PRORP (protein only RNase P catalytic subunit)

Gene

• Entrez ID: 9692
• Gene name: Protein only RNase P catalytic subunit
• Gene symbol: PRORP
• Synonyms (NCBI Gene): COXPD54, KIAA0391, MRPP3
• Chromosome: 14
• Chromosome location: 14q13.2

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs764714439	->A	Likely-pathogenic	Frameshift variant, coding sequence variant
rs777185638	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1169927428	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001682	Process	TRNA 5'-leader removal	IBA
GO:0004518	Function	Nuclease activity	IEA
GO:0004526	Function	Ribonuclease P activity	IBA
GO:0004526	Function	Ribonuclease P activity	IDA	25953853
GO:0004526	Function	Ribonuclease P activity	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	29880640
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0008033	Process	TRNA processing	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0030678	Component	Mitochondrial ribonuclease P complex	IBA
GO:0030678	Component	Mitochondrial ribonuclease P complex	IDA	25953853
GO:0030678	Component	Mitochondrial ribonuclease P complex	IPI	29880640
GO:0030678	Component	Mitochondrial ribonuclease P complex	TAS	23042678
GO:0042645	Component	Mitochondrial nucleoid	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0097745	Process	Mitochondrial tRNA 5'-end processing	IBA
GO:0097745	Process	Mitochondrial tRNA 5'-end processing	IDA	25953853, 29880640

Other IDs

• MIM: 609947
• HGNC: 19958
• e!Ensembl: ENSG00000100890

Protein

• UniProt ID: O15091
• Protein name: Mitochondrial ribonuclease P catalytic subunit (EC 3.1.26.5) (Mitochondrial ribonuclease P protein 3) (Mitochondrial RNase P protein 3) (Protein only RNase P catalytic subunit)
• Protein function: Catalytic ribonuclease component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3, which cleaves tRNA molecules in their 5'-ends (PubMed:18984158, PubMed:25953853, PubMed:34715011). The presenc
• PDB: 4ROU, 4XGL, 4XGM, 7ONU, 8CBK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF16953	PRORP	342 → 578	Protein-only RNase P	Domain

• Sequence:

  MTFYLFGIRSFPKLWKSPYLGLGPGHSYVSLFLADRCGIRNQQRLFSLKTMSPQNTKATN
  LIAKARYLRKDEGSNKQVYSVPHFFLAGAAKERSQMNSQTEDHALAPVRNTIQLPTQPLN
  SEEWDKLKEDLKENTGKTSFESWIISQMAGCHSSIDVAKSLLAWVAAKNNGIVSYDLLVK
  YLYLCVFHMQTSEVIDVFEIMKARYKTLEPRGYSLLIRGLIHSDRWREALLLLEDIKKVI
  TPSKKNYNDCIQGALLHQDVNTAWNLYQELLGHDIVPMLETLKAFFDFGKDIKDDNYSNK
  LLDILSYLRNNQLYPGESFAHSIKTWFESVPGKQWKGQFTTVRKSGQCSGCGKTIESIQL
  SPEEYECLKGKIMRDVIDGGDQYRKTTPQELKRFENFIKSRPPFDVVIDGLNVAKMFPKV
  RESQLLLNVVSQLAKRNLRLLVLGRKHMLRRSSQWSRDEMEEVQKQASCFFADDISEDDP
  FLLYATLHSGNHCRFITRDLMRDHKACLPDAKTQRLFFKWQQGHQLAIVNRFPGSKLTFQ
  RILSYDTVVQTTGDSWHIPYDEDLVERCSCEVPTKWLCLHQKT

• Sequence length: 583

Pathways

Reactome:

tRNA processing in the mitochondrion
tRNA modification in the mitochondrion
rRNA processing in the mitochondrion

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Childhood onset sensorineural hearing impairment	Likely pathogenic; Pathogenic	rs764714439, rs777185638	RCV001873232 RCV001869241	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Combined oxidative phosphorylation deficiency 54	Likely pathogenic; Pathogenic	rs759407337, rs764714439, rs777185638, rs1169927428	RCV002510554 RCV001824884 RCV001824883 RCV001824882	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lactic acidosis	Likely pathogenic; Pathogenic	rs764714439, rs777185638	RCV001873232 RCV001869241	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukoencephalopathy	Likely pathogenic; Pathogenic	rs764714439, rs777185638	RCV001873232 RCV001869241	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Perrault syndrome 1	Likely pathogenic; Pathogenic	rs1169927428	RCV000855453	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ATOPIC ECZEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILIARY LIVER CIRRHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CROHN'S DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GLOBAL DEVELOPMENTAL DELAY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INFLAMMATORY BOWEL DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME TYPE 1	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERRAULT SYNDROME TYPE 2	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY BILIARY CIRRHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRORP-related disorder	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
XX GONADAL DYSGENESIS-DEAFNESS SYNDROME-PROGRESSIVE NEUROLOGICAL MANIFESTATIONS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Arthritis Psoriatic	Psoriatic arthritis	Pubtator	20953189	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	GWASCAT_DG	26031901		★☆☆☆☆ Found in Text Mining only
Combined Oxidative Phosphorylation Deficiency 1	Combined oxidative phosphorylation deficiency	Pubtator	37558808	Associate	★☆☆☆☆ Found in Text Mining only
Combined Oxidative Phosphorylation Deficiency 3	Combined oxidative phosphorylation deficiency	Pubtator	37558808	Associate	★☆☆☆☆ Found in Text Mining only
Combined Oxidative Phosphorylation Deficiency 4	Combined oxidative phosphorylation deficiency	Pubtator	37558808	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	19624571		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	19624571		★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	19624571		★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	34715011	Associate	★☆☆☆☆ Found in Text Mining only
Juvenile arthritis	Arthritis	BEFREE	20136554		★☆☆☆☆ Found in Text Mining only
Leukodystrophy Metachromatic	Metachromatic leukodystrophy	Pubtator	37558808	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	34715011	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Infarction	Myocardial Infarction	BEFREE	19624571		★☆☆☆☆ Found in Text Mining only
Polyarthritis	Polyarthritis	BEFREE	20136554		★☆☆☆☆ Found in Text Mining only
Psoriasis	Psoriasis	GWASCAT_DG	20953189, 25574825		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Psoriasis	Psoriasis	GWASDB_DG	20953189		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Psoriasis	Psoriasis	Pubtator	20953189, 32221480	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Rheumatoid Arthritis	Rheumatoid arthritis	GWASCAT_DG	30166627		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	26198764		★★☆☆☆ Found in Text Mining + Unknown/Other Associations