NCSTN (nicastrin)

Gene

• Entrez ID: 23385
• Gene name: Nicastrin
• Gene symbol: NCSTN
• Synonyms (NCBI Gene): ATAG1874
• Chromosome: 1
• Chromosome location: 1q23.2
• Summary: This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs387906896	C>T	Pathogenic	Coding sequence variant, stop gained
rs1085307081	C>G,T	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, stop gained, downstream transcript variant
rs1347055289	G>A	Pathogenic	Splice donor variant
rs1553210405	C>T	Likely-pathogenic	Intron variant, coding sequence variant, missense variant
rs1553210984	G>A	Pathogenic	Splice donor variant, genic downstream transcript variant
rs1553211087	G>-	Pathogenic	Genic downstream transcript variant, frameshift variant, coding sequence variant
rs1571202126	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030869	hsa-miR-21-5p	Sequencing	20371350
MIRT047572	hsa-miR-10a-5p	CLASH	23622248
MIRT042811	hsa-miR-339-5p	CLASH	23622248
MIRT039146	hsa-miR-769-5p	CLASH	23622248
MIRT038892	hsa-miR-93-3p	CLASH	23622248
MIRT438454	hsa-miR-24-3p	Luciferase reporter assay, ELISA	25100943
MIRT438453	hsa-miR-186-5p	Luciferase reporter assay, ELISA	25100943
MIRT438452	hsa-miR-455-5p	Luciferase reporter assay, ELISA	25100943
MIRT438454	hsa-miR-24-3p	Luciferase reporter assay, ELISA	25100943
MIRT438453	hsa-miR-186-5p	Luciferase reporter assay, ELISA	25100943
MIRT438452	hsa-miR-455-5p	Luciferase reporter assay, ELISA	25100943
MIRT732051	hsa-miR-16-5p	ELISA, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26440600
MIRT732051	hsa-miR-16-5p	ELISA, Immunoprecipitaion, Luciferase reporter assay, qRT-PCR, Western blot	26440600
MIRT1177763	hsa-miR-1252	CLIP-seq
MIRT1177764	hsa-miR-1266	CLIP-seq
MIRT1177765	hsa-miR-1273g	CLIP-seq
MIRT1177766	hsa-miR-1302	CLIP-seq
MIRT1177767	hsa-miR-1321	CLIP-seq
MIRT1177768	hsa-miR-140-5p	CLIP-seq
MIRT1177769	hsa-miR-145	CLIP-seq
MIRT1177770	hsa-miR-1587	CLIP-seq
MIRT1177771	hsa-miR-1825	CLIP-seq
MIRT1177772	hsa-miR-1915	CLIP-seq
MIRT1177773	hsa-miR-199a-5p	CLIP-seq
MIRT1177774	hsa-miR-199b-5p	CLIP-seq
MIRT1177775	hsa-miR-2054	CLIP-seq
MIRT1177776	hsa-miR-2110	CLIP-seq
MIRT1177777	hsa-miR-24	CLIP-seq
MIRT1177778	hsa-miR-31	CLIP-seq
MIRT1177779	hsa-miR-3123	CLIP-seq
MIRT1177780	hsa-miR-3125	CLIP-seq
MIRT1177781	hsa-miR-3126-3p	CLIP-seq
MIRT1177782	hsa-miR-3128	CLIP-seq
MIRT1177783	hsa-miR-3135b	CLIP-seq
MIRT1177784	hsa-miR-3140-5p	CLIP-seq
MIRT1177785	hsa-miR-3148	CLIP-seq
MIRT1177786	hsa-miR-3150b-3p	CLIP-seq
MIRT1177787	hsa-miR-3153	CLIP-seq
MIRT1177788	hsa-miR-3154	CLIP-seq
MIRT1177789	hsa-miR-3160-3p	CLIP-seq
