NTAN1

Summary

NTAN1 (N-terminal asparagine amidase, HGNC:29909) is a protein-coding gene on chromosome 16p13.11, encoding Protein N-terminal asparagine amidohydrolase (Q96AB6). N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate.

The protein encoded by this gene functions in a step-wise process of protein degradation through the N-end rule pathway. This protein acts as a tertiary destabilizing enzyme that deamidates N-terminal L-Asn residues on proteins to produce N-terminal L-Asp. L-Asp substrates are subsequently conjugated to L-Arg, which is recognized by specific E3 ubiquitin ligases and targeted to the proteasome. Pseudogenes of this gene are located on the long arms of chromosomes 8, 10 and 12. Alternative splicing results in multiple transcript variants that encode different protein isoforms.

Source: NCBI Gene 123803 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 62 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_173474

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29909
Approved symbol	NTAN1
Name	N-terminal asparagine amidase
Location	16p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157045
Ensembl biotype	protein_coding
OMIM	615367
Entrez	123803

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000287706, ENST00000563940, ENST00000565187, ENST00000566419, ENST00000566542, ENST00000567030, ENST00000567420, ENST00000568320, ENST00000568738, ENST00000570292, ENST00000622833, ENST00000624579

RefSeq mRNA: 3 — MANE Select: NM_173474 NM_001270766, NM_001270767, NM_173474

CCDS: CCDS10558, CCDS73832

Canonical transcript exons

ENST00000287706 — 10 exons

Exon	Start	End
ENSE00001215048	15037857	15038210
ENSE00001318750	15055891	15056074
ENSE00003462795	15047997	15048099
ENSE00003502530	15041623	15041676
ENSE00003532614	15041068	15041121
ENSE00003546261	15047855	15047920
ENSE00003595886	15039969	15040066
ENSE00003673978	15044334	15044407
ENSE00003678651	15047442	15047550
ENSE00003788639	15038574	15038687

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 96.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9277 / max 753.3613, expressed in 1803 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156377	14.9039	1790
156378	4.2670	1659
156375	1.1649	768
156379	0.3468	121
156376	0.2452	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
subcutaneous adipose tissue	UBERON:0002190	96.22	gold quality
stromal cell of endometrium	CL:0002255	95.91	gold quality
mucosa of stomach	UBERON:0001199	95.84	gold quality
endocervix	UBERON:0000458	95.83	gold quality
adipose tissue	UBERON:0001013	95.69	gold quality
calcaneal tendon	UBERON:0003701	95.48	gold quality
omental fat pad	UBERON:0010414	95.09	gold quality
right lung	UBERON:0002167	95.03	gold quality
right coronary artery	UBERON:0001625	94.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.77	gold quality
left coronary artery	UBERON:0001626	94.61	gold quality
thoracic mammary gland	UBERON:0005200	94.38	gold quality
mammary gland	UBERON:0001911	94.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.30	gold quality
amygdala	UBERON:0001876	94.28	gold quality
myometrium	UBERON:0001296	94.26	gold quality
lower esophagus	UBERON:0013473	94.24	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.24	gold quality
temporal lobe	UBERON:0001871	94.22	gold quality
gall bladder	UBERON:0002110	94.15	gold quality
tibial artery	UBERON:0007610	94.14	gold quality
popliteal artery	UBERON:0002250	94.12	gold quality
smooth muscle tissue	UBERON:0001135	94.08	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.07	gold quality
vagina	UBERON:0000996	94.01	gold quality
body of uterus	UBERON:0009853	94.01	gold quality
ectocervix	UBERON:0012249	93.96	gold quality
left ovary	UBERON:0002119	93.86	gold quality
tibial nerve	UBERON:0001323	93.79	gold quality
aorta	UBERON:0000947	93.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	40.76
E-ANND-3	yes	7.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting NTAN1, 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-9-5P	100.00	72.28	2361
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-3667-5P	97.16	64.87	591
HSA-MIR-4661-3P	96.81	66.02	342
HSA-MIR-6839-5P	96.74	68.29	1088
HSA-MIR-378J	96.44	66.20	1020

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 1)

• Results indicate that hNTAN1 is highly selective for the hydrolysis of N-terminal peptidyl L-Asn. (PMID:21375249)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ntan1	ENSMUSG00000022681
rattus_norvegicus	Ntan1	ENSRNOG00000080737
drosophila_melanogaster	Ntan1	FBGN0034371

Protein

Protein identifiers

Protein N-terminal asparagine amidohydrolase — Q96AB6 (reviewed: Q96AB6)

Alternative names: Protein NH2-terminal asparagine amidohydrolase, Protein NH2-terminal asparagine deamidase

All UniProt accessions (7): Q96AB6, A0A087X0T5, H3BMX8, H3BNJ5, H3BPN7, H3BR97, H3BU50

UniProt curated annotations — full annotation on UniProt →

Function. N-terminal asparagine deamidase that mediates deamidation of N-terminal asparagine residues to aspartate. Required for the ubiquitin-dependent turnover of intracellular proteins that initiate with Met-Asn. These proteins are acetylated on the retained initiator methionine and can subsequently be modified by the removal of N-acetyl methionine by acylaminoacid hydrolase (AAH). Conversion of the resulting N-terminal asparagine to aspartate by NTAN1/PNAD renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. This enzyme does not act on substrates with internal or C-terminal asparagines and does not act on glutamine residues in any position, nor on acetylated N-terminal peptidyl Asn.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Activity regulation. Inhibited by micromolar concentrations of copper and zinc ions.

