NAALADL1

protein-coding

N-acetylated alpha-linked acidic dipeptidase like 1, the group of M28 metallopeptidases

Gene summary

Enables aminopeptidase activity; metal ion binding activity; and protein homodimerization activity. Involved in peptide catabolic process. Predicted to be located in apical plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_005468.3

Inheritance

—

ClinVar variants

P:1U:150B:8

Top phenotype

Retinal dystrophy

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr11:65,044,818-65,058,553

External References & Databases

Ensembl (ENSG00000168060)

Transcript & Mutation Effects

hg38 • Region Span ~13.7 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 NAALADL1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 142

Retinal dystrophyTotal: 15

Optic atrophyTotal: 3

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005468.3. 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			1 clinvar			1
missense			145 clinvar	8 clinvar		153
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	0	1	150	8	0	159

Highest pathogenic variant AF is 0.000087119864

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005468.3	RefSeq	NP_005459.2	18	MANE Select
ENST00000358658.8	Ensembl	ENSP00000351484.3	18	MANE Select
ENST00000340252.8	Ensembl	ENSP00000344244.4	17	Standard
ENST00000355721.7	Ensembl	ENSP00000347955.3	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

carboxypeptidase activity
peptidase activity
metallopeptidase activity
dipeptidase activity
metal ion binding

Cellular Component

integral component of membrane
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358658
Coding exons: 18
Length: 13732
Individuals with no LoFs: 125563
Homozygous LoFs: 0
Heterozygous LoFs: 185
Defined: 125748
p: 0.000736

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.170	447	457	0.978	0.0000281	4721
Missense (PolyPhen)		124	133.28	0.93036		1313
Synonymous	1.34	169	193	0.877	0.0000122	1565
Loss of Function	0.544	34	37.6	0.904	0.00000184	404

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.00075	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0013	0.0012	notable
Finnish	0.0023	0.0023	notable
European (Non-Finnish)	0.00048	0.00047	rare
South Asian	0.00039	0.00036	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: NAALADase-like activity unknown. Has no NAAG hydrolyzing activity. Exhibits a dipeptidyl-peptidase IV type activity. In vitro, cleaves Gly-Pro-AMC (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.957
RVIS EVS: -1.01
RVIS percentile EVS: 8.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.178

Gene Damage Prediction

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