MIRT1177790	hsa-miR-3179	CLIP-seq
MIRT1177791	hsa-miR-3202	CLIP-seq
MIRT1177792	hsa-miR-320a	CLIP-seq
MIRT1177793	hsa-miR-320b	CLIP-seq
MIRT1177794	hsa-miR-320c	CLIP-seq
MIRT1177795	hsa-miR-320d	CLIP-seq
MIRT1177796	hsa-miR-320e	CLIP-seq
MIRT1177797	hsa-miR-323b-5p	CLIP-seq
MIRT1177798	hsa-miR-3545-3p	CLIP-seq
MIRT1177799	hsa-miR-3545-5p	CLIP-seq
MIRT1177800	hsa-miR-3622b-5p	CLIP-seq
MIRT1177801	hsa-miR-3652	CLIP-seq
MIRT1177802	hsa-miR-3689d	CLIP-seq
MIRT1177803	hsa-miR-3909	CLIP-seq
MIRT1177804	hsa-miR-3916	CLIP-seq
MIRT1177805	hsa-miR-3925-5p	CLIP-seq
MIRT1177806	hsa-miR-3936	CLIP-seq
MIRT1177807	hsa-miR-4265	CLIP-seq
MIRT1177808	hsa-miR-4270	CLIP-seq
MIRT1177809	hsa-miR-4271	CLIP-seq
MIRT1177810	hsa-miR-4296	CLIP-seq
MIRT1177811	hsa-miR-4298	CLIP-seq
MIRT1177812	hsa-miR-4318	CLIP-seq
MIRT1177813	hsa-miR-4322	CLIP-seq
MIRT1177814	hsa-miR-4417	CLIP-seq
MIRT1177815	hsa-miR-4428	CLIP-seq
MIRT1177816	hsa-miR-4429	CLIP-seq
MIRT1177817	hsa-miR-4430	CLIP-seq
MIRT1177818	hsa-miR-4436b-3p	CLIP-seq
MIRT1177819	hsa-miR-4441	CLIP-seq
MIRT1177820	hsa-miR-4460	CLIP-seq
MIRT1177821	hsa-miR-4468	CLIP-seq
MIRT1177822	hsa-miR-4476	CLIP-seq
MIRT1177823	hsa-miR-4487	CLIP-seq
MIRT1177824	hsa-miR-4492	CLIP-seq
MIRT1177825	hsa-miR-4498	CLIP-seq
MIRT1177826	hsa-miR-4504	CLIP-seq
MIRT1177827	hsa-miR-4518	CLIP-seq
MIRT1177828	hsa-miR-4533	CLIP-seq
MIRT1177829	hsa-miR-4645-3p	CLIP-seq
MIRT1177830	hsa-miR-4648	CLIP-seq
MIRT1177831	hsa-miR-4654	CLIP-seq
MIRT1177832	hsa-miR-4656	CLIP-seq
MIRT1177833	hsa-miR-4663	CLIP-seq
MIRT1177834	hsa-miR-4668-5p	CLIP-seq
MIRT1177835	hsa-miR-4675	CLIP-seq
MIRT1177836	hsa-miR-4689	CLIP-seq
MIRT1177837	hsa-miR-4690-3p	CLIP-seq
MIRT1177838	hsa-miR-4708-5p	CLIP-seq
MIRT1177839	hsa-miR-4710	CLIP-seq
MIRT1177840	hsa-miR-4720-5p	CLIP-seq
MIRT1177841	hsa-miR-4725-3p	CLIP-seq
MIRT1177842	hsa-miR-4727-3p	CLIP-seq
MIRT1177843	hsa-miR-4731-5p	CLIP-seq
MIRT1177844	hsa-miR-4733-5p	CLIP-seq
MIRT1177845	hsa-miR-4739	CLIP-seq
MIRT1177846	hsa-miR-4741	CLIP-seq
MIRT1177847	hsa-miR-4747-5p	CLIP-seq
MIRT1177848	hsa-miR-4749-3p	CLIP-seq
MIRT1177849	hsa-miR-4756-3p	CLIP-seq
MIRT1177850	hsa-miR-4756-5p	CLIP-seq
MIRT1177851	hsa-miR-4769-5p	CLIP-seq
MIRT1177852	hsa-miR-4784	CLIP-seq
MIRT1177853	hsa-miR-4799-3p	CLIP-seq
MIRT1177854	hsa-miR-548n	CLIP-seq
MIRT1177855	hsa-miR-555	CLIP-seq
MIRT1177856	hsa-miR-558	CLIP-seq
MIRT1177857	hsa-miR-615-5p	CLIP-seq
MIRT1177858	hsa-miR-762	CLIP-seq
MIRT2051467	hsa-miR-1225-5p	CLIP-seq
MIRT2051468	hsa-miR-4447	CLIP-seq
MIRT2051469	hsa-miR-4472	CLIP-seq
MIRT1177822	hsa-miR-4476	CLIP-seq
