NTAQ1

Summary

NTAQ1 (N-terminal glutamine amidase 1, HGNC:25490) is a protein-coding gene on chromosome 8q24.13, encoding Protein N-terminal glutamine amidohydrolase (Q96HA8). Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation.

Predicted to enable protein-N-terminal glutamine amidohydrolase activity. Predicted to be involved in protein modification process. Predicted to be located in cytoplasm. Predicted to be active in cytosol and nucleus.

Source: NCBI Gene 55093 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• MANE Select transcript: NM_018024

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25490
Approved symbol	NTAQ1
Name	N-terminal glutamine amidase 1
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10204
Ensembl gene	ENSG00000156795
Ensembl biotype	protein_coding
OMIM	620846
Entrez	55093

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000287387, ENST00000517609, ENST00000518125, ENST00000519199, ENST00000522194, ENST00000523356, ENST00000523551, ENST00000523984, ENST00000524254, ENST00000650311, ENST00000913839

RefSeq mRNA: 3 — MANE Select: NM_018024 NM_001283024, NM_001283027, NM_018024

CCDS: CCDS6344, CCDS64965

Canonical transcript exons

ENST00000287387 — 6 exons

Exon	Start	End
ENSE00001165891	123416774	123416932
ENSE00002114153	123441306	123442240
ENSE00003499127	123436453	123436601
ENSE00003610528	123427924	123428023
ENSE00003679295	123437210	123437334
ENSE00003681110	123429983	123430033

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 92.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0213 / max 165.9154, expressed in 1798 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90486	13.7969	1794
90485	2.1346	1075
90484	1.0898	650

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.43	gold quality
ganglionic eminence	UBERON:0004023	91.96	gold quality
secondary oocyte	CL:0000655	91.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.36	gold quality
islet of Langerhans	UBERON:0000006	89.48	gold quality
oocyte	CL:0000023	89.28	gold quality
embryo	UBERON:0000922	89.09	gold quality
pons	UBERON:0000988	88.98	gold quality
heart left ventricle	UBERON:0002084	88.69	gold quality
gastrocnemius	UBERON:0001388	88.66	gold quality
cardiac ventricle	UBERON:0002082	88.49	gold quality
muscle of leg	UBERON:0001383	88.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.23	gold quality
ventricular zone	UBERON:0003053	87.80	gold quality
prefrontal cortex	UBERON:0000451	87.77	gold quality
spinal cord	UBERON:0002240	87.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.60	gold quality
adult organism	UBERON:0007023	87.57	gold quality
sperm	CL:0000019	87.44	gold quality
heart	UBERON:0000948	87.17	gold quality
hypothalamus	UBERON:0001898	87.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.10	gold quality
germinal epithelium of ovary	UBERON:0001304	86.71	gold quality
dorsal root ganglion	UBERON:0000044	86.62	gold quality
right atrium auricular region	UBERON:0006631	86.53	gold quality
left ovary	UBERON:0002119	86.17	gold quality
pancreas	UBERON:0001264	86.15	gold quality
muscle organ	UBERON:0001630	85.98	gold quality
cardiac atrium	UBERON:0002081	85.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	44.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting NTAQ1, 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-5696	99.98	72.36	4487
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-548U	99.65	67.78	1463
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-892B	98.00	67.11	821
HSA-MIR-4678	97.59	68.31	902
HSA-MIR-6807-5P	97.51	64.25	1046
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-331-5P	96.59	67.94	705
HSA-MIR-597-3P	96.46	68.03	1035
HSA-MIR-521	84.12	62.93	54

Literature-anchored findings (GeneRIF, showing 1)

• the peptide backbone recognition patch of hNtaq1 forms nonspecific interactions with N-terminal peptides of substrate proteins (PMID:25356641)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ntaq1	ENSDARG00000070403
mus_musculus	Ntaq1	ENSMUSG00000022359
rattus_norvegicus	Ntaq1	ENSRNOG00000006700
drosophila_melanogaster	tun	FBGN0034046
caenorhabditis_elegans	R06C7.6	WBGENE00011065

