NSUN4

Summary

NSUN4 (NOP2/Sun RNA methyltransferase 4, HGNC:31802) is a protein-coding gene on chromosome 1p33, encoding 5-cytosine rRNA methyltransferase NSUN4 (Q96CB9). Mitochondrial RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as rRNAs, mRNAs and some long non-coding RNAs (lncRNAs). It is a selective cancer dependency (DepMap: 34.4% of cell lines).

Enables mRNA (cytidine-5-)-methyltransferase activity and rRNA (cytosine-C5-)-methyltransferase activity. Involved in mitochondrial RNA catabolic process; mitochondrial RNA modification; and rRNA methylation. Located in mitochondrial matrix. Part of mitochondrial large ribosomal subunit.

Source: NCBI Gene 387338 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 62 total
• Cancer dependency (DepMap): dependent in 34.4% of screened cell lines
• MANE Select transcript: NM_199044

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31802
Approved symbol	NSUN4
Name	NOP2/Sun RNA methyltransferase 4
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	MGC22960, SHTAP
Ensembl gene	ENSG00000117481
Ensembl biotype	protein_coding
OMIM	615394
Entrez	387338

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000307089, ENST00000469918, ENST00000472157, ENST00000474844, ENST00000475281, ENST00000486270, ENST00000495427, ENST00000498008, ENST00000537428, ENST00000718455, ENST00000861323, ENST00000912599

RefSeq mRNA: 11 — MANE Select: NM_199044 NM_001256127, NM_001256128, NM_001387265, NM_001387266, NM_001387267, NM_001387268, NM_001387269, NM_001387270, NM_001387271, NM_001387272, NM_199044

CCDS: CCDS534, CCDS57996

Canonical transcript exons

ENST00000474844 — 6 exons

Exon	Start	End
ENSE00001836472	46340807	46340919
ENSE00001859109	46361570	46365018
ENSE00003467831	46360704	46360828
ENSE00003584028	46344801	46345144
ENSE00003603699	46346921	46347075
ENSE00003607758	46352868	46353028

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3655 / max 317.1127, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2737	10.0219	1781
2736	4.2528	1608
2735	0.7042	321
2738	0.3395	46
2739	0.0471	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.42	gold quality
left testis	UBERON:0004533	96.29	gold quality
right testis	UBERON:0004534	96.21	gold quality
pancreatic ductal cell	CL:0002079	93.69	gold quality
testis	UBERON:0000473	93.22	gold quality
left ventricle myocardium	UBERON:0006566	92.08	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.96	silver quality
tibialis anterior	UBERON:0001385	91.11	silver quality
kidney epithelium	UBERON:0004819	90.84	silver quality
ileal mucosa	UBERON:0000331	88.33	gold quality
adrenal tissue	UBERON:0018303	86.60	gold quality
adult organism	UBERON:0007023	86.32	gold quality
right adrenal gland	UBERON:0001233	85.98	gold quality
right adrenal gland cortex	UBERON:0035827	85.87	gold quality
left adrenal gland	UBERON:0001234	85.81	gold quality
adrenal gland	UBERON:0002369	85.59	gold quality
islet of Langerhans	UBERON:0000006	85.52	gold quality
left adrenal gland cortex	UBERON:0035825	85.30	gold quality
adrenal cortex	UBERON:0001235	84.92	gold quality
stromal cell of endometrium	CL:0002255	84.46	gold quality
deltoid	UBERON:0001476	84.41	silver quality
gastrocnemius	UBERON:0001388	84.28	gold quality
bone marrow cell	CL:0002092	84.08	gold quality
muscle of leg	UBERON:0001383	84.03	gold quality
myocardium	UBERON:0002349	83.99	silver quality
superficial temporal artery	UBERON:0001614	83.87	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	83.56	silver quality
hindlimb stylopod muscle	UBERON:0004252	83.39	gold quality
oocyte	CL:0000023	82.97	gold quality
pancreas	UBERON:0001264	82.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.22
E-MTAB-7606	no	236.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting NSUN4, 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-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-561-3P	99.64	70.90	3647

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 34.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• analysis of the 3D crystal structure of the human MTERF4-NSUN4 complex (PMID:22949673)
• It involves in epigenetic changes during the progression of Alzheimer disease pathology. (PMID:24387984)
• m5C RNA methyltransferase-related gene NSUN4 stimulates malignant progression of hepatocellular carcinoma and can be a prognostic marker. (PMID:34744073)
• NSUN4 mediated RNA 5-methylcytosine promotes the malignant progression of glioma through improving the CDC42 mRNA stabilization. (PMID:38876383)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nsun4	ENSDARG00000021324
rattus_norvegicus	Nsun4	ENSRNOG00000012020
drosophila_melanogaster	l(2)10685	FBGN0283525
caenorhabditis_elegans	nsun-4	WBGENE00021476