MIRT2051470	hsa-miR-4505	CLIP-seq
MIRT2051471	hsa-miR-4651	CLIP-seq
MIRT1177839	hsa-miR-4710	CLIP-seq
MIRT2051472	hsa-miR-608	CLIP-seq
MIRT1177763	hsa-miR-1252	CLIP-seq
MIRT1177765	hsa-miR-1273g	CLIP-seq
MIRT1177766	hsa-miR-1302	CLIP-seq
MIRT1177767	hsa-miR-1321	CLIP-seq
MIRT1177768	hsa-miR-140-5p	CLIP-seq
MIRT1177771	hsa-miR-1825	CLIP-seq
MIRT1177773	hsa-miR-199a-5p	CLIP-seq
MIRT1177774	hsa-miR-199b-5p	CLIP-seq
MIRT1177786	hsa-miR-3150b-3p	CLIP-seq
MIRT1177787	hsa-miR-3153	CLIP-seq
MIRT1177790	hsa-miR-3179	CLIP-seq
MIRT1177791	hsa-miR-3202	CLIP-seq
MIRT1177797	hsa-miR-323b-5p	CLIP-seq
MIRT1177799	hsa-miR-3545-5p	CLIP-seq
MIRT2280494	hsa-miR-3612	CLIP-seq
MIRT1177801	hsa-miR-3652	CLIP-seq
MIRT2280495	hsa-miR-3657	CLIP-seq
MIRT1177806	hsa-miR-3936	CLIP-seq
MIRT1177811	hsa-miR-4298	CLIP-seq
MIRT1177817	hsa-miR-4430	CLIP-seq
MIRT1177818	hsa-miR-4436b-3p	CLIP-seq
MIRT2051468	hsa-miR-4447	CLIP-seq
MIRT1177820	hsa-miR-4460	CLIP-seq
MIRT1177821	hsa-miR-4468	CLIP-seq
MIRT2051469	hsa-miR-4472	CLIP-seq
MIRT1177822	hsa-miR-4476	CLIP-seq
MIRT1177826	hsa-miR-4504	CLIP-seq
MIRT1177828	hsa-miR-4533	CLIP-seq
MIRT1177830	hsa-miR-4648	CLIP-seq
MIRT2051471	hsa-miR-4651	CLIP-seq
MIRT1177834	hsa-miR-4668-5p	CLIP-seq
MIRT2280496	hsa-miR-4669	CLIP-seq
MIRT1177836	hsa-miR-4689	CLIP-seq
MIRT1177839	hsa-miR-4710	CLIP-seq
MIRT1177842	hsa-miR-4727-3p	CLIP-seq
MIRT1177845	hsa-miR-4739	CLIP-seq
MIRT1177847	hsa-miR-4747-5p	CLIP-seq
MIRT1177850	hsa-miR-4756-5p	CLIP-seq
MIRT1177852	hsa-miR-4784	CLIP-seq
MIRT1177854	hsa-miR-548n	CLIP-seq
MIRT2280497	hsa-miR-592	CLIP-seq
MIRT2280498	hsa-miR-599	CLIP-seq
MIRT2051472	hsa-miR-608	CLIP-seq
MIRT2280499	hsa-miR-650	CLIP-seq
MIRT2280500	hsa-miR-658	CLIP-seq
MIRT1177765	hsa-miR-1273g	CLIP-seq
MIRT1177767	hsa-miR-1321	CLIP-seq
MIRT1177768	hsa-miR-140-5p	CLIP-seq
MIRT1177769	hsa-miR-145	CLIP-seq
MIRT1177771	hsa-miR-1825	CLIP-seq
MIRT1177772	hsa-miR-1915	CLIP-seq
MIRT1177773	hsa-miR-199a-5p	CLIP-seq
MIRT1177774	hsa-miR-199b-5p	CLIP-seq
MIRT1177797	hsa-miR-323b-5p	CLIP-seq
MIRT1177799	hsa-miR-3545-5p	CLIP-seq
MIRT2280495	hsa-miR-3657	CLIP-seq
MIRT1177808	hsa-miR-4270	CLIP-seq
MIRT1177819	hsa-miR-4441	CLIP-seq
MIRT1177820	hsa-miR-4460	CLIP-seq
MIRT1177826	hsa-miR-4504	CLIP-seq
MIRT2280496	hsa-miR-4669	CLIP-seq
MIRT1177842	hsa-miR-4727-3p	CLIP-seq
MIRT1177845	hsa-miR-4739	CLIP-seq
MIRT1177850	hsa-miR-4756-5p	CLIP-seq
MIRT2280497	hsa-miR-592	CLIP-seq
MIRT2280498	hsa-miR-599	CLIP-seq
MIRT2051467	hsa-miR-1225-5p	CLIP-seq
MIRT1177763	hsa-miR-1252	CLIP-seq
MIRT1177765	hsa-miR-1273g	CLIP-seq
MIRT1177766	hsa-miR-1302	CLIP-seq
