ZNF451

Summary

ZNF451 (zinc finger protein 451, HGNC:21091) is a protein-coding gene on chromosome 6p12.1, encoding E3 SUMO-protein ligase ZNF451 (Q9Y4E5). E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins.

Enables SUMO ligase activity; transcription corepressor activity; and transcription regulator inhibitor activity. Involved in negative regulation of transcription initiation by RNA polymerase II; negative regulation of transforming growth factor beta receptor signaling pathway; and protein sumoylation. Located in PML body.

Source: NCBI Gene 26036 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total
• MANE Select transcript: NM_001031623

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21091
Approved symbol	ZNF451
Name	zinc finger protein 451
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0576, COASTER, dJ417I1.1, KIAA1702, ZATT
Ensembl gene	ENSG00000112200
Ensembl biotype	protein_coding
OMIM	615708
Entrez	26036

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000357489, ENST00000370702, ENST00000370706, ENST00000370708, ENST00000370710, ENST00000370711, ENST00000444273, ENST00000491832, ENST00000502749, ENST00000504364, ENST00000504603, ENST00000508548, ENST00000508603, ENST00000509071, ENST00000509251, ENST00000510483, ENST00000510989, ENST00000515290, ENST00000856236, ENST00000856237, ENST00000927541, ENST00000927542, ENST00000927543

RefSeq mRNA: 3 — MANE Select: NM_001031623 NM_001031623, NM_001257273, NM_015555

CCDS: CCDS43477, CCDS4960, CCDS59026

Canonical transcript exons

ENST00000370706 — 15 exons

Exon	Start	End
ENSE00000757336	57153861	57154047
ENSE00000850652	57150719	57150862
ENSE00000850653	57152221	57152351
ENSE00001832816	57168423	57170305
ENSE00003464797	57124734	57124859
ENSE00003465528	57141302	57141455
ENSE00003483043	57147090	57148693
ENSE00003494345	57141948	57142095
ENSE00003531422	57128729	57128840
ENSE00003625750	57134744	57134870
ENSE00003657172	57161084	57161152
ENSE00003684501	57133042	57133192
ENSE00003705209	57090811	57090894
ENSE00003710547	57099061	57099141
ENSE00003842687	57090188	57090274

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 96.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6626 / max 291.3252, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68328	20.3454	1803
68326	2.8507	1265
68325	1.7239	925
68327	0.7425	437

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	96.68	gold quality
adrenal tissue	UBERON:0018303	96.65	gold quality
calcaneal tendon	UBERON:0003701	96.39	gold quality
trabecular bone tissue	UBERON:0002483	95.00	gold quality
tibia	UBERON:0000979	94.32	gold quality
right testis	UBERON:0004534	93.90	gold quality
bone marrow	UBERON:0002371	93.82	gold quality
nipple	UBERON:0002030	93.68	gold quality
left testis	UBERON:0004533	93.64	gold quality
lower lobe of lung	UBERON:0008949	93.11	gold quality
testis	UBERON:0000473	93.00	gold quality
tendon	UBERON:0000043	92.99	gold quality
sural nerve	UBERON:0015488	92.96	gold quality
cerebellar vermis	UBERON:0004720	92.94	gold quality
middle frontal gyrus	UBERON:0002702	92.67	gold quality
corpus epididymis	UBERON:0004359	92.64	gold quality
superficial temporal artery	UBERON:0001614	92.63	gold quality
inferior vagus X ganglion	UBERON:0005363	92.60	gold quality
colonic epithelium	UBERON:0000397	92.46	gold quality
caput epididymis	UBERON:0004358	92.46	gold quality
secondary oocyte	CL:0000655	92.22	gold quality
cartilage tissue	UBERON:0002418	91.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.84	gold quality
paraflocculus	UBERON:0005351	91.78	gold quality
visceral pleura	UBERON:0002401	91.65	gold quality
inferior olivary complex	UBERON:0002127	91.61	gold quality
pylorus	UBERON:0001166	91.54	gold quality
sperm	CL:0000019	91.49	gold quality
cauda epididymis	UBERON:0004360	91.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.08
E-MTAB-4850	no	1047.42
E-MTAB-6142	no	151.06
E-MTAB-6524	no	117.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
PIAS1
SMAD2	Repression
SMAD4	Repression

Upstream regulators (CollecTRI, top): E2F6, MYC

miRNA regulators (miRDB)

89 targeting ZNF451, 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-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-380-3P	99.89	70.18	1978
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3681-5P	99.82	66.88	387

Literature-anchored findings (GeneRIF, showing 8)

• Data describe ZNF451, a nuclear protein that can be associated with promyelocytic leukemia bodies, and exerts its effects via SUMO modification machinery and trafficking of transcription regulators between promyelocytic leukemia bodies and nucleoplasm. (PMID:18656483)
• ZNF451 acts as a transcriptional corepressor for Smad3/4 and negatively regulates TGF-beta signaling. (PMID:24324267)
• The authors show that ZNF451 is SUMO2 specific and that SUMO modification of ZNF451 may contribute to activity by providing a second molecule of SUMO that interacts with E2. (PMID:26524494)
• These findings uncover a ZNF451-TDP2-catalyzed and SUMO2-modulated pathway for direct resolution of TOP2 cleavage complex. (PMID:28912134)
• The findings of this study indicate that BC032020 suppresses the survival of PDAC cells by inhibiting ZNF451 expression. (PMID:29532883)
• Stress-induced nuclear condensation of NELF drives transcriptional downregulation. (PMID:33548202)
• Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1. (PMID:36209117)
• ZNF451 favors triple-negative breast cancer progression by enhancing SLUG-mediated CCL5 transcriptional expression. (PMID:37342906)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Zfp451	ENSMUSG00000042197
rattus_norvegicus	Zfp451	ENSRNOG00000012718
rattus_norvegicus		ENSRNOG00000075789

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

E3 SUMO-protein ligase ZNF451 — Q9Y4E5 (reviewed: Q9Y4E5)

Alternative names: Coactivator for steroid receptors, E3 SUMO-protein transferase ZNF451, Zinc finger protein 451

All UniProt accessions (9): Q9Y4E5, D6RAS1, D6RAV4, D6RB93, D6REC5, D6RIA1, E9PH99, Q5VVE8, Q5VVF0

UniProt curated annotations — full annotation on UniProt →

Function. E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins. Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation. Has no activity with SUMO1. Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site ‘Lys-11’. Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300-mediated acetylation of histone H3 at ‘Lys-9’. Plays a role in regulating the transcription of AR targets.

Subunit / interactions. Homooligomer. Interacts (via N-terminal region) with SUMO1. Interacts (via N-terminal region) with SUMO2. Interacts simultaneously with two SUMO2 chains. Identified in a complex with SUMO2 and UBE2I/UBC9, where one ZNF451 interacts with one UBE2I/UBC9 and two SUMO2 chains, one bound to the UBE2I/UBC9 active site and the other to another region of the same UBE2I/UBC9 molecule. Interacts (via C-terminus) with ubiquitin. Interacts (via N-terminal zinc-finger domains) with SMAD4 (via MH2 domain). Interacts with SMAD2 and SMAD3. Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4. Interacts with EP300. Inhibits interaction between EP300 and the SMAD4 complex. Interacts with SIMC1.

Subcellular location. Nucleus. PML body. Nucleoplasm.

Post-translational modifications. Sumoylated. Predominantly sumoylated on the N-terminal region that is important for interaction with SUMO1 and SUMO2. Sumoylation is important for localization in nuclear granules; desumoylation leads to diffuse nucleoplasmic location. Autosumoylated (in vitro). Sumoylation enhances E3 SUMO-protein ligase activity.

