NME9

Summary

NME9 (NME/NM23 family member 9, HGNC:21343) is a protein-coding gene on chromosome 3q22.3, encoding Thioredoxin domain-containing protein 6 (Q86XW9). May be a regulator of microtubule physiology.

Predicted to enable nucleoside diphosphate kinase activity. Predicted to be involved in CTP biosynthetic process; GTP biosynthetic process; and UTP biosynthetic process. Predicted to be located in dynein axonemal particle.

Source: NCBI Gene 347736 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001349018

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21343
Approved symbol	NME9
Name	NME/NM23 family member 9
Location	3q22.3
Locus type	gene with protein product
Status	Approved
Aliases	TXL-2, NM23-H9
Ensembl gene	ENSG00000181322
Ensembl biotype	protein_coding
OMIM	618584
Entrez	347736

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000317876, ENST00000333911, ENST00000383180, ENST00000474690, ENST00000475751, ENST00000478220, ENST00000484930, ENST00000488716, ENST00000492993, ENST00000953093, ENST00000953094

RefSeq mRNA: 8 — MANE Select: NM_001349018 NM_001349018, NM_001349020, NM_001349021, NM_001349022, NM_001349023, NM_001349024, NM_001349025, NM_178130

CCDS: CCDS3099, CCDS87141, CCDS87142

Canonical transcript exons

ENST00000333911 — 11 exons

Exon	Start	End
ENSE00001238024	138304873	138305027
ENSE00001238029	138306004	138306096
ENSE00001338422	138300999	138301704
ENSE00001338426	138315527	138315643
ENSE00001919226	138329303	138329851
ENSE00003479768	138318148	138318219
ENSE00003480077	138319478	138319581
ENSE00003526550	138303507	138303643
ENSE00003572872	138306398	138306480
ENSE00003593139	138314332	138314407
ENSE00003789909	138324873	138324930

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 93.53.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4512 / max 28.7072, expressed in 183 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44756	0.1888	101
44757	0.1595	96
44755	0.1028	67

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.53	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.97	gold quality
right frontal lobe	UBERON:0002810	76.08	gold quality
hypothalamus	UBERON:0001898	75.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.23	gold quality
cerebellar hemisphere	UBERON:0002245	74.22	gold quality
cerebellar cortex	UBERON:0002129	74.11	gold quality
gastrocnemius	UBERON:0001388	73.99	gold quality
anterior cingulate cortex	UBERON:0009835	73.88	gold quality
nucleus accumbens	UBERON:0001882	73.45	gold quality
prefrontal cortex	UBERON:0000451	73.42	gold quality
muscle of leg	UBERON:0001383	72.85	gold quality
caudate nucleus	UBERON:0001873	72.80	gold quality
right testis	UBERON:0004534	72.67	gold quality
left testis	UBERON:0004533	72.58	gold quality
fallopian tube	UBERON:0003889	72.52	gold quality
adenohypophysis	UBERON:0002196	72.51	gold quality
cerebellum	UBERON:0002037	71.91	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	70.98	gold quality
amygdala	UBERON:0001876	70.55	gold quality
bone marrow cell	CL:0002092	70.43	silver quality
testis	UBERON:0000473	70.40	gold quality
pituitary gland	UBERON:0000007	70.35	gold quality
oviduct epithelium	UBERON:0004804	69.77	silver quality
putamen	UBERON:0001874	69.07	gold quality
neocortex	UBERON:0001950	68.72	gold quality
monocyte	CL:0000576	68.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

84 targeting NME9, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-298	99.63	67.56	1916

Literature-anchored findings (GeneRIF, showing 5)

• This protein is characterized. It is a microtubule-binding thioredoxin expressed predominantly in the cilia of lung airway epithelium and spermatid manchette and axoneme (PMID:12569107)
• MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. Thioredoxin-like 2 was primarily seen in the bronchial epithelium (PMID:18753468)
• Thioredoxin-like protein 2 is overexpressed in colon cancer and promotes cancer cell metastasis by interaction with ran. (PMID:23311631)
• our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment. (PMID:25555669)
• Testis-Specific Thioredoxins TXNDC2, TXNDC3, and TXNDC6 Are Expressed in Both Testicular and Systemic DLBCL and Correlate with Clinical Disease Presentation. (PMID:33603952)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	nme9	ENSDARG00000098944
mus_musculus	Nme9	ENSMUSG00000046242

Paralogs (8): NME8 (ENSG00000086288), NME3 (ENSG00000103024), NME4 (ENSG00000103202), NME5 (ENSG00000112981), NME7 (ENSG00000143156), NME6 (ENSG00000172113), NME1 (ENSG00000239672), NME2 (ENSG00000243678)

Protein

Protein identifiers

Thioredoxin domain-containing protein 6 — Q86XW9 (reviewed: Q86XW9)

Alternative names: Thioredoxin-like protein 2

All UniProt accessions (5): Q86XW9, C9JXP5, F8WDB2, H7C5P8, Q3KNW3

UniProt curated annotations — full annotation on UniProt →

Function. May be a regulator of microtubule physiology.

Subunit / interactions. Monomer and homodimer.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Dynein axonemal particle.

Tissue specificity. Detected at very low levels in testis, lung and brain.

Miscellaneous. Shows no detectable enzyme activity.

Similarity. Belongs to the NDK family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86XW9-1	1	yes
Q86XW9-2	2
Q86XW9-3	3

RefSeq proteins (8): NP_001335947, NP_001335949, NP_001335950, NP_001335951, NP_001335952, NP_001335953, NP_001335954, NP_835231 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001564	Nucleoside_diP_kinase	Family
IPR013766	Thioredoxin_domain	Domain
IPR017937	Thioredoxin_CS	Conserved_site
IPR034907	NDK-like_dom	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036850	NDK-like_dom_sf	Homologous_superfamily
IPR051766	TXND_domain-containing	Family

Pfam: PF00085, PF00334

UniProt features (10 total): splice variant 4, region of interest 2, chain 1, domain 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XW9-F1	77.89	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_PYRIMIDINE_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PYRIMIDINE_NUCLEOTIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_TRIPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, chr3q22, GOBP_GTP_METABOLIC_PROCESS, GOBP_PURINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PYRIMIDINE_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS

GO Biological Process (3): GTP biosynthetic process (GO:0006183), UTP biosynthetic process (GO:0006228), CTP biosynthetic process (GO:0006241)

GO Molecular Function (1): nucleoside diphosphate kinase activity (GO:0004550)

GO Cellular Component (5): axoneme (GO:0005930), dynein axonemal particle (GO:0120293), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
pyrimidine ribonucleoside triphosphate biosynthetic process	2
pyrimidine ribonucleotide biosynthetic process	2
intracellular membraneless organelle	2
purine ribonucleotide biosynthetic process	1
purine ribonucleoside triphosphate biosynthetic process	1
GTP metabolic process	1
UTP metabolic process	1
CTP metabolic process	1
phosphotransferase activity, phosphate group as acceptor	1
nucleobase-containing compound kinase activity	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NME9	RP2	O75695	645
NME9	TXNDC2	Q86VQ3	522
NME9	TXNDC8	Q6A555	507
NME9	GLRX3	O76003	453
NME9	SPDYE2	Q495Y8	432
NME9	UTP14C	Q5TAP6	400
NME9	ZNF841	Q6ZN19	370
NME9	DNAAF8	Q8IYS4	367
NME9	EEF1G	P26641	349
NME9	BIN2	Q9UBW5	349
NME9	TEKT3	Q9BXF9	348
NME9	DNAL4	O96015	329
NME9	ABL1	P00519	309
NME9	DBR1	Q9UK59	304
NME9	UNC119B	A6NIH7	302

IntAct

2 interactions, top by confidence:

A	B	Type	Score
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (1): NME9 (Affinity Capture-MS)

ESM2 similar proteins: A2AIG8, A6NFX1, O15315, O35083, O35719, O35790, O43502, O54783, O54804, O55229, O73884, P16442, P20417, P35790, P35821, P47802, Q01134, Q08DW9, Q27HK4, Q2TBS1, Q3T9M1, Q3U129, Q4R3I0, Q4R766, Q4R7M4, Q5E9H2, Q5E9T4, Q5SUV1, Q5SX19, Q5VYX0, Q6GV29, Q86XW9, Q8BVM4, Q8CIW5, Q8N2K0, Q8NBA8, Q8QGV6, Q8R2J9, Q8TCT0, Q924H5

Diamond homologs: A0A1L1SUL6, A1V4K4, A2S299, A3M207, A3MK78, A3NA57, A3NVX4, A4F9J8, A4G4J8, A4XY36, A5F3F7, A5IC43, A5UDJ8, A5UI22, A6Q200, A6SZX4, A6V0V6, A6VMK7, A7I3D2, A7MU38, A8ERJ2, A9HJV3, A9IK55, B0RT49, B0USF1, B0V4U1, B0VKS3, B2FNQ5, B2I3E1, B2SXT3, B3E3P0, B3PDL7, B4SSW2, B5FAW8, B7H073, B7I5G3, B7UWI4, B7VJT4, B8IZ74, B9MFX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3405 predictions. Top by Δscore:

Variant	Effect	Δscore
3:138264129:A:AC	acceptor_loss	1.0000
3:138264129:A:AG	acceptor_gain	1.0000
3:138264129:AGAT:A	acceptor_gain	1.0000
3:138264130:G:GG	acceptor_gain	1.0000
3:138264130:GA:G	acceptor_gain	1.0000
3:138264130:GAT:G	acceptor_gain	1.0000
3:138264130:GATG:G	acceptor_gain	1.0000
3:138264130:GATGT:G	acceptor_gain	1.0000
3:138264211:AGG:A	donor_loss	1.0000
3:138264214:T:G	donor_loss	1.0000
3:138267149:CCATA:C	acceptor_loss	1.0000
3:138267150:CATA:C	acceptor_loss	1.0000
3:138267152:TAGG:T	acceptor_loss	1.0000
3:138267153:AGG:A	acceptor_loss	1.0000
3:138267239:GAG:G	donor_gain	1.0000
3:138267240:AGG:A	donor_loss	1.0000
3:138267241:GGTT:G	donor_loss	1.0000
3:138267242:G:T	donor_loss	1.0000
3:138267243:T:A	donor_loss	1.0000
3:138270027:T:TA	acceptor_gain	1.0000
3:138270032:A:AG	acceptor_gain	1.0000
3:138270032:AAT:A	acceptor_gain	1.0000
3:138270032:AATG:A	acceptor_gain	1.0000
3:138270033:A:G	acceptor_gain	1.0000
3:138270034:T:G	acceptor_gain	1.0000
3:138270034:T:TA	acceptor_gain	1.0000
3:138284425:TTCCA:T	acceptor_loss	1.0000
3:138284426:TCCAG:T	acceptor_loss	1.0000
3:138284427:CCAG:C	acceptor_loss	1.0000
3:138284428:CAGAC:C	acceptor_loss	1.0000

AlphaMissense

2173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:138318160:A:C	F85L	0.985
3:138318160:A:T	F85L	0.985
3:138318162:A:G	F85L	0.985
3:138319581:A:T	V31D	0.979
3:138304931:A:G	W245R	0.977
3:138304931:A:T	W245R	0.977
3:138319561:A:G	W38R	0.975
3:138319561:A:T	W38R	0.975
3:138319578:A:T	V32D	0.973
3:138319572:A:T	V34D	0.967
3:138304983:G:C	S227R	0.965
3:138304983:G:T	S227R	0.965
3:138304985:T:G	S227R	0.965
3:138318161:A:G	F85S	0.964
3:138324906:A:G	W20R	0.964
3:138324906:A:T	W20R	0.964
3:138315628:C:G	A95P	0.963
3:138306447:A:T	I165N	0.962
3:138306443:T:A	K166N	0.959
3:138306443:T:G	K166N	0.959
3:138318158:A:G	L86P	0.959
3:138303592:G:C	S281R	0.955
3:138303592:G:T	S281R	0.955
3:138303594:T:G	S281R	0.955
3:138318155:A:G	F87S	0.955
3:138304975:A:G	L230P	0.954
3:138319559:C:A	W38C	0.953
3:138319559:C:G	W38C	0.953
3:138304916:C:G	G250R	0.950
3:138315597:A:G	L105P	0.949

dbSNP variants (sampled 300 via entrez): RS1000022483 (3:138262137 G>A,C), RS1000266002 (3:138318274 T>A,C), RS1000282302 (3:138327874 C>G,T), RS1000327694 (3:138269253 A>C), RS1000338062 (3:138303529 G>A,C,T), RS1000379987 (3:138269681 C>G,T), RS1000381802 (3:138320435 T>C,G), RS1000399210 (3:138310838 A>G), RS1000457625 (3:138278792 A>G), RS1000487314 (3:138279125 A>G), RS1000491135 (3:138299638 GAGTCACC>G), RS1000599157 (3:138316601 A>G), RS1000625870 (3:138301770 C>T), RS1000651157 (3:138272602 C>A), RS1000651760 (3:138318351 A>G)

Disease associations

OMIM: gene MIM:618584 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000895_2	Whole-brain volume (Alzheimer’s disease interaction)	8.000000e-06
GCST002509_5	Amyotrophic lateral sclerosis	1.000000e-06
GCST005178_1	Modified Stumvoll Insulin Sensitivity Index	2.000000e-06
GCST007930_6	Medication use (agents acting on the renin-angiotensin system)	1.000000e-10
GCST010774_22	Essential hypertension (time to event)	9.000000e-09
GCST90020024_1270	A body shape index	8.000000e-10
GCST90020025_474	Waist-to-hip ratio adjusted for BMI	1.000000e-09
GCST90020027_1848	Waist-hip index	8.000000e-10

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005089	whole-brain volume
EFO:0004471	insulin sensitivity measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0004918	age at diagnosis
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Rotenone	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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