PITRM1

pitrilysin metallopeptidase 1, the group of M16 metallopeptidases

Basic information

Region (hg38): 10:3137728-3172841

Links

ENSG00000107959 ∙ NCBI:10531 ∙ OMIM:618211 ∙ HGNC:17663 ∙ Uniprot:Q5JRX3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spinocerebellar ataxia, autosomal recessive 30 (Limited), mode of inheritance: AR
• spinocerebellar ataxia, autosomal recessive 30 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 30	AR	General	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	Neurologic	26697887; 29764912; 33835239

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PITRM1 gene.

• not_provided (207 variants)
• not_specified (199 variants)
• PITRM1-related_disorder (21 variants)
• Spinocerebellar_ataxia,_autosomal_recessive_30 (6 variants)
• Irido-corneo-trabecular_dysgenesis (2 variants)
• Cerebellar_ataxia (1 variants)
• Infantile_onset_spinocerebellar_ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PITRM1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014889.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	62	7	71
missense	2		199	32	10	243
nonsense			2	1		3
start loss						0
frameshift	1	1	2	1		5
splice donor/acceptor (+/-2bp)						0
Total	3	1	205	96	17

Highest pathogenic variant AF is 0.000043995213

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PITRM1	protein_coding	protein_coding	ENST00000380989	27	35084

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.93e-21	0.456	124464	0	184	124648	0.000738

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.837	653	596	1.10	0.0000349	6808
Missense in Polyphen		199	202.42	0.98308		2350
Synonymous	-2.68	302	248	1.22	0.0000172	1926
Loss of Function	1.93	40	55.5	0.721	0.00000272	657

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00257	0.00256
Ashkenazi Jewish	0.000103	0.0000994
East Asian	0.000895	0.000890
Finnish	0.000331	0.000325
European (Non-Finnish)	0.000833	0.000823
Middle Eastern	0.000895	0.000890
South Asian	0.000726	0.000719
Other	0.000330	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing (PubMed:10360838, PubMed:16849325, PubMed:19196155, PubMed:24931469). Has an ATP-independent activity (PubMed:16849325). Specifically cleaves peptides in the range of 5 to 65 residues (PubMed:19196155). Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference (PubMed:10360838, PubMed:19196155, PubMed:24931469). Degrades the transit peptides of mitochondrial proteins after their cleavage (PubMed:19196155). Also degrades other unstructured peptides (PubMed:19196155). It is also able to degrade amyloid-beta protein 40, one of the peptides produced by APP processing, when it accumulates in mitochondrion (PubMed:16849325, PubMed:24931469). It is a highly efficient protease, at least toward amyloid-beta protein 40 (PubMed:24931469). Cleaves that peptide at a specific position and is probably not processive, releasing digested peptides intermediates that can be further cleaved subsequently (PubMed:24931469). {ECO:0000269|PubMed:10360838, ECO:0000269|PubMed:16849325, ECO:0000269|PubMed:19196155, ECO:0000269|PubMed:24931469}.

Recessive Scores

• pRec: 0.173

Intolerance Scores

• loftool: 0.982
• rvis_EVS: 3.22
• rvis_percentile_EVS: 99.36

Haploinsufficiency Scores

• pHI: 0.0999
• hipred: N
• hipred_score: 0.282
• ghis: 0.409

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.655

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pitrm1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: proteolysis;protein targeting to mitochondrion;protein processing;positive regulation of catalytic activity
• Cellular component: mitochondrion;mitochondrial matrix
• Molecular function: metalloendopeptidase activity;enzyme activator activity;metallopeptidase activity;zinc ion binding