EMP2

Summary

EMP2 (epithelial membrane protein 2, HGNC:3334) is a protein-coding gene on chromosome 16p13.13, encoding Epithelial membrane protein 2 (P54851). Functions as a key regulator of cell membrane composition by regulating protein surface expression.

This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10).

Source: NCBI Gene 2013 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephrotic syndrome, type 10 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 126 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_001424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3334
Approved symbol	EMP2
Name	epithelial membrane protein 2
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	XMP
Ensembl gene	ENSG00000213853
Ensembl biotype	protein_coding
OMIM	602334
Entrez	2013

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 14 protein_coding, 1 retained_intron

ENST00000342147, ENST00000359543, ENST00000536829, ENST00000867006, ENST00000867007, ENST00000867008, ENST00000867009, ENST00000867010, ENST00000867011, ENST00000867012, ENST00000867013, ENST00000867014, ENST00000971799, ENST00000971800, ENST00000971801

RefSeq mRNA: 1 — MANE Select: NM_001424 NM_001424

CCDS: CCDS10541

Canonical transcript exons

ENST00000359543 — 5 exons

Exon	Start	End
ENSE00000668244	10537928	10538074
ENSE00000668248	10543570	10543660
ENSE00001143564	10547540	10547677
ENSE00001280607	10528422	10533092
ENSE00001308963	10580549	10580598

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 99.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5569 / max 323.5007, expressed in 1420 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156206	9.3921	1073
156207	2.0864	773
156208	1.9626	1048
156204	1.1792	399
156202	0.4337	189
156205	0.3395	208
156203	0.1634	73

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.26	gold quality
upper arm skin	UBERON:0004263	99.21	gold quality
lower lobe of lung	UBERON:0008949	99.08	gold quality
mammalian vulva	UBERON:0000997	98.93	gold quality
right lung	UBERON:0002167	98.92	gold quality
endometrium epithelium	UBERON:0004811	98.84	gold quality
upper lobe of lung	UBERON:0008948	98.74	gold quality
upper lobe of left lung	UBERON:0008952	98.73	gold quality
nipple	UBERON:0002030	98.68	gold quality
gingival epithelium	UBERON:0001949	98.66	gold quality
gingiva	UBERON:0001828	98.52	gold quality
penis	UBERON:0000989	98.38	gold quality
visceral pleura	UBERON:0002401	98.34	gold quality
tongue squamous epithelium	UBERON:0006919	98.33	gold quality
lung	UBERON:0002048	98.32	gold quality
esophagus squamous epithelium	UBERON:0006920	98.29	gold quality
adult organism	UBERON:0007023	98.25	gold quality
epithelium of esophagus	UBERON:0001976	97.99	gold quality
squamous epithelium	UBERON:0006914	97.76	gold quality
oral cavity	UBERON:0000167	97.60	gold quality
pharyngeal mucosa	UBERON:0000355	97.54	gold quality
skin of hip	UBERON:0001554	97.53	gold quality
tibia	UBERON:0000979	97.51	gold quality
tendon of biceps brachii	UBERON:0008188	97.45	gold quality
esophagus mucosa	UBERON:0002469	97.42	gold quality
hair follicle	UBERON:0002073	97.29	gold quality
lower esophagus mucosa	UBERON:0035834	97.23	gold quality
skin of abdomen	UBERON:0001416	96.73	gold quality
zone of skin	UBERON:0000014	96.61	gold quality
bronchial epithelial cell	CL:0002328	96.57	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	6763.32
E-MTAB-6653	yes	6606.42
E-HCAD-15	yes	5935.40
E-CURD-126	yes	4941.10
E-ANND-2	yes	4593.35
E-MTAB-6308	yes	4156.93
E-HCAD-1	yes	3462.44
E-GEOD-81383	yes	644.66
E-CURD-114	yes	57.29
E-GEOD-135922	yes	20.73
E-HCAD-10	yes	15.84
E-GEOD-81547	yes	11.89
E-CURD-46	yes	10.15
E-CURD-112	yes	8.24
E-GEOD-137537	yes	6.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

160 targeting EMP2, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-381-3P	99.93	71.87	2854

Literature-anchored findings (GeneRIF, showing 32)

• evaluation as candidate gene for Charcot-Marie-Tooth disease type 1C on chromosome 16p (PMID:11713717)
• This protein is expressed in discrete anatomical regions of the eye. (PMID:12710941)
• EMP2 induces alphavbeta3 surface expression. (PMID:16216233)
• These findings identify EMP2 as a candidate host protein involved in infection of Chlamydia muridarum. [EMP-2] (PMID:17544801)
• EMP2 regulates caveolin-1 transcription and more substantially its protein levels. (PMID:17609206)
• Targeting of EMP2 to specific locations under the influence of these steroid hormones may be important for integrating the molecular responses required for implantation competence. (PMID:18400107)
• EMP2 may be a potential pharmacologic target for human endometrial cancer. (PMID:19010852)
• EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo. (PMID:20670949)
• support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo (PMID:23334331)
• EMP2 was identified as a tumor-suppressor gene in urinary tract urothelial carcinoma. (PMID:23838430)
• the role of EMP2 in the pathogenesis of GBM a (PMID:24644285)
• We showed that knockdown of EMP2 in podocytes and endothelial cells resulted in an increased amount of CAVEOLIN-1 and decreased cell proliferation, so EMP2 mutations causes a recessive Mendelian form of steroid-sensitive nephrotic syndrome. (PMID:24814193)
• Loss of EMP2 is associated with nasopharyngeal carcinoma. (PMID:25684502)
• EMP2 plays a tumor suppressor role by inducing G2/M cell cycle arrest, suppressing cell viability, proliferation, colony formation/ anchorage-independent cell growth via regulation of G2/M checkpoints in distinct-derived cell lines. (PMID:25940704)
• Data show that loss of epithelial membrane protein 2 (EMP2) is involved in sphingosylphosphorylcholine (SPC)-induced phosphorylation of keratin 8 (K8) via ubiquitination of protein phosphatase 2 (PP2A) through alpha4 phosphoprotein by caveolin-1 (cav-1). (PMID:26876307)
• The studies implicating GAS3 protein family (EMP1, EMP2, EMP3 and PMP22) in cancer pathogenesis as well as probe the structural similarities between the family members were highlighted. (PMID:27279240)
• All studied ERMs and PVR membranes express EMP2. Levels of EMP2 trended higher in all PVR subgroups than in ERMs, especially in inflammatory and traumatic PVR. (PMID:27294805)
• a novel SNP x SNP interaction between rs2267668 in PPARdelta and rs7191411 in EMP2 that has significant impact on circulating HDL-C levels in the Singaporean Chinese population. (PMID:27530449)
• Experiments in vitro using human trophoblast cells lines indicate that EMP2 modulates angiogenesis by altering HIF-1alpha expression. The results reveal a novel role for EMP2 in regulating trophoblast function and vascular development in mice and humans, and suggest that it may be a new biomarker for placental insufficiency. (PMID:28295343)
• These results support that loss of EMP2 is common, and its re-expression may serve as an approach to enhance radiation sensitivity in nasopharyngeal carcinoma. (PMID:28347228)
• High EMP2 expression is associated with endometrial cancer. (PMID:28604744)
• It is a biomarker in gliomas and may have use as a molecular target for the diagnosis and treatment of gliomas. (PMID:28887715)
• miR-133b effectively binds to EMP2, down-regulates its expression and negates its normal function in glioma. (PMID:29940748)
• EMP2 had a significantly higher capture efficiency on MDA-MB-231 cells when compared to MCF7 cells (PMID:30218306)
• Identification of epithelial membrane protein 2 (EMP2) as a molecular marker and correlate for angiogenesis in meningioma. (PMID:31981014)
• Coexpression of PBX1 and EMP2 as Prognostic Biomarkers in Estrogen Receptor-Negative Breast Cancer via Data Mining. (PMID:32216630)
• EMP2 Is a Novel Regulator of Stemness in Breast Cancer Cells. (PMID:32451329)
• Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway. (PMID:33799364)
• EMP2 induces cytostasis and apoptosis via the TGFbeta/SMAD/SP1 axis and recruitment of P2RX7 in urinary bladder urothelial carcinoma. (PMID:34339014)
• Expression of epithelial membrane protein (EMP) 1, EMP 2, and EMP 3 in thyroid cancer. (PMID:34617578)
• Epithelial membrane protein 2 (EMP2) regulates hypoxia-induced angiogenesis in the adult retinal pigment epithelial cell lines. (PMID:36371458)
• Epithelial membrane protein 2 (EMP2): A systematic review of its implications in pathogenesis. (PMID:36455339)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	emp2	ENSDARG00000044588
mus_musculus	Emp2	ENSMUSG00000022505
rattus_norvegicus	Emp2	ENSRNOG00000002664

Paralogs (10): LIM2 (ENSG00000105370), NKG7 (ENSG00000105374), PMP22 (ENSG00000109099), GSG1 (ENSG00000111305), EMP1 (ENSG00000134531), EMP3 (ENSG00000142227), CLDND2 (ENSG00000160318), GSG1L (ENSG00000169181), TMEM202 (ENSG00000187806), GSG1L2 (ENSG00000214978)

Protein

Protein identifiers

Epithelial membrane protein 2 — P54851 (reviewed: P54851)

Alternative names: Protein XMP

All UniProt accessions (1): P54851

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a key regulator of cell membrane composition by regulating protein surface expression. Also, plays a role in regulation of processes including cell migration, cell proliferation, cell contraction and cell adhesion. Regulates transepithelial migration of neutrophils into the alveolar lumen, potentially via mediation of cell surface expression of adhesion markers and lipid raft formation. Negatively regulates caveolae formation by reducing CAV1 expression and CAV1 amount by increasing lysosomal degradation. Facilitates surface trafficking and formation of lipid rafts bearing GPI-anchor proteins. Regulates surface expression of MHC1 and ICAM1 proteins increasing susceptibility to T-cell mediated cytotoxicity. Regulates the plasma membrane expression of the integrin heterodimers ITGA6-ITGB1, ITGA5-ITGB3 and ITGA5-ITGB1 resulting in modulation of cell-matrix adhesion. Also regulates many processes through PTK2. Regulates blood vessel endothelial cell migration and angiogenesis by regulating VEGF protein expression through PTK2 activation. Regulates cell migration and cell contraction through PTK2 and SRC activation. Regulates focal adhesion density, F-actin conformation and cell adhesion capacity through interaction with PTK2. Positively regulates cell proliferation. Plays a role during cell death and cell blebbing. Promotes angiogenesis and vasculogenesis through induction of VEGFA via a HIF1A-dependent pathway. Also plays a role in embryo implantation by regulating surface trafficking of integrin heterodimer ITGA5-ITGB3. Plays a role in placental angiogenesis and uterine natural killer cell regulation at the maternal-fetal placental interface, however not required in the maternal tissues for a viable pregnancy. Involved in the early stages of embryogenic development and cardiogenesis, potentially via regulation of epithelial-mesenchymal transition timing. May play a role in glomerular filtration.

Subunit / interactions. Interacts with PTK2; regulates PTK2 activation and localization. Interacts with ITGB3; regulates the levels of the heterodimer ITGA5-ITGB3 integrin surface expression. Interacts with P2RX7 (via C-terminus). Interacts with ITGB1; the interaction may be direct or indirect and ITGB1 has a heterodimer form.

Subcellular location. Golgi apparatus membrane. Cell membrane. Apical cell membrane. Membrane raft. Cytoplasm. Nucleus. Perinuclear region.

Tissue specificity. Expressed in ciliary body epithelia, sclera, cornea, and retinal pigment epithelium (at protein level). Expressed in lung and endometrial tissue; expression is particularly abundant in secretory endometrium (at protein level). Expressed in placental villous syncytiotrophoblasts and cytotrophoblasts and on the membrane of interstitial trophoblasts (at protein level).

Disease relevance. Nephrotic syndrome 10 (NPHS10) [MIM:615861] A form of nephrotic syndrome, a renal disease clinically characterized by focal segmental glomerulosclerosis, progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. NPHS10 is a steroid-sensitive form characterized by onset in childhood and remission without end-stage kidney disease. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PMP-22/EMP/MP20 family.

RefSeq proteins (1): NP_001415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003933	EMP-2	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR004032	PMP22_EMP_MP20	Family
IPR050579	PMP-22/EMP/MP20-like	Family

Pfam: PF00822

UniProt features (12 total): transmembrane region 4, glycosylation site 3, sequence conflict 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P54851-F1	94.89	0.86

Functional residue map

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

Glycosylation sites (3): 44, 47, 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 377 (showing top): MODULE_52, GOBP_REGULATION_OF_VASCULOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOBP_MEMBRANE_BIOGENESIS, GOBP_RENAL_SYSTEM_PROCESS_INVOLVED_IN_REGULATION_OF_BLOOD_VOLUME, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_PLASMA_MEMBRANE_ORGANIZATION

