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 (69 variants)
• not provided (6 variants)
• Osteogenesis imperfecta (3 variants)
• P3H1-related disorder (2 variants)
• Lamellar ichthyosis (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.

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			3	209	2	214
missense	1	1	234	9	1	246
nonsense	29	4		1		34
start loss		2				2
frameshift	34	10	1			45
inframe indel			4			4
splice donor/acceptor (+/-2bp)	6	15				21
splice region		3	20	26		49
non coding		3	11	134	30	178
Total	70	35	253	353	33

Highest pathogenic variant AF is 0.000591

Variants in P3H1

This is a list of pathogenic ClinVar variants found in the P3H1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-42746435-G-A		Osteogenesis Imperfecta, Recessive • Osteogenesis imperfecta type 8	Uncertain significance (Jan 13, 2018)
1-42746440-C-T		Osteogenesis Imperfecta, Recessive • Osteogenesis imperfecta type 8	Benign (Apr 11, 2023)
1-42746581-G-A		Osteogenesis Imperfecta, Recessive	Uncertain significance (Apr 27, 2017)
1-42746620-G-A		Osteogenesis Imperfecta, Recessive • Osteogenesis imperfecta type 8	Conflicting classifications of pathogenicity (Jun 17, 2018)
1-42746686-CCTGGACG-C		not specified	Likely benign (Jun 06, 2016)
1-42746692-C-T		Osteogenesis imperfecta	Uncertain significance (May 01, 2019)
1-42746699-A-G		Osteogenesis imperfecta type 8	Uncertain significance (Aug 31, 2022)
1-42746700-T-C		Osteogenesis imperfecta type 8	Likely benign (Dec 09, 2023)
1-42746700-T-G		Osteogenesis imperfecta type 8	Likely benign (Apr 13, 2023)
1-42746702-G-A		Osteogenesis imperfecta type 8	Likely benign (Aug 17, 2023)
1-42746710-T-C		Osteogenesis imperfecta type 8	Likely benign (Nov 15, 2023)
1-42746713-G-GGC		Osteogenesis imperfecta type 8	Likely pathogenic (Oct 21, 2021)
1-42746718-C-T		Osteogenesis imperfecta type 8	Likely benign (Jan 31, 2024)
1-42746727-G-A		Osteogenesis imperfecta type 8	Uncertain significance (Dec 08, 2020)
1-42746730-TGA-T		Osteogenesis imperfecta type 8	Likely pathogenic (Dec 26, 2023)
1-42746730-TGAGA-T		Osteogenesis imperfecta type 8	Conflicting classifications of pathogenicity (Aug 27, 2022)
1-42746739-C-T		Osteogenesis imperfecta type 8	Likely benign (Sep 01, 2023)
1-42746744-G-A		Osteogenesis imperfecta type 8	Pathogenic (May 09, 2023)
1-42746744-G-T		Osteogenesis imperfecta type 8 • not specified	Conflicting classifications of pathogenicity (Mar 14, 2023)
1-42746753-C-T		Osteogenesis imperfecta type 8 • Osteogenesis imperfecta • Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
1-42746753-CG-C		Osteogenesis imperfecta type 8	Pathogenic (Apr 19, 2023)
1-42746753-C-CG		Osteogenesis imperfecta type 8	Pathogenic (Aug 04, 2023)
1-42746754-G-A		Osteogenesis imperfecta • Osteogenesis imperfecta type 8	Conflicting classifications of pathogenicity (Sep 21, 2023)
1-42746754-G-C		Osteogenesis imperfecta type 8	Likely benign (Apr 19, 2023)
1-42746756-G-C		Osteogenesis imperfecta type 8 • Osteogenesis Imperfecta, Recessive • P3H1-related disorder	Conflicting classifications of pathogenicity (Jan 22, 2024)

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
2.29e-20	0.00680	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

Haploinsufficiency Scores

• pHI: 0.144
• hipred: N
• hipred_score: 0.205
• ghis: 0.516

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: P3h1
• Phenotype: muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

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