NCSTN nicastrin [Homo sapiens (human)] - Gene

Summary

Official Symbol: NCSTNprovided by HGNC
Official Full Name: nicastrinprovided by HGNC
Primary source: HGNC:HGNC:17091
See related: Ensembl:ENSG00000162736 MIM:605254; AllianceGenome:HGNC:17091
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ATAG1874
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 a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
Expression: Ubiquitous expression in placenta (RPKM 38.1), duodenum (RPKM 30.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.2

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (160343383..160358949)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (159480455..159496021)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (160313173..160328739)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Discovery and Potential Functional Characterization of Long Noncoding RNAs Associated with Familial Acne Inversa with NCSTN Mutation.
Title: Discovery and Potential Functional Characterization of Long Noncoding RNAs Associated with Familial Acne Inversa with NCSTN Mutation.
A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.
Title: A loss-of-function NCSTN mutation associated with familial Dowling Degos disease and hidradenitis suppurativa.
A novel mutation of the NCSTN gene in a Chinese hidradenitis suppurativa family with familial comedones as the main clinical manifestation.
Title: A novel mutation of the NCSTN gene in a Chinese hidradenitis suppurativa family with familial comedones as the main clinical manifestation.
Evolutionary distinct roles of gamma-secretase subunit nicastrin in zebrafish and humans.
Title: Evolutionary distinct roles of γ-secretase subunit nicastrin in zebrafish and humans.
Two novel nicastrin mutations in Chinese families with acne inversa.
Title: Two novel nicastrin mutations in Chinese families with acne inversa.
Genetic variations in gamma-secretase and PSTPIP1 in hidradenitis suppurativa in Singaporean Chinese.
Title: Genetic variations in gamma-secretase and PSTPIP1 in hidradenitis suppurativa in Singaporean Chinese.
NCSTN promotes hepatocellular carcinoma cell growth and metastasis via beta-catenin activation in a Notch1/AKT dependent manner.
Title: NCSTN promotes hepatocellular carcinoma cell growth and metastasis via β-catenin activation in a Notch1/AKT dependent manner.
The impaired EGFR signaling and its effects on epidermal differentiation were also observed in familial AI patients and Ncstn(DeltaKC) mice. Thus, our study showed that miR-30a-3p/RAB31/EGFR signaling pathway may play a key role in the pathogenesis of familial AI with NCSTN mutations.
Title: Nicastrin/miR-30a-3p/RAB31 Axis Regulates Keratinocyte Differentiation by Impairing EGFR Signaling in Familial Acne Inversa.
A heterozygous nonsense mutation (c.617C>A, p.S206X) was identified in NCSTN in the proband. This mutation in NCSTN also existed in the other AI patients but not in the two normal relatives and 50 control subjects.
Title: Mutations in the γ-secretase genes PSEN1, PSENEN, and NCSTN in a family with acne inversa.
Identification of a novel deletion mutation in exon 4 of NCSTN, which may underlie the molecular pathogenesis in this Acne inversa family.
Title: A novel NCSTN gene mutation in a Chinese family with acne inversa.

Submit: New GeneRIF Correction See all GeneRIFs (90)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Acne inversa, familial, 1 MedGen: C4551962 OMIM: 142690 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36199 (e-PCR)
- UniSTS:38410

