AOPEP

protein-coding

aminopeptidase O (putative), the group of M1 metallopeptidases|MicroRNA protein coding host genes

Gene summary

This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

Previous symbols:

C9orf3

MANE transcript

NM_001193329.3

Inheritance

ClinVar variants

P:12U:30B:9

Top phenotype

Dystonia 31

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr9:94,726,604-95,151,793

External References & Databases

Ensembl (ENSG00000148120)

Transcript & Mutation Effects

hg38 • Region Span ~425.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Dystonia 31AR

Manifestation: Neurologic

Intervention: Neurologic

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Most individuals have been described as not responsive to levodopa therapy

Refs: 34596301

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AOPEP variants in ClinVar

5 Conditions Cataloged

not providedTotal: 14

Dystonia 31Total: 12

Inborn genetic diseasesTotal: 12

not specifiedTotal: 4

AOPEP-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001193329.3. 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	8 clinvar		9
missense			24 clinvar		1 clinvar	25
nonsense	2 clinvar	3 clinvar				5
start loss						0
frameshift	1 clinvar	5 clinvar				6
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar			6
Total	4	8	30	8	1	51

Highest pathogenic variant AF is 0.00006009109

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 76 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001193329.3	RefSeq	NP_001180258.1	15	MANE Select
ENST00000375315.8	Ensembl	ENSP00000364464.2	15	MANE Select
NM_001193331.3	RefSeq	NP_001180260.1	7	Standard
NM_001386061.1	RefSeq	NP_001372990.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peptide hormone metabolism
Metabolism of proteins
Metabolism of Angiotensinogen to Angiotensins

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375315
Coding exons: 15
Length: 360459
Individuals with no LoFs: 125628
Homozygous LoFs: 1
Heterozygous LoFs: 119
Defined: 125748
p: 0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.461	411	438	0.938	0.0000237	5367
Missense (PolyPhen)		115	139.43	0.82477		1719
Synonymous	0.491	152	160	0.951	0.00000877	1556
Loss of Function	1.87	29	42.1	0.688	0.00000209	494

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00045	0.00043	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00071	0.00071	rare
Finnish	0.00061	0.00060	rare
European (Non-Finnish)	0.00065	0.00062	rare
South Asian	0.00014	0.000098	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Aminopeptidases catalyze the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates. Able to cleave angiotensin III to generate angiotensin IV, a bioactive peptide of the renin-angiotensin pathway. Not able to cleave angiotensin I and angiotensin II. May play a role in the proteolytic processing of bioactive peptides in tissues such as testis and heart. {ECO:0000269|PubMed:15687497}.;

Recessive Scores

pRec: 0.187

Intolerance Scores

LoFtool: 0.986
RVIS EVS: -0.11
RVIS percentile EVS: 45.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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