NT5DC1

Summary

NT5DC1 (5’-nucleotidase domain containing 1, HGNC:21556) is a protein-coding gene on chromosome 6q22.1, encoding 5’-nucleotidase domain-containing protein 1 (Q5TFE4).

While the exact function of the protein encoded by this gene is not known, it belongs to the 5’(3’)-deoxyribonucleotidase family.

Source: NCBI Gene 221294 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 119 total — 4 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_152729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21556
Approved symbol	NT5DC1
Name	5’-nucleotidase domain containing 1
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ486I3.1, MGC24302
Ensembl gene	ENSG00000178425
Ensembl biotype	protein_coding
OMIM	621076
Entrez	221294

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000319550, ENST00000417846, ENST00000419791, ENST00000460749, ENST00000880963, ENST00000880964, ENST00000880965, ENST00000959019

RefSeq mRNA: 1 — MANE Select: NM_152729 NM_152729

CCDS: CCDS5104

Canonical transcript exons

ENST00000319550 — 12 exons

Exon	Start	End
ENSE00001240265	116243909	116249497
ENSE00001243243	116221054	116221228
ENSE00001873818	116100853	116101023
ENSE00002179152	116223034	116223131
ENSE00002201677	116236966	116237084
ENSE00002210590	116110850	116110956
ENSE00002257752	116108364	116108435
ENSE00002312554	116117861	116117945
ENSE00002314863	116106244	116106335
ENSE00003467936	116238955	116239123
ENSE00003548480	116238187	116238348
ENSE00003756646	116115691	116115770

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 95.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7482 / max 217.0966, expressed in 1809 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69395	24.7482	1809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	95.42	gold quality
kidney epithelium	UBERON:0004819	95.31	gold quality
inferior vagus X ganglion	UBERON:0005363	93.82	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.54	gold quality
epithelium of nasopharynx	UBERON:0001951	93.49	gold quality
spinal cord	UBERON:0002240	93.16	gold quality
left ventricle myocardium	UBERON:0006566	93.15	gold quality
right adrenal gland	UBERON:0001233	92.69	gold quality
right adrenal gland cortex	UBERON:0035827	92.30	gold quality
left adrenal gland	UBERON:0001234	92.22	gold quality
heart right ventricle	UBERON:0002080	91.90	gold quality
descending thoracic aorta	UBERON:0002345	91.85	gold quality
buccal mucosa cell	CL:0002336	91.84	gold quality
right coronary artery	UBERON:0001625	91.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.69	gold quality
adrenal gland	UBERON:0002369	91.62	gold quality
subthalamic nucleus	UBERON:0001906	91.53	gold quality
left adrenal gland cortex	UBERON:0035825	91.40	gold quality
adrenal tissue	UBERON:0018303	91.33	gold quality
bronchial epithelial cell	CL:0002328	91.25	gold quality
liver	UBERON:0002107	91.25	gold quality
adrenal cortex	UBERON:0001235	91.19	gold quality
palpebral conjunctiva	UBERON:0001812	91.12	gold quality
right lobe of liver	UBERON:0001114	91.08	gold quality
popliteal artery	UBERON:0002250	91.06	gold quality
tibial artery	UBERON:0007610	91.05	gold quality
bronchus	UBERON:0002185	90.90	gold quality
ileal mucosa	UBERON:0000331	90.89	gold quality
deltoid	UBERON:0001476	90.84	gold quality
islet of Langerhans	UBERON:0000006	90.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting NT5DC1, 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-511-3P	99.99	68.85	1467
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305

Literature-anchored findings (GeneRIF, showing 2)

• The rs1052443 C allele of NT5DC1 was associated with a protective effect against the deterioration of pulmonary function. (PMID:22736055)
• Weighted gene co-expression network analysis identifies specific modules and hub genes related to subsyndromal symptomatic depression. (PMID:30489189)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nt5dc1	ENSDARG00000006797
mus_musculus	Nt5dc1	ENSMUSG00000039480
rattus_norvegicus	Nt5dc1	ENSRNOG00000000546
drosophila_melanogaster	Nt5a	FBGN0035204

Paralogs (4): NT5C2 (ENSG00000076685), NT5DC3 (ENSG00000111696), NT5DC4 (ENSG00000144130), NT5DC2 (ENSG00000168268)

Protein

Protein identifiers

5’-nucleotidase domain-containing protein 1 — Q5TFE4 (reviewed: Q5TFE4)

All UniProt accessions (3): Q5TFE4, H0YDA5, Q5QPD0

UniProt curated annotations — full annotation on UniProt →

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TFE4-1	1	yes
Q5TFE4-2	2

RefSeq proteins (1): NP_689942* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF05761

UniProt features (10 total): binding site 3, active site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TFE4-F1	88.76	0.78

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): 16 (nucleophile); 18 (proton donor)