GO Biological Process (29): membrane raft assembly (GO:0001765), natural killer cell proliferation (GO:0001787), T cell mediated cytotoxicity (GO:0001913), regulation of cell-matrix adhesion (GO:0001952), positive regulation of cell-matrix adhesion (GO:0001954), regulation of glomerular filtration (GO:0003093), apoptotic process (GO:0006915), actin filament organization (GO:0007015), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), embryo implantation (GO:0007566), positive regulation of cell population proliferation (GO:0008284), regulation of endothelial cell migration (GO:0010594), bleb assembly (GO:0032060), protein localization to cell surface (GO:0034394), blood vessel endothelial cell migration (GO:0043534), regulation of kinase activity (GO:0043549), plasma membrane raft assembly (GO:0044854), early endosome to late endosome transport (GO:0045022), regulation of angiogenesis (GO:0045765), positive regulation of angiogenesis (GO:0045766), embryonic process involved in female pregnancy (GO:0060136), heart formation (GO:0060914), positive regulation of cardiac epithelial to mesenchymal transition (GO:0062043), actin-mediated cell contraction (GO:0070252), protein localization to plasma membrane (GO:0072659), neutrophil migration (GO:1990266), positive regulation of integrin-mediated signaling pathway (GO:2001046), regulation of vasculogenesis (GO:2001212)

GO Molecular Function (3): integrin binding (GO:0005178), kinase binding (GO:0019900), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), cytoplasmic vesicle (GO:0031410), membrane raft (GO:0045121), apical part of cell (GO:0045177), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	4
cell-matrix adhesion	2
endothelial cell migration	2
intracellular membrane-bounded organelle	2
membrane raft organization	1
membrane assembly	1
natural killer cell activation	1
lymphocyte proliferation	1
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
regulation of cell-substrate adhesion	1
regulation of cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
glomerular filtration	1
regulation of renal system process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
cellular process	1
cell-substrate adhesion	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell migration	1
plasma membrane bounded cell projection assembly	1
intracellular protein localization	1
kinase activity	1
regulation of phosphorylation	1
regulation of transferase activity	1
membrane raft assembly	1
plasma membrane raft organization	1
vesicle-mediated transport between endosomal compartments	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1

Protein interactions and networks

STRING

616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EMP2	LITAF	Q99732	763
EMP2	LIM2	P55344	703
EMP2	ITSN1	Q15811	464
EMP2	COQ8B	Q96D53	445
EMP2	KANK4	Q5T7N3	438
EMP2	KANK2	Q63ZY3	428
EMP2	ITSN2	Q9NZM3	425
EMP2	CDK20	Q8IZL9	406
EMP2	DNAJC8	O75937	397
EMP2	COQ6	Q9Y2Z9	396
EMP2	PLCE1	Q9P212	395
EMP2	YDJC	A8MPS7	387
EMP2	NPHS2	Q9NP85	378
EMP2	FBXO16	Q8IX29	375
EMP2	NPHS1	O60500	372

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	EMP2	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): EMP2 (PCA), EPM2AIP1 (Two-hybrid), EMP2 (Affinity Capture-MS), PROCR (Cross-Linking-MS (XL-MS)), GLRX3 (Cross-Linking-MS (XL-MS)), PROCR (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5A6N6, D3ZQJ0, F1QIK8, O09117, O35912, O88662, P19075, P47801, P54848, P54849, P54850, P54851, P54852, P56748, Q12999, Q16563, Q2NKU9, Q32KP1, Q3ZBY0, Q4KL25, Q58DR6, Q5PPI7, Q5R9S6, Q5RAI2, Q5RAP8, Q5RCY3, Q5U1V9, Q5XHG6, Q66HH2, Q66IV3, Q6DHB5, Q6GPN9, Q6P742, Q6Y1E2, Q6ZUX7, Q7ZUB3, Q7ZWW7, Q7ZZL8, Q8BGA2, Q8BI08

Diamond homologs: A5A6N6, F1QIK8, O35912, O88662, P16646, P25094, P47801, P54848, P54849, P54850, P54851, P54852, Q01453, Q2NKU9, Q58DR6, Q5RAZ3, Q5RCY3, Q66HH2, Q6WL85, Q9QYW5, Q9TQZ3, P20274, Q2KIY2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	48
Likely benign	39
Benign	23

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
139532	NM_001424.6(EMP2):c.21C>G (p.Phe7Leu)	Pathogenic
3237408	NM_001424.6(EMP2):c.78+1G>C	Likely pathogenic
3600404	NM_001424.6(EMP2):c.87_89del (p.Trp29_Val30delinsTer)	Likely pathogenic