MIRT1177767	hsa-miR-1321	CLIP-seq
MIRT1177768	hsa-miR-140-5p	CLIP-seq
MIRT1177769	hsa-miR-145	CLIP-seq
MIRT1177771	hsa-miR-1825	CLIP-seq
MIRT2578921	hsa-miR-186	CLIP-seq
MIRT1177772	hsa-miR-1915	CLIP-seq
MIRT1177773	hsa-miR-199a-5p	CLIP-seq
MIRT1177774	hsa-miR-199b-5p	CLIP-seq
MIRT1177778	hsa-miR-31	CLIP-seq
MIRT1177782	hsa-miR-3128	CLIP-seq
MIRT1177784	hsa-miR-3140-5p	CLIP-seq
MIRT1177785	hsa-miR-3148	CLIP-seq
MIRT1177786	hsa-miR-3150b-3p	CLIP-seq
MIRT1177788	hsa-miR-3154	CLIP-seq
MIRT1177789	hsa-miR-3160-3p	CLIP-seq
MIRT2578922	hsa-miR-3162-5p	CLIP-seq
MIRT1177790	hsa-miR-3179	CLIP-seq
MIRT1177792	hsa-miR-320a	CLIP-seq
MIRT1177793	hsa-miR-320b	CLIP-seq
MIRT1177794	hsa-miR-320c	CLIP-seq
MIRT1177795	hsa-miR-320d	CLIP-seq
MIRT1177796	hsa-miR-320e	CLIP-seq
MIRT1177797	hsa-miR-323b-5p	CLIP-seq
MIRT1177798	hsa-miR-3545-3p	CLIP-seq
MIRT1177799	hsa-miR-3545-5p	CLIP-seq
MIRT1177801	hsa-miR-3652	CLIP-seq
MIRT2280495	hsa-miR-3657	CLIP-seq
MIRT2578923	hsa-miR-3667-3p	CLIP-seq
MIRT1177808	hsa-miR-4270	CLIP-seq
MIRT1177811	hsa-miR-4298	CLIP-seq
MIRT2578924	hsa-miR-4424	CLIP-seq
MIRT1177816	hsa-miR-4429	CLIP-seq
MIRT1177817	hsa-miR-4430	CLIP-seq
MIRT1177818	hsa-miR-4436b-3p	CLIP-seq
MIRT1177819	hsa-miR-4441	CLIP-seq
MIRT2051468	hsa-miR-4447	CLIP-seq
MIRT1177820	hsa-miR-4460	CLIP-seq
MIRT1177821	hsa-miR-4468	CLIP-seq
MIRT2051469	hsa-miR-4472	CLIP-seq
MIRT1177822	hsa-miR-4476	CLIP-seq
MIRT1177823	hsa-miR-4487	CLIP-seq
MIRT1177826	hsa-miR-4504	CLIP-seq
MIRT2051470	hsa-miR-4505	CLIP-seq
MIRT1177828	hsa-miR-4533	CLIP-seq
MIRT1177830	hsa-miR-4648	CLIP-seq
MIRT2051471	hsa-miR-4651	CLIP-seq
MIRT2578925	hsa-miR-4653-3p	CLIP-seq
MIRT1177833	hsa-miR-4663	CLIP-seq
MIRT2280496	hsa-miR-4669	CLIP-seq
MIRT1177836	hsa-miR-4689	CLIP-seq
MIRT2578926	hsa-miR-4699-3p	CLIP-seq
MIRT1177839	hsa-miR-4710	CLIP-seq
MIRT1177842	hsa-miR-4727-3p	CLIP-seq
MIRT1177843	hsa-miR-4731-5p	CLIP-seq
MIRT1177845	hsa-miR-4739	CLIP-seq
MIRT1177850	hsa-miR-4756-5p	CLIP-seq
MIRT1177852	hsa-miR-4784	CLIP-seq
MIRT2578927	hsa-miR-520d-5p	CLIP-seq
MIRT2578928	hsa-miR-524-5p	CLIP-seq
MIRT1177854	hsa-miR-548n	CLIP-seq
MIRT1177855	hsa-miR-555	CLIP-seq
MIRT1177856	hsa-miR-558	CLIP-seq
MIRT2280497	hsa-miR-592	CLIP-seq
MIRT2280498	hsa-miR-599	CLIP-seq
MIRT2051472	hsa-miR-608	CLIP-seq
MIRT1177857	hsa-miR-615-5p	CLIP-seq
MIRT2578929	hsa-miR-873	CLIP-seq
MIRT2051467	hsa-miR-1225-5p	CLIP-seq
MIRT1177763	hsa-miR-1252	CLIP-seq
MIRT1177765	hsa-miR-1273g	CLIP-seq
MIRT1177766	hsa-miR-1302	CLIP-seq
MIRT1177767	hsa-miR-1321	CLIP-seq
MIRT1177768	hsa-miR-140-5p	CLIP-seq
