VIRMA

Summary

VIRMA (vir like m6A methyltransferase associated, HGNC:24500) is a protein-coding gene on chromosome 8q22.1, encoding Protein virilizer homolog (Q69YN4). Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. It is a common-essential gene (DepMap: required in 96.1% of cancer cell lines).

Enables RNA binding activity. Involved in mRNA processing. Located in RNA N6-methyladenosine methyltransferase complex; cytosol; and nuclear speck.

Source: NCBI Gene 25962 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 191 total
• Cancer dependency (DepMap): dependent in 96.1% of screened cell lines (common-essential)
• MANE Select transcript: NM_015496

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24500
Approved symbol	VIRMA
Name	vir like m6A methyltransferase associated
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434I116, fSAP121
Ensembl gene	ENSG00000164944
Ensembl biotype	protein_coding
OMIM	616447
Entrez	25962

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000297591, ENST00000421249, ENST00000517624, ENST00000519001, ENST00000521080, ENST00000522196, ENST00000522263, ENST00000523263, ENST00000523405, ENST00000883557, ENST00000916406, ENST00000961582, ENST00000961583, ENST00000961584

RefSeq mRNA: 2 — MANE Select: NM_015496 NM_015496, NM_183009

CCDS: CCDS34923, CCDS47894

Canonical transcript exons

ENST00000297591 — 24 exons

Exon	Start	End
ENSE00001088844	94499374	94499506
ENSE00001088845	94518985	94519476
ENSE00001088851	94517788	94517942
ENSE00001088853	94529070	94529342
ENSE00001088856	94511996	94512089
ENSE00001088858	94526223	94527363
ENSE00001088865	94534839	94535007
ENSE00001088869	94543827	94543942
ENSE00001088874	94514869	94514951
ENSE00002121717	94487689	94488860
ENSE00002127505	94553385	94553469
ENSE00003467561	94537103	94537151
ENSE00003543815	94491578	94491909
ENSE00003545147	94510417	94510652
ENSE00003571691	94506500	94506717
ENSE00003580562	94495731	94495891
ENSE00003586411	94489939	94490082
ENSE00003592170	94538260	94538346
ENSE00003640309	94492652	94492818
ENSE00003654090	94530963	94531085
ENSE00003656888	94496328	94496480
ENSE00003674294	94494860	94494956
ENSE00003678960	94509688	94509940
ENSE00003680405	94511185	94511729

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 95.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.3850 / max 688.9735, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93991	28.9995	1806
93992	0.3855	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	95.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.14	gold quality
ganglionic eminence	UBERON:0004023	93.67	gold quality
embryo	UBERON:0000922	93.66	gold quality
colonic epithelium	UBERON:0000397	93.65	gold quality
cortical plate	UBERON:0005343	92.83	gold quality
calcaneal tendon	UBERON:0003701	92.59	gold quality
left ventricle myocardium	UBERON:0006566	92.57	gold quality
right testis	UBERON:0004534	92.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.23	gold quality
sural nerve	UBERON:0015488	91.98	gold quality
left testis	UBERON:0004533	91.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.74	silver quality
kidney epithelium	UBERON:0004819	91.72	silver quality
upper arm skin	UBERON:0004263	91.63	gold quality
stromal cell of endometrium	CL:0002255	91.41	gold quality
testis	UBERON:0000473	91.41	gold quality
tendon	UBERON:0000043	91.37	gold quality
tibial nerve	UBERON:0001323	91.35	gold quality
body of pancreas	UBERON:0001150	91.31	gold quality
adenohypophysis	UBERON:0002196	91.19	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.01	gold quality
right ovary	UBERON:0002118	91.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.99	gold quality
lower esophagus mucosa	UBERON:0035834	90.99	gold quality
granulocyte	CL:0000094	90.96	gold quality
mucosa of transverse colon	UBERON:0004991	90.88	gold quality
body of uterus	UBERON:0009853	90.79	gold quality
uterine cervix	UBERON:0000002	90.49	gold quality
right uterine tube	UBERON:0001302	90.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

103 targeting VIRMA, 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-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.1% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 36)

