.0×	2e-12
Dopamine Neurotransmitter Release Cycle	5	46.0×	3e-06
Long-term potentiation	5	44.1×	3e-06
Neurexins and neuroligins	10	36.5×	1e-11
Protein-protein interactions at synapses	6	29.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	82.0×	2e-16
receptor clustering	7	56.0×	7e-09
protein localization to synapse	5	49.1×	3e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
cell-cell adhesion	10	13.0×	5e-07
protein-containing complex assembly	7	10.2×	3e-04
chemical synaptic transmission	7	6.9×	2e-03
actin cytoskeleton organization	6	6.1×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	12
Uncertain significance	147
Likely benign	85
Benign	5

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1073424	NM_004646.4(NPHS1):c.90del (p.Arg32fs)	Pathogenic
2000361	NM_004646.4(NPHS1):c.212del (p.Leu71fs)	Pathogenic
2637930	NM_004646.4(NPHS1):c.67del (p.Gln23fs)	Pathogenic
2702250	NM_004646.4(NPHS1):c.134_135del (p.Glu45fs)	Pathogenic
2734615	NM_004646.4(NPHS1):c.12del (p.Thr5fs)	Pathogenic
2779659	NM_004646.4(NPHS1):c.104G>A (p.Trp35Ter)	Pathogenic
4085960	NM_004646.4(NPHS1):c.237del (p.Phe80fs)	Pathogenic
56440	NM_004646.4(NPHS1):c.139del (p.Ala47fs)	Pathogenic
56475	NM_004646.4(NPHS1):c.248dup (p.Tyr83Ter)	Pathogenic
56516	NM_004646.4(NPHS1):c.58+1G>T	Pathogenic
1724213	NM_004646.4(NPHS1):c.181_182insTT (p.Ala61fs)	Likely pathogenic
1726198	NM_004646.4(NPHS1):c.71T>A (p.Leu24Ter)	Likely pathogenic
1726782	NM_004646.4(NPHS1):c.187C>T (p.Gln63Ter)	Likely pathogenic
2109301	NM_004646.4(NPHS1):c.274+2T>A	Likely pathogenic
2677295	NM_004646.4(NPHS1):c.133dup (p.Glu45fs)	Likely pathogenic
2677310	NM_004646.4(NPHS1):c.173del (p.Pro58fs)	Likely pathogenic
2677329	NM_004646.4(NPHS1):c.59-1G>T	Likely pathogenic
3583759	NM_004646.4(NPHS1):c.3G>T (p.Met1Ile)	Likely pathogenic
371017	NM_004646.4(NPHS1):c.174del (p.Gly59fs)	Likely pathogenic
4815388	NM_004646.4(NPHS1):c.3G>A (p.Met1Ile)	Likely pathogenic
556441	NM_004646.4(NPHS1):c.58+1G>A	Likely pathogenic
847759	NM_004646.4(NPHS1):c.58+2T>C	Likely pathogenic

SpliceAI

2580 predictions. Top by Δscore:

Variant	Effect	Δscore
19:35851381:TCACC:T	acceptor_loss	1.0000
19:35851383:ACCT:A	acceptor_loss	1.0000
19:35851384:CCT:C	acceptor_loss	1.0000
19:35851385:CTG:C	acceptor_loss	1.0000
19:35851386:T:A	acceptor_loss	1.0000
19:35857172:G:GT	donor_gain	1.0000
19:35857176:AGCAG:A	donor_loss	1.0000
19:35857179:AG:A	donor_loss	1.0000
19:35857180:GG:G	donor_loss	1.0000
19:35857182:T:G	donor_loss	1.0000
19:35857194:G:T	donor_gain	1.0000
19:35858405:CAG:C	acceptor_loss	1.0000
19:35858406:A:AG	acceptor_gain	1.0000
19:35858406:A:C	acceptor_loss	1.0000
19:35858406:AG:A	acceptor_gain	1.0000
19:35858406:AGGGT:A	acceptor_gain	1.0000
19:35858407:G:GG	acceptor_gain	1.0000
19:35858407:G:GT	acceptor_loss	1.0000
19:35858407:GG:G	acceptor_gain	1.0000
19:35858407:GGGT:G	acceptor_gain	1.0000
19:35858407:GGGTG:G	acceptor_gain	1.0000
19:35858553:GCTGG:G	donor_gain	1.0000
19:35858554:CTGGG:C	donor_loss	1.0000
19:35858555:TGGGT:T	donor_loss	1.0000
19:35858556:GG:G	donor_gain	1.0000
19:35858557:GG:G	donor_gain	1.0000
19:35858557:GGT:G	donor_loss	1.0000
19:35858558:GTA:G	donor_loss	1.0000
19:35858559:T:G	donor_loss	1.0000
19:35859478:CAG:C	acceptor_loss	1.0000

AlphaMissense

4476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:35860522:G:C	W261C	0.999
19:35860522:G:T	W261C	0.999
19:35857451:G:C	W56C	0.998
19:35857451:G:T	W56C	0.998
19:35860520:T:A	W261R	0.997
19:35860520:T:C	W261R	0.997
19:35860610:T:A	C291S	0.997
19:35860611:G:A	C291Y	0.997
19:35860611:G:C	C291S	0.997
19:35860624:C:A	N295K	0.997
19:35860624:C:G	N295K	0.997
19:35861015:G:C	W345C	0.997
19:35861015:G:T	W345C	0.997
19:35860366:G:A	C248Y	0.995
19:35860367:C:G	C248W	0.995
19:35857449:T:A	W56R	0.994
19:35857449:T:C	W56R	0.994
19:35860365:T:A	C248S	0.994
19:35860366:G:C	C248S	0.994
19:35860610:T:C	C291R	0.994
19:35860365:T:C	C248R	0.993
19:35860623:A:T	N295I	0.993
19:35861810:G:C	W432C	0.993
19:35861810:G:T	W432C	0.993
19:35858503:T:A	C103S	0.992
19:35858504:G:C	C103S	0.992
19:35858820:T:A	W160R	0.992
19:35858820:T:C	W160R	0.992
19:35860612:C:G	C291W	0.992
19:35861013:T:A	W345R	0.992

dbSNP variants (sampled 300 via entrez): RS1000278889 (19:35850748 C>T), RS1000318733 (19:35862338 A>T), RS1000370933 (19:35849726 G>T), RS1000463736 (19:35856628 C>A), RS1000712587 (19:35851040 G>A,C), RS1000809243 (19:35867147 G>A,C), RS1000863069 (19:35867596 C>T), RS1000928022 (19:35867498 T>C), RS1001033859 (19:35861180 A>G), RS1001256808 (19:35854634 C>T), RS1001316458 (19:35849852 G>T), RS1001376486 (19:35861354 T>C), RS1001404812 (19:35861638 C>T), RS1001443627 (19:35861379 C>T), RS1001465520 (19:35855237 C>T)

Disease associations

OMIM: gene MIM:607762 | disease phenotypes: MIM:256300

GenCC curated gene-disease

Mondo (5): congenital nephrotic syndrome, Finnish type (MONDO:0009732), focal segmental glomerulosclerosis (MONDO:0100313), familial nephrotic syndrome (MONDO:0002350), nephrotic syndrome (MONDO:0005377), epilepsy (MONDO:0005027)

Orphanet (1): Congenital nephrotic syndrome, Finnish type (Orphanet:839)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005651_8	Urinary metabolite levels in chronic kidney disease	5.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3814995	KIRREL2, NPHS1	3	0.00	1	losartan

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	4
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1
Niclosamide	increases expression	1
Paraoxon	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

292 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
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy