KIRREL1

Summary

KIRREL1 (kirre like nephrin family adhesion molecule 1, HGNC:15734) is a protein-coding gene on chromosome 1q23.1, encoding Kin of IRRE-like protein 1 (Q96J84). Required for proper function of the glomerular filtration barrier.

NEPH1 is a member of the nephrin-like protein family, which includes NEPH2 (MIM 607761) and NEPH3 (MIM 607762). The cytoplasmic domains of these proteins interact with the C terminus of podocin (NPHS2; MIM 604766), and the genes are expressed in kidney podocytes, cells involved in ensuring size- and charge-selective ultrafiltration (Sellin et al., 2003 [PubMed 12424224]).

Source: NCBI Gene 55243 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 23 (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 151 total — 1 pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_018240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15734
Approved symbol	KIRREL1
Name	kirre like nephrin family adhesion molecule 1
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	NEPH1
Ensembl gene	ENSG00000183853
Ensembl biotype	protein_coding
OMIM	607428
Entrez	55243

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000359209, ENST00000360089, ENST00000368172, ENST00000368173, ENST00000929804, ENST00000929805, ENST00000960820, ENST00000960821

RefSeq mRNA: 2 — MANE Select: NM_018240 NM_001286349, NM_018240

CCDS: CCDS1172, CCDS72952

Canonical transcript exons

ENST00000359209 — 15 exons

Exon	Start	End
ENSE00001290086	158093339	158093446
ENSE00001290288	158084422	158084579
ENSE00001292196	158091358	158091556
ENSE00001296433	158087755	158087860
ENSE00001306330	158088006	158088154
ENSE00001306657	158088327	158088454
ENSE00001318015	158086596	158086746
ENSE00001318365	158093623	158093762
ENSE00001320196	158077991	158078140
ENSE00001327077	158089502	158089628
ENSE00001327523	158089718	158089818
ENSE00001433883	158094313	158094390
ENSE00001446476	158094644	158100262
ENSE00001821139	157993645	157993728
ENSE00003523190	158076113	158076262

Expression profiles

Bgee: expression breadth ubiquitous, 207 present calls, max score 95.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.8959 / max 272.7383, expressed in 1333 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5812	23.5942	1330
5811	0.7544	379
5810	0.5473	321

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	95.09	gold quality
right coronary artery	UBERON:0001625	92.56	gold quality
descending thoracic aorta	UBERON:0002345	90.77	gold quality
thoracic aorta	UBERON:0001515	89.86	gold quality
popliteal artery	UBERON:0002250	89.78	gold quality
tibial artery	UBERON:0007610	89.78	gold quality
aorta	UBERON:0000947	89.75	gold quality
ascending aorta	UBERON:0001496	89.68	gold quality
gall bladder	UBERON:0002110	88.58	gold quality
left coronary artery	UBERON:0001626	88.54	gold quality
coronary artery	UBERON:0001621	88.10	gold quality
left uterine tube	UBERON:0001303	86.87	gold quality
right ovary	UBERON:0002118	86.44	gold quality
tibia	UBERON:0000979	86.03	gold quality
omental fat pad	UBERON:0010414	85.87	gold quality
peritoneum	UBERON:0002358	85.86	gold quality
left ovary	UBERON:0002119	85.38	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.34	gold quality
ovary	UBERON:0000992	85.32	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.19	gold quality
body of uterus	UBERON:0009853	85.19	gold quality
mucosa of stomach	UBERON:0001199	85.06	gold quality
smooth muscle tissue	UBERON:0001135	84.06	gold quality
tendon of biceps brachii	UBERON:0008188	83.88	gold quality
upper lobe of left lung	UBERON:0008952	83.60	gold quality
saphenous vein	UBERON:0007318	83.29	gold quality
upper lobe of lung	UBERON:0008948	83.24	gold quality
pericardium	UBERON:0002407	83.16	gold quality
metanephros cortex	UBERON:0010533	83.16	gold quality
parietal pleura	UBERON:0002400	83.09	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	28.24
E-ANND-3	yes	5.54
E-MTAB-8060	no	243.01
E-GEOD-36552	no	32.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

161 targeting KIRREL1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-5680	99.91	69.83	3421

Literature-anchored findings (GeneRIF, showing 14)