• Abundance of N-6-methyladenosine and expression of VIRMA/YTHDF3 were different among testicular germ cell tumors subtypes, with higher levels in seminomas (SEs), suggesting a contribution to SE phenotype maintenance. (PMID:30866959)
• KIAA1429 could promote breast cancer progression and was correlated with pathogenesis. It may represent a promising therapeutic strategy on breast cancer, especially in combination with CDK1 treatment. (PMID:31285549)
• Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis. (PMID:31856849)
• circ_KIAA1429 accelerates hepatocellular carcinoma advancement through the mechanism of m(6)A-YTHDF3-Zeb1. (PMID:32653519)
• Prognostic risk signature based on the expression of three m6A RNA methylation regulatory genes in kidney renal papillary cell carcinoma. (PMID:33177247)
• KIAA1429 promotes the progression of lung adenocarcinoma by regulating the m6A level of MUC3A. (PMID:33249400)
• Aberrations of m6A regulators are associated with tumorigenesis and metastasis in head and neck squamous cell carcinoma. (PMID:33383437)
• Blocking circ-CNST suppresses malignant behaviors of osteosarcoma cells and inhibits glycolysis through circ-CNST-miR-578-LDHA/PDK1 ceRNA networks. (PMID:33962616)
• m(6) A transferase KIAA1429-stabilized LINC00958 accelerates gastric cancer aerobic glycolysis through targeting GLUT1. (PMID:34409730)
• The component of the m(6)A writer complex VIRMA is implicated in aggressive tumor phenotype, DNA damage response and cisplatin resistance in germ cell tumors. (PMID:34446080)
• VIRMA contributes to non-small cell lung cancer progression via N(6)-methyladenosine-dependent DAPK3 post-transcriptional modification. (PMID:34520821)
• N(6)-methyladenosine methyltransferase KIAA1429 elevates colorectal cancer aerobic glycolysis via HK2-dependent manner. (PMID:35546050)
• Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma. (PMID:35730068)
• N[6]-methyladenosine (m[6]A) writer KIAA1429 accelerates gastric cancer oxaliplatin chemoresistance by targeting FOXM1. (PMID:36326914)
• KIAA1429 mediates epithelial mesenchymal transition in sorafenib-resistant hepatocellular carcinoma through m6A methylation modification. (PMID:36420693)
• m6A ‘writer’ KIAA1429 regulates the proliferation and migration of endothelial cells in atherosclerosis. (PMID:36463391)
• KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/ MAPK pathway in an m[6]A-dependent manner. (PMID:36493511)
• CCL3 secreted by hepatocytes promotes the metastasis of intrahepatic cholangiocarcinoma by VIRMA-mediated N6-methyladenosine (m[6]A) modification. (PMID:36691046)
• N6-methyladenine- induced LINC00667 promoted breast cancer progression through m6A/KIAA1429 positive feedback loop. (PMID:36700472)
• VIRMA promotes nasopharyngeal carcinoma, tumorigenesis, and metastasis by upregulation of E2F7 in an m6A-dependent manner. (PMID:37028765)
• Circular RNA circ_KIAA1429 accelerates hepatocellular carcinoma progression via the miR-133a-3p/high mobility group AT-hook 2 (HMGA2) axis in an m6A-dependent manner. (PMID:37368192)
• VIRMA facilitates intrahepatic cholangiocarcinoma progression through epigenetic augmentation of TMED2 and PARD3B mRNA stabilization. (PMID:37391589)
• Pan-cancer analysis and experimental validation revealed the m6A methyltransferase KIAA1429 as a potential biomarker for diagnosis, prognosis, and immunotherapy. (PMID:37606975)
• CRISPR-Cas9 knockout screening identifies KIAA1429 as an essential gene in Ewing sarcoma. (PMID:37759224)
• N6-methyladenosine methyltransferase KIAA1429 promoted ovarian cancer aerobic glycolysis and progression through enhancing ENO1 expression. (PMID:37807062)
• KIAA1429 Promotes Nasopharyngeal Carcinoma Progression by Mediating m6A Modification of PTGS2. (PMID:37830191)
• KIAA1429 protects hepatocellular carcinoma cells from ferroptotic cell death with a m[6] A-dependent posttranscriptional modification of SLC7A11. (PMID:37830241)
• KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells. (PMID:38224863)
• Inhibin A contributes to the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated m6A modification. (PMID:38531807)
• VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating UBR5 mRNA and m6A levels. (PMID:38577917)
• Hirschsprung’s disease: m6A methylase VIRMA suppresses cell migration and proliferation by regulating GSK3beta. (PMID:38658662)
• KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating ARHGAP30 expression. (PMID:38717936)
• Role and mechanism of KIAA1429 in regulating cellular ferroptosis and radioresistance in colorectal cancer. (PMID:38843497)
• KIAA1429 Induces m6A Modification of LINC01106 to Enhance the Malignancy of Lung Adenocarcinoma Cells via the JAK/STAT3 Pathway. (PMID:38848293)
• KIAA1429 increases FOXM1 expression through YTHDF1-mediated m6A modification to promote aerobic glycolysis and tumorigenesis in multiple myeloma. (PMID:39060874)
• N6-Methyladenosine Methyltransferase Component KIAA1429 Is a Potential Target of Cancer Therapy. (PMID:39456252)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	virma	ENSDARG00000075824
mus_musculus	Virma	ENSMUSG00000040720
rattus_norvegicus	Virma	ENSRNOG00000014664
drosophila_melanogaster	vir	FBGN0003977

