NLN

protein-coding

neurolysin, the group of M3 metallopeptidase family

Gene summary

This gene encodes a member of the metallopeptidase M3 protein family that cleaves neurotensin at the Pro10-Tyr11 bond, leading to the formation of neurotensin(1-10) and neurotensin(11-13). The encoded protein is likely involved in the termination of the neurotensinergic signal in the central nervous system and in the gastrointestinal tract.[provided by RefSeq, Jun 2010]

Previous symbols:

AGTBP

MANE transcript

NM_020726.5

Inheritance

—

ClinVar variants

U:113B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr5:65,722,205-65,871,725

External References & Databases

Ensembl (ENSG00000123213)

Transcript & Mutation Effects

hg38 • Region Span ~149.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NLN variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 104

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020726.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar			4
missense			106 clinvar	3 clinvar		109
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	113	3	0	116

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020726.5	RefSeq	NP_065777.1	13	MANE Select
ENST00000380985.10	Ensembl	ENSP00000370372.5	13	MANE Select
ENST00000502464.5	Ensembl	ENSP00000423214.1	11	Standard
ENST00000509935.2	Ensembl	ENSP00000426959.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)

Biological Process

regulation of gluconeogenesis
proteolysis
peptide metabolic process
regulation of skeletal muscle fiber differentiation

Molecular Function

metalloendopeptidase activity
peptide binding
metal ion binding

Cellular Component

extracellular region
mitochondrial intermembrane space
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380985
Coding exons: 13
Length: 149531
Individuals with no LoFs: 125660
Homozygous LoFs: 0
Heterozygous LoFs: 87
Defined: 125747
p: 0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.249	369	383	0.964	0.0000194	4646
Missense (PolyPhen)		111	106.46	1.0427		1277
Synonymous	1.59	116	140	0.829	0.00000799	1296
Loss of Function	2.03	24	37.4	0.642	0.00000214	445

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00049	0.00048	rare
South Asian	0.00043	0.00042	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. {ECO:0000250}.;

Recessive Scores

pRec: 0.144

Intolerance Scores

LoFtool: 0.936
RVIS EVS: -0.35
RVIS percentile EVS: 29.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0490

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium