P4HA2

prolyl 4-hydroxylase subunit alpha 2, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 5:132190146-132295315

Links

ENSG00000072682 ∙ NCBI:8974 ∙ OMIM:600608 ∙ HGNC:8547 ∙ Uniprot:O15460 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopia 25, autosomal dominant (Limited), mode of inheritance: AD
• myopia 25, autosomal dominant (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopia 25, autosomal dominant	AD	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	25741866

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P4HA2 gene.

• Inborn genetic diseases (29 variants)
• not provided (18 variants)
• Myopia 25, autosomal dominant (2 variants)
• P4HA2-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P4HA2 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				6		6
missense			34	2	1	37
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region					2	2
non coding				1	1	2
Total	0	0	35	10	2

Variants in P4HA2

This is a list of pathogenic ClinVar variants found in the P4HA2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-132193032-C-T		not specified	Uncertain significance (Apr 13, 2023)
5-132193074-T-C		not specified	Uncertain significance (Dec 06, 2022)
5-132194970-C-T		not specified	Uncertain significance (Aug 08, 2023)
5-132194986-C-T		not specified	Uncertain significance (Sep 01, 2021)
5-132195404-G-T		P4HA2-related disorder	Benign/Likely benign (Feb 12, 2024)
5-132198205-C-T			Likely benign (Dec 31, 2019)
5-132198223-CCA-C		Myopia 25, autosomal dominant	Pathogenic (Dec 05, 2016)
5-132198228-C-T		not specified	Uncertain significance (Mar 21, 2023)
5-132198235-C-T		not specified	Uncertain significance (Jan 30, 2024)
5-132198263-C-G		not specified	Uncertain significance (Jun 27, 2022)
5-132198270-T-C		P4HA2-related disorder	Benign/Likely benign (Jun 06, 2019)
5-132198339-T-C		P4HA2-related disorder	Likely benign (Apr 19, 2019)
5-132198921-A-T			Uncertain significance (May 16, 2023)
5-132198937-G-A		P4HA2-related disorder	Likely benign (Feb 12, 2024)
5-132203769-T-C			Likely benign (Jul 06, 2018)
5-132203798-G-A		not specified	Uncertain significance (Jun 02, 2023)
5-132203819-C-T		not specified	Uncertain significance (May 25, 2022)
5-132203830-T-C		not specified	Uncertain significance (Mar 07, 2024)
5-132204104-C-A		not specified	Uncertain significance (Oct 12, 2022)
5-132204105-G-A			Likely benign (Jan 19, 2018)
5-132204107-C-T		not specified	Uncertain significance (Dec 26, 2023)
5-132204130-T-C		not specified	Uncertain significance (Jun 23, 2023)
5-132204137-C-T		not specified	Uncertain significance (Oct 14, 2021)
5-132207720-G-A			Likely benign (May 20, 2018)
5-132207762-G-A		P4HA2-related disorder	Likely benign (May 03, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P4HA2	protein_coding	protein_coding	ENST00000401867	14	103478

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000197	1.00	125554	0	194	125748	0.000772

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.821	272	313	0.869	0.0000182	3479
Missense in Polyphen		135	145.02	0.9309		1579
Synonymous	-0.0166	123	123	1.00	0.00000726	1045
Loss of Function	3.20	16	37.0	0.433	0.00000223	369

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00457	0.00458
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000739	0.000739
Middle Eastern	0.000272	0.000272
South Asian	0.000360	0.000359
Other	0.000815	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the post-translational formation of 4- hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
• Disease: DISEASE: Myopia 25, autosomal dominant (MYP25) [MIM:617238]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:25741866}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Amino Acid metabolism;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Arginine Proline metabolism (Consensus)

Recessive Scores

• pRec: 0.193

Intolerance Scores

• loftool: 0.956
• rvis_EVS: -1
• rvis_percentile_EVS: 8.47

Haploinsufficiency Scores

• pHI: 0.308
• hipred: Y
• hipred_score: 0.542
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: P4ha2

Gene ontology

• Biological process: peptidyl-proline hydroxylation to 4-hydroxy-L-proline;electron transport chain
• Cellular component: nucleoplasm;endoplasmic reticulum;endoplasmic reticulum lumen;cytosol;intracellular membrane-bounded organelle
• Molecular function: procollagen-proline 4-dioxygenase activity;iron ion binding;electron transfer activity;oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen;L-ascorbic acid binding