MORC3

Summary

MORC3 (MORC family CW-type zinc finger 3, HGNC:23572) is a protein-coding gene on chromosome 21q22.12, encoding MORC family CW-type zinc finger protein 3 (Q14149). Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response.

This gene encodes a protein that localizes to the nuclear matrix and forms nuclear bodies via an ATP-dependent mechanism. The protein is predicted to have coiled-coil and zinc finger domains and has RNA binding activity. Alternative splicing produces multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 23515 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 118 total
• MANE Select transcript: NM_015358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23572
Approved symbol	MORC3
Name	MORC family CW-type zinc finger 3
Location	21q22.12
Locus type	gene with protein product
Status	Approved
Aliases	ZCW5, NXP2, KIAA0136
Ensembl gene	ENSG00000159256
Ensembl biotype	protein_coding
OMIM	610078
Entrez	23515

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding

ENST00000400485, ENST00000484028, ENST00000485299, ENST00000485933, ENST00000487909, ENST00000492336, ENST00000546482, ENST00000547657, ENST00000549948, ENST00000551367, ENST00000551788, ENST00000552581

RefSeq mRNA: 3 — MANE Select: NM_015358 NM_001320445, NM_001320446, NM_015358

CCDS: CCDS42924

Canonical transcript exons

ENST00000400485 — 17 exons

Exon	Start	End
ENSE00003477961	36341399	36341546
ENSE00003482680	36336874	36337006
ENSE00003522346	36360184	36360258
ENSE00003549856	36364093	36364259
ENSE00003566823	36333646	36333718
ENSE00003570014	36356620	36356724
ENSE00003579316	36344579	36344707
ENSE00003615780	36337732	36337946
ENSE00003620224	36362183	36362228
ENSE00003621847	36349311	36349408
ENSE00003623420	36359955	36360077
ENSE00003636120	36344912	36345031
ENSE00003657062	36320197	36320303
ENSE00003663455	36375143	36376632
ENSE00003667982	36338774	36338921
ENSE00003676247	36368988	36369876
ENSE00003693820	36372374	36372531

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 96.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.3755 / max 497.3944, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188987	35.8636	1815
188991	0.5119	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.08	gold quality
paraflocculus	UBERON:0005351	95.06	gold quality
middle frontal gyrus	UBERON:0002702	95.00	gold quality
epithelium of nasopharynx	UBERON:0001951	94.19	gold quality
colonic epithelium	UBERON:0000397	93.98	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.17	gold quality
frontal pole	UBERON:0002795	93.14	gold quality
gingival epithelium	UBERON:0001949	93.13	gold quality
palpebral conjunctiva	UBERON:0001812	92.64	gold quality
tibia	UBERON:0000979	92.31	gold quality
monocyte	CL:0000576	92.25	gold quality
mononuclear cell	CL:0000842	92.08	gold quality
esophagus squamous epithelium	UBERON:0006920	92.01	gold quality
leukocyte	CL:0000738	91.97	gold quality
tonsil	UBERON:0002372	91.16	gold quality
left ovary	UBERON:0002119	90.90	gold quality
gingiva	UBERON:0001828	90.73	gold quality
ovary	UBERON:0000992	90.43	gold quality
adrenal tissue	UBERON:0018303	90.42	gold quality
vagina	UBERON:0000996	90.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.07	gold quality
amniotic fluid	UBERON:0000173	90.06	gold quality
bone marrow	UBERON:0002371	89.92	gold quality
esophagus mucosa	UBERON:0002469	89.72	gold quality
right ovary	UBERON:0002118	89.70	gold quality
sperm	CL:0000019	89.68	gold quality
choroid plexus epithelium	UBERON:0003911	89.63	gold quality
ectocervix	UBERON:0012249	89.59	gold quality
corpus callosum	UBERON:0002336	89.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
IFNB1	Repression

miRNA regulators (miRDB)

122 targeting MORC3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
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-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-513B-5P	99.99	69.96	2150
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 20)