Paralogs (2): NSUN2 (ENSG00000037474), NSUN3 (ENSG00000178694)

Protein

Protein identifiers

5-cytosine rRNA methyltransferase NSUN4 — Q96CB9 (reviewed: Q96CB9)

Alternative names: 5-cytosine tRNA methyltransferase NSUN4, NOL1/NOP2/Sun domain family member 4, mRNA cytosine C(5)-methyltransferase NSUN4

All UniProt accessions (6): A0A087WT36, A0A087WUV3, A0A087X0V6, M0R1K5, Q6ZRQ1, Q96CB9

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as rRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Involved in mitochondrial ribosome small subunit (SSU) maturation by catalyzing methylation of mitochondrial 12S rRNA; the function is independent of MTERFD2/MTERF4 and assembled mitochondrial ribosome large subunit (LSU). Targeted to LSU by MTERFD2/MTERF4 and probably is involved in a final step in ribosome biogenesis to ensure that SSU and LSU are assembled. In vitro can methylate 16S rRNA of the LSU; the methylation is enhanced by MTERFD/MTERF4. Also acts as a regulator of innate immunity by marking double-stranded mitochondrial RNAs(mt-dsRNAs) generated in response to stress: catalyzes m5C modification on mitochondrial RNAs, such as a mRNAs and lncRNAs, with a preference for the termini of light-strand lncRNAs, promoting their degradation and cytosolic release. Modified light-strand lncRNAs are then recognized by C1QBP reader and recruited to the mitochondrial degradosome complex, which promotes their degradation.

Subunit / interactions. Heterodimer with MTERFD2/MTERF4; this interaction seems to be required for NSUN4 recruitment to the mitochondrial large ribosomal subunit.

Subcellular location. Mitochondrion.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q96CB9-1	1	yes
Q96CB9-2	2
Q96CB9-3	3
Q96CB9-4	4

RefSeq proteins (11): NP_001243056, NP_001243057, NP_001374194, NP_001374195, NP_001374196, NP_001374197, NP_001374198, NP_001374199, NP_001374200, NP_001374201, NP_950245* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001678	MeTrfase_RsmB-F_NOP2_dom	Domain
IPR023267	RCMT	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR049560	MeTrfase_RsmB-F_NOP2_cat	Domain

Pfam: PF01189

Catalyzed reactions (Rhea), 2 shown:

• a cytidine in mRNA + S-adenosyl-L-methionine = a 5-methylcytidine in mRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:61464)
• a cytidine in rRNA + S-adenosyl-L-methionine = a 5-methylcytidine in rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:61484)

UniProt features (63 total): helix 19, strand 13, binding site 8, mutagenesis site 6, splice variant 4, sequence variant 4, turn 4, transit peptide 1, chain 1, modified residue 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
4FZV	X-RAY DIFFRACTION	2
7OF0	ELECTRON MICROSCOPY	2.2
7OF7	ELECTRON MICROSCOPY	2.5
7O9M	ELECTRON MICROSCOPY	2.6
7OF3	ELECTRON MICROSCOPY	2.7
4FP9	X-RAY DIFFRACTION	2.9
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8QSJ	ELECTRON MICROSCOPY	3
8PK0	ELECTRON MICROSCOPY	3.03
7O9K	ELECTRON MICROSCOPY	3.1
7ODS	ELECTRON MICROSCOPY	3.1
7ODT	ELECTRON MICROSCOPY	3.1
7OIC	ELECTRON MICROSCOPY	3.1
7PD3	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96CB9-F1	91.14	0.86

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): 310 (nucleophile)

Ligand- & substrate-binding residues (8): 255; 185; 186; 187; 204; 209; 237; 238

Post-translational modifications (1): 206

Mutagenesis-validated functional residues (6):

Position	Phenotype
65	disrupts complex with mterfd2; when associated with a-136, r-139 and a-141.
136	disrupts complex with mterfd2; when associated with r-65, r-139 and a-141.
139	disrupts complex with mterfd2; when associated with r-65, a-136, and a-141.
141	disrupts complex with mterfd2; when associated with r-65, a-136 and r-139.
258	abolished methyltransferase activity; when associated with w-310.
310	abolished methyltransferase activity; when associated with w-258.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6793080	rRNA modification in the mitochondrion

MSigDB gene sets: 163 (showing top): GOBP_RIBOSOME_BIOGENESIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RIBOSOME_ASSEMBLY, RACCACAR_AML_Q6, GOBP_RNA_METHYLATION, MARTINEZ_RB1_TARGETS_UP, CAGCAGG_MIR370, GOBP_RNA_MODIFICATION, GOBP_RIBOSOMAL_LARGE_SUBUNIT_ASSEMBLY, WANG_LMO4_TARGETS_DN, AML_Q6, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY

GO Biological Process (9): mitochondrial RNA catabolic process (GO:0000957), rRNA methylation (GO:0031167), mitochondrial RNA modification (GO:1900864), mitochondrial large ribosomal subunit assembly (GO:1902775), RNA methylation (GO:0001510), rRNA processing (GO:0006364), RNA processing (GO:0006396), methylation (GO:0032259), ribosome biogenesis (GO:0042254)

GO Molecular Function (11): methyltransferase activity (GO:0008168), RNA methyltransferase activity (GO:0008173), rRNA methyltransferase activity (GO:0008649), rRNA (cytosine-C5-)-methyltransferase activity (GO:0009383), mRNA (cytidine-5-)-methyltransferase activity (GO:0062152), mitochondrial ribosomal large subunit rRNA binding (GO:1990400), RNA binding (GO:0003723), protein binding (GO:0005515), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740), rRNA binding (GO:0019843)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), mitochondrial large ribosomal subunit (GO:0005762)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the mitochondrion	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
mitochondrial RNA metabolic process	2
RNA modification	2
methyltransferase activity	2
RNA catabolic process	1
rRNA modification	1
RNA methylation	1
ribosomal large subunit assembly	1
mitochondrial ribosome assembly	1
macromolecule methylation	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
metabolic process	1
ribonucleoprotein complex biogenesis	1
transferase activity, transferring one-carbon groups	1
catalytic activity, acting on RNA	1
RNA methyltransferase activity	1
S-adenosylmethionine-dependent methyltransferase activity	1
catalytic activity, acting on a rRNA	1
C-methyltransferase activity	1
rRNA (cytosine) methyltransferase activity	1
mRNA methyltransferase activity	1
large ribosomal subunit rRNA binding	1
nucleic acid binding	1
binding	1
catalytic activity	1
RNA binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1

Protein interactions and networks

STRING

2168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NSUN4	MTERF4	Q7Z6M4	998
NSUN4	NSUN5	Q96P11	909
NSUN4	MALSU1	Q96EH3	840
NSUN4	NSUN7	Q8NE18	830
NSUN4	TRDMT1	O14717	795
NSUN4	MTG1	Q9BT17	788
NSUN4	MTERF3	Q96E29	755
NSUN4	MRM2	Q9UI43	733
NSUN4	MRM3	Q9HC36	710
NSUN4	MTG2	Q9H4K7	697
NSUN4	MRM1	Q6IN84	692
NSUN4	GTPBP10	A4D1E9	681
NSUN4	RPUSD4	Q96CM3	679
NSUN4	ERAL1	O75616	672
NSUN4	ALYREF	Q86V81	670

IntAct

129 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
YWHAH	FAM83G	psi-mi:“MI:0914”(association)	0.710
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
CA10	WDHD1	psi-mi:“MI:0914”(association)	0.640
BPNT1	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ZNF324B	ZNF316	psi-mi:“MI:0914”(association)	0.530
SLC25A41	NUDT19	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
INSL3	GAPDHS	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
SSMEM1	NDUFA7	psi-mi:“MI:0914”(association)	0.530
KBTBD7	PLD2	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490

BioGRID (112): NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Two-hybrid), NSUN4 (Two-hybrid), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS), NSUN4 (Affinity Capture-MS)

ESM2 similar proteins: A0JN95, A4IF87, A6NJ78, B5DEQ3, B7ZMP1, D3ZLY0, E9Q4Z2, F1QDI9, G1SPE9, O14717, O15228, O22268, O55055, O95453, O95671, P37287, P69341, P97770, Q05B63, Q08J23, Q0V8R7, Q0VGM9, Q10D00, Q1HFZ0, Q2T9W2, Q4G073, Q5R5T5, Q5R962, Q5R9W8, Q5RC51, Q5RJZ1, Q6GR37, Q6H1L8, Q6NYU2, Q6YJI5, Q7TNK6, Q7YS61, Q7Z4G4, Q8JZM0, Q8R2Y8

Diamond homologs: A0KKI5, A0KW34, A1AC00, A1RIZ0, A1S788, A1SWV0, A3D5D5, A3QDA2, A4SMI9, A4WBJ4, A4Y7J8, A6TB06, A6WP46, A7MKH5, A7N0K6, A7ZMV8, A8A133, A8AFL6, A8FWM8, A8GDM6, A8H3W2, A9L4E6, A9MNH4, A9MV57, B0TIZ6, B1J0Q3, B1KQN1, B1LD37, B1XHA3, B2U477, B2VJ83, B4SV89, B4TKI0, B4TY18, B5BHA6, B5F3P3, B5FE06, B5FTI4, B5R2S1, B5R8V2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NSUN4	“form complex”	“MTERF4-NSUN4 mitochondiral ribosomal assembly complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 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
Response of EIF2AK4 (GCN2) to amino acid deficiency	10	11.6×	8e-06
Peptide chain elongation	8	10.6×	6e-05
Viral mRNA Translation	8	10.6×	6e-05
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	8	10.5×	6e-05
Mitochondrial ribosome-associated quality control	8	10.2×	6e-05
Selenocysteine synthesis	8	10.0×	6e-05
Eukaryotic Translation Termination	8	10.0×	6e-05
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	8	9.8×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	9	13.0×	3e-05
translation	10	8.0×	2e-04