MIRT1177769	hsa-miR-145	CLIP-seq
MIRT1177771	hsa-miR-1825	CLIP-seq
MIRT1177772	hsa-miR-1915	CLIP-seq
MIRT1177773	hsa-miR-199a-5p	CLIP-seq
MIRT1177774	hsa-miR-199b-5p	CLIP-seq
MIRT1177778	hsa-miR-31	CLIP-seq
MIRT1177782	hsa-miR-3128	CLIP-seq
MIRT1177784	hsa-miR-3140-5p	CLIP-seq
MIRT1177785	hsa-miR-3148	CLIP-seq
MIRT1177786	hsa-miR-3150b-3p	CLIP-seq
MIRT1177788	hsa-miR-3154	CLIP-seq
MIRT1177789	hsa-miR-3160-3p	CLIP-seq
MIRT2578922	hsa-miR-3162-5p	CLIP-seq
MIRT1177790	hsa-miR-3179	CLIP-seq
MIRT1177792	hsa-miR-320a	CLIP-seq
MIRT1177793	hsa-miR-320b	CLIP-seq
MIRT1177794	hsa-miR-320c	CLIP-seq
MIRT1177795	hsa-miR-320d	CLIP-seq
MIRT1177796	hsa-miR-320e	CLIP-seq
MIRT1177797	hsa-miR-323b-5p	CLIP-seq
MIRT1177798	hsa-miR-3545-3p	CLIP-seq
MIRT1177799	hsa-miR-3545-5p	CLIP-seq
MIRT1177801	hsa-miR-3652	CLIP-seq
MIRT2280495	hsa-miR-3657	CLIP-seq
MIRT2578923	hsa-miR-3667-3p	CLIP-seq
MIRT1177808	hsa-miR-4270	CLIP-seq
MIRT1177811	hsa-miR-4298	CLIP-seq
MIRT2578924	hsa-miR-4424	CLIP-seq
MIRT1177816	hsa-miR-4429	CLIP-seq
MIRT1177817	hsa-miR-4430	CLIP-seq
MIRT1177818	hsa-miR-4436b-3p	CLIP-seq
MIRT1177819	hsa-miR-4441	CLIP-seq
MIRT2051468	hsa-miR-4447	CLIP-seq
MIRT1177820	hsa-miR-4460	CLIP-seq
MIRT1177821	hsa-miR-4468	CLIP-seq
MIRT2051469	hsa-miR-4472	CLIP-seq
MIRT1177822	hsa-miR-4476	CLIP-seq
MIRT1177823	hsa-miR-4487	CLIP-seq
MIRT1177826	hsa-miR-4504	CLIP-seq
MIRT2051470	hsa-miR-4505	CLIP-seq
MIRT1177828	hsa-miR-4533	CLIP-seq
MIRT1177830	hsa-miR-4648	CLIP-seq
MIRT2051471	hsa-miR-4651	CLIP-seq
MIRT2578925	hsa-miR-4653-3p	CLIP-seq
MIRT1177833	hsa-miR-4663	CLIP-seq
MIRT2280496	hsa-miR-4669	CLIP-seq
MIRT1177836	hsa-miR-4689	CLIP-seq
MIRT1177839	hsa-miR-4710	CLIP-seq
MIRT1177842	hsa-miR-4727-3p	CLIP-seq
MIRT1177843	hsa-miR-4731-5p	CLIP-seq
MIRT1177845	hsa-miR-4739	CLIP-seq
MIRT1177850	hsa-miR-4756-5p	CLIP-seq
MIRT1177852	hsa-miR-4784	CLIP-seq
MIRT1177854	hsa-miR-548n	CLIP-seq
MIRT1177855	hsa-miR-555	CLIP-seq
MIRT1177856	hsa-miR-558	CLIP-seq
MIRT2280497	hsa-miR-592	CLIP-seq
MIRT2280498	hsa-miR-599	CLIP-seq
MIRT2051472	hsa-miR-608	CLIP-seq
MIRT1177857	hsa-miR-615-5p	CLIP-seq
MIRT2578929	hsa-miR-873	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	NAS	15274632
GO:0002262	Process	Myeloid cell homeostasis	IEA
GO:0004175	Function	Endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	12297508, 15322109, 15890777, 16641999, 18201567, 19376115, 26094765, 26280335, 29611543, 30559186
GO:0005764	Component	Lysosome	IEA
GO:0005765	Component	Lysosomal membrane	HDA	17897319
GO:0005765	Component	Lysosomal membrane	IEA
