NT5C2

5'-nucleotidase, cytosolic II, the group of 5'-nucleotidases

Basic information

Region (hg38): 10:103087185-103277605

Previous symbols: [ "NT5B", "SPG45" ]

Links

ENSG00000076685 ∙ NCBI:22978 ∙ OMIM:600417 ∙ HGNC:8022 ∙ Uniprot:P49902 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spastic paraplegia 45 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 45 (Moderate), mode of inheritance: AR
• hereditary spastic paraplegia 45 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic paraplegia 45, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	19415352; 24482476

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NT5C2 gene.

• Hereditary_spastic_paraplegia_45 (176 variants)
• Inborn_genetic_diseases (35 variants)
• not_provided (28 variants)
• Hereditary_spastic_paraplegia (8 variants)
• not_specified (5 variants)
• NT5C2-related_disorder (3 variants)
• Neurodevelopmental_disorder (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NT5C2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001351169.2. 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				49	1	50
missense	1	1	66	2		70
nonsense	7	1				8
start loss						0
frameshift	6	1				7
splice donor/acceptor (+/-2bp)	5	5				10
Total	19	8	66	51	1

Highest pathogenic variant AF is 0.000007447902

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NT5C2	protein_coding	protein_coding	ENST00000343289	17	107117

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000214	0.999	125688	0	58	125746	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.64	181	312	0.579	0.0000170	3714
Missense in Polyphen		35	80.908	0.43259		1032
Synonymous	-0.761	117	107	1.09	0.00000513	1017
Loss of Function	2.88	15	32.8	0.458	0.00000169	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000177
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000163	0.000163
Finnish	0.00107	0.00106
European (Non-Finnish)	0.000204	0.000202
Middle Eastern	0.000163	0.000163
South Asian	0.0000655	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a critical role in the maintenance of a constant composition of intracellular purine/pyrimidine nucleotides in cooperation with other nucleotidases. Preferentially hydrolyzes inosine 5'-monophosphate (IMP) and other purine nucleotides.
• Disease: DISEASE: Spastic paraplegia 45, autosomal recessive (SPG45) [MIM:613162]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Some SPG45 patients manifest mental retardation, contractures and learning disability. {ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:28884889}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Nicotinate and nicotinamide metabolism - Homo sapiens (human);Purine metabolism - Homo sapiens (human);Purine Nucleoside Phosphorylase Deficiency;Mercaptopurine Action Pathway;Azathioprine Action Pathway;Pyrimidine Metabolism;Nicotinate and Nicotinamide Metabolism;Xanthine Dehydrogenase Deficiency (Xanthinuria);Adenylosuccinate Lyase Deficiency;AICA-Ribosiduria;Thioguanine Action Pathway;Adenine phosphoribosyltransferase deficiency (APRT);Mitochondrial DNA depletion syndrome;Myoadenylate deaminase deficiency;Purine Metabolism;UMP Synthase Deiciency (Orotic Aciduria);MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Molybdenum Cofactor Deficiency;Adenosine Deaminase Deficiency;Gout or Kelley-Seegmiller Syndrome;Lesch-Nyhan Syndrome (LNS);Xanthinuria type I;Xanthinuria type II;Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Nucleobase catabolism;Metabolism of nucleotides;guanosine nucleotides degradation;Purine metabolism;urate biosynthesis/inosine 5,-phosphate degradation;adenosine nucleotides degradation;purine nucleotides degradation;Vitamin B3 (nicotinate and nicotinamide) metabolism;Abacavir metabolism;Abacavir transport and metabolism;Metabolism;Nicotinate Nicotinamide metabolism;Pyrimidine metabolism;Purine nucleotides nucleosides metabolism;Pyrimidine nucleotides nucleosides metabolism;Purine catabolism (Consensus)

Recessive Scores

• pRec: 0.281

Intolerance Scores

• loftool: 0.657
• rvis_EVS: -0.2
• rvis_percentile_EVS: 38.82

Haploinsufficiency Scores

• pHI: 0.658
• hipred: Y
• hipred_score: 0.639
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.338

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nt5c2
• Phenotype: hematopoietic system phenotype

Gene ontology

• Biological process: purine nucleotide catabolic process;phosphorylation;dephosphorylation;drug metabolic process;IMP metabolic process;adenosine metabolic process
• Cellular component: cytosol
• Molecular function: nucleotide binding;protein binding;5'-nucleotidase activity;metal ion binding;nucleoside phosphotransferase activity