NXNL2

Summary

NXNL2 (nucleoredoxin like 2, HGNC:30482) is a protein-coding gene on chromosome 9q22.1, encoding Nucleoredoxin-like protein 2 (Q5VZ03). May be involved in the maintenance of both the function and the viability of sensory neurons, including photoreceptors and olfactory neurons.

Predicted to be involved in sensory perception of smell and visual perception.

Source: NCBI Gene 158046 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001161625

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30482
Approved symbol	NXNL2
Name	nucleoredoxin like 2
Location	9q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RdCVF2
Ensembl gene	ENSG00000130045
Ensembl biotype	protein_coding
OMIM	615299
Entrez	158046

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000375854, ENST00000375855, ENST00000478686, ENST00000649870, ENST00000884229, ENST00000939980, ENST00000943781

RefSeq mRNA: 2 — MANE Select: NM_001161625 NM_001161625, NM_145283

CCDS: CCDS55325, CCDS6679

Canonical transcript exons

ENST00000375854 — 2 exons

Exon	Start	End
ENSE00002277862	88535178	88535736
ENSE00003832801	88544379	88544973

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 96.53.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2192 / max 47.5862, expressed in 197 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97267	0.8628	179
97268	0.1926	97
97269	0.1638	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.53	gold quality
endocervix	UBERON:0000458	83.26	gold quality
calcaneal tendon	UBERON:0003701	81.72	gold quality
stromal cell of endometrium	CL:0002255	79.15	gold quality
buccal mucosa cell	CL:0002336	79.01	gold quality
fallopian tube	UBERON:0003889	78.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.57	gold quality
body of uterus	UBERON:0009853	77.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.33	gold quality
left uterine tube	UBERON:0001303	76.21	gold quality
oviduct epithelium	UBERON:0004804	76.09	gold quality
popliteal artery	UBERON:0002250	75.30	gold quality
tibial artery	UBERON:0007610	75.28	gold quality
left ovary	UBERON:0002119	73.85	gold quality
ectocervix	UBERON:0012249	73.14	gold quality
aorta	UBERON:0000947	73.10	gold quality
right ovary	UBERON:0002118	72.99	gold quality
right coronary artery	UBERON:0001625	72.39	gold quality
ascending aorta	UBERON:0001496	70.75	gold quality
thoracic aorta	UBERON:0001515	70.62	gold quality
metanephros cortex	UBERON:0010533	70.38	gold quality
uterine cervix	UBERON:0000002	70.22	gold quality
descending thoracic aorta	UBERON:0002345	69.94	gold quality
vagina	UBERON:0000996	68.14	gold quality
ovary	UBERON:0000992	68.11	gold quality
adult mammalian kidney	UBERON:0000082	67.88	gold quality
left coronary artery	UBERON:0001626	67.66	gold quality
uterus	UBERON:0000995	67.10	gold quality
coronary artery	UBERON:0001621	66.54	gold quality
tendon	UBERON:0000043	66.10	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.28
E-MTAB-6386	no	61.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting NXNL2, 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-188-3P	100.00	68.76	1240
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-889-5P	99.41	68.75	1025
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-4462	95.10	66.27	172
HSA-MIR-137-5P	94.03	60.01	43
HSA-MIR-675-5P	92.97	60.95	66

Literature-anchored findings (GeneRIF, showing 2)

• regulation of the Nucleoredoxin-like genes involves a CRX responsive element that can act as both as a positive regulator of promoter activity and as a modulator of cell-type specificity (PMID:20949100)
• NXNL2 Promotes Colon Cancer Proliferation and Metastasis by Regulating AKT Pathway. (PMID:37084033)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nxnl2	ENSDARG00000003934
mus_musculus	Nxnl2	ENSMUSG00000021396
rattus_norvegicus	Nxnl2	ENSRNOG00000014538
caenorhabditis_elegans		WBGENE00011038
caenorhabditis_elegans		WBGENE00019717

Paralogs (2): NXN (ENSG00000167693), NXNL1 (ENSG00000171773)

Protein

Protein identifiers

Nucleoredoxin-like protein 2 — Q5VZ03 (reviewed: Q5VZ03)

Alternative names: Rod-derived cone viability factor 2

All UniProt accessions (1): Q5VZ03

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the maintenance of both the function and the viability of sensory neurons, including photoreceptors and olfactory neurons.