GO:0005769	Component	Early endosome	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	15274632
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	NAS	15274632
GO:0005794	Component	Golgi apparatus	IDA	15274632
GO:0005794	Component	Golgi apparatus	IEA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	15274632
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	ISS
GO:0005886	Component	Plasma membrane	TAS
GO:0005925	Component	Focal adhesion	HDA	21423176
GO:0006508	Process	Proteolysis	NAS	10993067
GO:0006509	Process	Membrane protein ectodomain proteolysis	IDA	15274632
GO:0007212	Process	G protein-coupled dopamine receptor signaling pathway	IEA
GO:0007215	Process	Glutamate receptor signaling pathway	IEA
GO:0007219	Process	Notch signaling pathway	IEA
GO:0007220	Process	Notch receptor processing	IBA
GO:0007220	Process	Notch receptor processing	IDA	27608597
GO:0007220	Process	Notch receptor processing	IMP	12297508
GO:0007220	Process	Notch receptor processing	NAS	10206645
GO:0007220	Process	Notch receptor processing	TAS	15274632
GO:0007611	Process	Learning or memory	IEA
GO:0008021	Component	Synaptic vesicle	IEA
GO:0008233	Function	Peptidase activity	IEA
GO:0010008	Component	Endosome membrane	TAS
GO:0012505	Component	Endomembrane system	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IDA	25043039, 26280335
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	NAS	10993067
GO:0016485	Process	Protein processing	IBA
GO:0016485	Process	Protein processing	IDA	15274632, 27608597
GO:0016485	Process	Protein processing	IEA
GO:0016485	Process	Protein processing	IGI	12763021
GO:0016485	Process	Protein processing	IMP	12297508
GO:0021549	Process	Cerebellum development	IEA
GO:0022010	Process	Central nervous system myelination	IEA
GO:0030534	Process	Adult behavior	IEA
GO:0030659	Component	Cytoplasmic vesicle membrane	IEA
GO:0030674	Function	Protein-macromolecule adaptor activity	IGI	12763021
GO:0030674	Function	Protein-macromolecule adaptor activity	IMP	12297508
GO:0031293	Process	Membrane protein intracellular domain proteolysis	IDA	15274632
GO:0031293	Process	Membrane protein intracellular domain proteolysis	ISS
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0034205	Process	Amyloid-beta formation	IDA	27608597
GO:0034205	Process	Amyloid-beta formation	IEA
GO:0034205	Process	Amyloid-beta formation	IGI	12763021
GO:0034205	Process	Amyloid-beta formation	IMP	12297508, 25043039, 26280335
GO:0035577	Component	Azurophil granule membrane	TAS
GO:0042098	Process	T cell proliferation	IEA
GO:0042383	Component	Sarcolemma	IEA
GO:0042470	Component	Melanosome	IEA