RefSeq proteins (3): NP_001257695, NP_001257696, NP_775745* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026750	NTAN1	Family

Pfam: PF14736

Enzyme classification (BRENDA):

• EC 3.5.1.121 — protein N-terminal asparagine amidohydrolase (BRENDA: 7 organisms, 28 substrates, 15 inhibitors, 2 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• N-terminal L-asparaginyl-[protein] + H2O + H(+) = N-terminal L-aspartyl-[protein] + NH4(+) (RHEA:50676)

UniProt features (42 total): strand 20, helix 10, turn 4, sequence variant 2, mutagenesis site 2, sequence conflict 2, chain 1, site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6A0E	X-RAY DIFFRACTION	1.95
6A0I	X-RAY DIFFRACTION	2
6A0F	X-RAY DIFFRACTION	2.38
6A0H	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96AB6-F1	95.83	0.95

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 (1): 75 (essential for catalytic activity)

Mutagenesis-validated functional residues (2):

Position	Phenotype
2	3-fold reduction in catalytic activity.
75	abolishes catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ADULT_BEHAVIOR, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, GGAMTNNNNNTCCY_UNKNOWN, DAVICIONI_RHABDOMYOSARCOMA_PAX_FOXO1_FUSION_UP, ONKEN_UVEAL_MELANOMA_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP

GO Biological Process (3): ubiquitin-dependent protein catabolic process (GO:0006511), memory (GO:0007613), adult locomotory behavior (GO:0008344)

GO Molecular Function (3): protein-N-terminal asparagine amidohydrolase activity (GO:0008418), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	1
modification-dependent protein catabolic process	1
learning or memory	1
locomotory behavior	1
adult behavior	1
protein asparagine deamidase activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTAN1	SELL	P14151	995
NTAN1	CHST4	Q8NCG5	962
NTAN1	CHST2	Q9Y4C5	913
NTAN1	MADCAM1	Q13477	859
NTAN1	CCR7	P32248	790
NTAN1	PDXDC1	Q6P996	724
NTAN1	NTAQ1	Q96HA8	718
NTAN1	CCL21	O00585	709
NTAN1	SELP	P16109	702
NTAN1	VCAM1	P19320	701
NTAN1	SELPLG	Q14242	686
NTAN1	UBR1	Q8IWV7	638
NTAN1	CHST1	O43916	636
NTAN1	UBR2	Q8IWV8	636
NTAN1	ATE1	O95260	616

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MEOX2	NTAN1	psi-mi:“MI:0915”(physical association)	0.560
NTAN1	RIPK1	psi-mi:“MI:0915”(physical association)	0.500
NTAN1	RIPK1	psi-mi:“MI:0914”(association)	0.500
NTAN1	RIPK1	psi-mi:“MI:0915”(physical association)	0.400
NTAN1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): RIPK1 (Affinity Capture-MS), NTAN1 (Co-fractionation), RIPK1 (Affinity Capture-MS), NTAN1 (Two-hybrid), NTAN1 (Two-hybrid), NTAN1 (Two-hybrid), NTAN1 (Two-hybrid), UBR2 (Reconstituted Complex), NTAN1 (Affinity Capture-Western), NTAN1 (Two-hybrid), NTAN1 (Affinity Capture-RNA), NTAN1 (Affinity Capture-MS), RIPK1 (Affinity Capture-MS), MGAT5B (Affinity Capture-MS), PLAA (Co-fractionation)

ESM2 similar proteins: A0A1L1SUL6, F1LQY6, O35465, O43379, O75293, O88910, O88954, P0C0T1, P21964, P22339, P41214, P50747, Q13368, Q13572, Q14318, Q16342, Q1HAQ0, Q28955, Q2T9Z1, Q3B7U9, Q3TFD2, Q3TMX7, Q496Y0, Q4AC99, Q5BIM1, Q5E9A5, Q5R812, Q5RA63, Q5SZD4, Q64311, Q6DC64, Q6P5G6, Q6PFY8, Q80YV4, Q8BNV1, Q8BYN3, Q8NFZ0, Q8R1C6, Q8R1T1, Q8TCU6

Diamond homologs: O64876, Q28955, Q64311, Q96AB6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1774 predictions. Top by Δscore:

Variant	Effect	Δscore
16:15038683:ATCAT:A	acceptor_gain	1.0000
16:15038684:TCAT:T	acceptor_gain	1.0000
16:15038685:CAT:C	acceptor_gain	1.0000
16:15038685:CATC:C	acceptor_gain	1.0000
16:15038686:AT:A	acceptor_gain	1.0000
16:15038688:C:CC	acceptor_gain	1.0000
16:15039967:A:AC	donor_gain	1.0000
16:15039968:C:CA	donor_gain	1.0000
16:15039968:CTG:C	donor_gain	1.0000
16:15039968:CTGGT:C	donor_gain	1.0000
16:15039975:T:TA	donor_gain	1.0000
16:15041063:CTTA:C	donor_loss	1.0000
16:15041064:TTACC:T	donor_loss	1.0000
16:15041065:T:TG	donor_loss	1.0000
16:15041066:A:T	donor_loss	1.0000
16:15041117:TAATT:T	acceptor_gain	1.0000
16:15041118:AATTC:A	acceptor_loss	1.0000
16:15041120:TT:T	acceptor_gain	1.0000
16:15041120:TTC:T	acceptor_loss	1.0000
16:15041121:TCTAC:T	acceptor_loss	1.0000
16:15041122:C:CA	acceptor_loss	1.0000
16:15041122:C:CC	acceptor_gain	1.0000
16:15044329:CTTA:C	donor_loss	1.0000
16:15044330:TTAC:T	donor_loss	1.0000
16:15044331:TA:T	donor_loss	1.0000
16:15044332:A:AC	donor_gain	1.0000
16:15044332:AC:A	donor_loss	1.0000
16:15044333:C:CC	donor_gain	1.0000
16:15044333:CTAA:C	donor_gain	1.0000
16:15055887:TCA:T	donor_loss	1.0000

AlphaMissense

2017 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:15044380:G:C	F129L	0.999
16:15044380:G:T	F129L	0.999
16:15044382:A:G	F129L	0.999
16:15048035:A:T	V49D	0.998
16:15044387:C:T	G127E	0.997
16:15041114:A:C	N165K	0.996
16:15041114:A:T	N165K	0.996
16:15044390:A:T	V126D	0.996
16:15044381:A:G	F129S	0.995
16:15048017:G:T	A55E	0.995
16:15044339:A:G	L143P	0.994
16:15047869:A:T	V79D	0.994
16:15047880:A:C	C75W	0.994
16:15047882:A:G	C75R	0.994
16:15047891:C:G	A72P	0.994
16:15047900:A:G	S69P	0.994
16:15048026:C:A	R52I	0.994
16:15038172:A:C	F264L	0.993
16:15038172:A:T	F264L	0.993
16:15038174:A:G	F264L	0.993
16:15044388:C:G	G127R	0.993
16:15044388:C:T	G127R	0.993
16:15044393:A:G	L125P	0.993
16:15047527:G:C	H92D	0.993
16:15047881:C:T	C75Y	0.993
16:15047902:C:T	G68D	0.993
16:15041643:A:G	L156S	0.992
16:15044384:C:T	G128D	0.992
16:15047890:G:T	A72D	0.992
16:15038060:A:G	W302R	0.991

dbSNP variants (sampled 300 via entrez): RS1000100096 (16:15051935 T>C), RS1000287147 (16:15046029 T>C), RS1000521888 (16:15046203 G>A,C), RS1000573907 (16:15046214 T>C), RS1000685994 (16:15052572 C>T), RS1000829647 (16:15046410 C>A,T), RS1000969056 (16:15050427 G>A), RS1001082482 (16:15056191 GT>G), RS1001177168 (16:15045142 AAAAG>A), RS1001284590 (16:15056031 G>A,C,T), RS1001550424 (16:15040720 A>G), RS1001733059 (16:15044965 CA>C,CAA), RS1001812949 (16:15052098 C>A), RS1001969682 (16:15049064 T>G), RS1002082937 (16:15048755 C>T)

Disease associations

OMIM: gene MIM:615367 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000611_1	Height	7.000000e-06
GCST002444_7	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	2.000000e-67
GCST002444_8	Plasma omega-6 polyunsaturated fatty acid levels (dihomo-gamma-linolenic acid)	5.000000e-25
GCST002446_5	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	1.000000e-15
GCST002446_8	Plasma omega-6 polyunsaturated fatty acid levels (linoleic acid)	4.000000e-14
GCST002449_7	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	2.000000e-10
GCST002450_10	Plasma omega-6 polyunsaturated fatty acid levels (gamma-linolenic acid)	2.000000e-12
GCST005650_207	Serum metabolite ratios in chronic kidney disease	3.000000e-13
GCST007691_4	Femoral neck bone mineral density	2.000000e-10
GCST008129_26	Body mass index	2.000000e-09
GCST008152_71	Weight	2.000000e-06
GCST008839_113	Height	4.000000e-16
GCST009391_2068	Metabolite levels	8.000000e-06
GCST010136_16	Fruit consumption	2.000000e-08
GCST90000025_85	Appendicular lean mass	3.000000e-16
GCST90000026_25	Appendicular lean mass	9.000000e-10
GCST90000027_46	Appendicular lean mass	8.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0007785	femoral neck bone mineral density
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0010346	cholesteryl ester 18:3 measurement
EFO:0008111	diet measurement
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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentabromodiphenyl ether	decreases expression	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Isotretinoin	decreases expression	1
Copper Sulfate	increases 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_E1KH	HyCyte HEK293T KO-hNTAN1	Transformed cell line	Female

Clinical trials (associated diseases)

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