• determination of nuclear matrix-binding, RNA-binding, and coiled-coil domans (PMID:11927593)
• When tethered to a promoter by fusion to Gal4, NXP-2 repressed transcription, consistent with a role for NXP-2 in SUMO-mediated repression (PMID:16567619)
• MORC3 (microrchidia3)-ATPase activated p53 and induced cellular senescence in normal fibroblasts but not p53-/- fibroblasts (PMID:17332504)
• MORC3 colocalizes with PML by a two-step molecular mechanism. (PMID:20501696)
• Anti-NXP2 Ab may be associated with adult idiopathic inflammatory myopathies with malignancy. (PMID:22258483)
• An anti-MJ antibody that recognizes NXP-2 was found to be a useful biomarker in dermatomyositis-polymyositis patients. (PMID:22546500)
• These studies demonstrate that anti-NXP-2 and anti-TIF-1gamma antibodies are frequent DM specificities (found in 55% of patients) and are present in most patients with cancer-associated dermatomhyositis. (PMID:24037894)
• Case Report: Pemphigus foliaceus associated with anti-NXP2 autoantibody-positive amyopathic dermatomyositis. (PMID:24217940)
• Case Report: manifestations of interstitial lung disease in adult dermatomyositis patient with anti-NPX2 autoantibodies. (PMID:26028648)
• Downregulation of NXP2/MORC3 by use of two independent short hairpin RNAs reduced virus titers in low-multiplicity infections. Analysis of viral RNA in high-multiplicity infections showed a reduction of viral RNA and mRNA after NXP2/MORC3 downregulation. (PMID:26202233)
• MORC3 has antiviral activity during herpes simplex virus 1 and human cytomegalovirus infections. (PMID:27440897)
• our studies provide a molecular framework detailing MORC3 functions and suggest that its modulation may contribute to human disease. (PMID:27653685)
• Dermatomyositis patients with anti-NXP-2 antibodies have a distinct and often severe systemic phenotype that includes myalgia, peripheral edema, and significant dysphagia, despite having milder inflammatory skin disease. (PMID:28129490)
• Mechanism for autoinhibition and activation (PMID:30850548)
• Data show that MORC family CW-type zinc finger 3 (MORC3) ATPase is a new target of NS1 protein, influenza A virus (NS1) from H3N2-subtype influenza virus. (PMID:31006586)
• Morc3 silences endogenous retroviruses by enabling Daxx-mediated histone H3.3 incorporation. (PMID:34650047)
• Self-guarding of MORC3 enables virulence factor-triggered immunity. (PMID:34759314)
• En garde! The duel functions of MORC3. (PMID:35026136)
• MORC3 restricts human cytomegalovirus infection by suppressing the major immediate-early promoter activity. (PMID:35879101)
• MORC3 represses the HCMV major immediate early promoter in myeloid cells in the absence of PML nuclear bodies. (PMID:38009611)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	morc3a	ENSDARG00000056679
mus_musculus	Morc3	ENSMUSG00000039456
rattus_norvegicus	Morc3	ENSRNOG00000026236

Paralogs (1): MORC4 (ENSG00000133131)

Protein

Protein identifiers

MORC family CW-type zinc finger protein 3 — Q14149 (reviewed: Q14149)

Alternative names: Nuclear matrix protein 2, Zinc finger CW-type coiled-coil domain protein 3

All UniProt accessions (3): Q14149, H0YHQ4, H0YIR5

UniProt curated annotations — full annotation on UniProt →

Function. Nuclear matrix protein which forms MORC3-NBs (nuclear bodies) via an ATP-dependent mechanism and plays a role in innate immunity by restricting different viruses through modulation of the IFN response. Mechanistically, possesses a primary antiviral function through a MORC3-regulated element that activates IFNB1, and this function is guarded by a secondary IFN-repressing function. Sumoylated MORC3-NBs associates with PML-NBs and recruits TP53 and SP100, thus regulating TP53 activity. Binds RNA in vitro. Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) ‘Lys-4’ on histone H3. The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0. (Microbial infection) May be required for influenza A transcription during viral infection.

Subunit / interactions. Homodimer. The sumoylated form interacts with PML (via SUMO-interacting motif). Interacts with TP53. (Microbial infection) Interacts with influenza A virus PA and PB1 polymerase subunits during infection. Interacts (via CW domain) with influenza A protein NS1. (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 protein ICP0; this interaction mediates MORC3 degradation, which leads to de-repression of a MORC3-regulated DNA element (MRE) adjacent to the IFNB1 locus.

Subcellular location. Nucleus. Nucleoplasm. Nucleus matrix. PML body. Chromosome.

Tissue specificity. Expressed in heart, placenta, skeletal muscle, brain, pancreas, lung, liver, but not kidney.