GO:0042500	Function	Aspartic endopeptidase activity, intramembrane cleaving	IEA
GO:0042734	Component	Presynaptic membrane	IEA
GO:0042982	Process	Amyloid precursor protein metabolic process	IDA	25043039, 26280335
GO:0042982	Process	Amyloid precursor protein metabolic process	IEA
GO:0042983	Process	Amyloid precursor protein biosynthetic process	IEA
GO:0042986	Process	Positive regulation of amyloid precursor protein biosynthetic process	IEA
GO:0042987	Process	Amyloid precursor protein catabolic process	IDA	15274632, 27608597
GO:0042987	Process	Amyloid precursor protein catabolic process	IGI	12763021
GO:0042987	Process	Amyloid precursor protein catabolic process	ISS
GO:0042987	Process	Amyloid precursor protein catabolic process	TAS	15274632
GO:0050435	Process	Amyloid-beta metabolic process	IEA
GO:0050673	Process	Epithelial cell proliferation	IEA
GO:0051117	Function	ATPase binding	IPI	26094765
GO:0051402	Process	Neuron apoptotic process	IEA
GO:0061133	Function	Endopeptidase activator activity	IGI	12763021
GO:0061133	Function	Endopeptidase activator activity	IMP	12297508
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337
GO:0070765	Component	Gamma-secretase complex	IDA	12297508, 25043039, 26280335
GO:0070765	Component	Gamma-secretase complex	IEA
GO:0070765	Component	Gamma-secretase complex	IGI	12763021
GO:0070765	Component	Gamma-secretase complex	IPI	26280335
GO:0070765	Component	Gamma-secretase complex	ISS
GO:0070765	Component	Gamma-secretase complex	NAS	22086926
GO:0070851	Function	Growth factor receptor binding	IPI	26094765
GO:0071277	Process	Cellular response to calcium ion	IEA
GO:0097060	Component	Synaptic membrane	IEA
GO:0099503	Component	Secretory vesicle	IEA
GO:1900271	Process	Regulation of long-term synaptic potentiation	IEA
GO:1990926	Process	Short-term synaptic potentiation	IEA

Other IDs

• MIM: 605254
• HGNC: 17091
• e!Ensembl: ENSG00000162736

Protein

• UniProt ID: Q92542
• Protein name: Nicastrin
• Protein function: Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:10993067, PubMed:12679784,
• PDB: 2N7Q, 2N7R, 4UIS, 5A63, 5FN2, 5FN3, 5FN4, 5FN5, 6IDF, 6IYC, 6LQG, 6LR4, 7C9I, 7D8X, 7Y5T, 7Y5X, 7Y5Z, 8IM7, 8K8E, 8KCO, 8KCP, 8KCS, 8KCT, 8KCU, 8OQY, 8OQZ, 8X52, 8X53, 8X54
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18266	Ncstrn_small	49 → 223	Nicastrin small lobe	Domain
  PF05450	Nicastrin	274 → 499		Family

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain (at protein level) (PubMed:10993067). Widely expressed (PubMed:11396676). {ECO:0000269|PubMed:10993067, ECO:0000269|PubMed:11396676}.
