GeneBe

NT5C3A

protein-coding

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

Gene summary

This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates. The encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and pseudogenes of this gene are located on the long arm of chromosomes 3 and 4. [provided by RefSeq, Mar 2012]

Previous symbols:
  • NT5C3

MANE transcript

NM_001002010.5

Inheritance

AR

ClinVar variants

P:19U:73B:20

Top phenotype

Anemia, congenital, nonspherocytic hemolytic, 8

gnomAD constraint

pLI —, LoF o/e 0.36

Max pathogenic AF

—

Genomic locus

chr7:33,014,113-33,062,796

External References & Databases

Ensembl (ENSG00000122643)NCBI Gene (51251)OMIM (606224)HGNC:17820GenCCUniProt (Q9H0P0)AlphaFoldClinVar (NT5C3A)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~48.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hemolytic anemia due to pyrimidine 5' nucleotidase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009946

Submitter: PanelApp Australia

hemolytic anemia due to pyrimidine 5' nucleotidase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009946

Submitter: Ambry Genetics

hemolytic anemia due to pyrimidine 5' nucleotidase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009946

Submitter: Orphanet

hemolytic anemia due to pyrimidine 5' nucleotidase deficiencyDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009946

Submitter: G2P

hemolytic anemia due to pyrimidine 5' nucleotidase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009946

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Anemia, congenital, nonspherocytic hemolytic, 8AR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: The condition may manifest with hereditary hemolytic anemia, and transfusions have been reported as necessary (though only infrequently in the described individuals)

Refs: 4372252; 6317231; 6307548; 3352512; 11369620; 16402212; 17128459; 18499901Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NT5C3A variants in ClinVar

4 Conditions Cataloged
not providedTotal: 61
Hemolytic anemia due to pyrimidine 5' nucleotidase deficiencyTotal: 54
not specifiedTotal: 44
NT5C3A-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001002010.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
16
clinvar
1
clinvar
 18
missense
2
clinvar
1
clinvar
69
clinvar
3
clinvar
 75
nonsense
5
clinvar
 5
start loss
0
frameshift
5
clinvar
2
clinvar
 7
splice donor/acceptor (+/-2bp)
2
clinvar
2
clinvar
3
clinvar
 7
Total14573191112

Highest pathogenic variant AF is 0.000060120066

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001002010.5RefSeqNP_001002010.29MANE Select
ENST00000610140.7EnsemblENSP00000476480.29MANE Select
NM_001002009.3RefSeqNP_001002009.19Standard
NM_001166118.3RefSeqNP_001159590.18Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • pyrimidine nucleoside metabolic process
  • nucleotide metabolic process
  • dephosphorylation
  • adenosine metabolic process
  • pyrimidine nucleoside catabolic process

Molecular Function

  • nucleotide binding
  • tRNA 2'-phosphotransferase activity
  • magnesium ion binding
  • 5'-nucleotidase activity

Cellular Component

  • cytoplasm
  • endoplasmic reticulum
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000242210
Coding exons
9
Length
48668
Individuals with no LoFs
125726
Homozygous LoFs
0
Heterozygous LoFs
22
Defined
125748
p
0.0000875
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.2471731820.9480.000008712210
Missense (PolyPhen)3041.450.72377525
Synonymous-0.3377167.51.050.00000359618
Loss of Function2.45616.80.3567.71e-7227

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000620.000062rare
Latino/Admixed American0.0000580.000058rare
Ashkenazi Jewish0.000300.00030rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.000110.00011rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.296

Intolerance Scores

RVIS EVS
0.13
RVIS percentile EVS
63

Essentials

Essential (CRISPR)
N
Essential (gene trap)
N

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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