Protein

Protein identifiers

Protein N-terminal glutamine amidohydrolase — Q96HA8 (reviewed: Q96HA8)

Alternative names: Protein NH2-terminal glutamine deamidase, WDYHV motif-containing protein 1

All UniProt accessions (7): Q96HA8, A0A3B3IS49, A0A3B3ITD7, A0A3B3ITI2, E5RHC2, E5RIY9, H0YBV4

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. Does not act on substrates with internal or C-terminal glutamine and does not act on non-glutamine residues in any position. Does not deaminate acetylated N-terminal glutamine. With the exception of proline, all tested second-position residues on substrate peptides do not greatly influence the activity. In contrast, a proline at position 2, virtually abolishes deamidation of N-terminal glutamine.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Similarity. Belongs to the NTAQ1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96HA8-1	1	yes
Q96HA8-2	2

RefSeq proteins (3): NP_001269953, NP_001269956, NP_060494* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023128	Prot_N_Gln_amidohydro_ab_roll	Domain
IPR037132	N_Gln_amidohydro_ab_roll_sf	Homologous_superfamily
IPR039733	NTAQ1	Family

Pfam: PF09764

Enzyme classification (BRENDA):

• EC 3.5.1.122 — protein N-terminal glutamine amidohydrolase (BRENDA: 7 organisms, 10 substrates, 0 inhibitors, 1 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• N-terminal L-glutaminyl-[protein] + H2O = N-terminal L-glutamyl-[protein] + NH4(+) (RHEA:50680)

UniProt features (33 total): strand 13, helix 10, sequence variant 4, active site 3, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8JJW	X-RAY DIFFRACTION	1.4
8JJG	X-RAY DIFFRACTION	1.45
8JK0	X-RAY DIFFRACTION	1.45
8JJU	X-RAY DIFFRACTION	1.46
3C9Q	X-RAY DIFFRACTION	1.5
4W79	X-RAY DIFFRACTION	1.5
8JJF	X-RAY DIFFRACTION	1.51
8JJH	X-RAY DIFFRACTION	1.61
8JJY	X-RAY DIFFRACTION	1.69
8JJX	X-RAY DIFFRACTION	1.7
8JK2	X-RAY DIFFRACTION	1.74
6KGJ	X-RAY DIFFRACTION	1.8
8JJZ	X-RAY DIFFRACTION	2.03
8JK1	X-RAY DIFFRACTION	2.07
8JJI	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HA8-F1	94.97	0.92

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 (3): 28; 81; 97

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 99 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MUELLER_PLURINET, MORI_PLASMA_CELL_UP, FISCHER_DREAM_TARGETS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, BOYAULT_LIVER_CANCER_SUBCLASS_G3_UP, SENESE_HDAC1_AND_HDAC2_TARGETS_UP, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS_IN_LINEAR_AMIDES, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_CARBON_NITROGEN_BUT_NOT_PEPTIDE_BONDS, chr8q24, SIRNA_EIF4GI_DN, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, GSE14699_NAIVE_VS_ACT_CD8_TCELL_UP, HOXC6_TARGET_GENES

GO Biological Process (1): protein modification process (GO:0036211)

GO Molecular Function (5): protein-N-terminal asparagine amidohydrolase activity (GO:0008418), protein-N-terminal glutamine amidohydrolase activity (GO:0070773), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein metabolic process	1
macromolecule modification	1
protein asparagine deamidase activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTAQ1	ATE1	O95260	728
NTAQ1	NTAN1	Q96AB6	718
NTAQ1	UBR2	Q8IWV8	717
NTAQ1	UBR1	Q8IWV7	697
NTAQ1	UBE2A	P49459	612
NTAQ1	COPZ2	Q9P299	574
NTAQ1	ATAD2	Q6PL18	564
NTAQ1	TRABD	Q9H4I3	530
NTAQ1	QTRT1	Q9BXR0	492
NTAQ1	FAM91A1	Q658Y4	490
NTAQ1	PCMTD1	Q96MG8	475
NTAQ1	OSTM1	Q86WC4	447
NTAQ1	BCKDK	O14874	442
NTAQ1	GCDH	Q92947	436
NTAQ1	NUDT22	Q9BRQ3	427