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	44
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1037 predictions. Top by Δscore:

Variant	Effect	Δscore
1:46347073:GCC:G	donor_gain	1.0000
1:46347076:G:GG	donor_gain	1.0000
1:46353026:CGGGT:C	donor_loss	1.0000
1:46353027:GGGT:G	donor_loss	1.0000
1:46353029:GT:G	donor_loss	1.0000
1:46353030:T:A	donor_loss	1.0000
1:46353031:GAGT:G	donor_loss	1.0000
1:46360781:G:GT	donor_gain	1.0000
1:46360826:TGC:T	donor_gain	1.0000
1:46360827:GC:G	donor_gain	1.0000
1:46360827:GCG:G	donor_gain	1.0000
1:46360829:G:GG	donor_gain	1.0000
1:46361561:T:TA	acceptor_gain	1.0000
1:46361568:A:AG	acceptor_gain	1.0000
1:46361568:AG:A	acceptor_gain	1.0000
1:46361569:G:GG	acceptor_gain	1.0000
1:46361569:GG:G	acceptor_gain	1.0000
1:46340917:TGGG:T	donor_loss	0.9900
1:46340918:GG:G	donor_gain	0.9900
1:46340918:GGGT:G	donor_loss	0.9900
1:46340919:GG:G	donor_gain	0.9900
1:46340920:G:GA	donor_loss	0.9900
1:46340920:G:GG	donor_gain	0.9900
1:46344798:TA:T	acceptor_loss	0.9900
1:46344799:A:AG	acceptor_gain	0.9900
1:46344799:AG:A	acceptor_gain	0.9900
1:46344800:G:GG	acceptor_gain	0.9900
1:46344800:GG:G	acceptor_gain	0.9900
1:46344800:GGCT:G	acceptor_gain	0.9900
1:46345189:G:GT	donor_gain	0.9900

AlphaMissense

2480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:46344898:G:C	R64P	0.995
1:46361642:C:A	N317K	0.995
1:46361642:C:G	N317K	0.995
1:46344885:T:A	W60R	0.994
1:46344885:T:C	W60R	0.994
1:46347026:T:G	C181W	0.994
1:46360767:T:C	F273L	0.994
1:46360769:T:A	F273L	0.994
1:46360769:T:G	F273L	0.994
1:46361641:A:T	N317I	0.994
1:46361613:T:C	S308P	0.993
1:46361817:T:G	Y376D	0.993
1:46344903:A:C	S66R	0.992
1:46344905:T:A	S66R	0.992
1:46344905:T:G	S66R	0.992
1:46347016:T:C	L178P	0.992
1:46347022:T:C	L180P	0.992
1:46360731:G:C	D261H	0.992
1:46360822:T:C	L291P	0.992
1:46361608:T:A	V306D	0.992
1:46361610:T:G	Y307D	0.992
1:46361805:T:C	F372L	0.992
1:46361807:T:A	F372L	0.992
1:46361807:T:G	F372L	0.992
1:46344887:G:C	W60C	0.991
1:46344887:G:T	W60C	0.991
1:46361575:G:A	G295E	0.991
1:46361772:G:T	G361W	0.991
1:46344907:T:C	L67P	0.990
1:46347044:G:C	K187N	0.990

dbSNP variants (sampled 300 via entrez): RS1000083703 (1:46357908 T>G), RS1000171426 (1:46367963 C>T), RS1000250411 (1:46377399 A>G), RS1000303679 (1:46364714 G>C), RS1000379367 (1:46351969 G>C), RS1000406157 (1:46371571 T>G), RS1000428348 (1:46383818 CT>C,CTT), RS1000457158 (1:46371374 T>C), RS1000536722 (1:46357236 A>G), RS1000562071 (1:46364025 T>C), RS1000687771 (1:46351373 A>G), RS1000720060 (1:46351090 G>C), RS1000741285 (1:46369945 T>G), RS1000766973 (1:46377162 G>T), RS1000790375 (1:46369593 A>T)

Disease associations

OMIM: gene MIM:615394 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005951_37	Body mass index	8.000000e-10
GCST012298_4	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	3.000000e-06
GCST012301_3	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008343	sex interaction 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
Nickel	increases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
bisphenol S	decreases methylation	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Theophylline	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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