METAP1

protein-coding

methionyl aminopeptidase 1, the group of Aminopeptidases|M24 metallopeptidase family|MicroRNA protein coding host genes

Gene summary

Enables aminopeptidase activity. Involved in protein maturation. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015143.3

Inheritance

ClinVar variants

U:40B:1

Top phenotype

Intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr4:98,995,659-99,062,809

External References & Databases

Ensembl (ENSG00000164024)

Transcript & Mutation Effects

hg38 • Region Span ~67.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to METAP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 2

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015143.3. 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			36 clinvar			36
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	40	0	1	41

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015143.3	RefSeq	NP_055958.2	11	MANE Select
ENST00000296411.11	Ensembl	ENSP00000296411.6	11	MANE Select
ENST00000503247.5	Ensembl	ENSP00000424462.1	2	Standard
ENST00000506238.5	Ensembl	ENSP00000426702.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
G alpha (i) signalling events
Inactivation, recovery and regulation of the phototransduction cascade
The phototransduction cascade

Biological Process

regulation of translation
proteolysis
peptidyl-methionine modification
regulation of rhodopsin mediated signaling pathway
N-terminal protein amino acid modification

Molecular Function

aminopeptidase activity
metalloexopeptidase activity
metal ion binding
metalloaminopeptidase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296411
Coding exons: 11
Length: 67194
Individuals with no LoFs: 124616
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 124623
p: 0.0000281

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.87	127	202	0.629	0.0000103	2504
Missense (PolyPhen)		27	70.302	0.38406		919
Synonymous	1.09	58	69.6	0.833	0.00000344	725
Loss of Function	3.20	6	22.3	0.269	0.00000123	275

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000072	0.000065	rare
Latino/Admixed American	0.000034	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000057	0.000056	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle. {ECO:0000255|HAMAP- Rule:MF_03174, ECO:0000269|PubMed:16274222, ECO:0000269|PubMed:17114291}.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.551
RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.464

Gene Damage Prediction

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