Similarity. Belongs to the nucleoredoxin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VZ03-1	1	yes
Q5VZ03-3	2

RefSeq proteins (2): NP_001155097, NP_660326 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012336	Thioredoxin-like_fold	Domain
IPR029519	RdCVF2	Family
IPR036249	Thioredoxin-like_sf	Homologous_superfamily

Pfam: PF13905

UniProt features (4 total): chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZ03-F1	91.36	0.83

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SENSORY_PERCEPTION, chr9q22, GOBP_RETINA_HOMEOSTASIS, TGGAAA_NFAT_Q4_01, GOBP_HOMEOSTATIC_PROCESS, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP

GO Biological Process (4): visual perception (GO:0007601), sensory perception of smell (GO:0007608), photoreceptor cell maintenance (GO:0045494), sensory perception (GO:0007600)

GO Molecular Function (0):

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory perception of light stimulus	1
sensory perception of chemical stimulus	1
retina homeostasis	1
multicellular organismal process	1
nervous system process	1

Protein interactions and networks

STRING

423 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NXNL2	DVL1	O14640	902
NXNL2	TXN	P10599	593
NXNL2	TXNDC2	Q86VQ3	475
NXNL2	SIL1	Q9H173	472
NXNL2	REEP6	Q96HR9	444
NXNL2	ARR3	P36575	432
NXNL2	GRK1	Q15835	424
NXNL2	COL26A1	Q96A83	409
NXNL2	CALML6	Q8TD86	394
NXNL2	CALML3	P27482	394
NXNL2	CALML4	Q96GE6	394
NXNL2	CALML5	Q9NZT1	394
NXNL2	CALM1	P02593	392
NXNL2	GNB3	P16520	381
NXNL2	TXN2	Q99757	380

IntAct

4 interactions, top by confidence:

A	B	Type	Score
NXNL2	USP19	psi-mi:“MI:0914”(association)	0.350
uxaA	NXNL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): PDCL (Affinity Capture-MS), GRIN2A (Affinity Capture-MS), USP19 (Affinity Capture-MS), B3GNT2 (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), NXNL2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A5PK19, A6QLU8, D3Z6P0, D3ZAA9, P00435, P04041, P09102, P11352, P11909, P21195, P22352, P23764, P37141, P38660, P46412, P47823, P97346, Q08602, Q13087, Q13144, Q14168, Q148E0, Q15084, Q4AEH3, Q4AEH4, Q4AEH5, Q503L9, Q58E26, Q5CZL1, Q5R6T1, Q5RCH2, Q5RFG3, Q5RGJ5, Q5VZ03, Q63081, Q64350, Q6DKJ4, Q6GM16, Q6IQS6, Q8CHW4

Diamond homologs: A5PMF7, Q5VZ03, Q68EV9, Q8VC33, Q96CM4, Q9D531, A6QLU8, O77404, O80763, P97346, Q503L9, Q6DKJ4, Q6GM16, Q7Y0E8, Q7Y0F2, Q8VZQ0, A0RBT0, P80579, Q0JIL1, Q42403, Q63DQ8, Q6HL81, Q73B22, Q75GM1, Q7XPE8, Q81FU5, Q81SZ9, Q8CXF3, Q93VQ9, Q9KCJ4, Q6NQN8, P43221, O31820

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	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

289 predictions. Top by Δscore:

