P4HA1

prolyl 4-hydroxylase subunit alpha 1

Basic information

Region (hg38): 10:73007217-73096974

Previous symbols: [ "P4HA" ]

Links

ENSG00000122884 ∙ NCBI:5033 ∙ OMIM:176710 ∙ HGNC:8546 ∙ Uniprot:P13674 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P4HA1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P4HA1 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				7	1	8
missense			21	1	1	23
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	1	21	8	2

Variants in P4HA1

This is a list of pathogenic ClinVar variants found in the P4HA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-73009811-T-C		P4HA1-related disorder	Likely benign (Dec 20, 2023)
10-73009826-C-T		P4HA1-related disorder	Likely benign (Sep 18, 2024)
10-73014217-G-A			Benign (Dec 31, 2019)
10-73016844-A-C			Uncertain significance (Jan 28, 2019)
10-73016876-T-C		P4HA1-related disorder	Likely benign (Oct 24, 2022)
10-73030342-C-G		not specified	Uncertain significance (Oct 04, 2022)
10-73030353-T-C		not specified	Uncertain significance (Dec 17, 2023)
10-73043919-T-C		P4HA1-related disorder	Likely benign (Oct 28, 2019)
10-73043951-G-A		Congenital disorder of connective tissue	Likely pathogenic (-)
10-73045005-G-A		P4HA1-related disorder	Likely benign (Jul 27, 2023)
10-73045046-C-CCT			Uncertain significance (Jan 29, 2019)
10-73046949-G-A		P4HA1-related disorder	Likely benign (Feb 18, 2019)
10-73047002-T-G		not specified	Uncertain significance (Sep 29, 2023)
10-73047038-T-G		not specified	Uncertain significance (Nov 03, 2022)
10-73047065-G-A		P4HA1-related disorder	Benign (May 01, 2019)
10-73047074-A-G		not specified	Uncertain significance (May 18, 2022)
10-73051085-C-T		not specified	Uncertain significance (Apr 25, 2022)
10-73051130-T-C		not specified	Uncertain significance (Jun 06, 2023)
10-73051172-A-T		not specified	Uncertain significance (Jan 17, 2024)
10-73051230-A-C		P4HA1-related disorder	Likely benign (Mar 22, 2019)
10-73051247-G-T		P4HA1-related disorder • not specified	Uncertain significance (Sep 12, 2023)
10-73053386-T-C		P4HA1-related disorder	Uncertain significance (Feb 12, 2024)
10-73053419-C-T		not specified	Uncertain significance (May 27, 2022)
10-73053430-T-C		P4HA1-related disorder	Benign (Oct 28, 2019)
10-73053491-T-A		not specified	Uncertain significance (Jan 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P4HA1	protein_coding	protein_coding	ENST00000412021	14	89758

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.932	0.0683	125723	0	20	125743	0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.01	195	292	0.668	0.0000154	3500
Missense in Polyphen		52	125.02	0.41592		1494
Synonymous	0.407	96	101	0.949	0.00000513	994
Loss of Function	4.29	5	30.6	0.163	0.00000138	385

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000217	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000884	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the post-translational formation of 4- hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
• Pathway: Arginine and proline metabolism - Homo sapiens (human);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: 0.345

Intolerance Scores

• loftool: 0.745
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.329
• hipred: Y
• hipred_score: 0.613
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.988

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: P4ha1
• Phenotype: cellular phenotype; 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); 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); growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype; embryo phenotype

Gene ontology

• Biological process: peptidyl-proline hydroxylation to 4-hydroxy-L-proline;collagen fibril organization;oxidation-reduction process
• Cellular component: mitochondrion;endoplasmic reticulum;endoplasmic reticulum lumen;membrane;procollagen-proline 4-dioxygenase complex;intracellular membrane-bounded organelle
• Molecular function: procollagen-proline 4-dioxygenase activity;iron ion binding;protein binding;oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen;L-ascorbic acid binding;identical protein binding