MIPEP

mitochondrial intermediate peptidase, the group of M3 metallopeptidase family

Basic information

Region (hg38): 13:23730189-23889400

Links

ENSG00000027001 ∙ NCBI:4285 ∙ OMIM:602241 ∙ HGNC:7104 ∙ Uniprot:Q99797 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (Strong), mode of inheritance: AR
• lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (Supportive), mode of inheritance: AR
• mitochondrial disease (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 31	AR	Cardiovascular	The condition can include hypertrophic cardiomyopathy, and awareness may allow early diagnosis and interventions	Biochemical; Cardiovascular; Craniofacial; Neurologic; Ophthalmologic	27799064

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MIPEP gene.

• Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (3 variants)
• not provided (2 variants)
• Cardiomyopathy;Left ventricular noncompaction;Infantile muscular hypotonia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MIPEP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	29	4	34
missense		3	81	8	8	100
nonsense	1	2				3
start loss						0
frameshift	1		2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	3				4
splice region			3	11	2	16
non coding				14	27	41
Total	3	8	85	51	39

Highest pathogenic variant AF is 0.0000197

Variants in MIPEP

This is a list of pathogenic ClinVar variants found in the MIPEP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-23730353-C-T		Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	Uncertain significance (Feb 01, 2019)
13-23730375-G-C			Uncertain significance (Jul 05, 2022)
13-23730388-A-G		Inborn genetic diseases	Uncertain significance (May 24, 2024)
13-23730398-C-T		Inborn genetic diseases • Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	Conflicting classifications of pathogenicity (Sep 20, 2024)
13-23730402-G-A			Likely benign (Jul 19, 2018)
13-23730410-C-T		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
13-23730445-C-T		Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome • not specified	Uncertain significance (May 02, 2024)
13-23756519-ATGGTGCCATTT-A			Likely benign (Jul 29, 2022)
13-23756598-C-T		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
13-23756604-C-T			Likely benign (Jan 20, 2024)
13-23756605-G-A		Microcephaly • Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
13-23756612-G-A			Benign/Likely benign (Jul 01, 2024)
13-23756614-C-A		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
13-23760076-T-G		Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	Benign (Jan 30, 2024)
13-23760088-C-A			Uncertain significance (Aug 20, 2022)
13-23760093-T-C			Uncertain significance (Dec 21, 2023)
13-23760094-A-T		Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	Pathogenic (May 12, 2023)
13-23760108-T-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
13-23760136-T-C			Uncertain significance (May 01, 2024)
13-23760142-C-T		Inborn genetic diseases	Benign/Likely benign (Jan 01, 2024)
13-23760143-G-C		MIPEP-related disorder	Likely benign (Apr 29, 2020)
13-23760185-C-T			Benign/Likely benign (Mar 01, 2024)
13-23760186-C-T		Inborn genetic diseases	Uncertain significance (Dec 18, 2023)
13-23760204-C-T			Uncertain significance (Oct 17, 2023)
13-23760212-C-T		Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	Likely pathogenic (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MIPEP	protein_coding	protein_coding	ENST00000382172	19	159231

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.59e-15	0.304	125622	0	126	125748	0.000501

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.222	366	378	0.968	0.0000205	4633
Missense in Polyphen		120	126.19	0.95094		1382
Synonymous	0.300	128	132	0.967	0.00000718	1350
Loss of Function	1.38	28	37.1	0.755	0.00000197	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000482	0.000478
Ashkenazi Jewish	0.000119	0.0000992
East Asian	0.000335	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000657	0.000651
Middle Eastern	0.000335	0.000326
South Asian	0.000776	0.000719
Other	0.00114	0.00114

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaves proteins, imported into the mitochondrion, to their mature size.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 31 (COXPD31) [MIM:617228]: An autosomal recessive, severe mitochondrial disease with multisystemic manifestations appearing soon after birth or in early infancy. Clinical features include left ventricular non-compaction, global developmental delay, severe hypotonia, seizures, cataract, and abnormal movements. Death may occur in early childhood. {ECO:0000269|PubMed:27799064}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.121

Intolerance Scores

• loftool: 0.961
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.53

Haploinsufficiency Scores

• pHI: 0.146
• hipred: N
• hipred_score: 0.426
• ghis: 0.479

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.552

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mipep

Gene ontology

• Biological process: proteolysis;peptide metabolic process;protein processing involved in protein targeting to mitochondrion
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: metalloendopeptidase activity;metal ion binding