NAALAD2

protein-coding

N-acetylated alpha-linked acidic dipeptidase 2, the group of M28 metallopeptidases

Gene summary

This gene is a member of the N-acetylated alpha-linked acidic dipeptidase (NAALADase) gene family. The representative member of this family is the gene encoding human prostate-specific membrane antigen (PSM), which is a marker of prostatic carcinomas and is the first to be shown to possess NAALADase activity. NAALADase cleaves N-acetyl-L-aspartate-L-glutamate (NAAG), which is a neuropeptide expressed both in the central nervous systems and in the periphery and is thought to function as a neurotransmitter. The product of this gene is a type II integral membrane protein. Transient transfection of this gene confers both NAALADase and dipetidyl peptidase IV activities to mammalian cells. This gene is highly expressed in ovary and testis as well as within discrete brain areas. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

MANE transcript

NM_005467.4

Inheritance

—

ClinVar variants

U:98B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr11:90,131,515-90,192,894

External References & Databases

Ensembl (ENSG00000077616)

Transcript & Mutation Effects

hg38 • Region Span ~61.4 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 NAALAD2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 101

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005467.4. 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				2 clinvar		2
missense			97 clinvar	4 clinvar		101
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	98	6	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005467.4	RefSeq	NP_005458.1	19	MANE Select
ENST00000534061.6	Ensembl	ENSP00000432481.1	19	MANE Select
NM_001300930.2	RefSeq	NP_001287859.1	18	Standard
ENST00000321955.8	Ensembl	ENSP00000320083.4	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of amino acids and derivatives
Metabolism
Amino acid synthesis and interconversion (transamination)

Biological Process

proteolysis
cellular amino acid biosynthetic process
neurotransmitter catabolic process

Molecular Function

carboxypeptidase activity
serine-type peptidase activity
metallopeptidase activity
dipeptidyl-peptidase activity
dipeptidase activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000534061
Coding exons: 19
Length: 61380
Individuals with no LoFs: 125542
Homozygous LoFs: 2
Heterozygous LoFs: 204
Defined: 125748
p: 0.000819

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.474	359	385	0.932	0.0000186	4828
Missense (PolyPhen)		145	163.52	0.88677		2027
Synonymous	0.334	126	131	0.963	0.00000603	1387
Loss of Function	1.07	35	42.6	0.822	0.00000208	546

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.0011	0.0011	notable
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0021	0.0019	notable
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00063	0.00060	rare
South Asian	0.0011	0.0010	notable
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivate the peptide neurotransmitter N- acetylaspartylglutamate. {ECO:0000269|PubMed:10085079}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.969
RVIS EVS: 0.07
RVIS percentile EVS: 59.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.136

Gene Damage Prediction

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