NT5C3A

Summary

NT5C3A (5’-nucleotidase, cytosolic IIIA, HGNC:17820) is a protein-coding gene on chromosome 7p14.3, encoding Cytosolic 5’-nucleotidase 3A (Q9H0P0). Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP).

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.

Source: NCBI Gene 51251 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 332 total — 21 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 49
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001002010

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17820
Approved symbol	NT5C3A
Name	5’-nucleotidase, cytosolic IIIA
Location	7p14.3
Locus type	gene with protein product
Status	Approved
Aliases	UMPH1, PSN1, PN-I, UMPH, P5’N-1, cN-III, p36, POMP, hUMP1
Ensembl gene	ENSG00000122643
Ensembl biotype	protein_coding
OMIM	606224
Entrez	51251

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000409467, ENST00000409787, ENST00000449201, ENST00000456458, ENST00000461851, ENST00000464840, ENST00000473083, ENST00000497542, ENST00000610140, ENST00000643244, ENST00000930183, ENST00000930184, ENST00000930185

RefSeq mRNA: 10 — MANE Select: NM_001002010 NM_001002009, NM_001002010, NM_001166118, NM_001356996, NM_001374335, NM_001374336, NM_001374337, NM_001374338, NM_001374339, NM_016489

CCDS: CCDS34616, CCDS34617, CCDS55101

Canonical transcript exons

ENST00000610140 — 9 exons

Exon	Start	End
ENSE00003465169	33017439	33017601
ENSE00003541720	33024039	33024108
ENSE00003548050	33015670	33015870
ENSE00003572660	33022053	33022099
ENSE00003582811	33021272	33021357
ENSE00003643224	33019635	33019724
ENSE00003705264	33062568	33062776
ENSE00003759567	33026817	33026915
ENSE00004034562	33014130	33014831

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.4342 / max 1249.5183, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83514	24.5261	1820
83513	10.7480	534
83515	1.4752	825
83516	0.6849	394

Top tissues by expression

138 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	98.48	gold quality
monocyte	CL:0000576	97.68	gold quality
leukocyte	CL:0000738	97.34	gold quality
thymus	UBERON:0002370	96.81	gold quality
rectum	UBERON:0001052	96.21	gold quality
gastrocnemius	UBERON:0001388	94.89	gold quality
duodenum	UBERON:0002114	94.89	gold quality
muscle of leg	UBERON:0001383	94.86	gold quality
cortical plate	UBERON:0005343	94.54	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.45	gold quality
islet of Langerhans	UBERON:0000006	94.05	gold quality
mucosa of transverse colon	UBERON:0004991	94.00	gold quality
cerebellar vermis	UBERON:0004720	93.67	gold quality
ganglionic eminence	UBERON:0004023	93.61	gold quality
lymph node	UBERON:0000029	93.50	gold quality
adrenal tissue	UBERON:0018303	93.32	gold quality
vermiform appendix	UBERON:0001154	93.12	gold quality
body of pancreas	UBERON:0001150	93.09	gold quality
calcaneal tendon	UBERON:0003701	92.98	gold quality
pancreas	UBERON:0001264	92.77	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.67	gold quality
gall bladder	UBERON:0002110	92.40	gold quality
blood	UBERON:0000178	92.32	gold quality
transverse colon	UBERON:0001157	92.31	gold quality
endometrium	UBERON:0001295	92.21	gold quality
granulocyte	CL:0000094	91.96	gold quality
skeletal muscle tissue	UBERON:0001134	91.87	gold quality
ventricular zone	UBERON:0003053	91.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.39	gold quality
bone marrow	UBERON:0002371	91.28	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	33.29
E-HCAD-4	yes	32.55
E-HCAD-1	yes	6.66
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF

miRNA regulators (miRDB)

36 targeting NT5C3A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-656-3P	100.00	72.15	2788
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-5094	98.63	67.11	1062
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-8086	97.21	64.13	331

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 15)

