NT5DC4

Summary

NT5DC4 (5’-nucleotidase domain containing 4, HGNC:27678) is a protein-coding gene on chromosome 2q14.1, encoding 5’-nucleotidase domain-containing protein 4 (Q86YG4).

Predicted to enable 5’-nucleotidase activity.

Source: NCBI Gene 284958 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_001393655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27678
Approved symbol	NT5DC4
Name	5’-nucleotidase domain containing 4
Location	2q14.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144130
Ensembl biotype	protein_coding
Entrez	284958

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000327581, ENST00000462854, ENST00000470675, ENST00000484666, ENST00000491170, ENST00000497526, ENST00000688554, ENST00000689550, ENST00000690591

RefSeq mRNA: 2 — MANE Select: NM_001393655 NM_001350494, NM_001393655

CCDS: CCDS86877, CCDS92846

Canonical transcript exons

ENST00000688554 — 17 exons

Exon	Start	End
ENSE00000963719	112722183	112722278
ENSE00000963721	112722714	112722771
ENSE00001000617	112725174	112725240
ENSE00001246213	112723081	112723174
ENSE00001332648	112724094	112724126
ENSE00003477029	112726238	112726289
ENSE00003516346	112725382	112725552
ENSE00003526039	112723418	112723468
ENSE00003526420	112726678	112726738
ENSE00003535058	112721986	112722103
ENSE00003549565	112721818	112721891
ENSE00003565602	112729627	112729704
ENSE00003684205	112723719	112723802
ENSE00003928650	112724781	112724906
ENSE00003930278	112738913	112739095
ENSE00003934116	112721020	112721153
ENSE00003934954	112722483	112722589

Expression profiles

Bgee: expression breadth ubiquitous, 129 present calls, max score 83.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3710 / max 97.1539, expressed in 94 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22012	0.2364	59
22011	0.0870	32
22013	0.0477	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.69	gold quality
left testis	UBERON:0004533	81.31	gold quality
right testis	UBERON:0004534	80.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.40	gold quality
testis	UBERON:0000473	77.06	gold quality
sperm	CL:0000019	76.59	gold quality
buccal mucosa cell	CL:0002336	67.33	gold quality
vermiform appendix	UBERON:0001154	66.44	gold quality
spleen	UBERON:0002106	66.24	gold quality
blood	UBERON:0000178	66.14	gold quality
ventricular zone	UBERON:0003053	64.06	gold quality
monocyte	CL:0000576	63.02	gold quality
leukocyte	CL:0000738	62.28	gold quality
granulocyte	CL:0000094	62.20	gold quality
right lung	UBERON:0002167	61.80	gold quality
lymph node	UBERON:0000029	61.60	gold quality
caecum	UBERON:0001153	60.76	gold quality
ganglionic eminence	UBERON:0004023	56.73	gold quality
right uterine tube	UBERON:0001302	56.54	gold quality
lower lobe of lung	UBERON:0008949	56.47	silver quality
colonic epithelium	UBERON:0000397	56.39	silver quality
upper lobe of lung	UBERON:0008948	54.49	gold quality
upper lobe of left lung	UBERON:0008952	54.33	gold quality
lower esophagus mucosa	UBERON:0035834	51.34	gold quality
mucosa of transverse colon	UBERON:0004991	49.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	49.15	gold quality
lung	UBERON:0002048	48.67	gold quality
small intestine	UBERON:0002108	48.13	gold quality
rectum	UBERON:0001052	46.81	gold quality
duodenum	UBERON:0002114	46.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.26

Regulation

Is transcription factor: no

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5c2l1	ENSDARG00000034852
drosophila_melanogaster	Nt5c	FBGN0033426
drosophila_melanogaster	Nt5b	FBGN0052549
caenorhabditis_elegans		WBGENE00022201

Paralogs (4): NT5C2 (ENSG00000076685), NT5DC3 (ENSG00000111696), NT5DC2 (ENSG00000168268), NT5DC1 (ENSG00000178425)

Protein

Protein identifiers

5’-nucleotidase domain-containing protein 4 — Q86YG4 (reviewed: Q86YG4)

All UniProt accessions (3): Q86YG4, A0A8I5KQP2, A0A8I5KQQ4

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. Gene prediction based on conservation.

Similarity. Belongs to the 5’(3’)-deoxyribonucleotidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86YG4-1	1	yes
Q86YG4-2	2

RefSeq proteins (2): NP_001337423, NP_001380584* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008380	HAD-SF_hydro_IG_5-nucl	Family
IPR016695	Pur_nucleotidase	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily

Pfam: PF05761

UniProt features (11 total): splice variant 4, binding site 3, active site 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YG4-F1	87.66	0.76

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): 22 (nucleophile); 24 (proton donor)

Ligand- & substrate-binding residues (3): 22; 24; 317

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_MONOPHOSPHATE_METABOLIC_PROCESS, GOBP_GMP_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, chr2q14, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_NUCLEOTIDASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, GOBP_PURINE_NUCLEOSIDE_MONOPHOSPHATE_METABOLIC_PROCESS, GOMF_PHOSPHATASE_ACTIVITY, GOBP_PURINE_DEOXYRIBONUCLEOTIDE_METABOLIC_PROCESS, CBX7_TARGET_GENES, NME2_TARGET_GENES

