P3H1

prolyl 3-hydroxylase 1, the group of Prolyl 3-hydroxylase family

Basic information

Region (hg38): 1:42746335-42767084

Previous symbols: [ "LEPRE1" ]

Links

ENSG00000117385 ∙ NCBI:64175 ∙ OMIM:610339 ∙ HGNC:19316 ∙ Uniprot:Q32P28 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• osteogenesis imperfecta type 8 (Strong), mode of inheritance: AR
• osteogenesis imperfecta type 2 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 3 (Supportive), mode of inheritance: AD
• osteogenesis imperfecta type 8 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteogenesis imperfecta, type VIII	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	Musculoskeletal	17277775; 19088120; 22281939; 22608605; 23613367

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P3H1 gene.

• Osteogenesis_imperfecta_type_8 (827 variants)
• not_provided (121 variants)
• Inborn_genetic_diseases (118 variants)
• not_specified (45 variants)
• P3H1-related_disorder (39 variants)
• Osteogenesis_Imperfecta,_Recessive (38 variants)
• Osteogenesis_imperfecta (32 variants)
• Osteogenesis_imperfecta_type_III (3 variants)
• Long_QT_syndrome_12 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P3H1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000022356.4. 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	1		7	264	4	276
missense	1	3	281	14	1	300
nonsense	27	13				40
start loss		2				2
frameshift	39	20	1			60
splice donor/acceptor (+/-2bp)	9	21	3			33
Total	77	59	292	278	5

Highest pathogenic variant AF is 0.00012637589

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P3H1	protein_coding	protein_coding	ENST00000236040	14	20750

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125619	0	129	125748	0.000513

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.755	410	455	0.900	0.0000266	5179
Missense in Polyphen		120	131.27	0.91411		1487
Synonymous	0.527	181	190	0.951	0.0000116	1616
Loss of Function	0.481	32	35.1	0.912	0.00000190	400

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00379	0.00379
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000328	0.000326
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.000328	0.000326
South Asian	0.000392	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro- Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts. {ECO:0000269|PubMed:10951563}.
• Disease: DISEASE: Osteogenesis imperfecta 8 (OI8) [MIM:610915]: A form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI8 is characterized by disproportionate short stature, severe osteoporosis, shortening of the long bones, white sclerae, a round face and a short barrel- shaped chest. {ECO:0000269|PubMed:17277775, ECO:0000269|PubMed:19088120}. Note=The disease is caused by mutations affecting the gene represented in this entry. A splice site mutation leading to the absence of isoform 1 has been reported in 2 OI8 patients. Isoform 1 is the only form predicted to be located in the endoplasmic reticulum, which the appropriate location for the catalysis of collagen hydroxylation. These patients show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120). {ECO:0000269|PubMed:19088120}.
• Pathway: Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• rvis_EVS: 0.36
• rvis_percentile_EVS: 74.68

Essentials

• essential_gene_gene_trap: N

Gene ontology

• Biological process: protein folding;negative regulation of cell population proliferation;positive regulation of neuron projection development;protein hydroxylation;peptidyl-proline hydroxylation;collagen metabolic process;regulation of protein secretion;protein stabilization;oxidation-reduction process;bone development;chaperone-mediated protein folding;negative regulation of post-translational protein modification
• Cellular component: endoplasmic reticulum;endoplasmic reticulum lumen;membrane;protein-containing complex;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: molecular_function;iron ion binding;protein binding;collagen binding;procollagen-proline 3-dioxygenase activity;L-ascorbic acid binding