PHEX

phosphate regulating endopeptidase X-linked, the group of M13 metallopeptidases

Basic information

Region (hg38): X:22032325-22494713

Previous symbols: [ "HYP", "HPDR" ]

Links

ENSG00000102174 ∙ NCBI:5251 ∙ OMIM:300550 ∙ HGNC:8918 ∙ Uniprot:P78562 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked dominant hypophosphatemic rickets (Definitive), mode of inheritance: XL
• X-linked dominant hypophosphatemic rickets (Strong), mode of inheritance: XL
• X-linked dominant hypophosphatemic rickets (Supportive), mode of inheritance: XL
• X-linked dominant hypophosphatemic rickets (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypophosphatemic rickets, X-linked dominant	XL	Cardiovascular; Renal	Frequent oral administration of phosphate and high-dose calcitriol can be beneficial for bowing of long bones during growth and for pain; Diagnosis can help avoid therapies that may result in adverse sequelae; Due to reported cardiovascular manifestations (eg, hypertension, left ventricular hypertrophy), surveillance may allow early diagnosis and management	Cardiovascular; Dental; Musculoskeletal; Neurologic; Renal	4305189; 4333173; 188828; 2984933; 3839245; 2571821; 1660099; 1660098; 1414477; 1464657; 7550339; 9106524; 9253316; 9768646; 10874297; 12915641; 14769584; 16055933; 18252791; 21050253; 21524226; 22319799

ClinVar

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

• not_provided (1069 variants)
• Familial_X-linked_hypophosphatemic_vitamin_D_refractory_rickets (421 variants)
• not_specified (48 variants)
• Inborn_genetic_diseases (44 variants)
• PHEX-related_disorder (27 variants)
• Hypophosphatemic_rickets (26 variants)
• Hypophosphataemia_or_rickets (4 variants)
• See_cases (4 variants)
• Autosomal_dominant_hypophosphatemic_rickets (1 variants)
• Intellectual_disability (1 variants)
• Vitamin_D-dependent_rickets,_type_2 (1 variants)
• Lower_limb_pain (1 variants)
• Hypophosphatemia (1 variants)
• Bowing_of_the_legs (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHEX gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000444.6. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	3	27	54	21	106
missense	74	91	245	39	10	459
nonsense	153	12	10			175
start loss	5					5
frameshift	302	36	2			340
splice donor/acceptor (+/-2bp)	134	38	16	1		189
Total	669	180	300	94	31

Highest pathogenic variant AF is 0.00008277783

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHEX	protein_coding	protein_coding	ENST00000379374	22	218869

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125711	3	3	125717	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	211	293	0.719	0.0000229	4974
Missense in Polyphen		76	131.25	0.57906		2183
Synonymous	-0.309	110	106	1.04	0.00000846	1341
Loss of Function	5.18	1	33.2	0.0301	0.00000245	561

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000724	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000368	0.0000264
Middle Eastern	0.0000724	0.0000544
South Asian	0.000105	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably involved in bone and dentin mineralization and renal phosphate reabsorption.

Recessive Scores

• pRec: 0.616

Intolerance Scores

• loftool: 0.0626
• rvis_EVS: -1.13
• rvis_percentile_EVS: 6.43

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0861

Gene Damage Prediction

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

Gene ontology

• Biological process: skeletal system development;cellular protein modification process;proteolysis;cell-cell signaling;organophosphate metabolic process;bone mineralization;lung development;bone development;response to growth hormone;cellular response to vitamin D;cellular response to parathyroid hormone stimulus;response to sodium phosphate;response to insulin-like growth factor stimulus
• Cellular component: endoplasmic reticulum;Golgi apparatus;plasma membrane;integral component of plasma membrane;perinuclear region of cytoplasm
• Molecular function: aminopeptidase activity;metalloendopeptidase activity;zinc ion binding