Variant	Effect	Δscore
9:88535733:GGCA:G	donor_gain	1.0000
9:88535734:GCA:G	donor_gain	1.0000
9:88535734:GCAG:G	donor_gain	1.0000
9:88535737:G:GG	donor_gain	1.0000
9:88544378:GTGA:G	acceptor_gain	1.0000
9:88535732:CGGCA:C	donor_gain	0.9900
9:88535733:GGCAG:G	donor_gain	0.9900
9:88535735:CAGT:C	donor_loss	0.9900
9:88535736:AG:A	donor_loss	0.9900
9:88535737:G:A	donor_loss	0.9900
9:88535738:TGA:T	donor_loss	0.9900
9:88535739:G:GT	donor_loss	0.9900
9:88535740:AG:A	donor_loss	0.9900
9:88544369:T:TA	acceptor_gain	0.9900
9:88544375:GCAG:G	acceptor_loss	0.9900
9:88544376:CAGTG:C	acceptor_gain	0.9900
9:88544377:A:AG	acceptor_gain	0.9900
9:88544377:AGT:A	acceptor_gain	0.9900
9:88544377:AGTGA:A	acceptor_gain	0.9900
9:88544378:G:GT	acceptor_gain	0.9900
9:88544378:GT:G	acceptor_gain	0.9900
9:88544378:GTG:G	acceptor_gain	0.9900
9:88544378:GTGAG:G	acceptor_gain	0.9900
9:88535735:CA:C	donor_gain	0.9800
9:88535741:G:C	donor_loss	0.9800
9:88544374:T:TA	acceptor_gain	0.9700
9:88535735:C:T	donor_gain	0.9400
9:88542861:G:T	donor_gain	0.9400
9:88535666:G:GT	donor_gain	0.9300
9:88536154:G:GT	donor_gain	0.9200

AlphaMissense

1011 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:88535531:T:C	F33L	0.983
9:88535533:C:A	F33L	0.983
9:88535533:C:G	F33L	0.983
9:88544508:G:C	W144C	0.975
9:88544508:G:T	W144C	0.975
9:88544506:T:A	W144R	0.974
9:88544506:T:C	W144R	0.974
9:88535637:T:A	V68D	0.968
9:88535564:T:C	F44L	0.965
9:88535566:C:A	F44L	0.965
9:88535566:C:G	F44L	0.965
9:88544420:T:A	L115H	0.962
9:88544461:G:T	G129W	0.958
9:88544426:T:A	I117N	0.957
9:88535523:C:A	A30E	0.956
9:88535532:T:C	F33S	0.956
9:88535717:T:C	F95L	0.955
9:88535719:C:A	F95L	0.955
9:88535719:C:G	F95L	0.955
9:88544414:C:A	P113H	0.955
9:88535702:T:A	W90R	0.953
9:88535702:T:C	W90R	0.953
9:88535555:A:C	S41R	0.950
9:88535557:C:A	S41R	0.950
9:88535557:C:G	S41R	0.950
9:88535565:T:C	F44S	0.948
9:88544474:T:C	I133T	0.946
9:88535643:T:A	V70E	0.945
9:88544461:G:A	G129R	0.945
9:88544461:G:C	G129R	0.945

dbSNP variants (sampled 300 via entrez): RS1000089284 (9:88558409 A>G), RS1000093247 (9:88577654 G>A), RS1000141993 (9:88545513 C>T), RS1000223509 (9:88579546 C>G,T), RS1000289842 (9:88573707 A>G), RS1000295915 (9:88538274 C>G), RS1000313376 (9:88535534 G>C), RS1000428743 (9:88556395 GAA>G), RS1000619310 (9:88554846 T>C), RS1000636736 (9:88548778 C>T), RS1000673631 (9:88543572 T>G), RS1000696208 (9:88547410 C>A,T), RS1000706552 (9:88550116 C>G,T), RS1000753567 (9:88555113 C>A,T), RS1000765787 (9:88566912 A>C,G,T)

Disease associations

OMIM: gene MIM:615299 | 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
GCST010396_68	Gut microbiota (bacterial taxa, hurdle binary method)	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression	3
Benzo(a)pyrene	affects methylation, increases methylation	2
bisphenol A	increases expression	1
titanium dioxide	decreases methylation	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
pentanal	decreases expression	1
clothianidin	increases expression	1
Zoledronic Acid	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation	1
Thiram	decreases expression	1
Valproic Acid	increases methylation	1
Zearalenone	increases expression	1
Aflatoxin B1	increases methylation	1
Genistein	increases expression	1

Clinical trials (associated diseases)

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