NAXE (NAD(P)HX epimerase)

Gene

• Entrez ID: 128240
• Gene name: NAD(P)HX epimerase
• Gene symbol: NAXE
• Synonyms (NCBI Gene): AIBP, APOA1BP, PEBEL, YJEFN1
• Chromosome: 1
• Chromosome location: 1q22
• Summary: The product of this gene interacts with apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoproteins (HDLs). It is secreted into some bodily fluids, and its synthesis and secretion are stimulated in vitro by incubating cells with apo

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs139093330	G>A	Pathogenic	Splice donor variant
rs371872027	C>A,T	Pathogenic	Coding sequence variant, synonymous variant, stop gained
rs759251812	C>T	Pathogenic	Coding sequence variant, stop gained
rs879255647	C>A	Pathogenic	Missense variant, coding sequence variant
rs886041064	A>T	Pathogenic	Coding sequence variant, missense variant
rs1064796609	CCAGTGTCAGA>ATCCCTTTCCTTGGGG	Pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0002040	Process	Sprouting angiogenesis	IMP	23719382
GO:0005515	Function	Protein binding	IPI	11991719, 23719382
GO:0005576	Component	Extracellular region	IDA	11991719
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IEA
GO:0005615	Component	Extracellular space	ISS	22261194
GO:0005634	Component	Nucleus	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IEA
GO:0005929	Component	Cilium	IEA
GO:0006869	Process	Lipid transport	IEA
GO:0010874	Process	Regulation of cholesterol efflux	IMP	23719382
GO:0016525	Process	Negative regulation of angiogenesis	IMP	23719382
GO:0016853	Function	Isomerase activity	IEA
GO:0031580	Process	Membrane raft distribution	IMP	23719382
GO:0042802	Function	Identical protein binding	IEA
GO:0044297	Component	Cell body	IEA
GO:0046496	Process	Nicotinamide nucleotide metabolic process	IMP	27616477
GO:0046872	Function	Metal ion binding	IEA
GO:0052856	Function	NAD(P)HX epimerase activity	IBA
GO:0052856	Function	NAD(P)HX epimerase activity	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0110051	Process	Metabolite repair	IEA

Other IDs

• MIM: 608862
• HGNC: 18453
• e!Ensembl: ENSG00000163382

Protein

• UniProt ID: Q8NCW5
• Protein name: NAD(P)H-hydrate epimerase (EC 5.1.99.6) (Apolipoprotein A-I-binding protein) (AI-BP) (NAD(P)HX epimerase) (NAXE) (YjeF N-terminal domain-containing protein 1) (YjeF_N1)
• Protein function: Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration (By similarity) (PubMed:27616477). This is a prerequisite for the S-specific NAD(P)H-hydrate dehyd
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03853	YjeF_N	80 → 247	YjeF-related protein N-terminus	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in kidney, heart and liver. Present in cerebrospinal fluid and urine but not in serum from healthy patients. Present in serum of sepsis patients (at protein level). {ECO:0000269|PubMed:119917
• Sequence:

  MSRLRALLGLGLLVAGSRVPRIKSQTIACRSGPTWWGPQRLNSGGRWDSEVMASTVVKYL
  SQEEAQAVDQELFNEYQFSVDQLMELAGLSCATAIAKAYPPTSMSRSPPTVLVICGPGNN
  GGDGLVCARHLKLFGYEPTIYYPKRPNKPLFTALVTQCQKMDIPFLGEMPAEPMTIDELY
  ELVVDAIFGFSFKGDVREPFHSILSVLKGLTVPIASIDIPSGWDVEKGNAGGIQPDLLIS
  LTAPKKSATQFTGRYHYLGGRFVPPALEKKYQLNLPPYPDTECVYRLQ

• Sequence length: 288

Pathways

Reactome:

Nicotinamide salvaging

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
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy	Pathogenic	rs879255647, rs371872027, rs759251812, rs139093330, rs886041063, rs886041064	RCV004576934 RCV004576936 RCV004576937 RCV004576938 RCV004576940 RCV004576941	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1	Pathogenic; Likely pathogenic	rs2102489248, rs2102491191, rs2102489197, rs765587923, rs1205686109, rs1677397982, rs1677398842	RCV001844359 RCV001775336 RCV001775337 RCV003236334 RCV001782498 RCV001808873 RCV001095389	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
NAXE-related disorder	Likely pathogenic	rs1258884250	RCV003403045	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	ClinGen, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Ataxia	Ataxia	Pubtator	27616477	Associate	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	LHGDN	17521614		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	30705153		★☆☆☆☆ Found in Text Mining only
Brain atrophy	Brain atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	34678889	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	18277965	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	29618705	Inhibit	★☆☆☆☆ Found in Text Mining only
Cerebellar edema	Cerebellar edema	BEFREE	27616477		★☆☆☆☆ Found in Text Mining only
Cerebellar edema	Cerebellar edema	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	31101050		★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Edema	Edema	Pubtator	27616477	Associate	★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
ENCEPHALOPATHY, PROGRESSIVE, EARLY-ONSET, WITH BRAIN EDEMA AND/OR LEUKOENCEPHALOPATHY	Encephalopathy	GENOMICS_ENGLAND_DG	27122014, 27616477		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ENCEPHALOPATHY, PROGRESSIVE, EARLY-ONSET, WITH BRAIN EDEMA AND/OR LEUKOENCEPHALOPATHY	Encephalopathy	ORPHANET_DG	27122014, 27616477, 29884839		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ENCEPHALOPATHY, PROGRESSIVE, EARLY-ONSET, WITH BRAIN EDEMA AND/OR LEUKOENCEPHALOPATHY	Encephalopathy	UNIPROT_DG	27122014, 27616477		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ENCEPHALOPATHY, PROGRESSIVE, EARLY-ONSET, WITH BRAIN EDEMA AND/OR LEUKOENCEPHALOPATHY	Encephalopathy	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ENCEPHALOPATHY, PROGRESSIVE, EARLY-ONSET, WITH BRAIN EDEMA AND/OR LEUKOENCEPHALOPATHY	Encephalopathy	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intestinal Neoplasms	Intestinal Neoplasms	BEFREE	31101050		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	27122014		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31101050		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	BEFREE	31745726		★☆☆☆☆ Found in Text Mining only
NAD(P)HX epimerase deficiency	Encephalopathy with brain edema and/or leukoencephalopathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31101050		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	31745726		★☆☆☆☆ Found in Text Mining only
Nonorganic psychosis	Nonorganic Psychosis	BEFREE	31745726		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychosis	BEFREE	31745726		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	BEFREE	31745726		★☆☆☆☆ Found in Text Mining only
Respiratory Failure	Respiratory Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	27616477	Associate	★☆☆☆☆ Found in Text Mining only
Skin Erosion	Skin Erosion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skin lesion	Skin Lesion	BEFREE	27616477		★☆☆☆☆ Found in Text Mining only
Spinal Cord Diseases	Spinal Cord Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Diseases	Stomach disease	Pubtator	34818622	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34818622	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only