LNPEP

protein-coding

leucyl and cystinyl aminopeptidase, the group of Aminopeptidases|M1 metallopeptidases

Gene summary

This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005575.3

Inheritance

—

ClinVar variants

U:120B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr5:96,935,394-97,037,513

External References & Databases

Ensembl (ENSG00000113441)

Transcript & Mutation Effects

hg38 • Region Span ~102.1 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 LNPEP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 115

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005575.3. 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						0
missense			113 clinvar	3 clinvar		116
nonsense			3 clinvar			3
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	120	3	0	123

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005575.3	RefSeq	NP_005566.2	18	MANE Select
ENST00000231368.10	Ensembl	ENSP00000231368.5	18	MANE Select
NM_175920.4	RefSeq	NP_787116.2	17	Standard
ENST00000395770.3	Ensembl	ENSP00000379117.3	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Renin-angiotensin system - Homo sapiens (human)
Vesicle-mediated transport
Membrane Trafficking
TCR
Immune System

Biological Process

protein polyubiquitination
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent
proteolysis
cell-cell signaling
female pregnancy

Molecular Function

aminopeptidase activity
protein binding
metallopeptidase activity
zinc ion binding
peptide binding

Cellular Component

extracellular region
cytoplasm
lysosomal membrane
cytosol
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000231368
Coding exons: 18
Length: 102122
Individuals with no LoFs: 125721
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125743
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.44	432	525	0.823	0.0000254	6724
Missense (PolyPhen)		141	194.72	0.72412		2591
Synonymous	0.706	179	191	0.935	0.00000937	1930
Loss of Function	5.87	7	53.2	0.132	0.00000281	645

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. {ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:11707427, ECO:0000269|PubMed:1731608}.;

Recessive Scores

pRec: 0.305

Intolerance Scores

LoFtool: 0.358
RVIS EVS: 0.18
RVIS percentile EVS: 66.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.820

Gene Damage Prediction

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