NSUN7

Summary

NSUN7 (NOP2/Sun RNA methyltransferase family member 7, HGNC:25857) is a protein-coding gene on chromosome 4p14, encoding Putative methyltransferase NSUN7 (Q8NE18). May have S-adenosyl-L-methionine-dependent methyl-transferase activity.

Predicted to enable RNA binding activity and methyltransferase activity. Predicted to be involved in RNA methylation and RNA processing. Predicted to act upstream of or within flagellated sperm motility and sperm mitochondrion organization.

Source: NCBI Gene 79730 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 111 total
• MANE Select transcript: NM_024677

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25857
Approved symbol	NSUN7
Name	NOP2/Sun RNA methyltransferase family member 7
Location	4p14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14001
Ensembl gene	ENSG00000179299
Ensembl biotype	protein_coding
OMIM	617185
Entrez	79730

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000316607, ENST00000381782, ENST00000423784, ENST00000463952, ENST00000469033, ENST00000473399, ENST00000478857, ENST00000870597, ENST00000870598, ENST00000916434, ENST00000916435, ENST00000916436, ENST00000916437, ENST00000951253

RefSeq mRNA: 2 — MANE Select: NM_024677 NM_001330648, NM_024677

CCDS: CCDS3461, CCDS82917

Canonical transcript exons

ENST00000381782 — 12 exons

Exon	Start	End
ENSE00001257380	40749955	40750300
ENSE00001294441	40790602	40790745
ENSE00001306295	40776049	40776259
ENSE00003482027	40808307	40811184
ENSE00003516341	40774265	40774417
ENSE00003523204	40798787	40798904
ENSE00003533992	40774767	40774950
ENSE00003545590	40760434	40760492
ENSE00003625327	40750603	40750991
ENSE00003629652	40794375	40794476
ENSE00003649561	40761171	40761301
ENSE00003678458	40807061	40807184

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 97.51.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6560 / max 89.7659, expressed in 801 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47444	2.6207	710
47448	1.1116	422
47445	0.8638	400
47446	0.0446	6
47447	0.0153	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.51	gold quality
bronchial epithelial cell	CL:0002328	97.04	gold quality
right uterine tube	UBERON:0001302	94.56	gold quality
male germ cell	CL:0000015	93.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.80	gold quality
epithelium of bronchus	UBERON:0002031	87.81	gold quality
bronchus	UBERON:0002185	86.86	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.82	gold quality
body of pancreas	UBERON:0001150	85.58	gold quality
ventricular zone	UBERON:0003053	85.40	gold quality
epithelium of nasopharynx	UBERON:0001951	84.19	gold quality
metanephros cortex	UBERON:0010533	82.76	gold quality
right testis	UBERON:0004534	82.46	gold quality
left testis	UBERON:0004533	82.10	gold quality
testis	UBERON:0000473	81.32	gold quality
mucosa of stomach	UBERON:0001199	80.86	gold quality
ascending aorta	UBERON:0001496	80.72	gold quality
thoracic aorta	UBERON:0001515	80.67	gold quality
pancreas	UBERON:0001264	80.41	gold quality
left lobe of thyroid gland	UBERON:0001120	80.29	gold quality
descending thoracic aorta	UBERON:0002345	80.08	gold quality
right lobe of thyroid gland	UBERON:0001119	79.92	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.90	gold quality
minor salivary gland	UBERON:0001830	79.71	gold quality
thyroid gland	UBERON:0002046	79.68	gold quality
aorta	UBERON:0000947	78.98	gold quality
saliva-secreting gland	UBERON:0001044	78.77	gold quality
right lung	UBERON:0002167	78.45	gold quality
nasal cavity mucosa	UBERON:0001826	78.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.84
E-MTAB-7606	no	3.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting NSUN7, 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-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368

Literature-anchored findings (GeneRIF, showing 4)

