NT5C3A

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

Basic information

Region (hg38): 7:33014113-33062796

Previous symbols: [ "NT5C3" ]

Links

ENSG00000122643 ∙ NCBI:51251 ∙ OMIM:606224 ∙ HGNC:17820 ∙ Uniprot:Q9H0P0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (Definitive), mode of inheritance: AR
• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (Strong), mode of inheritance: AR
• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (Supportive), mode of inheritance: AR
• hemolytic anemia due to pyrimidine 5' nucleotidase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, congenital, nonspherocytic hemolytic, 8	AR	Hematologic	The condition may manifest with hereditary hemolytic anemia, and transfusions have been reported as necessary (though only infrequently in the described individuals)	Hematologic	4372252; 6317231; 6307548; 3352512; 11369620; 16402212; 17128459; 18499901

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NT5C3A gene.

• not_provided (54 variants)
• Hemolytic_anemia_due_to_pyrimidine_5'_nucleotidase_deficiency (51 variants)
• not_specified (33 variants)
• NT5C3A-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NT5C3A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001002010.5. 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				13	2	15
missense	2	1	58	3		64
nonsense	5					5
start loss						0
frameshift	5	2				7
splice donor/acceptor (+/-2bp)	2	2				4
Total	14	5	58	16	2

Highest pathogenic variant AF is 0.0000601201

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NT5C3A	protein_coding	protein_coding	ENST00000242210	9	48668

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0151	0.980	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.247	173	182	0.948	0.00000871	2210
Missense in Polyphen		30	41.45	0.72377		525
Synonymous	-0.337	71	67.5	1.05	0.00000359	618
Loss of Function	2.45	6	16.8	0.356	7.71e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000119
Ashkenazi Jewish	0.000303	0.000298
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP) (PubMed:24603684). CMP seems to be the preferred substrate (PubMed:15968458). {ECO:0000269|PubMed:15968458, ECO:0000269|PubMed:24603684}.
• Disease: DISEASE: P5N deficiency (P5ND) [MIM:266120]: Autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. {ECO:0000269|PubMed:11369620, ECO:0000269|PubMed:12930399, ECO:0000269|PubMed:15238149, ECO:0000269|PubMed:15604219, ECO:0000269|PubMed:15968458, ECO:0000269|PubMed:16461318, ECO:0000269|PubMed:18499901, ECO:0000269|PubMed:25153905}. 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);miR-targeted genes in lymphocytes - TarBase;Pyrimidine catabolism;Nucleobase catabolism;Metabolism of nucleotides;Purine metabolism;adenosine nucleotides degradation;purine nucleotides degradation;Vitamin B3 (nicotinate and nicotinamide) metabolism;Metabolism;Nicotinate Nicotinamide metabolism;Pyrimidine metabolism;Purine nucleotides nucleosides metabolism;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.296

Intolerance Scores

• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.202
• hipred: N
• hipred_score: 0.394
• ghis: 0.587

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nt5c3

Gene ontology

• Biological process: pyrimidine nucleoside metabolic process;nucleotide metabolic process;dephosphorylation;adenosine metabolic process;pyrimidine nucleoside catabolic process;defense response to virus
• Cellular component: cytoplasm;endoplasmic reticulum;cytosol
• Molecular function: nucleotide binding;tRNA 2'-phosphotransferase activity;magnesium ion binding;5'-nucleotidase activity