P4HTM (prolyl 4-hydroxylase, transmembrane)

Gene

• Entrez ID: 54681
• Gene name: Prolyl 4-hydroxylase, transmembrane
• Gene symbol: P4HTM
• Synonyms (NCBI Gene): EGLN4, HIDEA, HIFPH4, P4H-TM, PH-4, PH4, PHD4
• Chromosome: 3
• Chromosome location: 3p21.31|3p21.3
• Summary: The product of this gene belongs to the family of prolyl 4-hydroxylases. This protein is a prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. It plays a role in adaptation to hypoxia and m

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs182812551	G>A	Pathogenic	Coding sequence variant, missense variant
rs1576601503	->C	Uncertain-significance, pathogenic	Frameshift variant, coding sequence variant
rs1576606484	A>C	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs1576608329	G>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1209249	hsa-miR-1289	CLIP-seq
MIRT1209250	hsa-miR-3198	CLIP-seq
MIRT1209251	hsa-miR-4294	CLIP-seq
MIRT1209252	hsa-miR-4309	CLIP-seq
MIRT1209253	hsa-miR-4534	CLIP-seq
MIRT1209254	hsa-miR-4731-3p	CLIP-seq
MIRT1209255	hsa-miR-4801	CLIP-seq
MIRT2060102	hsa-miR-1273	CLIP-seq
MIRT1209249	hsa-miR-1289	CLIP-seq
MIRT1209250	hsa-miR-3198	CLIP-seq
MIRT1209251	hsa-miR-4294	CLIP-seq
MIRT1209252	hsa-miR-4309	CLIP-seq
MIRT1209254	hsa-miR-4731-3p	CLIP-seq
MIRT1209255	hsa-miR-4801	CLIP-seq
MIRT2060103	hsa-miR-635	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004656	Function	Procollagen-proline 4-dioxygenase activity	IBA
GO:0005506	Function	Iron ion binding	IEA
GO:0005509	Function	Calcium ion binding	IEA
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016705	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	IEA
GO:0016706	Function	2-oxoglutarate-dependent dioxygenase activity	IDA	22955912
GO:0031418	Function	L-ascorbic acid binding	IEA
GO:0045646	Process	Regulation of erythrocyte differentiation	IBA
GO:0045646	Process	Regulation of erythrocyte differentiation	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051213	Function	Dioxygenase activity	IEA
GO:0160082	Function	Hypoxia-inducible factor-proline dioxygenase activity	IEA

Other IDs

• MIM: 614584
• HGNC: 28858
• e!Ensembl: ENSG00000178467

Protein

• UniProt ID: Q9NXG6
• Protein name: Transmembrane prolyl 4-hydroxylase (P4H-TM) (EC 1.14.11.29) (Hypoxia-inducible factor prolyl hydroxylase 4) (HIF-PH4) (HIF-prolyl hydroxylase 4) (HPH-4)
• Protein 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 H
• PDB: 6TP5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13499	EF-hand_7	190 → 252	EF-hand domain pair	Domain
  PF13640	2OG-FeII_Oxy_3	314 → 459	2OG-Fe(II) oxygenase superfamily	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed with highest levels in adult pancreas, heart, skeletal muscle, brain, placenta, kidney and adrenal gland. Expressed at lower levels in epiphyseal cartilage and in fibroblasts. {ECO:0000269|PubMed:12163023, ECO:0000269|
• Sequence:

  MAAAAVTGQRPETAAAEEASRPQWAPPDHCQAQAAAGLGDGEDAPVRPLCKPRGICSRAY
  FLVLMVFVHLYLGNVLALLLFVHYSNGDESSDPGPQHRAQGPGPEPTLGPLTRLEGIKVG
  HERKVQLVTDRDHFIRTLSLKPLLFEIPGFLTDEECRLIIHLAQMKGLQRSQILPTEEYE
  EAMSTMQVSQLDLFRLLDQNRDGHLQLREVLAQTRLGNGWWMTPESIQEMYAAIKADPDG
  DGVLSLQEFSNMDLRDFHKYMRSHKAESSELVRNSHHTWLYQGEGAHHIMRAIRQRVLRL
  TRLSPEIVELSEPLQVVRYGEGGHYHAHVDSGPVYPETICSHTKLVANESVPFETSCRYM
  TVLFYLNNVTGGGETVFPVADNRTYDEMSLIQDDVDLRDTRRHCDKGNLRVKPQQGTAVF
  WYNYLPDGQGWVGDVDDYSLHGGCLVTRGTKWIANNWINVDPSRARQALFQQEMARLARE
  GGTDSQPEWALDRAYRDARVEL

• Sequence length: 502

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities	Likely pathogenic; Pathogenic	rs2471545464, rs758831068, rs182812551, rs1576610000	RCV003326725 RCV003337750 RCV000787322 RCV000787325	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Likely pathogenic	rs757914897	RCV001261381	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
P4HTM-related disorder	Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEVERE INTELLECTUAL DISABILITY, HYPOTONIA, STRABISMUS, COARSE FACE, PLANOVALGUS SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Age related macular degeneration	Age-related macular degeneration	BEFREE	27466183		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	31029587		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	31029587		★☆☆☆☆ Found in Text Mining only
Astigmatism	Astigmatism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Attention deficit hyperactivity disorder	Attention Deficit Hyperactivity Disorder	BEFREE	28693702		★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	29672740		★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysautonomia	Dysautonomia	GENOMICS_ENGLAND_DG	25078763		★☆☆☆☆ Found in Text Mining only
Exotropia	Exotropia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eye Abnormalities	Eye abnormalities	Pubtator	30940925, 34285383	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver, Alcoholic	Alcoholic Fatty Liver	BEFREE	30802717		★☆☆☆☆ Found in Text Mining only
Flexion contracture - elbow	Elbow flexion contracture	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	25078763, 30940925		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperopia	Hyperopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	17726031	Stimulate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	25078763, 30940925		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Intellectual developmental disorder	Pubtator	30940925, 33298456, 34285383	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Kidney Diseases	Kidney disease	Pubtator	24475278	Inhibit	★☆☆☆☆ Found in Text Mining only
Linear atrophy	Atrophy	BEFREE	31029587		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	20527723		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	34285383	Associate	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	24048703		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	17726031	Associate	★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	BEFREE	28685750		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	24048703		★☆☆☆☆ Found in Text Mining only
Pendular Nystagmus	Pendular nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary Dysautonomias	Dysautonomia	Pubtator	30940925, 34285383	Associate	★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma	Rhabdomyosarcoma	BEFREE	22419069		★☆☆☆☆ Found in Text Mining only
Rhabdomyosarcoma	Rhabdomyosarcoma	Pubtator	22419069	Associate	★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Apnea Syndromes	Sleep Apnea	GENOMICS_ENGLAND_DG	25078763		★☆☆☆☆ Found in Text Mining only
Sleep Apnea Syndromes	Sleep Apnea	HPO_DG			★☆☆☆☆ Found in Text Mining only