Ligand- & substrate-binding residues (3): 16; 18; 313

Post-translational modifications (1): 171

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 91 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, MOTAMED_RESPONSE_TO_ANDROGEN_DN, HEIDENBLAD_AMPLICON_8Q24_DN, CHANDRAN_METASTASIS_DN, BASAKI_YBX1_TARGETS_DN, VECCHI_GASTRIC_CANCER_EARLY_DN, RIGGI_EWING_SARCOMA_PROGENITOR_UP, CHANDRAN_METASTASIS_TOP50_DN, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_NUCLEOTIDASE_ACTIVITY, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, chr6q22, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_UP, WHITFIELD_CELL_CYCLE_S, JOHNSTONE_PARVB_TARGETS_3_UP

GO Biological Process (0):

GO Molecular Function (4): 5’-nucleotidase activity (GO:0008253), metal ion binding (GO:0046872), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleotidase activity	1
cation binding	1
binding	1
catalytic activity	1

Protein interactions and networks

STRING

488 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NT5DC1	CALHM4	Q5JW98	541
NT5DC1	TSPYL4	Q9UJ04	507
NT5DC1	CALHM5	Q8N5C1	500
NT5DC1	OR6C65	A6NJZ3	480
NT5DC1	CCDC152	Q4G0S7	472
NT5DC1	SEC23IP	Q9Y6Y8	451
NT5DC1	CTXN2	P0C2S0	444
NT5DC1	MTMR11	A4FU01	422
NT5DC1	NT5DC4	Q86YG4	412
NT5DC1	OR4D1	Q15615	398
NT5DC1	CALHM6	Q5R3K3	395
NT5DC1	ARL6IP1	Q15041	391
NT5DC1	TSPYL1	Q9H0U9	391
NT5DC1	B4GALT4	O60513	389
NT5DC1	NUDT8	Q8WV74	387

IntAct

16 interactions, top by confidence:

A	B	Type	Score
NT5DC1	HSP90AA4P	psi-mi:“MI:0915”(physical association)	0.560
LRRK2		psi-mi:“MI:0914”(association)	0.350
NT5DC1	GFAP	psi-mi:“MI:0914”(association)	0.350
NT5DC1	ACACB	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
OSBPL11	DNM1L	psi-mi:“MI:0914”(association)	0.350
PEX7	UBA6	psi-mi:“MI:0914”(association)	0.350
rep	ARPC1B	psi-mi:“MI:2364”(proximity)	0.270
CFTR	UBA6	psi-mi:“MI:2364”(proximity)	0.270
NT5DC1	bfmbAb	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): HSP90AA4P (Affinity Capture-MS), GFAP (Affinity Capture-MS), PKLR (Affinity Capture-MS), HBD (Affinity Capture-MS), PKLR (Affinity Capture-MS), GFAP (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), NT5DC1 (Affinity Capture-MS), NT5DC1 (Proximity Label-MS), NT5DC1 (Affinity Capture-MS), NT5DC1 (Proximity Label-MS), NT5DC1 (Reconstituted Complex), HSP90AA4P (Affinity Capture-MS), TRABD (Affinity Capture-MS), ACACB (Affinity Capture-MS)

ESM2 similar proteins: A1KXW8, A6QL50, E1BGQ2, H0Y354, O94955, P47224, Q08326, Q0IIH8, Q1JQA1, Q1RMS8, Q1RMZ1, Q2TBU5, Q3T1H6, Q4R372, Q4R528, Q4R9C4, Q5F480, Q5F4A1, Q5I0G3, Q5RCQ0, Q5RFG8, Q5TFE4, Q5TYM5, Q641X7, Q6L9T8, Q6PIP5, Q7L622, Q7Z6J8, Q7ZX59, Q86X60, Q8BFZ8, Q8BKW4, Q8BM85, Q8BX13, Q8CEL2, Q8N5C7, Q8N635, Q8NHU2, Q8TCF1, Q8TCJ0

Diamond homologs: A4IHT9, Q3UHB1, Q54XC1, Q5TFE4, Q6GN91, Q6Q0N3, Q75K12, Q86UY8, Q86YG4, Q9H857, Q2TBU5, Q8C5P5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	89
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
17465	NM_000493.4(COL10A1):c.1792T>G (p.Tyr598Asp)	Pathogenic
17471	NM_000493.4(COL10A1):c.1858_1859del (p.Pro620fs)	Pathogenic
17478	NM_000493.4(COL10A1):c.1896C>A (p.Tyr632Ter)	Pathogenic
17479	NM_000493.4(COL10A1):c.1784G>A (p.Gly595Glu)	Pathogenic