Protein

Protein identifiers

Protein virilizer homolog — Q69YN4 (reviewed: Q69YN4)

All UniProt accessions (4): Q69YN4, H0YB68, H0YBN5, H0YC41

UniProt curated annotations — full annotation on UniProt →

Function. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Acts as a key regulator of m6A methylation by promoting m6A methylation of mRNAs in the 3’-UTR near the stop codon: recruits the catalytic core components METTL3 and METTL14, thereby guiding m6A methylation at specific sites. Required for mRNA polyadenylation via its role in selective m6A methylation: m6A methylation of mRNAs in the 3’-UTR near the stop codon correlating with alternative polyadenylation (APA).

Subunit / interactions. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). Interacts with WTAP. Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3. Interacts with NUDT21 and CPSF6.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm. Cytoplasm.

Similarity. Belongs to the vir family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q69YN4-1	1	yes
Q69YN4-2	2
Q69YN4-3	3
Q69YN4-4	4

RefSeq proteins (2): NP_056311, NP_892121 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026736	Virilizer	Family
IPR031801	VIR_N	Domain

Pfam: PF15912

UniProt features (145 total): helix 65, strand 27, modified residue 15, compositionally biased region 11, sequence conflict 8, turn 7, splice variant 5, region of interest 4, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7VF2	ELECTRON MICROSCOPY	3
7VF5	ELECTRON MICROSCOPY	3
7YG4	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q69YN4-F1	70.17	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15): 2, 133, 138, 173, 184, 222, 914, 1579, 1708, 1723, 1741, 1741, 1773, 1775, 1793

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 127 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, WANG_LMO4_TARGETS_DN, MARTINEZ_RB1_TARGETS_DN, AAAGACA_MIR511, GOBP_RNA_SPLICING, TATCTGG_MIR488, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, chr8q22, CTTTGTA_MIR524, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOCC_NUCLEAR_SPECK, GOCC_TRANSFERASE_COMPLEX, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_METHYLTRANSFERASE_COMPLEX

GO Biological Process (2): mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear body (GO:0016604), nuclear speck (GO:0016607), RNA N6-methyladenosine methyltransferase complex (GO:0036396), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
methyltransferase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

6139 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VIRMA	METTL3	Q86U44	999
VIRMA	METTL14	Q9HCE5	999
VIRMA	ZC3H13	Q5T200	998
VIRMA	WTAP	Q15007	998
VIRMA	RBM15B	Q8NDT2	998
VIRMA	RBM15	Q96T37	998
VIRMA	METTL16	Q86W50	997
VIRMA	CBLL1	Q75N03	997
VIRMA	NUDT21	O43809	959
VIRMA	CPSF6	Q16630	948
VIRMA	METTL4	Q8N3J2	942
VIRMA	YTHDF3	Q7Z739	924
VIRMA	YTHDC2	Q9H6S0	910
VIRMA	YTHDC1	Q96MU7	909
VIRMA	YTHDF1	Q9BYJ9	896