• Data show that PN-I shows a higher affinity for oxynucleosides rather than deoxynucleosides, while the opposite is true for PN-II. (PMID:12418222)
• All investigated mutant proteins display impaired catalytic properties and/or reduced thermostability, providing a rationale for the pathological effects of the mutations. (PMID:15604219)
• These data highlight hUMP1/POMP role in proteasome assembly and further strengthen the prospect of genetic manipulation of the proteasomal system. (PMID:17349762)
• 3 newly described missense mutations (c.187T>C, c.469G>C & c.740T>C) identified in patients with hemolytic anemia were characterized at protein level; the enzymes were altered in both thermal stability and catalytic efficiency (PMID:18499901)
• In leukoblasts from 82 patients with acute myeloid leukemia, various extent and frequency of differential allelic expression in the CDA, DCK, NT5C2, NT5C3, and TP53 genes was observed. (PMID:18775979)
• genetic variation in NT5C3 might affect protein function and potentially influence drug response (PMID:19623099)
• New missense homozygous mutation (Q270Ter) in the pyrimidine 5’ nucleotidase type I-related gene in two Indian families with hereditary non-spherocytic hemolytic anemia. (PMID:23139015)
• analysis of Drosophila and human 7-methyl GMP-specific nucleotidases (PMID:23223233)
• Results show that NT5C3 expression levels were significantly increased in patients with risk allele homozygote. (PMID:25000516)
• Pyrimidine-5’-nucleotidase Campinas is a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5’-nucleotidase type I deficiency. (PMID:25153905)
• Results from a study on gene expression variability markers in early-stage human embryos shows that NT5C3A is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• reduced expression of transketolase in pyrimidine 5’-nucleotidase deficient patients (PMID:27381654)
• Data indicate an anti-inflammatory pathway that depends on the catalytic activity of pyrimidine 5’-nucleotidase (NT5C3A) and functions as a negative feedback regulator of inflammatory cytokine signaling. (PMID:29463777)
• A New Homozygous Mutation (c.393-394del TA/c.393-394del TA) in the NT5C3 Gene Associated With Pyrimidine-5’-Nucleotidase Deficiency. (PMID:30951028)
• [Two novel mutations (c.830A>G, c.252+1G>A) in NT5C3A associated with hereditary pyrimidine 5’-nucleotidase deficiency: two cases report and literature review]. (PMID:34547876)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5c3a	ENSDARG00000058597
mus_musculus	Nt5c3	ENSMUSG00000029780
rattus_norvegicus	Nt5c3a	ENSRNOG00000005981
drosophila_melanogaster	cN-IIIB	FBGN0034988
caenorhabditis_elegans		WBGENE00012423
caenorhabditis_elegans		WBGENE00017775

Paralogs (1): NT5C3B (ENSG00000141698)

Protein

Protein identifiers

Cytosolic 5’-nucleotidase 3A — Q9H0P0 (reviewed: Q9H0P0)

Alternative names: 7-methylguanosine phosphate-specific 5’-nucleotidase, Cytosolic 5’-nucleotidase 3, Cytosolic 5’-nucleotidase III, Pyrimidine 5’-nucleotidase 1, Uridine 5’-monophosphate hydrolase 1, p36

All UniProt accessions (6): A0A090N7U2, B9A035, C9K084, Q9H0P0, F8WDR0, X6RM59

UniProt curated annotations — full annotation on UniProt →

Function. Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP). CMP seems to be the preferred substrate.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm Endoplasmic reticulum.

Tissue specificity. Isoforms 1, 3 and 4 are expressed in reticulocytes. Isoform 4 is hardly detectable in bone marrow and fetal liver.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. Isoform 2 is induced by interferon alpha in Raji cells in association with lupus inclusions.

Similarity. Belongs to the pyrimidine 5’-nucleotidase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H0P0-4	2	yes
Q9H0P0-1	1, P5N-I
Q9H0P0-2	3, p36
Q9H0P0-3	4, P5N-R

RefSeq proteins (10): NP_001002009, NP_001002010, NP_001159590, NP_001343925, NP_001361264, NP_001361265, NP_001361266, NP_001361267, NP_001361268, NP_057573 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006434	Pyrimidine_nucleotidase_eu	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF05822

Enzyme classification (BRENDA):

• EC 3.1.3.91 — 7-methylguanosine nucleotidase (BRENDA: 2 organisms, 4 substrates, 4 inhibitors, 2 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N7-METHYL-GMP	0.0078–0.013	2

Catalyzed reactions (Rhea), 3 shown:

• a ribonucleoside 5’-phosphate + H2O = a ribonucleoside + phosphate (RHEA:12484)
• CMP + H2O = cytidine + phosphate (RHEA:29367)
• N(7)-methyl-GMP + H2O = N(7)-methylguanosine + phosphate (RHEA:37107)

UniProt features (60 total): helix 14, strand 10, binding site 8, sequence variant 8, mutagenesis site 7, splice variant 3, sequence conflict 3, turn 3, active site 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2VKQ	X-RAY DIFFRACTION	2.5
2CN1	X-RAY DIFFRACTION	2.67
2JGA	X-RAY DIFFRACTION	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0P0-F1	92.29	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 88 (nucleophile); 90 (proton donor)

Ligand- & substrate-binding residues (8): 277; 88; 90; 135; 135; 156; 203–204; 252

Post-translational modifications (1): 278

Mutagenesis-validated functional residues (7):

Position	Phenotype
88	loss of nucleotidase and phosphotransferase activity.
89	almost complete loss of nucleotidase and phosphotransferase activity.
90	loss of nucleotidase and phosphotransferase activity.
135	no effect on nucleotidase activity. almost complete loss of phosphotransferase activity.
232	no effect on nucleotidase and phosphotransferase activity.
233	almost complete loss of nucleotidase and phosphotransferase activity.
234	no effect on nucleotidase and phosphotransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-73621	Pyrimidine catabolism

MSigDB gene sets: 540 (showing top): REACTOME_PYRIMIDINE_CATABOLISM, KEGG_PROTEASOME, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, GOBP_PROTEASOME_ASSEMBLY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_CATABOLIC_PROCESS, IRF7_01, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOBP_PYRIMIDINE_NUCLEOTIDE_CATABOLIC_PROCESS, GGAANCGGAANY_UNKNOWN, IRF1_Q6

GO Biological Process (8): pyrimidine nucleoside metabolic process (GO:0006213), CMP catabolic process (GO:0006248), dCMP catabolic process (GO:0006249), UMP catabolic process (GO:0046050), dTMP catabolic process (GO:0046074), dUMP catabolic process (GO:0046079), defense response to virus (GO:0051607), nucleotide metabolic process (GO:0009117)

GO Molecular Function (8): nucleotide binding (GO:0000166), tRNA 2’-phosphotransferase activity (GO:0000215), magnesium ion binding (GO:0000287), 5’-nucleotidase activity (GO:0008253), protein binding (GO:0005515), transferase activity (GO:0016740), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Nucleotide catabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pyrimidine deoxyribonucleoside monophosphate catabolic process	3
pyrimidine deoxyribonucleotide catabolic process	3
cellular anatomical structure	3
cytoplasm	3
pyrimidine ribonucleoside monophosphate catabolic process	2
pyrimidine ribonucleotide catabolic process	2
catalytic activity	2
intracellular membrane-bounded organelle	2
nucleoside metabolic process	1
pyrimidine-containing compound metabolic process	1
CMP metabolic process	1
dCMP metabolic process	1
UMP metabolic process	1
dTMP metabolic process	1
dUMP metabolic process	1
defense response	1
response to virus	1
nucleoside phosphate metabolic process	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a tRNA	1
metal ion binding	1
nucleotidase activity	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5C3A	NT5C	Q8TCD5	960
NT5C3A	PRPS2	P11908	784
NT5C3A	PRPS1L1	P21108	778
NT5C3A	NT5M	Q9NPB1	773
NT5C3A	PRPS1	P09329	737
NT5C3A	NT5C2	P49902	623
NT5C3A	NT5C1A	Q9BXI3	588
NT5C3A	EPB42	P16452	531
NT5C3A	NT5C1B	Q96P26	492
NT5C3A	DCK	P27707	480
NT5C3A	CDAN1	Q8IWY9	475
NT5C3A	TK1	P04183	461
NT5C3A	RBM41	Q96IZ5	460
NT5C3A	CMPK1	P30085	447
NT5C3A	AMPD3	Q01432	434