IntAct

1321 interactions, top by confidence:

A	B	Type	Score
NTAQ1	HSD17B14	psi-mi:“MI:0915”(physical association)	0.920
NTAQ1	HPRT1	psi-mi:“MI:0915”(physical association)	0.880
HPRT1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.880
RABAC1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.840
NTAQ1	RABAC1	psi-mi:“MI:0915”(physical association)	0.840
NTAQ1	RPIA	psi-mi:“MI:0915”(physical association)	0.830
NTAQ1	THAP1	psi-mi:“MI:0915”(physical association)	0.830
RPIA	NTAQ1	psi-mi:“MI:0915”(physical association)	0.830
THAP1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.830
BIRC2	NTAQ1	psi-mi:“MI:0915”(physical association)	0.800
NTAQ1	BIRC2	psi-mi:“MI:0915”(physical association)	0.800
NTAQ1	NECAB2	psi-mi:“MI:0915”(physical association)	0.790
GOLGA2	NTAQ1	psi-mi:“MI:0915”(physical association)	0.790
NTAQ1	KLHL12	psi-mi:“MI:0915”(physical association)	0.790
NECAB2	NTAQ1	psi-mi:“MI:0915”(physical association)	0.790
NTAQ1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.790
CRYAA	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
ASL	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
CDA	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
ACTG1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
EIF2B1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
PNMA5	NTAQ1	psi-mi:“MI:0915”(physical association)	0.780
NTAQ1	CRYAA	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (557): WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid), WDYHV1 (Two-hybrid)

ESM2 similar proteins: A1L251, A3KPF2, A8MVJ9, A8Y183, A9XLE1, A9XLE2, A9XLG1, B3MCF3, B3NQ86, B4HSF8, B4J8A0, B4KPY6, B4MDT2, B4MQL4, B4P6V4, B4QGZ1, B8AXU2, F6S9E6, O13648, O14215, O22944, O81395, P04176, P16331, P40483, P45350, P51820, Q05763, Q10075, Q10313, Q1LWX3, Q21775, Q27883, Q28WL0, Q28YQ7, Q2QRX6, Q32NQ7, Q5BJV9, Q5PPU8, Q60E61

Diamond homologs: A8Y183, B3MCF3, B3NQ86, B4HSF8, B4J8A0, B4KPY6, B4MDT2, B4MQL4, B4P6V4, B4QGZ1, B8AXU2, O22944, Q1LWX3, Q21775, Q28WL0, Q3T0D3, Q5BJV9, Q5PPU8, Q60E61, Q7K2Y9, Q7Q968, Q80WB5, Q96HA8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
Keratinization	7	8.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563555	GRCh37/hg19 8q24.12-24.3(chr8:121694649-146295771)x3	Pathogenic

SpliceAI

1080 predictions. Top by Δscore:

Variant	Effect	Δscore
8:123427918:TTTCA:T	acceptor_loss	1.0000
8:123427919:TTCA:T	acceptor_loss	1.0000
8:123427921:CAG:C	acceptor_loss	1.0000
8:123427922:A:AG	acceptor_gain	1.0000
8:123427922:A:AT	acceptor_loss	1.0000
8:123427922:AGT:A	acceptor_gain	1.0000
8:123427923:G:GT	acceptor_gain	1.0000
8:123427923:GT:G	acceptor_gain	1.0000
8:123427923:GTG:G	acceptor_gain	1.0000
8:123427923:GTGA:G	acceptor_gain	1.0000
8:123427923:GTGAA:G	acceptor_gain	1.0000
8:123428020:GATG:G	donor_gain	1.0000
8:123428022:TGGTA:T	donor_loss	1.0000
8:123428023:GGT:G	donor_loss	1.0000
8:123428024:G:GC	donor_loss	1.0000
8:123428024:G:GG	donor_gain	1.0000
8:123428025:TAA:T	donor_loss	1.0000
8:123428028:GTTG:G	donor_gain	1.0000
8:123436447:TTTTA:T	acceptor_loss	1.0000
8:123436448:TTTAG:T	acceptor_loss	1.0000
8:123436449:TTAG:T	acceptor_loss	1.0000
8:123436450:TA:T	acceptor_loss	1.0000
8:123436451:A:C	acceptor_loss	1.0000
8:123436452:G:A	acceptor_loss	1.0000
8:123436482:AAGT:A	acceptor_gain	1.0000
8:123436483:A:G	acceptor_gain	1.0000
8:123436639:G:GG	donor_gain	1.0000
8:123437206:GCAG:G	acceptor_loss	1.0000
8:123437208:A:AC	acceptor_loss	1.0000
8:123437208:A:AG	acceptor_gain	1.0000

AlphaMissense

1378 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:123437219:A:C	R131S	0.994
8:123437219:A:T	R131S	0.994
8:123427927:A:C	E29D	0.993
8:123427927:A:T	E29D	0.993
8:123436459:C:G	H81D	0.993
8:123437263:G:C	R146P	0.993
8:123427926:A:T	E29V	0.992
8:123428004:T:A	I55K	0.992
8:123437251:T:C	F142S	0.992
8:123437273:G:A	M149I	0.992
8:123437273:G:C	M149I	0.992
8:123437273:G:T	M149I	0.992
8:123427998:T:A	V53D	0.991
8:123428001:T:C	F54S	0.990
8:123428011:T:A	N57K	0.990
8:123428011:T:G	N57K	0.990
8:123428006:T:C	S56P	0.989
8:123437218:G:C	R131T	0.989
8:123437272:T:C	M149T	0.989
8:123427929:A:T	E30V	0.988
8:123430033:G:C	W78C	0.988
8:123430033:G:T	W78C	0.988
8:123436461:T:A	H81Q	0.988
8:123436461:T:G	H81Q	0.988
8:123437256:T:C	S144P	0.988
8:123436508:A:C	D97A	0.987
8:123437238:T:G	Y138D	0.987
8:123437263:G:T	R146L	0.987
8:123427933:T:A	N31K	0.986
8:123427933:T:G	N31K	0.986

dbSNP variants (sampled 300 via entrez): RS1000016239 (8:123417955 A>T), RS1000067192 (8:123456036 C>A), RS1000198619 (8:123454914 G>A), RS1000204153 (8:123448208 A>C), RS1000277034 (8:123432541 A>G), RS1000277930 (8:123460566 T>C), RS1000333780 (8:123454637 C>T), RS1000337754 (8:123444139 AT>A), RS1000396914 (8:123414946 T>C), RS1000414250 (8:123420916 A>G), RS1000444138 (8:123460765 G>C), RS1000474518 (8:123426053 T>A), RS1000531525 (8:123473381 C>T), RS1000618645 (8:123416608 T>C,G), RS1000670120 (8:123456024 T>C,G)

Disease associations

OMIM: gene MIM:620846 | 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
GCST90000025_375	Appendicular lean mass	4.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Cyclosporine	increases expression	3
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	decreases expression	1
nickel sulfate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
abrine	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases mutagenesis	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Dihydrotestosterone	increases expression	1
Testosterone	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1KI	HyCyte HEK293T KO-hNTAQ1	Transformed cell line	Female

Clinical trials (associated diseases)

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