• mutant protein structures of Nsun7 indicated that the amino acid serine was converted to alanine, the structure of the helix, coil and strand was changed, and the protein folding and ligand binding sites were changed in samples from asthenospermic men with a transversion mutation in exon 7, indicating impairment of protein function. Because Nsun7 plays a role in sperm motility, mutation in exon 7 may lead to infertility. (PMID:24384068)
• Nsun7 (A11337)-deletion mutation, causes reduction of its protein rate and associated with sperm motility defect in infertile men. (PMID:25702163)
• Our findings revealed that genetic polymorphisms in exon7 of the NSUN7 gene are not associated with asthenospermia in Chinese Han men. (PMID:26345859)
• Epigenetic inactivation of the 5-methylcytosine RNA methyltransferase NSUN7 is associated with clinical outcome and therapeutic vulnerability in liver cancer. (PMID:37173708)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nsun7	ENSMUSG00000029206
rattus_norvegicus	Nsun7	ENSRNOG00000025494
drosophila_melanogaster	CG44836	FBGN0266099

Protein

Protein identifiers

Putative methyltransferase NSUN7 — Q8NE18 (reviewed: Q8NE18)

Alternative names: NOL1/NOP2/Sun domain family member 7

All UniProt accessions (1): Q8NE18

UniProt curated annotations — full annotation on UniProt →

Function. May have S-adenosyl-L-methionine-dependent methyl-transferase activity.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8NE18-1	1	yes
Q8NE18-2	2
Q8NE18-3	3

RefSeq proteins (2): NP_001317577, NP_078953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR042620	NSUN7	Family
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain
IPR049561	NSUN5_7_fdxn-like	Domain

Pfam: PF01189, PF21148

UniProt features (16 total): splice variant 4, region of interest 3, compositionally biased region 3, sequence variant 2, sequence conflict 2, chain 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NE18-F1	73.71	0.44

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): 439 (nucleophile)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): ZHAN_MULTIPLE_MYELOMA_CD1_UP, HAN_SATB1_TARGETS_DN, GOBP_METHYLATION, NUYTTEN_EZH2_TARGETS_DN, MATZUK_SPERMATOZOA, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, MODULE_139, CHEMNITZ_RESPONSE_TO_PROSTAGLANDIN_E2_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR3658, MIR4262, MIR181A_5P_MIR181B_5P, MIR181D_5P

GO Biological Process (3): methylation (GO:0032259), RNA methylation (GO:0001510), RNA processing (GO:0006396)

GO Molecular Function (3): RNA binding (GO:0003723), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
RNA modification	1
macromolecule methylation	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
nucleic acid binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1

Protein interactions and networks

STRING

1574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSUN7	NSUN3	Q9H649	845
NSUN7	NSUN4	Q96CB9	830
NSUN7	NSUN6	Q8TEA1	827
NSUN7	NSUN2	Q08J23	816
NSUN7	TRDMT1	O14717	806
NSUN7	NOP2	P46087	806
NSUN7	ALYREF	Q86V81	670
NSUN7	DNMT1	P26358	601
NSUN7	METTL3	Q86U44	543
NSUN7	ALKBH5	Q6P6C2	542
NSUN7	YTHDC2	Q9H6S0	521
NSUN7	ALKBH1	Q13686	508
NSUN7	FTO	Q9C0B1	502
NSUN7	METTL6	Q8TCB7	496
NSUN7	NSUN5	Q96P11	491

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NSUN7	SEMG1	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A3Q2TTB3, A0JMR6, A4IIA7, F4JNY0, F6RRD7, I3XHK1, O60934, O88622, P14629, P28715, P79457, Q08DZ8, Q12789, Q17RS7, Q1LWH4, Q28I29, Q32PL8, Q3B7T1, Q4R7Q1, Q5FWP4, Q5M954, Q5QJC2, Q5RA37, Q5RCV3, Q5ZIN2, Q66J91, Q6GQV7, Q6NVF4, Q6P1E7, Q6P1H6, Q6P256, Q6P7W5, Q76CY8, Q7TP65, Q86W56, Q8BMI4, Q8C0W1, Q8C5W4, Q8GT06, Q8IXW5

Diamond homologs: Q14AW5, Q4R7Q1, Q8NE18, B2VJ83, O14039, P53972, Q3KNT7, Q63ZY6, Q8GYE8, Q8K4F6, Q96P11, Q9NAA7, Q9VDZ4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2396 predictions. Top by Δscore:

Variant	Effect	Δscore
4:40750298:GGG:G	donor_gain	1.0000
4:40750299:GG:G	donor_gain	1.0000
4:40750299:GGG:G	donor_gain	1.0000
4:40750300:GG:G	donor_gain	1.0000
4:40750987:GAAAT:G	donor_gain	1.0000
4:40750992:G:GG	donor_gain	1.0000
4:40760432:A:AG	acceptor_gain	1.0000
4:40760433:G:GG	acceptor_gain	1.0000
4:40760488:CAATA:C	donor_gain	1.0000
4:40760489:AATA:A	donor_gain	1.0000
4:40760490:ATA:A	donor_gain	1.0000
4:40760491:TA:T	donor_gain	1.0000
4:40760493:G:GG	donor_gain	1.0000
4:40760501:A:G	donor_gain	1.0000
4:40761170:GCCA:G	acceptor_gain	1.0000
4:40773036:T:TA	acceptor_gain	1.0000
4:40773038:T:TA	acceptor_gain	1.0000
4:40773043:T:TA	acceptor_gain	1.0000
4:40794445:GCA:G	donor_gain	1.0000
4:40794448:G:GG	donor_gain	1.0000
4:40798785:A:AG	acceptor_gain	1.0000
4:40798786:G:GG	acceptor_gain	1.0000
4:40808305:A:AG	acceptor_gain	1.0000
4:40808306:G:GG	acceptor_gain	1.0000
4:40750301:G:GA	donor_loss	0.9900
4:40750301:G:GG	donor_gain	0.9900
4:40750302:T:G	donor_loss	0.9900
4:40750306:G:GT	donor_gain	0.9900
4:40750307:G:T	donor_gain	0.9900
4:40750601:A:AG	acceptor_gain	0.9900

AlphaMissense

4696 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:40774303:G:C	R176P	0.997
4:40798808:T:A	V435D	0.996
4:40808353:C:A	A524D	0.996
4:40776061:A:C	S280R	0.995
4:40776063:T:A	S280R	0.995
4:40776063:T:G	S280R	0.995
4:40794459:T:C	L422P	0.995
4:40807161:T:C	F501L	0.995
4:40807163:T:A	F501L	0.995
4:40807163:T:G	F501L	0.995
4:40808352:G:C	A524P	0.994
4:40794467:G:C	A425P	0.993
4:40798810:T:G	Y436D	0.993
4:40774883:T:C	F253S	0.992
4:40798853:T:A	V450D	0.992
4:40761228:T:C	F139L	0.991
4:40761230:T:A	F139L	0.991
4:40761230:T:G	F139L	0.991
4:40776065:T:C	L281P	0.991
4:40794468:C:A	A425E	0.991
4:40798805:T:A	V434D	0.991
4:40761295:T:C	L161P	0.990
4:40774393:C:A	A206D	0.990
4:40774940:T:C	L272P	0.990
4:40798801:G:C	A433P	0.990
4:40750986:T:C	L98P	0.989
4:40761205:T:C	L131P	0.989
4:40774849:G:C	A242P	0.989
4:40774940:T:A	L272H	0.989
4:40807162:T:C	F501S	0.989

dbSNP variants (sampled 300 via entrez): RS1000015640 (4:40770142 G>A), RS1000015877 (4:40783246 C>G), RS1000084268 (4:40759727 C>T), RS1000120602 (4:40760316 G>A,T), RS1000150326 (4:40760890 T>C), RS1000213628 (4:40803826 C>G,T), RS1000267806 (4:40792561 C>A), RS1000286703 (4:40784323 G>C), RS1000296020 (4:40777168 G>A), RS1000356768 (4:40784006 G>T), RS1000491728 (4:40748749 T>C), RS1000498423 (4:40790517 A>C,G), RS1000516166 (4:40769652 G>A), RS1000560821 (4:40759371 G>A), RS1000565779 (4:40803582 G>C)

Disease associations

OMIM: gene MIM:617185 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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 cotreatment, decreases expression, affects expression, increases expression	8
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	decreases expression	2
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Norethindrone Acetate	affects cotreatment, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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