IntAct

109 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAZ	VIRMA	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
IGF2BP3	PTCD1	psi-mi:“MI:0914”(association)	0.530
ZC3H18	SRPK2	psi-mi:“MI:0914”(association)	0.530
VIRMA	PRPF6	psi-mi:“MI:0915”(physical association)	0.500
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
gag-pol	GRB2	psi-mi:“MI:0914”(association)	0.460
VIRMA	PCNA	psi-mi:“MI:0915”(physical association)	0.370
THOC2		psi-mi:“MI:0914”(association)	0.350
TSNAX		psi-mi:“MI:0914”(association)	0.350
BCLAF1	PABPN1	psi-mi:“MI:0914”(association)	0.350
Osgep	RPSA	psi-mi:“MI:0914”(association)	0.350
SNCA	SRRM1	psi-mi:“MI:0914”(association)	0.350
Srsf1	SRRM1	psi-mi:“MI:0914”(association)	0.350
BACH1		psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
DDX41	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
METTL3	TRIM28	psi-mi:“MI:0914”(association)	0.350

BioGRID (3209): KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), BPTF (Co-fractionation), KIAA1429 (Co-fractionation), KIAA1429 (Co-fractionation), ZC3H13 (Co-fractionation), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS), KIAA1429 (Affinity Capture-MS)

ESM2 similar proteins: A0JMD0, A1A535, A1ZAB5, A2AIV2, A8E7C5, A8PJX4, A8XAA9, B0W2S0, B3MIW0, B3NPV8, B4GAM1, B4JW99, B4KT50, B4LQ23, B4MY63, B4P6P7, D3YVL2, E9PXF8, F4HS99, F4HZK4, F4J5S1, F4JKH6, O60502, O75153, O88379, P34466, P69735, Q0IHW8, Q0VA04, Q15042, Q17N71, Q291J5, Q5PQS3, Q5SW19, Q5TYW4, Q5U430, Q69YN4, Q6NTN5, Q6ZT12, Q7PZD5

Diamond homologs: A2AIV2, Q69YN4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
Activation of BAD and translocation to mitochondria	7	56.1×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	49.5×	3e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	49.5×	3e-09
Activation of BH3-only proteins	7	36.6×	2e-08
mRNA 3’-end processing	14	29.0×	5e-15
RHO GTPases activate PKNs	8	26.7×	2e-08
Intrinsic Pathway for Apoptosis	8	24.7×	3e-08
Transport of Mature Transcript to Cytoplasm	6	24.0×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	45.4×	2e-08
RNA splicing, via transesterification reactions	5	26.4×	1e-04
spliceosomal complex assembly	5	25.5×	1e-04
mRNA splicing, via spliceosome	21	16.3×	6e-17
protein targeting	5	15.5×	1e-03
regulation of alternative mRNA splicing, via spliceosome	7	14.5×	7e-05
mRNA export from nucleus	5	12.5×	3e-03
mRNA transport	5	11.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	158
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3940 predictions. Top by Δscore:

Variant	Effect	Δscore
8:94488857:TAAC:T	acceptor_gain	1.0000
8:94488858:AAC:A	acceptor_gain	1.0000
8:94488859:AC:A	acceptor_gain	1.0000
8:94488860:CC:C	acceptor_gain	1.0000
8:94488861:C:CC	acceptor_gain	1.0000
8:94489901:C:A	donor_gain	1.0000
8:94489934:TATA:T	donor_loss	1.0000
8:94489935:ATAC:A	donor_loss	1.0000
8:94489937:A:AT	donor_loss	1.0000
8:94490007:T:A	donor_gain	1.0000
8:94490078:GTTTC:G	acceptor_gain	1.0000
8:94490079:TTTC:T	acceptor_gain	1.0000
8:94490080:TTC:T	acceptor_gain	1.0000
8:94490081:TC:T	acceptor_gain	1.0000
8:94490082:CC:C	acceptor_gain	1.0000
8:94490083:C:CA	acceptor_loss	1.0000
8:94490083:C:CC	acceptor_gain	1.0000
8:94490083:C:T	acceptor_gain	1.0000
8:94490088:C:CT	acceptor_gain	1.0000
8:94490090:C:CT	acceptor_gain	1.0000
8:94491679:A:AC	donor_gain	1.0000
8:94491680:C:CC	donor_gain	1.0000
8:94491907:CCA:C	acceptor_gain	1.0000
8:94491908:CA:C	acceptor_gain	1.0000
8:94491908:CAC:C	acceptor_gain	1.0000
8:94491910:C:CC	acceptor_gain	1.0000
8:94492683:T:TA	donor_gain	1.0000
8:94492684:C:A	donor_gain	1.0000
8:94492817:ACCTG:A	acceptor_loss	1.0000
8:94492819:C:CG	acceptor_loss	1.0000

AlphaMissense

11890 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:94491747:A:C	F1657L	1.000
8:94491747:A:T	F1657L	1.000
8:94491748:A:C	F1657C	1.000
8:94491748:A:G	F1657S	1.000
8:94491749:A:C	F1657V	1.000
8:94491749:A:G	F1657L	1.000
8:94491751:T:A	D1656V	1.000
8:94491751:T:C	D1656G	1.000
8:94491751:T:G	D1656A	1.000
8:94491752:C:G	D1656H	1.000
8:94491753:A:C	D1655E	1.000
8:94491753:A:T	D1655E	1.000
8:94491754:T:A	D1655V	1.000
8:94491754:T:C	D1655G	1.000
8:94491754:T:G	D1655A	1.000
8:94491755:C:A	D1655Y	1.000
8:94491755:C:G	D1655H	1.000
8:94491757:A:G	V1654A	1.000
8:94491757:A:T	V1654E	1.000
8:94491759:A:C	H1653Q	1.000
8:94491759:A:T	H1653Q	1.000
8:94491760:T:C	H1653R	1.000
8:94491761:G:C	H1653D	1.000
8:94491761:G:T	H1653N	1.000
8:94491763:A:C	M1652R	1.000
8:94491766:G:A	S1651F	1.000
8:94491766:G:T	S1651Y	1.000
8:94491769:G:C	P1650R	1.000
8:94491769:G:T	P1650Q	1.000
8:94491770:G:A	P1650S	1.000

dbSNP variants (sampled 300 via entrez): RS1000051858 (8:94516747 T>G), RS1000057673 (8:94499679 G>A), RS1000127070 (8:94510305 A>C), RS1000149430 (8:94535739 C>T), RS1000203134 (8:94536072 C>G), RS1000310698 (8:94510569 G>C), RS1000316237 (8:94492240 T>C), RS1000378924 (8:94545352 C>T), RS1000431216 (8:94541767 C>T), RS1000452778 (8:94542241 C>T), RS1000532280 (8:94551737 C>T), RS1000542731 (8:94492543 A>T), RS1000629873 (8:94516368 T>C,G), RS1000630985 (8:94516653 T>C), RS1000655406 (8:94528461 T>C)

Disease associations

OMIM: gene MIM:616447 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002783_368	Body mass index	3.000000e-06
GCST004166_19	Nonsyndromic cleft lip with cleft palate	1.000000e-12
GCST004904_42	Body mass index	2.000000e-11
GCST004904_60	Body mass index	2.000000e-09
GCST005830_26	Hand grip strength	2.000000e-08
GCST010988_306	Adult body size	1.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0003959	cleft lip
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	increases phosphorylation	1
9-hydroxyoctadecadienoic acid	decreases expression	1
quinone	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
trichostatin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
1-nitropyrene	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
bisphenol S	increases methylation	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cycloheximide	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Endosulfan	decreases expression	1
Ivermectin	decreases expression	1
Mercuric Chloride	affects cotreatment, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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