IMMP2L

protein-coding

inner mitochondrial membrane peptidase subunit 2

Gene summary

This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

Previous symbols:

IMMP2L-IT1

MANE transcript

NM_032549.4

Inheritance

ClinVar variants

U:25B:5

Top phenotype

IMMP2L-related disorder

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr7:110,662,644-111,562,517

External References & Databases

Ensembl (ENSG00000184903)

Transcript & Mutation Effects

hg38 • Region Span ~899.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autismLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005260

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IMMP2L variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 113

not providedTotal: 8

IMMP2L-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032549.4. 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			25 clinvar	2 clinvar	1 clinvar	28
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	25	2	3	30

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032549.4	RefSeq	NP_115938.1	5	MANE Select
ENST00000405709.7	Ensembl	ENSP00000384966.2	5	MANE Select
NM_001244606.2	RefSeq	NP_001231535.1	5	Standard
NM_001350959.2	RefSeq	NP_001337888.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein export - Homo sapiens (human)

Biological Process

ovarian follicle development
signal peptide processing
protein processing involved in protein targeting to mitochondrion
superoxide metabolic process
cellular response to DNA damage stimulus

Molecular Function

peptidase activity
serine-type peptidase activity

Cellular Component

integral component of membrane
mitochondrial inner membrane peptidase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000405709
Coding exons: 5
Length: 899464
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125745
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.173	96	101	0.951	0.00000558	1130
Missense (PolyPhen)		35	36.59	0.95655		407
Synonymous	-0.380	36	33.2	1.08	0.00000156	339
Loss of Function	1.21	4	7.60	0.526	3.20e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO. {ECO:0000269|PubMed:15814844}.;

Recessive Scores

pRec: 0.142

Intolerance Scores

LoFtool: 0.284
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.173

Gene Damage Prediction

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