IntAct

65 interactions, top by confidence:

A	B	Type	Score
BZW2	ENDOD1	psi-mi:“MI:0914”(association)	0.640
NT5C3A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
DESI1	NT5C3A	psi-mi:“MI:0915”(physical association)	0.560
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
GPC3	CLGN	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
RSPH14	UBB	psi-mi:“MI:0914”(association)	0.530
NT5C3A	UBQLN1	psi-mi:“MI:0915”(physical association)	0.490
MTAP	NT5C3A	psi-mi:“MI:0915”(physical association)	0.400
NT5C3A	GNAQ	psi-mi:“MI:0915”(physical association)	0.370
NDUFAB1	NT5C3A	psi-mi:“MI:0915”(physical association)	0.370
NT5C3A	VANGL1	psi-mi:“MI:0915”(physical association)	0.370
NT5C3A	VWA8	psi-mi:“MI:0914”(association)	0.350
	PTPRF	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
HTRA2	VWA8	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
ADAM18	WDR27	psi-mi:“MI:0914”(association)	0.350
CDH23	GTPBP10	psi-mi:“MI:0914”(association)	0.350
ORAI1	POTEF	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
OR2A4	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (124): NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Synthetic Growth Defect), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), UBQLN1 (Two-hybrid), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS), NT5C3A (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RL25, A0A0U1WZ18, A0A1S4A695, B4G0F3, B8BKI7, B9N1F9, C6JS30, E0CSI1, M2VWL5, O14023, O15305, O24653, O35077, O35621, O57656, O80840, P00949, P38652, Q02908, Q08DP0, Q1W374, Q1W377, Q1ZXC6, Q23651, Q259G4, Q29NT9, Q2R483, Q3SZJ9, Q3ULJ0, Q4R5E4, Q5TNH5, Q5XIZ6, Q5ZID6, Q5ZJ08, Q5ZKF6, Q60HD6, Q60LW7, Q7SYN4, Q7XPW5, Q8GWU0

Diamond homologs: Q09315, Q2TAG6, Q3UFY7, Q5ZID6, Q5ZKF6, Q6AYP7, Q7SYN4, Q7ZWS2, Q969T7, Q9D020, Q9H0P0, Q9W197

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
R-HSA-425366	5	19.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	6	27.5×	4e-05
calcium ion transport	6	16.0×	4e-04
transport across blood-brain barrier	5	13.2×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — AML.

Clinical variants and AI predictions

ClinVar

332 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	4
Uncertain significance	153
Likely benign	85
Benign	37

