METAP1D

protein-coding

methionyl aminopeptidase type 1D, mitochondrial, the group of Aminopeptidases

Gene summary

The N-terminal methionine excision pathway is an essential process in which the N-terminal methionine is removed from many proteins, thus facilitating subsequent protein modification. In mitochondria, enzymes that catalyze this reaction are celled methionine aminopeptidases (MetAps, or MAPs; EC 3.4.11.18) (Serero et al., 2003 [PubMed 14532271]).[supplied by OMIM, Mar 2008]

MANE transcript

NM_199227.3

Inheritance

—

ClinVar variants

U:65B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr2:171,999,943-172,082,430

External References & Databases

Ensembl (ENSG00000172878)

Transcript & Mutation Effects

hg38 • Region Span ~82.5 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 METAP1D variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_199227.3. 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			63 clinvar	1 clinvar		64
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	65	1	0	66

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_199227.3	RefSeq	NP_954697.1	10	MANE Select
ENST00000315796.5	Ensembl	ENSP00000315152.4	10	MANE Select
NM_001322278.2	RefSeq	NP_001309207.1	7	Standard
NM_001322279.2	RefSeq	NP_001309208.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
peptidyl-methionine modification
N-terminal protein amino acid modification
protein initiator methionine removal

Molecular Function

aminopeptidase activity
metalloexopeptidase activity
metal ion binding
metalloaminopeptidase activity

Cellular Component

mitochondrion
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315796
Coding exons: 10
Length: 82669
Individuals with no LoFs: 125565
Homozygous LoFs: 0
Heterozygous LoFs: 183
Defined: 125748
p: 0.000728

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.637	160	184	0.868	0.00000953	2198
Missense (PolyPhen)		59	70.135	0.84124		815
Synonymous	0.885	58	67.2	0.863	0.00000393	643
Loss of Function	1.23	11	16.4	0.671	7.51e-7	211

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00088	0.00087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00088	0.00088	rare
South Asian	0.00037	0.00036	rare
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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). Requires deformylation of the N(alpha)-formylated initiator methionine before it can be hydrolyzed (By similarity). May play a role in colon tumorigenesis. {ECO:0000255|HAMAP-Rule:MF_03174, ECO:0000269|PubMed:16568094}.;

Intolerance Scores

RVIS EVS: -0.09
RVIS percentile EVS: 46.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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