Domain organisation. Binds UBE2I/UBC9 and two SUMO2 molecules via its N-terminus. The most N-terminal region interacts with the SUMO2 chain that is covalently bound to the UBE2I/UBC9 active site, while the second region interacts with another SUMO2 that is non-covalently associated with the same UBE2I/UBC9 chain.

Pathway. Protein modification; protein sumoylation.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y4E5-1	1	yes
Q9Y4E5-2	2
Q9Y4E5-4	3

RefSeq proteins (3): NP_001026794, NP_001244202, NP_056370 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR041192	PIN_11	Domain
IPR058156	Znf-C2H2_ZNF451	Domain
IPR058946	Zf-C2H2_ZNF451_C	Domain
IPR058947	Zf-C2H2_ZNF451_2nd	Domain
IPR058948	Zf-C2H2_ZNF451_6th	Domain
IPR058949	Zf-C2H2_ZNF451_1st	Domain
IPR058950	Zf-C2H2_ZNF451_5th	Domain

Pfam: PF18479, PF23101, PF23102, PF23103, PF23104, PF23107, PF23108

UniProt features (97 total): cross-link 58, zinc finger region 11, mutagenesis site 11, region of interest 7, modified residue 3, splice variant 2, strand 2, chain 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5D2M	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4E5-F1	69.61	0.05

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 (61): 155, 158, 432, 75, 77, 106, 139, 144, 153, 167, 270, 275, 283, 288, 301, 309, 357, 423, 434, 446 …

Mutagenesis-validated functional residues (11):

Position	Phenotype
31–34	nearly abolishes e3 sumo-protein ligase activity (in vitro).
37	nearly abolishes e3 sumo-protein ligase activity (in vitro).
38–41	reduces e3 sumo-protein ligase activity by 97% (in vitro).
38–41	nearly abolishes e3 sumo-protein ligase activity (in vitro).
39	nearly abolishes e3 sumo-protein ligase activity (in vitro).
40	reduces e3 sumo-protein ligase activity by 96% (in vitro).
46–49	nearly abolishes e3 sumo-protein ligase activity (in vitro).
48–49	impairs interaction with sumo1. no effect on negative regulation of smad4-mediated transcription activation.
188	mildly reduces e3 sumo-protein ligase activity.
192	mildly reduces e3 sumo-protein ligase activity.
706	no effect on negative regulation of smad4-mediated transcription activation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MODULE_151, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_PEPTIDYL_LYSINE_MODIFICATION, ONKEN_UVEAL_MELANOMA_UP, chr6p12, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_PROTEIN_SUMOYLATION, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GARY_CD5_TARGETS_DN, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER

GO Biological Process (3): protein sumoylation (GO:0016925), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of transcription initiation by RNA polymerase II (GO:0060633)

GO Molecular Function (9): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), SUMO ligase activity (GO:0061665), transcription regulator inhibitor activity (GO:0140416), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), PML body (GO:0016605), nucleoplasm (GO:0005654), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
peptidyl-lysine modification	1
protein modification by small protein conjugation	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of transcription by RNA polymerase II	1
transcription initiation at RNA polymerase II promoter	1
regulation of transcription initiation by RNA polymerase II	1
negative regulation of DNA-templated transcription initiation	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
transition metal ion binding	1
DNA binding	1
SUMO transferase activity	1
ubiquitin-like protein ligase activity	1
regulation of gene expression	1
transcription regulator activity	1
molecular function inhibitor activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear body	1
nuclear lumen	1

Protein interactions and networks

STRING

1403 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF451	UBE2I	P50550	829
ZNF451	TDP2	O95551	768
ZNF451	SUMO2	P55855	733
ZNF451	PIAS1	O75925	610
ZNF451	SDAD1	Q9NVU7	606
ZNF451	SAE1	Q9UBE0	600
ZNF451	TOP2A	P11388	596
ZNF451	SUMO1	P55856	596
ZNF451	RANBP2	P49792	592
ZNF451	TOP1	P11387	574
ZNF451	ZNF362	Q5T0B9	572
ZNF451	ZNF512	Q96ME7	570
ZNF451	NIPBL	Q6KC79	550
ZNF451	PDS5A	Q29RF7	536
ZNF451	PIAS2	O75928	529

IntAct

59 interactions, top by confidence:

A	B	Type	Score
ZNF451	UBE2I	psi-mi:“MI:0915”(physical association)	0.750
UBE2I	ZNF451	psi-mi:“MI:0915”(physical association)	0.750
PLOD3	PLOD2	psi-mi:“MI:0914”(association)	0.530
ZNF451	SIMC1	psi-mi:“MI:0915”(physical association)	0.490
ZNF451	PLEC	psi-mi:“MI:0915”(physical association)	0.400
Top2b		psi-mi:“MI:0915”(physical association)	0.400
ZNF451	PIK3R3	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	iglC2	psi-mi:“MI:0915”(physical association)	0.370
PCBD1	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
LZTR1	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	CPTP	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	HTT	psi-mi:“MI:0915”(physical association)	0.370
PRPF40A	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	SNIP1	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	RAP1GDS1	psi-mi:“MI:0915”(physical association)	0.370
FXR2	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
RNF40	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
SUV39H1	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
KDM1A	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
JMJD6	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
PRMT8	ZNF451	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	PRMT1	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	CDCA4	psi-mi:“MI:0915”(physical association)	0.370
ZNF451	FAM118A	psi-mi:“MI:0915”(physical association)	0.370
TOP2A	RPL6	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
BATF3	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): ZNF451 (Biochemical Activity), ZNF451 (Two-hybrid), ZNF451 (Reconstituted Complex), ZNF451 (Reconstituted Complex), AR (Two-hybrid), UBE2I (Two-hybrid), PIAS1 (Two-hybrid), PIAS2 (Two-hybrid), ZNF451 (Co-localization), ZNF451 (Reconstituted Complex), ZNF451 (Two-hybrid), ZNF451 (Two-hybrid), ZNF451 (Two-hybrid), ZNF451 (Two-hybrid), ZNF451 (Two-hybrid)

ESM2 similar proteins: A1ZA92, A1ZAC4, B3NLX1, B4GBA9, B4GT53, B4P6W7, B4P8I0, B6VQ60, B7ZQJ9, G5EBL2, G5EEU2, P25158, P25823, P34344, P34423, P52351, Q05209, Q08119, Q09293, Q09354, Q09377, Q0V9S3, Q10077, Q18317, Q1XG89, Q23238, Q23647, Q24617, Q24747, Q28Z18, Q290S5, Q2KHT3, Q2NKX8, Q32KD2, Q504Y3, Q5RA75, Q621Q3, Q7TPV2, Q7ZXG4, Q86BY9

Diamond homologs: Q8C0P7, Q9HCI6, Q9Y4E5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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
mRNA Splicing	6	14.0×	6e-04
Processing of Capped Intron-Containing Pre-mRNA	7	12.2×	4e-04
mRNA Polyadenylation	6	11.2×	2e-03
Signaling by Nuclear Receptors	5	10.8×	6e-03
mRNA Splicing - Major Pathway	8	9.3×	4e-04
Dengue Virus-Host Interactions	7	6.8×	6e-03
Metabolism of RNA	7	6.2×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	6	23.6×	1e-04
mRNA transport	5	21.2×	8e-04
RNA splicing	7	10.0×	1e-03
mRNA processing	7	8.9×	2e-03
mRNA splicing, via spliceosome	6	8.9×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3431 predictions. Top by Δscore:

Variant	Effect	Δscore
6:57090272:GAG:G	donor_gain	1.0000
6:57090272:GAGGT:G	donor_loss	1.0000
6:57090274:GGT:G	donor_loss	1.0000
6:57090275:GTGA:G	donor_loss	1.0000
6:57090890:TCAGT:T	donor_gain	1.0000
6:57090891:CAGT:C	donor_gain	1.0000
6:57090892:AGTGT:A	donor_loss	1.0000
6:57090893:GT:G	donor_gain	1.0000
6:57090895:G:GG	donor_gain	1.0000
6:57090896:TAA:T	donor_loss	1.0000
6:57090897:A:AG	donor_loss	1.0000
6:57099052:T:TA	acceptor_gain	1.0000
6:57099056:TATA:T	acceptor_loss	1.0000
6:57099057:ATAG:A	acceptor_gain	1.0000
6:57099058:TAGG:T	acceptor_loss	1.0000
6:57099059:A:AG	acceptor_gain	1.0000
6:57099059:AG:A	acceptor_gain	1.0000
6:57099060:G:GA	acceptor_gain	1.0000
6:57099060:GG:G	acceptor_gain	1.0000
6:57099060:GGA:G	acceptor_gain	1.0000
6:57099060:GGAA:G	acceptor_gain	1.0000
6:57099137:CTGAT:C	donor_gain	1.0000
6:57099138:TGAT:T	donor_gain	1.0000
6:57099139:GAT:G	donor_gain	1.0000
6:57099139:GATG:G	donor_gain	1.0000
6:57099140:AT:A	donor_gain	1.0000
6:57099140:ATGTA:A	donor_loss	1.0000
6:57099141:TGT:T	donor_loss	1.0000
6:57099142:G:GG	donor_gain	1.0000
6:57099142:GTAA:G	donor_loss	1.0000

AlphaMissense

7151 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:57150776:T:A	V889D	1.000
6:57150785:A:C	D892A	1.000
6:57150785:A:G	D892G	1.000
6:57150785:A:T	D892V	1.000
6:57150786:T:A	D892E	1.000
6:57150786:T:G	D892E	1.000
6:57150791:A:C	D894A	1.000
6:57150791:A:T	D894V	1.000
6:57150796:T:A	W896R	1.000
6:57150796:T:C	W896R	1.000
6:57150850:T:A	W914R	1.000
6:57150850:T:C	W914R	1.000
6:57150856:T:C	F916L	1.000
6:57150857:T:C	F916S	1.000
6:57150858:T:A	F916L	1.000
6:57150858:T:G	F916L	1.000
6:57150862:G:A	G918R	1.000
6:57150862:G:C	G918R	1.000
6:57152235:T:A	W923R	1.000
6:57152235:T:C	W923R	1.000
6:57152237:G:C	W923C	1.000
6:57152237:G:T	W923C	1.000
6:57152331:G:C	D955H	1.000
6:57152332:A:C	D955A	1.000
6:57152332:A:G	D955G	1.000
6:57152332:A:T	D955V	1.000
6:57152333:T:A	D955E	1.000
6:57152333:T:G	D955E	1.000
6:57152334:T:C	F956L	1.000
6:57152335:T:C	F956S	1.000

dbSNP variants (sampled 300 via entrez): RS1000021965 (6:57115510 A>G), RS1000038052 (6:57124258 C>A,G,T), RS1000040591 (6:57152200 TG>T), RS1000058192 (6:57167371 T>C), RS1000122505 (6:57149720 G>A), RS1000135064 (6:57108296 C>G), RS1000197214 (6:57145019 G>C), RS1000202794 (6:57110061 A>G), RS1000248471 (6:57159838 A>C,G), RS1000268910 (6:57096086 A>G), RS1000272908 (6:57157364 T>C), RS1000283727 (6:57152542 A>G), RS1000297669 (6:57108656 C>G), RS1000342760 (6:57103718 T>G), RS1000393303 (6:57129946 TAA>T)

Disease associations

OMIM: gene MIM:615708 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	6
sodium arsenite	increases abundance, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	decreases expression, increases abundance, affects cotreatment	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Leflunomide	increases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Air Pollutants	increases abundance, affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Demecolcine	increases expression	1
Endosulfan	decreases expression	1
Ethyl Methanesulfonate	increases expression	1

Clinical trials (associated diseases)

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