P3H2

prolyl 3-hydroxylase 2, the group of Prolyl 3-hydroxylase family

Basic information

Region (hg38): 3:189956727-190122437

Previous symbols: [ "LEPREL1" ]

Links

ENSG00000090530 ∙ NCBI:55214 ∙ OMIM:610341 ∙ HGNC:19317 ∙ Uniprot:Q8IVL5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopia, high, with cataract and vitreoretinal degeneration (Strong), mode of inheritance: AR
• myopia, high, with cataract and vitreoretinal degeneration (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia, high, with cataract and vitreoretinal degeneration	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	Ophthalmologic	21885030; 24172257; 25469533

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P3H2 gene.

• not provided (625 variants)
• Inborn genetic diseases (37 variants)
• Myopia, high, with cataract and vitreoretinal degeneration (13 variants)
• P3H2-related condition (3 variants)
• not specified (1 variants)
• Retinitis pigmentosa (1 variants)
• Rare isolated myopia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P3H2 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	104	9	114
missense			253	4	6	263
nonsense	14	3	2			19
start loss			1			1
frameshift	14	1	1			16
inframe indel			19			19
splice donor/acceptor (+/-2bp)	1	6	1			8
splice region			15	18	5	38
non coding			5	86	63	154
Total	29	10	283	194	78

Highest pathogenic variant AF is 0.0000658

Variants in P3H2

This is a list of pathogenic ClinVar variants found in the P3H2 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-189957700-AAGAG-A			Benign (Sep 13, 2019)
3-189957700-A-AAG			Benign (Aug 26, 2019)
3-189957700-A-AAGAG			Benign (Nov 06, 2019)
3-189957700-A-AAGAGAG			Likely benign (Aug 24, 2019)
3-189957700-A-AAGAGAGAG			Benign (Aug 31, 2019)
3-189957700-A-AAGAGAGAGAG			Likely benign (Feb 06, 2020)
3-189957778-C-T			Likely benign (Jan 16, 2019)
3-189957926-T-C		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
3-189957933-G-A			Likely benign (Oct 03, 2022)
3-189957972-A-C			Uncertain significance (Dec 15, 2021)
3-189957985-TC-AA			Uncertain significance (Jan 14, 2022)
3-189957995-G-A			Uncertain significance (Jul 28, 2019)
3-189958000-C-T			Uncertain significance (Oct 13, 2022)
3-189958001-G-A		P3H2-related disorder	Uncertain significance (Sep 15, 2023)
3-189958007-G-C			Uncertain significance (Sep 07, 2022)
3-189958017-CA-C			Likely benign (Jun 20, 2022)
3-189963671-C-T			Benign (Feb 14, 2019)
3-189963695-C-T			Benign (Jun 28, 2018)
3-189963769-C-G			Benign (Jun 28, 2018)
3-189963938-T-C			Likely benign (Jul 17, 2023)
3-189963942-C-A			Likely benign (Aug 10, 2023)
3-189963942-C-T			Benign (Jan 22, 2024)
3-189963943-G-A			Likely benign (Oct 17, 2022)
3-189963947-G-A			Likely benign (Aug 22, 2022)
3-189963949-GA-G			Likely benign (Oct 21, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P3H2	protein_coding	protein_coding	ENST00000319332	15	165710

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.79e-21	0.0133	125606	0	142	125748	0.000565

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.235	389	376	1.03	0.0000201	4529
Missense in Polyphen		110	98.896	1.1123		1182
Synonymous	-0.643	155	145	1.07	0.00000792	1383
Loss of Function	0.771	34	39.2	0.867	0.00000227	451

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000844	0.000840
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000324	0.000323
European (Non-Finnish)	0.000827	0.000827
Middle Eastern	0.000163	0.000163
South Asian	0.000461	0.000457
Other	0.000652	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Prolyl 3-hydroxylase that catalyzes the post- translational formation of 3-hydroxyproline on collagens (PubMed:18487197). Contributes to proline 3-hydroxylation of collagen COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens capsule (By similarity). Has high activity with the type IV collagen COL4A1, and lower activity with COL1A1 (PubMed:18487197). Catalyzes hydroxylation of the first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline (PubMed:18487197). Has no activity on substrates that lack 4- hydroxyproline in the third position (PubMed:18487197). {ECO:0000250|UniProtKB:Q8CG71, ECO:0000269|PubMed:18487197}.
• Pathway: Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.8

Haploinsufficiency Scores

• pHI: 0.142
• hipred: N
• hipred_score: 0.394
• ghis: 0.501

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: P3h2
• Phenotype: 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); vision/eye phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: negative regulation of cell population proliferation;peptidyl-proline hydroxylation;collagen metabolic process;oxidation-reduction process
• Cellular component: basement membrane;endoplasmic reticulum;endoplasmic reticulum lumen;Golgi apparatus;sarcoplasmic reticulum
• Molecular function: iron ion binding;procollagen-proline 3-dioxygenase activity;L-ascorbic acid binding