GO Biological Process (2): GMP metabolic process (GO:0046037), dGMP metabolic process (GO:0046054)

GO Molecular Function (3): 5’-nucleotidase activity (GO:0008253), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine ribonucleotide metabolic process	1
purine ribonucleoside monophosphate metabolic process	1
purine deoxyribonucleotide metabolic process	1
purine deoxyribonucleoside monophosphate metabolic process	1
nucleotidase activity	1
cation binding	1
catalytic activity	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5DC4	NT5DC1	Q5TFE4	412
NT5DC4	APOL5	Q9BWW9	393
NT5DC4	HERPUD2	Q9BSE4	377
NT5DC4	CYB561A3	Q8NBI2	376
NT5DC4	CDC14C	A4D256	373
NT5DC4	CHCHD5	Q9BSY4	370
NT5DC4	XPNPEP2	O43895	358
NT5DC4	ACY3	Q96HD9	322
NT5DC4	B3GNT7	Q8NFL0	315
NT5DC4	ADSS1	Q8N142	314
NT5DC4	CKAP2L	Q8IYA6	305
NT5DC4	ELP2	Q6IA86	305
NT5DC4	WBP1L	Q9NX94	297
NT5DC4	TIAM2	Q8IVF5	284
NT5DC4	APOO	Q9BUR5	271

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): NT5DC4 (Affinity Capture-MS), NT5DC4 (Affinity Capture-RNA), NT5DC4 (Affinity Capture-MS)

ESM2 similar proteins: A1E9I4, A1E9R7, A1EA01, A2T321, A4GGA8, A4GYP7, A4QJA4, A4QK94, A4QL95, A6H5F6, A6MMJ6, A7M8Z3, A7M955, A8W3B3, A8W3H9, A8Y9G3, A9L985, A9QC56, B0YPM1, B0Z4M8, B0Z4W2, B0Z5D0, B1NWD9, P06354, P08242, P0C480, P0C481, P0C482, P16037, P17933, P27068, P41605, Q06FX2, Q06RE2, Q14FG8, Q32RY1, Q3BAQ3, Q4FG66, Q4VZP4, Q5SCY1

Diamond homologs: A4IHT9, Q3UHB1, Q54XC1, Q5TFE4, Q6GN91, Q6Q0N3, Q75K12, Q86UY8, Q86YG4, Q9H857, D3ZMY7, O46411, P49902, Q3V1L4, Q5EBF1, Q5RA22, Q5ZIZ4, Q6DKB0, Q2TBU5, Q8C5P5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3511 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112722102:AGGTG:A	donor_loss	1.0000
2:112722104:G:GA	donor_loss	1.0000
2:112722105:T:G	donor_loss	1.0000
2:112722276:GGA:G	donor_gain	1.0000
2:112722277:GA:G	donor_gain	1.0000
2:112722277:GAG:G	donor_gain	1.0000
2:112722279:G:GG	donor_gain	1.0000
2:112722768:C:CG	donor_gain	1.0000
2:112722772:G:GG	donor_gain	1.0000
2:112722808:G:GG	donor_gain	1.0000
2:112722824:G:GT	donor_gain	1.0000
2:112722825:G:T	donor_gain	1.0000
2:112723069:T:A	acceptor_gain	1.0000
2:112723073:T:TA	acceptor_gain	1.0000
2:112723077:CCA:C	acceptor_loss	1.0000
2:112723079:A:AG	acceptor_gain	1.0000
2:112723079:AGTT:A	acceptor_gain	1.0000
2:112723080:G:GG	acceptor_gain	1.0000
2:112723080:GT:G	acceptor_gain	1.0000
2:112723080:GTT:G	acceptor_gain	1.0000
2:112723080:GTTG:G	acceptor_gain	1.0000
2:112723080:GTTGT:G	acceptor_gain	1.0000
2:112723171:GTCG:G	donor_gain	1.0000
2:112723173:CGGTG:C	donor_loss	1.0000
2:112723175:GTGA:G	donor_gain	1.0000
2:112723177:GA:G	donor_gain	1.0000
2:112723179:G:GG	donor_gain	1.0000
2:112723718:GCCAC:G	acceptor_gain	1.0000
2:112723798:CCAAT:C	donor_gain	1.0000
2:112723801:AT:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000099265 (2:112729739 G>A), RS1000155036 (2:112726133 C>T), RS1000165157 (2:112728542 A>G), RS1000209677 (2:112730513 A>C,G), RS1000240737 (2:112730205 C>T), RS1000389830 (2:112725062 C>T), RS1000390570 (2:112742568 T>C), RS1000456706 (2:112725166 C>T), RS1000509832 (2:112731647 T>C), RS1000547170 (2:112729353 C>A,G,T), RS1000614013 (2:112725940 G>A), RS1000726696 (2:112726172 G>C), RS1000815046 (2:112720188 T>A,G), RS1000829518 (2:112736313 T>C), RS1001130692 (2:112735472 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002407_60	White blood cell count	4.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
OTX015	decreases expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Diuron	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Clinical trials (associated diseases)

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