Post-translational modifications. Sumoylation is involved in interaction with PML and localization to PML nuclear bodies.

Activity regulation. Dimerization of the ATPase domain is strictly required for the catalytic activity and binding to double-stranded DNA. Disrupting the interface between ATPase and the CW domains releases autoinhibition since the CW domain sterically impedes binding of the ATPase domain to DNA.

Domain organisation. The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3.

RefSeq proteins (3): NP_001307374, NP_001307375, NP_056173* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011124	Znf_CW	Domain
IPR036890	HATPase_C_sf	Homologous_superfamily
IPR041006	Morc_S5	Domain
IPR045261	MORC_ATPase	Family

Pfam: PF07496, PF13589, PF17942

UniProt features (83 total): strand 18, cross-link 17, helix 15, mutagenesis site 11, modified residue 5, binding site 4, region of interest 4, turn 4, compositionally biased region 2, chain 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5SVY	X-RAY DIFFRACTION	1.05
6O5W	X-RAY DIFFRACTION	1.41
5SVX	X-RAY DIFFRACTION	1.56
5SVI	X-RAY DIFFRACTION	1.61
4QQ4	X-RAY DIFFRACTION	1.75
6O1E	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14149-F1	71.75	0.35

Functional residue map

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

Ligand- & substrate-binding residues (4): 416; 435; 446; 413

Post-translational modifications (22): 503, 514, 540, 560, 765, 191, 205, 231, 280, 293, 555, 597, 597, 650, 650, 651, 651, 740, 740, 794 …

Mutagenesis-validated functional residues (11):

Position	Phenotype
35	fails to localize to pml nuclear bodies and activate tp53.
67	forms nuclear bodies, but rapidly diffuses throughout the nucleus under conditions of atp depletion.
101	diffuse nuclear localization. fails to form nuclear bodies in the presence of atp.
419	about threefold increase in catalytic activity.
419	diffuse nuclear localization, possibly due to loss of dna or nucleosome binding.
431	strong decrease of binding to ns1.
597	loss of sumoylation; when associated with r-650; r-651; r-740 and r-794.
650	loss of sumoylation; when associated with r-597; r-651; r-740 and r-794.
651	loss of sumoylation; when associated with r-597; r-650; r-740 and r-794.
740	loss of sumoylation; when associated with r-597; r-650; r-651 and r-794.
794	loss of sumoylation; when associated with r-597; r-650; r-651 and r-740.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 242 (showing top): RNGTGGGC_UNKNOWN, MODULE_255, TTTGTAG_MIR520D, GOBP_PEPTIDYL_SERINE_MODIFICATION, MODULE_317, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_CELLULAR_SENESCENCE, CTATGCA_MIR153, CAGCTG_AP4_Q5, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, MORF_RAF1, RICKMAN_METASTASIS_DN, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MARTINEZ_RB1_TARGETS_DN

GO Biological Process (14): negative regulation of transcription by RNA polymerase II (GO:0000122), protein phosphorylation (GO:0006468), post-embryonic development (GO:0009791), peptidyl-serine phosphorylation (GO:0018105), negative regulation of interferon-beta production (GO:0032688), negative regulation of fibroblast proliferation (GO:0048147), protein stabilization (GO:0050821), maintenance of protein location in nucleus (GO:0051457), antiviral innate immune response (GO:0140374), positive regulation of cellular senescence (GO:2000774), immune system process (GO:0002376), chromatin organization (GO:0006325), innate immune response (GO:0045087), type I interferon-mediated signaling pathway (GO:0060337)

GO Molecular Function (8): DNA binding (GO:0003677), RNA binding (GO:0003723), zinc ion binding (GO:0008270), ATP hydrolysis activity (GO:0016887), protein-macromolecule adaptor activity (GO:0030674), histone H3K4me3 reader activity (GO:0140002), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear matrix (GO:0016363), PML body (GO:0016605), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleic acid binding	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
phosphorylation	1
protein modification process	1
multicellular organism development	1
multicellular organismal process	1
protein phosphorylation	1
peptidyl-serine modification	1
negative regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
negative regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
regulation of protein stability	1
nucleus	1
protein localization to nucleus	1
maintenance of protein localization in organelle	1
innate immune response	1
defense response to virus	1
positive regulation of cellular process	1
cellular senescence	1
regulation of cellular senescence	1
biological_process	1
cellular component organization	1
immune response	1
defense response to symbiont	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
transition metal ion binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
molecular adaptor activity	1
histone H3 reader activity	1
binding	1