• A striking finding in this study is the lack of contribution of NEPH1, NPHS1, and NPHS2 genes in 15 Asian families with steroid-resistant nephrotic syndrome. (PMID:16968734)
• common variants in LRRC7, KIRREL, NPHS2 and ACTN4 do not appeear to contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes (PMID:17968527)
• Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner. (PMID:18258597)
• Neph1-Nephrin proteins bind the Par3-Par6-atypical protein kinase C (aPKC) complex to regulate podocyte cell polarity (PMID:18562307)
• tyrosine phosphorylation of Neph1 mediated by Fyn results in significantly increased Neph1 and ZO-1 binding, suggesting a critical role for Neph1 tyrosine phosphorylation in reorganizing the Neph1-ZO-1 complex. (PMID:18922801)
• Localization of Neph1 to the podocyte cell membrane is altered in the presence of mutant Myo1c, and is actin dependent. Knockdown of Myo1c inhibits Neph1 membrane localization. Neph1 is critical for the maintenance of glomerular function. (PMID:21402783)
• Neph1-CD adopts a global shape in solution, and its interaction with ZO-1 involves multiple sites. (PMID:22262837)
• maintaining high levels of Neph1 at the membrane using a podocyte cell line overexpressing chimeric Neph1 increased the ability of podocytes to resist PAN-induced injury and PAN-induced albumin leakage (PMID:24554715)
• Analysis of interaction surfaces between NEPH1 and MYO1c led to the identification of a critical residue in Neph1 involved in binding to Myo1c. Indeed, a point mutant from this site abolished interaction between Neph1 and Myo1c. (PMID:27044863)
• Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome. (PMID:31472902)
• Overexpression of kin of IRRE-Like protein 1 (KIRREL) as a prognostic biomarker for breast cancer. (PMID:32534710)
• Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites. (PMID:35177623)
• Transmembrane protein KIRREL1 regulates Hippo signaling via a feedback loop and represents a therapeutic target in YAP/TAZ-active cancers. (PMID:36044856)
• KIRREL promotes the proliferation of gastric cancer cells and angiogenesis through the PI3K/AKT/mTOR pathway. (PMID:37909722)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	kirrel1a	ENSDARG00000001634
danio_rerio	kirrel1b	ENSDARG00000056998
mus_musculus	Kirrel1	ENSMUSG00000041734
rattus_norvegicus	Kirrel1	ENSRNOG00000016408
drosophila_melanogaster	ed	FBGN0000547
drosophila_melanogaster	rst	FBGN0003285
drosophila_melanogaster	kirre	FBGN0028369
drosophila_melanogaster	fred	FBGN0051774
caenorhabditis_elegans		WBGENE00006365
caenorhabditis_elegans		WBGENE00018215

Paralogs (3): KIRREL2 (ENSG00000126259), KIRREL3 (ENSG00000149571), NPHS1 (ENSG00000161270)

Protein

Protein identifiers

Kin of IRRE-like protein 1 — Q96J84 (reviewed: Q96J84)

Alternative names: Kin of irregular chiasm-like protein 1, Nephrin-like protein 1

All UniProt accessions (4): B4DN67, Q96J84, Q5W0F9, Q5W0G0

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper function of the glomerular filtration barrier. It is involved in the maintenance of a stable podocyte architecture with interdigitating foot processes connected by specialized cell-cell junctions, known as the slit diaphragm. It is a signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1.

Subunit / interactions. Interacts with TJP1/ZO-1 and with NPHS2/podocin (via the C-terminus). Interacts with NPHS1/nephrin (via the Ig-like domains); this interaction is dependent on KIRREL1 glycosylation. Homodimer (via the Ig-like domains). Interacts when tyrosine-phosphorylated with GRB2.

Subcellular location. Cell membrane.

Tissue specificity. Abundantly expressed in kidney. Specifically expressed in podocytes of kidney glomeruli.

Post-translational modifications. Phosphorylation probably regulates the interaction with NSH2. Phosphorylated at Tyr-605 and Tyr-606 by FYN, leading to GRB2 binding. N-glycosylated.

Disease relevance. Nephrotic syndrome 23 (NPHS23) [MIM:619201] 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. NPHS23 is an autosomal recessive form characterized by onset of proteinuria in the first or second decade of life, and variable outcome. Some patients have normal renal function after many years, whereas others may progress to chronic kidney disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the immunoglobulin superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96J84-1	1	yes
Q96J84-2	2
Q96J84-3	3

RefSeq proteins (2): NP_001273278, NP_060710* (*=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 (32 total): modified residue 6, disulfide bond 5, domain 5, glycosylation site 4, sequence variant 3, topological domain 2, splice variant 2, signal peptide 1, chain 1, region of interest 1, short sequence motif 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96J84-F1	75.58	0.56

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 (6): 574, 605, 606, 622, 625, 724

Disulfide bonds (5): 42–100, 143–200, 244–287, 329–371, 413–472

Glycosylation sites (4): 46, 140, 297, 471

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: 176 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_ACTIN_FILAMENT_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY

GO Biological Process (5): glomerular filtration (GO:0003094), positive regulation of actin filament polymerization (GO:0030838), cell-cell junction maintenance (GO:0045217), renal protein absorption (GO:0097017), cell-cell adhesion (GO:0098609)

