NOTCH2NLR

Summary

NOTCH2NLR (notch 2 N-terminal like R, HGNC:53925) is a protein-coding gene on chromosome 1p11.2, encoding Notch homolog 2 N-terminal-like protein R (A0A096LNW5).

Predicted to enable calcium ion binding activity.

Source: NCBI Gene 101929796 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001396072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:53925
Approved symbol	NOTCH2NLR
Name	notch 2 N-terminal like R
Location	1p11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000286106
Ensembl biotype	protein_coding
OMIM	618026
Entrez	101929796

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000624419, ENST00000690847

RefSeq mRNA: 1 — MANE Select: NM_001396072 NM_001396072

CCDS: CCDS91030

Canonical transcript exons

ENST00000624419 — 5 exons

Exon	Start	End
ENSE00003759615	120763628	120763709
ENSE00003846651	120793161	120793496
ENSE00003848426	120784974	120785233
ENSE00003978256	120723945	120724250
ENSE00003978257	120793747	120794851

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 83.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0957 / max 10.7173, expressed in 29 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
201645	0.0957	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.38	silver quality
ventricular zone	UBERON:0003053	79.46	gold quality
right coronary artery	UBERON:0001625	72.88	gold quality
lower esophagus mucosa	UBERON:0035834	70.23	gold quality
smooth muscle tissue	UBERON:0001135	69.29	gold quality
monocyte	CL:0000576	69.00	gold quality
leukocyte	CL:0000738	68.97	gold quality
popliteal artery	UBERON:0002250	67.77	gold quality
tibial artery	UBERON:0007610	67.71	gold quality
mucosa of stomach	UBERON:0001199	67.36	gold quality
skin of leg	UBERON:0001511	67.35	gold quality
blood	UBERON:0000178	67.23	gold quality
zone of skin	UBERON:0000014	67.00	gold quality
skin of abdomen	UBERON:0001416	66.40	gold quality
thoracic aorta	UBERON:0001515	66.25	gold quality
placenta	UBERON:0001987	66.07	gold quality
ascending aorta	UBERON:0001496	65.77	gold quality
descending thoracic aorta	UBERON:0002345	65.40	gold quality
ganglionic eminence	UBERON:0004023	64.82	gold quality
right lung	UBERON:0002167	64.30	gold quality
calcaneal tendon	UBERON:0003701	64.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	63.72	gold quality
esophagus mucosa	UBERON:0002469	63.61	gold quality
right uterine tube	UBERON:0001302	63.21	gold quality
vermiform appendix	UBERON:0001154	62.81	gold quality
left coronary artery	UBERON:0001626	62.24	gold quality
gall bladder	UBERON:0002110	62.20	gold quality
esophagus	UBERON:0001043	61.89	gold quality
granulocyte	CL:0000094	61.48	gold quality
sural nerve	UBERON:0015488	60.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.45
E-CURD-10	no	61.72

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	notchl	ENSDARG00000088308
drosophila_melanogaster	N	FBGN0004647
caenorhabditis_elegans		WBGENE00003001

Paralogs (7): NOTCH3 (ENSG00000074181), NOTCH2 (ENSG00000134250), NOTCH1 (ENSG00000148400), SNED1 (ENSG00000162804), NOTCH2NLA (ENSG00000264343), NOTCH2NLB (ENSG00000286019), NOTCH2NLC (ENSG00000286219)

Protein

Protein identifiers

Notch homolog 2 N-terminal-like protein R — A0A096LNW5 (reviewed: A0A096LNW5)

All UniProt accessions (2): A0A096LNW5, A0A8I5KY86

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Lower expressed during corticogenesis.

Polymorphism. The protein is absent in 14% of the human population.

Similarity. Belongs to the NOTCH family.

RefSeq proteins (1): NP_001383001* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR013032	EGF-like_CS	Conserved_site
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR049883	NOTCH1_EGF-like	Domain

Pfam: PF00008, PF07645, PF12661

UniProt features (25 total): disulfide bond 17, domain 6, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A096LNW5-F1	84.61	0.60

Functional residue map

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

Disulfide bonds (17): 53–62, 68–79, 73–90, 92–101, 109–121, 115–131, 133–142, 148–159, 153–168, 170–179, 186–198, 192–207, 209–218, 225–236, 230–246, 28–41, 35–51

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9911233	Expression of NOTCH2NL genes

MSigDB gene sets: 4 (showing top): REACTOME_SIGNALING_BY_NOTCH, chr1p11, REACTOME_EXPRESSION_OF_NOTCH2NL_GENES, REACTOME_PRE_NOTCH_EXPRESSION_AND_PROCESSING