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
116	NC_000013.11:g.28659090del	Pathogenic
1687500	NM_001002010.5(NT5C3A):c.718G>T (p.Glu240Ter)	Pathogenic
1967665	NM_001002010.5(NT5C3A):c.579del (p.Val194fs)	Pathogenic
2844286	NM_001002010.5(NT5C3A):c.440G>A (p.Trp147Ter)	Pathogenic
2854800	NM_001002010.5(NT5C3A):c.499_502del (p.Glu167fs)	Pathogenic
3245919	NC_000007.13:g.(?33054342)(33054463_?)del	Pathogenic
3716179	NM_001002010.5(NT5C3A):c.139-9021dup	Pathogenic
4480	NM_001002010.5(NT5C3A):c.631C>T (p.Gln211Ter)	Pathogenic
4481	NM_001002010.5(NT5C3A):c.694-1G>T	Pathogenic
4482	NM_001002010.5(NT5C3A):c.844_845dup (p.Val283fs)	Pathogenic
4483	NM_001002010.5(NT5C3A):c.645T>G (p.Tyr215Ter)	Pathogenic
4484	NM_001002010.5(NT5C3A):c.486dup (p.Ala163fs)	Pathogenic
4485	NM_001002010.5(NT5C3A):c.694-1G>C	Pathogenic
4486	NM_001002010.5(NT5C3A):c.671A>G (p.Asn224Ser)	Pathogenic
4487	NM_001002010.5(NT5C3A):c.679del (p.Asp227fs)	Pathogenic
4488	NM_001002010.5(NT5C3A):c.823G>C (p.Gly275Arg)	Pathogenic
522801	NM_015932.6(POMP):c.334_335del (p.Ile112fs)	Pathogenic
548959	NM_015932.6(POMP):c.340_344dup (p.Glu115fs)	Pathogenic
548960	NM_015932.6(POMP):c.342_348delinsACC (p.Phe114fs)	Pathogenic
687354	GRCh37/hg19 7p14.3(chr7:33074784-33084764)x1	Pathogenic
992939	NM_001002010.5(NT5C3A):c.166C>T (p.Arg56Ter)	Pathogenic
1299469	NM_001002010.5(NT5C3A):c.342dup (p.Cys115fs)	Likely pathogenic
2683351	NM_001002010.5(NT5C3A):c.693+1G>A	Likely pathogenic
4081562	NM_001002010.5(NT5C3A):c.333del (p.Thr112fs)	Likely pathogenic
546726	NM_015932.6(POMP):c.326dup (p.Asp109fs)	Likely pathogenic

SpliceAI

2809 predictions. Top by Δscore:

Variant	Effect	Δscore
13:28659184:GATG:G	donor_gain	1.0000
13:28659188:G:GA	donor_loss	1.0000
13:28659188:G:GG	donor_gain	1.0000
13:28659189:T:A	donor_loss	1.0000
13:28659192:G:GG	donor_gain	1.0000
13:28662408:A:AG	acceptor_gain	1.0000
13:28662409:G:GG	acceptor_gain	1.0000
13:28662409:GA:G	acceptor_gain	1.0000
13:28662483:A:T	donor_gain	1.0000
13:28662506:GG:G	donor_gain	1.0000
13:28662507:GGTA:G	donor_gain	1.0000
13:28662517:G:GT	donor_gain	1.0000
13:28662517:G:T	donor_gain	1.0000
13:28662521:T:G	donor_gain	1.0000
13:28664507:A:AG	acceptor_gain	1.0000
13:28664508:G:GG	acceptor_gain	1.0000
13:28668469:GTAGT:G	acceptor_loss	1.0000
13:28668471:A:AG	acceptor_gain	1.0000
13:28668472:G:GA	acceptor_gain	1.0000
13:28668472:GTTCC:G	acceptor_gain	1.0000
13:28668571:GCAG:G	donor_gain	1.0000
13:28668572:CAGGT:C	donor_loss	1.0000
13:28668573:AGGTG:A	donor_loss	1.0000
13:28668574:GGTG:G	donor_loss	1.0000
13:28668575:GT:G	donor_loss	1.0000
13:28668576:T:A	donor_loss	1.0000
13:28668767:GC:G	donor_gain	1.0000
13:28672433:G:A	donor_loss	1.0000
13:28672434:TAAGT:T	donor_loss	1.0000
7:33015662:ATACT:A	donor_loss	1.0000

AlphaMissense

2188 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032823 (7:33019245 G>A,C), RS1000069452 (7:33062482 C>G,T), RS1000093175 (7:33020983 C>T), RS1000128459 (7:33021503 G>C,T), RS1000138299 (7:33063235 G>A), RS1000202495 (7:33023195 A>G), RS1000206087 (7:33026041 C>T), RS1000249980 (7:33056355 G>A), RS1000265992 (7:33032476 A>C,T), RS1000319700 (7:33046962 C>G,T), RS1000399148 (7:33038893 G>A), RS1000469784 (7:33028212 G>A,C), RS1000538732 (7:33045620 T>C), RS1000552577 (7:33018903 A>G), RS1000654849 (7:33024274 C>A,T)

