P4HTM

prolyl 4-hydroxylase, transmembrane

Basic information

Region (hg38): 3:48989889-49007153

Links

ENSG00000178467

∙ NCBI:54681 ∙ OMIM:614584 ∙ HGNC:28858 ∙ Uniprot:Q9NXG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (Moderate), mode of inheritance: AR
hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (Definitive), mode of inheritance: AR
hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities	AR	Pulmonary	Individuals have been described with respiratory difficulties, including bradypnea, hypoventilation, recurrent pneunomia, and sleep apnea (often requiring nighttime BiPAP), and awareness may allow early management of pulmonary issues	Craniofacial; Neurologic; Ophthalmologic; Pulmonary	25078763; 30940925

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P4HTM gene.

Inborn_genetic_diseases (67 variants)
not_provided (26 variants)
Hypotonia,_hypoventilation,_impaired_intellectual_development,_dysautonomia,_epilepsy,_and_eye_abnormalities (12 variants)
P4HTM-related_disorder (3 variants)
Intellectual_disability (3 variants)
Poirier-Bienvenu_neurodevelopmental_syndrome (1 variants)
not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P4HTM gene is commonly pathogenic or not. These statistics are base on transcript: NM_000177939.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar		7
missense	1 clinvar	3 clinvar	67 clinvar	3 clinvar		74
nonsense	3 clinvar					3
start loss						0
frameshift	1 clinvar	2 clinvar	2 clinvar			5
splice donor/acceptor (+/-2bp)						0
Total	5	5	69	10	0

Highest pathogenic variant AF is 0.00003717435

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P4HTM	protein_coding	protein_coding	ENST00000343546	9	17269

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.92e-9	0.795	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	253	332	0.762	0.0000188	3632
Missense in Polyphen		88	135.43	0.64979		1482
Synonymous	0.233	134	137	0.975	0.00000763	1165
Loss of Function	1.54	17	25.4	0.670	0.00000117	263

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000423	0.000421
Ashkenazi Jewish	0.00	0.00
East Asian	0.000171	0.000163
Finnish	0.0000935	0.0000924
European (Non-Finnish)	0.000101	0.0000967
Middle Eastern	0.000171	0.000163
South Asian	0.000265	0.000261
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the post-translational formation of 4- hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. {ECO:0000269|PubMed:17726031}.;

Recessive Scores

pRec: 0.153

Intolerance Scores

loftool: 0.215
rvis_EVS: -0.09
rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

pHI
hipred: Y
hipred_score: 0.563
ghis: 0.545

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.644

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: P4htm
Phenotype: homeostasis/metabolism phenotype; hematopoietic system phenotype; vision/eye phenotype; renal/urinary system phenotype;

Zebrafish Information Network

Gene name: p4htm
Affected structure: lens capsule
Phenotype tag: abnormal
Phenotype quality: broken

Gene ontology

Biological process: peptidyl-proline hydroxylation to 4-hydroxy-L-proline;regulation of erythrocyte differentiation;oxidation-reduction process
Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
Molecular function: procollagen-proline 4-dioxygenase activity;iron ion binding;calcium ion binding;2-oxoglutarate-dependent dioxygenase activity;L-ascorbic acid binding