Protein interactions and networks

STRING

1066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MORC3	TRIM33	Q9UPN9	924
MORC3	IFIH1	Q9BYX4	864
MORC3	SAE1	Q9UBE0	852
MORC3	EXOSC10	Q01780	720
MORC3	TRIM21	P19474	717
MORC3	TRIM24	O15164	713
MORC3	CHD3	Q12873	696
MORC3	NT5C1A	Q9BXI3	670
MORC3	CHD4	Q14839	643
MORC3	HMGCR	P04035	623
MORC3	SNRNP70	P08621	583
MORC3	RO60	P10155	571
MORC3	SUMO2	P55855	563
MORC3	HARS1	P12081	507
MORC3	TP53	P04637	501

IntAct

67 interactions, top by confidence:

A	B	Type	Score
TP53	MDM2	psi-mi:“MI:0914”(association)	1.000
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
MORC3	RNF216	psi-mi:“MI:0915”(physical association)	0.560
DYNLL1	SHMT2	psi-mi:“MI:0914”(association)	0.510
DYNLL2	SHMT2	psi-mi:“MI:0914”(association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
Dynll1		psi-mi:“MI:0915”(physical association)	0.400
MORC3	KPNA2	psi-mi:“MI:0915”(physical association)	0.370
MORC3	RDH10	psi-mi:“MI:0914”(association)	0.350
C6orf141	KRBA1	psi-mi:“MI:0914”(association)	0.350
HRAS	MET	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
GDF15	CCDC85C	psi-mi:“MI:0914”(association)	0.350
RAD23A	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
ROR1	TBC1D4	psi-mi:“MI:0914”(association)	0.350
ROR1	TRIM21	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): MORC3 (Proximity Label-MS), MORC3 (Proximity Label-MS), HTT (Affinity Capture-MS), SNTB1 (Affinity Capture-MS), MOGS (Affinity Capture-MS), DYNLL1 (Affinity Capture-MS), CRIPT (Affinity Capture-MS), TRIB1 (Affinity Capture-MS), SYNE2 (Affinity Capture-MS), DEPDC1 (Affinity Capture-MS), DOCK8 (Affinity Capture-MS), RDH10 (Affinity Capture-MS), MORC3 (Affinity Capture-MS), MORC3 (Reconstituted Complex), MORC3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JZ79, A1ZA92, A6QQR4, A7E2Z2, A8JQ65, A8WRG3, B3NYS4, B4K6T8, B4R0A5, B6VQ60, F4JZ68, O75164, O94640, P06700, P33294, P42124, P50526, P70351, Q04688, Q08BS4, Q14149, Q15910, Q21921, Q28D84, Q28Z18, Q2NKX8, Q4R381, Q4V863, Q5RD88, Q5RDS6, Q5RDX4, Q60L58, Q61188, Q61IS6, Q640I9, Q6DTM3, Q6PL18, Q757M7, Q8CDM1, Q8K3E5

Diamond homologs: F4JPP0, F4JRS4, F4K2G3, F4KAF2, F7BJB9, Q14149, Q56Y74, Q5FV35, Q84WV6, Q8BMD7, Q8TE76, Q86VD1, Q9WVL5, Q8C5W4, Q5CCK4, Q69ZX6, Q6IR42, Q9M1I1, Q9Y6X9, Q0DIQ5, Q6Z3U3, A4LBC0, O65420, O82595, O82799, P26307, P37398, P82280, Q01593, Q0D5G4, Q0DXB1, Q1PFR7, Q53QI0, Q5VS55, Q6EU30, Q6L4H4, Q6Z1Z3, Q7EZD5, Q7F9W2, Q7XKC4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	76.0×	3e-08
SUMOylation of transcription factors	7	75.4×	1e-09
Activation of BAD and translocation to mitochondria	5	71.8×	5e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	63.4×	9e-07
Activation of BH3-only proteins	5	46.8×	4e-06
SUMOylation of intracellular receptors	5	31.7×	2e-05
RHO GTPases activate PKNs	5	29.9×	3e-05
Intrinsic Pathway for Apoptosis	5	27.6×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein sumoylation	5	26.6×	8e-04
intracellular protein localization	6	10.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3060 predictions. Top by Δscore:

Variant	Effect	Δscore
21:36320299:GCGCG:G	donor_gain	1.0000
21:36320301:GCG:G	donor_gain	1.0000
21:36320304:G:GG	donor_gain	1.0000
21:36333644:A:AG	acceptor_gain	1.0000
21:36333645:G:GA	acceptor_gain	1.0000
21:36333645:GCTTT:G	acceptor_gain	1.0000
21:36333714:AATAG:A	donor_loss	1.0000
21:36333716:TAGG:T	donor_loss	1.0000
21:36333718:GGT:G	donor_loss	1.0000
21:36333719:G:T	donor_loss	1.0000
21:36333720:T:A	donor_loss	1.0000
21:36336872:A:AG	acceptor_gain	1.0000
21:36336873:G:GG	acceptor_gain	1.0000
21:36336873:GATA:G	acceptor_gain	1.0000
21:36337730:A:AG	acceptor_gain	1.0000
21:36337731:G:GA	acceptor_gain	1.0000
21:36337731:GCTTT:G	acceptor_gain	1.0000
21:36337892:G:GT	donor_gain	1.0000
21:36338843:C:CA	acceptor_gain	1.0000
21:36341398:GCTAC:G	acceptor_gain	1.0000
21:36341543:GAGG:G	donor_gain	1.0000
21:36341545:GG:G	donor_gain	1.0000
21:36341546:GG:G	donor_gain	1.0000
21:36341547:G:GC	donor_loss	1.0000
21:36341547:G:GG	donor_gain	1.0000
21:36341548:TAT:T	donor_loss	1.0000
21:36344573:TTCCA:T	acceptor_gain	1.0000
21:36344574:TCCAG:T	acceptor_gain	1.0000
21:36344575:CCA:C	acceptor_gain	1.0000
21:36344576:CAGG:C	acceptor_gain	1.0000

AlphaMissense

6293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:36333658:T:C	F18L	1.000
21:36333660:T:A	F18L	1.000
21:36333660:T:G	F18L	1.000
21:36333672:T:A	N22K	1.000
21:36333672:T:G	N22K	1.000
21:36333679:A:C	S25R	1.000
21:36333681:T:A	S25R	1.000
21:36333681:T:G	S25R	1.000
21:36333682:C:A	H26N	1.000
21:36333682:C:G	H26D	1.000
21:36333682:C:T	H26Y	1.000
21:36333683:A:G	H26R	1.000
21:36333684:C:A	H26Q	1.000
21:36333684:C:G	H26Q	1.000
21:36333697:A:C	S31R	1.000
21:36333699:T:A	S31R	1.000
21:36333699:T:G	S31R	1.000
21:36333707:C:A	A34D	1.000
21:36333710:A:T	E35V	1.000
21:36333711:A:C	E35D	1.000
21:36333711:A:T	E35D	1.000
21:36333713:T:C	L36S	1.000
21:36333718:G:C	D38H	1.000
21:36336874:A:T	D38V	1.000
21:36336878:T:A	N39K	1.000
21:36336878:T:G	N39K	1.000
21:36337778:G:A	G98R	1.000
21:36337778:G:C	G98R	1.000
21:36337779:G:A	G98E	1.000
21:36337787:G:A	G101R	1.000

dbSNP variants (sampled 300 via entrez): RS1000045077 (21:36319998 G>A,C), RS1000047023 (21:36376840 G>C), RS1000052633 (21:36355771 T>C), RS1000137092 (21:36366483 A>T), RS1000140209 (21:36340719 C>G,T), RS1000191830 (21:36371469 GTTAGCCTA>G), RS1000252169 (21:36346270 C>A,T), RS1000290998 (21:36329325 A>G), RS1000347484 (21:36346013 T>C), RS1000433075 (21:36374755 C>T), RS1000467165 (21:36352519 A>G), RS1000489335 (21:36355482 A>G), RS1000524048 (21:36339244 C>T), RS1000560129 (21:36359919 T>C), RS1000575081 (21:36365668 G>A)

Disease associations

OMIM: gene MIM:610078 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006630_20	Diastolic blood pressure	2.000000e-09
GCST008839_172	Height	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Formaldehyde	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases methylation	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	increases expression	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Sunitinib	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Gold	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases abundance, affects cotreatment, increases oxidation	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1

Clinical trials (associated diseases)

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