Disease associations

OMIM: gene MIM:606224 | disease phenotypes: MIM:601952, MIM:618048, MIM:266120

GenCC curated gene-disease

Disease	Classification	Inheritance
hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency	Definitive	Autosomal recessive
keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome	Strong	Autosomal recessive
proteasome-associated autoinflammatory syndrome 2	Strong	Autosomal dominant

Mondo (3): keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (MONDO:0011169), proteasome-associated autoinflammatory syndrome 2 (MONDO:0054700), hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency (MONDO:0009946)

Orphanet (2): Keratosis linearis-ichthyosis congenita-sclerosing keratoderma syndrome (Orphanet:281201), Hemolytic anemia due to pyrimidine 5’ nucleotidase deficiency (Orphanet:35120)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000982	Palmoplantar keratoderma
HP:0000988	Skin rash
HP:0001036	Parakeratosis
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001482	Subcutaneous nodule
HP:0001508	Failure to thrive
HP:0001795	Hyperconvex nail
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001923	Reticulocytosis
HP:0001945	Fever
HP:0002716	Lymphadenopathy
HP:0002718	Recurrent bacterial infections
HP:0002829	Arthralgia
HP:0002904	Hyperbilirubinemia
HP:0003237	Increased circulating IgG concentration
HP:0003261	Increased circulating IgA concentration
HP:0003493	Antinuclear antibody positivity
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003577	Congenital onset
HP:0003596	Middle age onset
HP:0003621	Juvenile onset
HP:0003623	Neonatal onset
HP:0003641	Hemoglobinuria
HP:0004429	Recurrent viral infections
HP:0007465	Honeycomb palmoplantar hyperkeratosis
HP:0007479	Congenital nonbullous ichthyosiform erythroderma

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002265_1	Breast cancer (menopausal hormone therapy interaction)	8.000000e-06
GCST004604_58	Hematocrit	6.000000e-10
GCST004615_95	Hemoglobin concentration	4.000000e-10
GCST004621_112	Red cell distribution width	5.000000e-68
GCST008059_150	Estimated glomerular filtration rate	1.000000e-11
GCST010002_181	Refractive error	4.000000e-32
GCST010083_204	Hemoglobin levels	3.000000e-17
GCST012020_381	Serum metabolite levels	5.000000e-48
GCST90002383_20	Hematocrit	5.000000e-24
GCST90002384_323	Hemoglobin	1.000000e-23
GCST90002396_383	Mean reticulocyte volume	7.000000e-10
GCST90002397_499	Mean spheric corpuscular volume	8.000000e-15
GCST90002403_467	Red blood cell count	8.000000e-21
GCST90002404_285	Red cell distribution width	3.000000e-137

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003961	hormone replacement therapy
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0009188	Red cell distribution width
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566600	Keratosis Linearis with Ichthyosis Congenita and Sclerosing Keratoderma (supp.)
C564859	Uridine 5-Prime Monophosphate Hydrolase Deficiency, Hemolytic Anemia due to (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs3750117	Efficacy	3	cytarabine;idarubicin	Leukemia;Myeloid;Acute
rs3750117	Metabolism/PK	3	gemcitabine	Neoplasms

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3750117	NT5C3A	3	3.00	2	cytarabine;idarubicin;gemcitabine
rs6946062	NT5C3A		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Adenosine turnover

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	3
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
GSK-J4	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
chromium hexavalent ion	increases abundance, increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
Temozolomide	increases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Arsenic	increases abundance, decreases expression	1
Lead	decreases activity	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Thiram	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Valproic Acid	increases expression	1
Zidovudine	increases expression, affects cotreatment	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1GP	Abcam A-549 NT5C3A KO 2	Cancer cell line	Male
CVCL_B2P7	Abcam A-549 NT5C3A KO 1	Cancer cell line	Male
CVCL_TB20	HAP1 NT5C3A (-) 1	Cancer cell line	Male
CVCL_TB21	HAP1 NT5C3A (-) 2	Cancer cell line	Male
CVCL_TB22	HAP1 NT5C3A (-) 3	Cancer cell line	Male
CVCL_TB23	HAP1 NT5C3A (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.