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
16:10532916:T:TA	donor_gain	1.0000
16:10537926:A:AC	donor_gain	1.0000
16:10537927:C:CC	donor_gain	1.0000
16:10537927:CATGA:C	donor_gain	1.0000
16:10547534:ACTT:A	donor_loss	1.0000
16:10547535:CTT:C	donor_loss	1.0000
16:10547536:TTA:T	donor_loss	1.0000
16:10547537:TA:T	donor_loss	1.0000
16:10547538:A:AC	donor_gain	1.0000
16:10547538:ACA:A	donor_loss	1.0000
16:10547539:C:CC	donor_gain	1.0000
16:10547539:C:CG	donor_loss	1.0000
16:10547539:CA:C	donor_gain	1.0000
16:10547539:CAT:C	donor_gain	1.0000
16:10547674:TGTG:T	acceptor_gain	1.0000
16:10547678:C:CC	acceptor_gain	1.0000
16:10580547:AC:A	donor_gain	1.0000
16:10580548:CC:C	donor_gain	1.0000
16:10532856:T:C	donor_gain	0.9900
16:10532874:A:AC	donor_gain	0.9900
16:10532875:C:CC	donor_gain	0.9900
16:10532894:G:C	donor_gain	0.9900
16:10532917:C:A	donor_gain	0.9900
16:10537922:ACT:A	donor_loss	0.9900
16:10537923:CTTAC:C	donor_loss	0.9900
16:10537924:T:TA	donor_loss	0.9900
16:10537925:TACA:T	donor_loss	0.9900
16:10537926:ACA:A	donor_loss	0.9900
16:10537927:C:CT	donor_loss	0.9900
16:10537927:CATG:C	donor_gain	0.9900

AlphaMissense

1110 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:10537959:A:C	F95L	0.999
16:10537959:A:T	F95L	0.999
16:10537961:A:G	F95L	0.999
16:10543622:C:A	W39C	0.998
16:10543622:C:G	W39C	0.998
16:10532941:G:C	S156R	0.997
16:10532941:G:T	S156R	0.997
16:10532943:T:G	S156R	0.997
16:10532970:A:G	W147R	0.997
16:10532970:A:T	W147R	0.997
16:10537960:A:C	F95C	0.997
16:10537998:G:C	F82L	0.997
16:10537998:G:T	F82L	0.997
16:10538000:A:G	F82L	0.997
16:10543657:A:G	W28R	0.997
16:10543657:A:T	W28R	0.997
16:10532917:C:A	R164S	0.996
16:10532917:C:G	R164S	0.996
16:10532918:C:A	R164M	0.996
16:10537960:A:G	F95S	0.996
16:10538032:G:A	S71F	0.996
16:10543624:A:G	W39R	0.996
16:10543624:A:T	W39R	0.996
16:10543652:C:A	W29C	0.996
16:10543652:C:G	W29C	0.996
16:10543655:C:A	W28C	0.996
16:10543655:C:G	W28C	0.996
16:10537987:A:G	L86P	0.995
16:10532918:C:G	R164T	0.994
16:10532990:C:A	G140V	0.994

dbSNP variants (sampled 300 via entrez): RS1000007386 (16:10571164 G>A), RS1000008178 (16:10540197 A>G), RS1000037214 (16:10574071 G>A), RS1000121706 (16:10566840 C>A), RS1000132027 (16:10536929 G>A), RS1000186469 (16:10548582 T>C), RS1000191118 (16:10531410 G>A), RS1000224008 (16:10561589 C>A,T), RS1000231629 (16:10571993 A>C), RS1000321652 (16:10558252 C>G), RS1000353093 (16:10580825 G>A,T), RS1000389599 (16:10576596 T>C), RS1000391801 (16:10545352 C>A), RS1000396943 (16:10549054 G>A), RS1000446219 (16:10571406 C>A)

Disease associations

OMIM: gene MIM:602334 | disease phenotypes: MIM:615861

GenCC curated gene-disease

Disease	Classification	Inheritance
nephrotic syndrome, type 10	Strong	Autosomal recessive
familial idiopathic steroid-resistant nephrotic syndrome	Supportive	Autosomal dominant

Mondo (2): nephrotic syndrome, type 10 (MONDO:0014373), familial idiopathic steroid-resistant nephrotic syndrome (MONDO:0019006)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
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

7 associations (top):

Study	Trait	p-value
GCST000684_5	Attention deficit hyperactivity disorder	7.000000e-07
GCST001822_17	Metabolite levels (MHPG)	6.000000e-06
GCST001960_7	Eating disorders	5.000000e-06
GCST006979_246	Heel bone mineral density	5.000000e-10
GCST007001_9	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST008481_9	Lung function (FEV1/FVC)	8.000000e-10
GCST009391_2104	Metabolite levels	5.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005133	MHPG measurement
EFO:0009270	heel bone mineral density
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004713	FEV/FVC ratio
EFO:0010373	phosphatidylcholine 32:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	6
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Acetaminophen	decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation, increases mutagenesis, affects methylation	3
bisphenol A	increases expression, affects cotreatment	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Dexamethasone	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
8-Bromo Cyclic Adenosine Monophosphate	decreases expression, affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
seocalcitol	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

Clinical trials (associated diseases)

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