GO Molecular Function (3): myosin binding (GO:0017022), cell adhesion molecule binding (GO:0050839), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), dendritic shaft (GO:0043198), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020)

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
cellular anatomical structure	3
renal filtration	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
cell junction maintenance	1
cell-cell junction organization	1
renal absorption	1
cell adhesion	1
cytoskeletal protein binding	1
protein binding	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
dendrite	1
cytoplasm	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KIRREL1	NPHS2	Q9NP85	999
KIRREL1	NPHS1	O60500	991
KIRREL1	CD2AP	Q9Y5K6	990
KIRREL1	TJP1	Q07157	975
KIRREL1	FAT1	Q14517	906
KIRREL1	GRB2	P29354	840
KIRREL1	KIRREL3	Q8IZU9	840
KIRREL1	CDH3	P22223	775
KIRREL1	PDZK1	Q5T2W1	768
KIRREL1	ITK	Q08881	717
KIRREL1	TRPC6	Q9Y210	649
KIRREL1	NCK1	P16333	646
KIRREL1	DDN	O94850	551
KIRREL1	ACTN4	O43707	545
KIRREL1	LRRC7	Q96NW7	545

IntAct

207 interactions, top by confidence:

A	B	Type	Score
KIRREL1	TJP1	psi-mi:“MI:0915”(physical association)	0.760
KIRREL1	TJP1	psi-mi:“MI:0407”(direct interaction)	0.760
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CCKBR	PRKAG1	psi-mi:“MI:0914”(association)	0.640
PICK1	KIRREL1	psi-mi:“MI:0407”(direct interaction)	0.590
KIRREL1	UBR3	psi-mi:“MI:0915”(physical association)	0.560
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
ANTXR1	POTEF	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
SKP2	DPYSL4	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
KIRREL1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI1	KIRREL1	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI3	KIRREL1	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
KIRREL1	TAX1BP3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (195): KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Proximity Label-MS), KIRREL (Affinity Capture-MS), KIRREL (Proximity Label-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS), KIRREL (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, B0JYH6, F1LW30, O35112, O46634, O46651, P0C673, P17948, P26453, P35969, P42292, P53767, Q08DK1, Q13740, Q15198, Q1WIM2, Q2PFX1, Q504C1, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5RJP7, Q5U2P2, Q5VJ70, Q61490, Q6DJ83, Q6PE55, Q6UXZ4, Q6X936, Q7T2Z5, Q7TSN7, Q80W68, Q8BLQ9, Q8BR86, Q8IZU9, Q8K1S2, Q8N3J6, Q8QHL3

Diamond homologs: B3NS99, B4HNW4, B4P5Q9, B4QC63, O75121, P22648, P25033, P31398, P34082, Q5MD89, Q68FQ2, Q6AWJ9, Q6X936, Q80W68, Q8AXY6, Q8C310, Q8TDY8, Q96I82, Q96J84, Q9D8B7, Q9EQS9, Q9Y624, Q08180, Q3UQ28, Q8BR86, Q92626, A2AAJ9, A2AJ76, P98160, Q2EY13, Q5VST9, Q6UWL6, Q7TSU7, Q8HW98, Q8IUL8, Q8IZU9, Q8JG38, D3ZB51, E9PZ19, Q14982

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FYN	“up-regulates activity”	KIRREL1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 186 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	8	39.0×	6e-09
Unblocking of NMDA receptors, glutamate binding and activation	5	23.2×	1e-04
Negative regulation of NMDA receptor-mediated neuronal transmission	5	23.2×	1e-04
Long-term potentiation	5	20.3×	2e-04
Assembly and cell surface presentation of NMDA receptors	9	19.5×	1e-07
Neurexins and neuroligins	10	16.8×	9e-08
Protein-protein interactions at synapses	6	13.6×	2e-04
RND3 GTPase cycle	5	11.1×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	34.4×	1e-10
protein localization to synapse	6	27.2×	2e-05
receptor clustering	7	25.9×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	5	14.7×	2e-03
establishment of cell polarity	5	11.3×	7e-03
cell-cell adhesion	11	6.6×	2e-04
protein-containing complex assembly	9	6.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	120
Likely benign	19
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
998095	NM_018240.7(KIRREL1):c.1318C>T (p.Arg440Cys)	Pathogenic

SpliceAI

2486 predictions. Top by Δscore:

Variant	Effect	Δscore
1:157993725:CAAGG:C	donor_loss	1.0000
1:157993726:AAGGT:A	donor_loss	1.0000
1:157993727:AGGTA:A	donor_loss	1.0000
1:157993728:GGT:G	donor_loss	1.0000
1:157993729:G:GA	donor_loss	1.0000
1:158076260:AAG:A	donor_gain	1.0000
1:158076261:AG:A	donor_gain	1.0000
1:158076261:AGG:A	donor_loss	1.0000
1:158076262:GG:G	donor_gain	1.0000
1:158076262:GGTG:G	donor_loss	1.0000
1:158076263:G:GA	donor_loss	1.0000
1:158076263:G:GG	donor_gain	1.0000
1:158077988:CAGCC:C	acceptor_loss	1.0000
1:158077989:A:AG	acceptor_gain	1.0000
1:158077989:A:C	acceptor_loss	1.0000
1:158077989:AGCCT:A	acceptor_gain	1.0000
1:158077990:G:GC	acceptor_gain	1.0000
1:158077990:GC:G	acceptor_gain	1.0000
1:158077990:GCC:G	acceptor_gain	1.0000
1:158077990:GCCT:G	acceptor_gain	1.0000
1:158077990:GCCTG:G	acceptor_gain	1.0000
1:158078136:GCTCA:G	donor_gain	1.0000
1:158078141:G:GG	donor_gain	1.0000
1:158084417:CACA:C	acceptor_loss	1.0000
1:158084418:ACAG:A	acceptor_loss	1.0000
1:158084419:CAG:C	acceptor_loss	1.0000
1:158084420:A:AG	acceptor_gain	1.0000
1:158084421:G:GG	acceptor_gain	1.0000
1:158084421:GT:G	acceptor_gain	1.0000
1:158084421:GTC:G	acceptor_gain	1.0000

AlphaMissense

4909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:158076184:T:C	C42R	1.000
1:158076185:G:A	C42Y	1.000
1:158076186:T:G	C42W	1.000
1:158076217:T:A	W53R	1.000
1:158076217:T:C	W53R	1.000
1:158076218:G:C	W53S	1.000
1:158076219:G:C	W53C	1.000
1:158076219:G:T	W53C	1.000
1:158078042:T:C	L85P	1.000
1:158078086:T:A	C100S	1.000
1:158078086:T:C	C100R	1.000
1:158078087:G:A	C100Y	1.000
1:158078087:G:C	C100S	1.000
1:158078088:C:G	C100W	1.000
1:158078129:T:C	L114P	1.000
1:158084491:T:C	L141P	1.000
1:158084496:T:C	C143R	1.000
1:158084535:T:A	W156R	1.000
1:158084535:T:C	W156R	1.000
1:158084537:G:C	W156C	1.000
1:158084537:G:T	W156C	1.000
1:158086639:T:C	L185P	1.000
1:158086683:T:A	C200S	1.000
1:158086683:T:C	C200R	1.000
1:158086684:G:C	C200S	1.000
1:158087761:C:A	P223H	1.000
1:158087812:T:A	V240D	1.000
1:158087818:T:C	F242S	1.000
1:158087823:T:A	C244S	1.000
1:158087823:T:C	C244R	1.000

dbSNP variants (sampled 300 via entrez): RS1000002875 (1:158047774 A>T), RS1000038228 (1:158038849 T>C), RS1000108544 (1:158063929 G>C), RS1000152371 (1:158004724 A>G), RS1000168490 (1:158087204 T>G), RS1000207673 (1:158095469 T>G), RS1000215955 (1:158088919 C>G), RS1000247226 (1:158002282 C>A,G,T), RS1000248312 (1:158075160 G>A,T), RS1000253098 (1:158081831 A>G), RS1000275875 (1:157998498 G>A,T), RS1000304458 (1:158002544 T>C), RS1000326081 (1:158051168 G>A), RS1000326429 (1:158044975 G>A), RS1000368730 (1:158040149 A>G)

Disease associations

OMIM: gene MIM:607428 | disease phenotypes: MIM:619201

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 23	Moderate	Autosomal recessive

Mondo (1): nephrotic syndrome, type 23 (MONDO:0030962)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0003621	Juvenile onset
HP:0011463	Childhood onset
HP:0012574	Mesangial hypercellularity
HP:0012579	Minimal change glomerulonephritis
HP:0012588	Steroid-resistant nephrotic syndrome
HP:0031266	Podocyte foot process effacement

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001762_251	Obesity-related traits	8.000000e-06
GCST006291_77	Spherical equivalent or myopia (age of diagnosis)	6.000000e-10
GCST010002_368	Refractive error	7.000000e-38

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	3
entinostat	decreases expression, increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression	2
FR900359	decreases phosphorylation	1
geldanamycin	increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	increases expression	1
dimethylarsinous acid	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases expression, affects cotreatment, increases reaction	1
Methotrexate	increases expression	1
Naled	affects expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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