GO Biological Process (3): positive regulation of signal transduction (GO:0009967), animal organ development (GO:0048513), system development (GO:0048731)

GO Molecular Function (1): calcium ion binding (GO:0005509)

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pre-NOTCH Transcription and Translation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	2
signal transduction	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
multicellular organism development	1
metal ion binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

504 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOTCH2NLR	CNMD	O75829	447
NOTCH2NLR	KCNJ18	B7U540	402
NOTCH2NLR	NBPF1	Q3BBV0	370
NOTCH2NLR	GPRIN2	O60269	328
NOTCH2NLR	OVGP1	Q12889	313
NOTCH2NLR	MUC3A	Q02505	279
NOTCH2NLR	PRIM2	P49643	273
NOTCH2NLR	MUC19	Q7Z5P9	269
NOTCH2NLR	PDE4DIP	Q5VU43	251
NOTCH2NLR	DUSP22	Q9NRW4	231
NOTCH2NLR	SRGAP2	O75044	224
NOTCH2NLR	SRGAP3	O43295	223
NOTCH2NLR	NES	P48681	176
NOTCH2NLR	HES5	Q5TA89	166
NOTCH2NLR	TERT	O14746	157

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A096LNW5, B8JI71, D3ZHH1, G3I6Z6, O00548, O35516, O57409, P0DPK3, P0DPK4, P35442, P46531, P78504, P97677, Q01705, Q04721, Q05793, Q07008, Q08E66, Q2QI47, Q5G872, Q5ZQU0, Q61483, Q63722, Q66PY1, Q6DI48, Q6NZL8, Q70E20, Q7TQN3, Q7Z3S9, Q8IWY4, Q8IX30, Q8JZM4, Q8K3K1, Q8NFT8, Q8TER0, Q8TEU8, Q8UWJ4, Q8VHS2, Q90Y54, Q90Y57

Diamond homologs: A0A096LNW5, A2RUV0, B4DH59, B8JI71, G3I6Z6, O35516, O75882, P07207, P0DPK3, P0DPK4, P10040, P21783, P46530, P46531, P98160, Q01705, Q04721, Q04756, Q07008, Q20911, Q7Z3S9, Q99466, Q99J86, Q9QW30, Q9UM47, Q9WU60, O35474, O75095, O89019, P13508, P20749, P31695, P82279, Q499M5, Q502K3, Q5RBP1, Q61982, Q6UXI9, Q6UY11, Q810B6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1779 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:120785233:G:T	G139C	0.995
1:120785104:T:C	F96L	0.994
1:120785106:T:A	F96L	0.994
1:120785106:T:G	F96L	0.994
1:120785119:T:A	C101S	0.994
1:120785120:G:C	C101S	0.994
1:120793169:T:A	C142S	0.994
1:120793170:G:C	C142S	0.994
1:120793301:T:A	C186S	0.994
1:120793302:G:C	C186S	0.994
1:120785002:T:A	C62S	0.991
1:120785003:G:C	C62S	0.991
1:120785035:T:A	C73S	0.991
1:120785036:G:C	C73S	0.991
1:120785121:C:G	C101W	0.990
1:120793161:G:T	G139V	0.990
1:120785092:T:A	C92S	0.988
1:120785093:G:C	C92S	0.988
1:120793280:T:A	C179S	0.988
1:120793281:G:C	C179S	0.988
1:120793319:T:A	C192S	0.988
1:120793320:G:C	C192S	0.988
1:120793397:T:A	C218S	0.988
1:120793398:G:C	C218S	0.988
1:120784975:T:A	C53S	0.986
1:120784976:G:C	C53S	0.986
1:120785004:T:G	C62W	0.986
1:120785120:G:A	C101Y	0.986
1:120793171:C:G	C142W	0.986
1:120793364:T:A	C207S	0.986

dbSNP variants (sampled 300 via entrez): RS1156237849 (1:120766054 G>A), RS1156264132 (1:120782433 T>C), RS1156296561 (1:120728330 T>C), RS1156370654 (1:120765176 C>T), RS1156393972 (1:120750643 A>G), RS1156402943 (1:120751858 C>A), RS1156457536 (1:120729542 G>A), RS1156583621 (1:120780297 A>G), RS1156671654 (1:120724842 TG>T), RS1156673967 (1:120763302 AG>A), RS1156707718 (1:120792909 A>G,T), RS1156708319 (1:120779458 A>T), RS1156736978 (1:120764233 C>A), RS1156767852 (1:120748927 CTT>C), RS1156778570 (1:120727399 G>A,T)

Disease associations

OMIM: gene MIM:618026 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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