RH11634 (e-PCR)
- UniSTS:22843

RH71333 (e-PCR)
- UniSTS:27969

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables aspartic endopeptidase activity, intramembrane cleaving	IEA Inferred from Electronic Annotation more info
enables growth factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch receptor processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch receptor processing	IDA Inferred from Direct Assay more info	PubMed
involved_in Notch receptor processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Notch receptor processing	NAS Non-traceable Author Statement more info	PubMed
involved_in Notch receptor processing	TAS Traceable Author Statement more info	PubMed
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in adult behavior	IEA Inferred from Electronic Annotation more info
involved_in amyloid precursor protein biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in amyloid precursor protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid precursor protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in amyloid precursor protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in amyloid precursor protein metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid-beta formation	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in amyloid-beta formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to calcium ion	IEA Inferred from Electronic Annotation more info
involved_in central nervous system myelination	IEA Inferred from Electronic Annotation more info
involved_in cerebellum development	IEA Inferred from Electronic Annotation more info
involved_in dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in glutamate receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in learning or memory	IEA Inferred from Electronic Annotation more info
involved_in membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein intracellular domain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein intracellular domain proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in myeloid cell homeostasis	IEA Inferred from Electronic Annotation more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of amyloid precursor protein biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of catalytic activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endopeptidase activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IGI Inferred from Genetic Interaction more info	PubMed
involved_in protein processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of long-term synaptic potentiation	IEA Inferred from Electronic Annotation more info
involved_in short-term synaptic potentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	NAS Non-traceable Author Statement more info	PubMed
located_in azurophil granule membrane	TAS Traceable Author Statement more info
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	NAS Non-traceable Author Statement more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
part_of gamma-secretase complex	IDA Inferred from Direct Assay more info	PubMed
part_of gamma-secretase complex	IGI Inferred from Genetic Interaction more info	PubMed
part_of gamma-secretase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of gamma-secretase complex	ISS Inferred from Sequence or Structural Similarity more info
part_of gamma-secretase complex	NAS Non-traceable Author Statement more info	PubMed
located_in lysosomal membrane	HDA more info	PubMed
located_in melanosome	IEA Inferred from Electronic Annotation more info
located_in membrane	HDA more info	PubMed
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in presynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in sarcolemma	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: nicastrin

Names: anterior pharynx-defective 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027935.1 RefSeqGene

Range

5111..20677

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_223

mRNA and Protein(s)

NM_001290184.2 → NP_001277113.1 nicastrin isoform 2

See identical proteins and their annotated locations for NP_001277113.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has a different 5' structure resulting in translation initiation at an alternate AUG compared to variant 1; the 5'-most AUG, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the alternate AUG resulting in a shorter isoform (2) with a distinct N-terminus compared to isoform 1.

Source sequence(s)

AL445230, BC047621, CN429672

UniProtKB/TrEMBL

A0A8V8TNI3

Conserved Domains (1) summary

cd03881
Location:155 → 462

M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex
NM_001290186.2 → NP_001277115.1 nicastrin isoform 3 precursor

See identical proteins and their annotated locations for NP_001277115.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks three alternate in-frame exons in the coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AF240468, AK299142, AL445230, CN429672

Consensus CDS

CCDS91084.1

UniProtKB/TrEMBL

A0A8V8TPR8, B4DR82

Related

ENSP00000514429.1, ENST00000699549.1

Conserved Domains (1) summary

cl14876
Location:195 → 361

Zinc_peptidase_like; Zinc peptidases M18, M20, M28, and M42
NM_001349729.2 → NP_001336658.1 nicastrin isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. It encodes isoform 5, which is shorter than isoform 1.

Source sequence(s)

AL445230, H15133

UniProtKB/TrEMBL

A0A8V8TNI3

Related

ENSP00000514420.1, ENST00000699528.1

Conserved Domains (1) summary

cd03881
Location:175 → 482

M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex
NM_015331.3 → NP_056146.1 nicastrin isoform 1 precursor

See identical proteins and their annotated locations for NP_056146.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF240468, BC047621, CN429672

Consensus CDS

CCDS1203.1

UniProtKB/Swiss-Prot

Q5T207, Q5T208, Q86VV5, Q92542

UniProtKB/TrEMBL

A0A8V8TNI3

Related

ENSP00000294785.5, ENST00000294785.10

Conserved Domains (1) summary

cd03881
Location:52 → 654

M28_Nicastrin; M28 Zn-peptidase nicastrin, a main component of gamma-secretase complex

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

160343383..160358949

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005245053.6 → XP_005245110.1 nicastrin isoform X1

UniProtKB/TrEMBL

A0A8V8TNC8, A0A8V8TPQ8

Related

ENSP00000514419.1, ENST00000699527.1

Conserved Domains (1) summary

cd03881
Location:175 → 395

M28_Nicastrin; M28 Zn-Peptidase Nicastrin, a main component of gamma-secretase complex