SpliceAI

3035 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116101020:CCCGG:C	donor_loss	1.0000
6:116101021:CCGGT:C	donor_loss	1.0000
6:116101022:CGGT:C	donor_loss	1.0000
6:116101024:G:GC	donor_loss	1.0000
6:116101024:G:GG	donor_gain	1.0000
6:116101025:T:G	donor_loss	1.0000
6:116106236:A:AG	acceptor_gain	1.0000
6:116106237:T:G	acceptor_gain	1.0000
6:116106240:GCA:G	acceptor_loss	1.0000
6:116106241:CAGCT:C	acceptor_loss	1.0000
6:116106242:A:AG	acceptor_gain	1.0000
6:116106243:G:GA	acceptor_gain	1.0000
6:116106243:GCTC:G	acceptor_gain	1.0000
6:116106243:GCTCA:G	acceptor_gain	1.0000
6:116106333:CTGGT:C	donor_loss	1.0000
6:116106334:TGG:T	donor_loss	1.0000
6:116106335:GGTA:G	donor_loss	1.0000
6:116106336:G:GA	donor_loss	1.0000
6:116106336:G:GG	donor_gain	1.0000
6:116106337:TAAGT:T	donor_loss	1.0000
6:116108359:TTCA:T	acceptor_loss	1.0000
6:116108360:TCA:T	acceptor_loss	1.0000
6:116108361:CAGTT:C	acceptor_loss	1.0000
6:116108362:A:AG	acceptor_gain	1.0000
6:116108362:AG:A	acceptor_loss	1.0000
6:116108363:G:GT	acceptor_gain	1.0000
6:116108363:GTT:G	acceptor_gain	1.0000
6:116115685:TTTTA:T	acceptor_loss	1.0000
6:116115686:TTTA:T	acceptor_loss	1.0000
6:116115687:TTA:T	acceptor_loss	1.0000

AlphaMissense

3002 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:116223082:G:C	K251N	0.999
6:116223082:G:T	K251N	0.999
6:116100977:A:T	D16V	0.998
6:116100980:T:C	L17P	0.998
6:116100983:A:T	D18V	0.998
6:116221180:C:T	T219I	0.998
6:116237025:G:T	G288W	0.998
6:116238200:G:T	G312V	0.998
6:116238203:A:C	D313A	0.998
6:116238203:A:T	D313V	0.998
6:116100971:G:A	G14E	0.997
6:116100978:C:A	D16E	0.997
6:116100978:C:G	D16E	0.997
6:116100984:C:A	D18E	0.997
6:116100984:C:G	D18E	0.997
6:116115717:T:C	F131L	0.997
6:116115719:T:A	F131L	0.997
6:116115719:T:G	F131L	0.997
6:116221071:T:C	F183L	0.997
6:116221073:T:A	F183L	0.997
6:116221073:T:G	F183L	0.997
6:116221182:A:C	S220R	0.997
6:116221184:T:A	S220R	0.997
6:116221184:T:G	S220R	0.997
6:116223075:C:A	A249E	0.997
6:116223089:T:C	F254L	0.997
6:116223091:C:A	F254L	0.997
6:116223091:C:G	F254L	0.997
6:116237025:G:A	G288R	0.997
6:116237025:G:C	G288R	0.997

dbSNP variants (sampled 300 via entrez): RS1000019405 (6:116228984 T>A), RS1000033516 (6:116155885 G>A), RS1000043820 (6:116216754 ATTTATCTCT>A), RS1000049843 (6:116206990 T>C), RS1000068351 (6:116137384 G>T), RS1000069339 (6:116247598 A>G), RS1000113914 (6:116200180 G>A,T), RS1000149318 (6:116155568 A>G), RS1000158201 (6:116112478 C>G,T), RS1000191000 (6:116103581 G>C), RS1000195704 (6:116225816 G>A), RS1000195940 (6:116189728 A>G), RS1000202309 (6:116174839 A>T), RS1000215489 (6:116178374 G>A), RS1000219478 (6:116129799 G>A,T)

Disease associations

OMIM: gene MIM:621076 | disease phenotypes: MIM:156500

GenCC curated gene-disease

Mondo (1): Schmid metaphyseal chondrodysplasia (MONDO:0007983)

Orphanet (1): Metaphyseal chondrodysplasia, Schmid type (Orphanet:174)

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001713_16	Dental caries	2.000000e-06
GCST003997_6	Myopia	2.000000e-13
GCST007643_3	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	3.000000e-06
GCST008070_13	HDL cholesterol levels	6.000000e-06
GCST008078_106	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-13
GCST008078_21	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	8.000000e-12
GCST008079_152	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-15
GCST008079_21	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5.000000e-13
GCST008086_29	LDL cholesterol levels in current drinkers	7.000000e-07
GCST008086_71	LDL cholesterol levels in current drinkers	8.000000e-09
GCST008789_10	Adolescent idiopathic scoliosis	2.000000e-08
GCST010002_333	Refractive error	2.000000e-36
GCST011348_7	High density lipoprotein cholesterol levels	8.000000e-09
GCST90002383_453	Hematocrit	6.000000e-10
GCST90011900_57	Serum alkaline phosphatase levels	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004348	hematocrit
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537352	Metaphyseal chondrodysplasia Schmid type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295852 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects expression	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol A	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Benzo(a)pyrene	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression, increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	increases expression, affects cotreatment	1
Clorgyline	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dimethyl Sulfoxide	increases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118796	Binding	Binding affinity to NT5DC1 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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