• Sequence:

  MATAGGGSGADPGSRGLLRLLSFCVLLAGLCRGNSVERKIYIPLNKTAPCVRLLNATHQI
  GCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAG
  LAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPI
  FLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTF
  SINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVA
  SFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVD
  SFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQ
  PLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFV
  TDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQ
  DLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLY
  EYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARI
  FLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY

• Sequence length: 709

Pathways

KEGG:

Notch signaling pathway
Alzheimer disease

Reactome:

Nuclear signaling by ERBB4
Regulated proteolysis of p75NTR
NRIF signals cell death from the nucleus
Constitutive Signaling by NOTCH1 PEST Domain Mutants
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
EPH-ephrin mediated repulsion of cells
Neutrophil degranulation
NOTCH3 Activation and Transmission of Signal to the Nucleus
Noncanonical activation of NOTCH3
Amyloid fiber formation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the skin	Pathogenic	rs2101909450	RCV001814539	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Acne inversa, familial, 1	Pathogenic	rs2101889658, rs771414318, rs1085307081, rs2525536152, rs1553211087, rs1553210984, rs387906896, rs1347055289	RCV001535813 RCV001535814 RCV000490379 RCV003128285 RCV000023405 RCV000023406 RCV000023407 RCV000515754	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ALZHEIMERS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NCSTN-related disorder	Likely benign; Benign; Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PASH SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
ACNE INVERSA, FAMILIAL, 1	ACNE INVERSA	CLINVAR_DG	20929727, 22358060		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ACNE INVERSA, FAMILIAL, 1	ACNE INVERSA	GENOMICS_ENGLAND_DG	20929727, 21412258, 22622421		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ACNE INVERSA, FAMILIAL, 1	ACNE INVERSA	UNIPROT_DG	20929727, 21430701, 21495993		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Acute Confusional Senile Dementia	Senile Dementia	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	11992262, 21364883, 29045054	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Early Onset	Alzheimer disease	BEFREE	11992262, 14664923, 15249634, 16423463		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Early Onset	Alzheimer disease	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	11992262		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease, Focal Onset	Alzheimer disease	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	29331531, 30803762		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	20224929, 23012411, 24223915, 24337538, 24919951		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	24919951	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	19366792	Associate	★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	15567563		★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	BEFREE	30120935		★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	BEFREE	15781968		★☆☆☆☆ Found in Text Mining only
Familial Alzheimer Disease (FAD)	Alzheimer disease	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Hidradenitis Suppurativa	Hidradenitis suppurativa	BEFREE	21495993, 22834455, 26224166, 26473517, 29968387, 30030622		★☆☆☆☆ Found in Text Mining only
Hidradenitis Suppurativa	Hidradenitis suppurativa	GENOMICS_ENGLAND_DG	22622421		★☆☆☆☆ Found in Text Mining only
Hidradenitis Suppurativa	Hidradenitis suppurativa	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hidradenitis suppurativa, familial	Hidradenitis suppurativa	CTD_human_DG	20929727		★☆☆☆☆ Found in Text Mining only
Hidradenitis suppurativa, familial	Hidradenitis suppurativa	BEFREE	26473517, 30120935, 30656721		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	19366792		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	20224929, 23012411, 24223915, 24337538, 24919951		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	30944650		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	21725355, 23012411, 25663545		★☆☆☆☆ Found in Text Mining only
Melanoma Cutaneous Malignant	Melanoma	Pubtator	25953768	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21890747, 23012411, 24337538		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	15370186, 17401156		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Hidradenitis suppurativa	Hidradenitis suppurativa	Orphanet			★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	32078194	Associate	★☆☆☆☆ Found in Text Mining only
Obsessive compulsive behavior	Obsessive-Compulsive Disorder	BEFREE	27008863		★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	30944650		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	25808939		★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	15567563		★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	CTD_human_DG	17192785		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	27008863		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Skin lesion	Skin Lesion	BEFREE	20929727		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	27349552	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	27581326	Associate	★☆☆☆☆ Found in Text Mining only