RC3H2

Summary

RC3H2 (ring finger and CCCH-type domains 2, HGNC:21461) is a protein-coding gene on chromosome 9q33.2, encoding Roquin-2 (Q9HBD1). Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3’-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs.

Enables DNA binding activity; RNA binding activity; and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane.

Source: NCBI Gene 54542 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 149 total
• MANE Select transcript: NM_001100588

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21461
Approved symbol	RC3H2
Name	ring finger and CCCH-type domains 2
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20301, FLJ20713, RNF164
Ensembl gene	ENSG00000056586
Ensembl biotype	protein_coding
OMIM	615231
Entrez	54542

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 21 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000335387, ENST00000357244, ENST00000373670, ENST00000398671, ENST00000423239, ENST00000454740, ENST00000471874, ENST00000478216, ENST00000495727, ENST00000498479, ENST00000885804, ENST00000915902, ENST00000915903, ENST00000915904, ENST00000915905, ENST00000954276, ENST00000954278, ENST00000954280, ENST00000954282, ENST00000954284, ENST00000954286, ENST00000954287, ENST00000954288, ENST00000954289

RefSeq mRNA: 6 — MANE Select: NM_001100588 NM_001100588, NM_001354478, NM_001354479, NM_001354482, NM_001354486, NM_018835

CCDS: CCDS43874, CCDS48014, CCDS87685

Canonical transcript exons

ENST00000357244 — 21 exons

Exon	Start	End
ENSE00001410871	122905110	122905359
ENSE00003491394	122854531	122854615
ENSE00003502697	122859917	122860131
ENSE00003527129	122854185	122854266
ENSE00003560336	122858669	122859102
ENSE00003601290	122855732	122855878
ENSE00003622758	122857923	122858093
ENSE00003651047	122853952	122854086
ENSE00003655798	122851323	122851436
ENSE00003667969	122851081	122851229
ENSE00003692738	122855184	122855397
ENSE00003889174	122879755	122879873
ENSE00003889437	122844556	122849822
ENSE00003889450	122892909	122893026
ENSE00003889800	122877471	122877583
ENSE00003892459	122897279	122897576
ENSE00003892526	122865349	122865657
ENSE00003892828	122890312	122890545
ENSE00003893155	122879993	122880125
ENSE00003894040	122883204	122883379
ENSE00003895098	122880594	122880794

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 95.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6350 / max 112.9415, expressed in 1776 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102396	6.1556	1710
102397	4.2164	1555
102398	0.2630	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	95.74	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.87	gold quality
lower lobe of lung	UBERON:0008949	94.77	gold quality
cortical plate	UBERON:0005343	93.33	gold quality
superficial temporal artery	UBERON:0001614	93.03	gold quality
cauda epididymis	UBERON:0004360	93.00	gold quality
dorsal root ganglion	UBERON:0000044	92.77	gold quality
oral cavity	UBERON:0000167	92.71	gold quality
nipple	UBERON:0002030	92.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.56	gold quality
trigeminal ganglion	UBERON:0001675	92.33	gold quality
cardia of stomach	UBERON:0001162	92.31	gold quality
lateral globus pallidus	UBERON:0002476	92.30	gold quality
trabecular bone tissue	UBERON:0002483	92.28	gold quality
biceps brachii	UBERON:0001507	92.22	gold quality
postcentral gyrus	UBERON:0002581	92.17	gold quality
penis	UBERON:0000989	92.13	gold quality
parietal lobe	UBERON:0001872	92.07	gold quality
superior surface of tongue	UBERON:0007371	92.05	gold quality
entorhinal cortex	UBERON:0002728	91.96	gold quality
mammalian vulva	UBERON:0000997	91.93	gold quality
pylorus	UBERON:0001166	91.90	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.85	gold quality
jejunum	UBERON:0002115	91.73	gold quality
parietal pleura	UBERON:0002400	91.61	gold quality
saphenous vein	UBERON:0007318	91.49	gold quality
caput epididymis	UBERON:0004358	91.37	gold quality
inferior vagus X ganglion	UBERON:0005363	91.36	gold quality
jejunal mucosa	UBERON:0000399	91.28	gold quality
ventral tegmental area	UBERON:0002691	91.24	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.55
E-MTAB-7303	no	1415.22
E-MTAB-6058	no	242.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting RC3H2, 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-186-5P	99.99	70.83	3707
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-7849-3P	99.47	68.17	1224
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3622A-5P	97.43	67.11	356
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-1298-3P	94.05	64.84	620

Literature-anchored findings (GeneRIF, showing 4)

• Roquin-1 and roquin-2 proteins function redundantly in mRNA degradation. (PMID:26249698)
• Crystal structures, small-angle X-ray scattering, and E2 profiling revealed that while the two paralogs are highly homologous, RC3H2 and RC3H1 are different in their structures and functions. (PMID:26489670)
• Loss of KLHL6 promotes diffuse large B-cell lymphoma growth and survival by stabilizing the mRNA decay factor roquin2. (PMID:29695787)
• Roquin2 suppresses breast cancer progression by inhibiting tumor angiogenesis via selectively destabilizing proangiogenic factors mRNA. (PMID:34345214)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rc3h2	ENSDARG00000063050
mus_musculus	Rc3h2	ENSMUSG00000075376
rattus_norvegicus	Rc3h2	ENSRNOG00000009196
drosophila_melanogaster	roq	FBGN0036621

Paralogs (5): RC3H1 (ENSG00000135870), RNF227 (ENSG00000179859), RNF182 (ENSG00000180537), RNF224 (ENSG00000233198), RNF228 (ENSG00000288658)

Protein

Protein identifiers

Roquin-2 — Q9HBD1 (reviewed: Q9HBD1)

Alternative names: Membrane-associated nucleic acid-binding protein, RING finger and CCCH-type zinc finger domain-containing protein 2, RING finger protein 164, RING-type E3 ubiquitin transferase Roquin-2

All UniProt accessions (4): A6NHN2, Q9HBD1, H0Y5D9, Q4VXB2

UniProt curated annotations — full annotation on UniProt →

Function. Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3’-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF and in many more mRNAs. Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs. In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity. In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression. Also recognizes CDE in its own mRNA and in that of paralogous RC3H1, possibly leading to feedback loop regulation. miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3’ end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression. Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2B, UBE2D2, UBE2E2, UBE2E3, UBE2G2, UBE2K and UBE2Q2 and produces polyubiquitin chains. Shows the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains. Involved in the ubiquitination of MAP3K5. Able to interact with double-stranded RNA (dsRNA).

Subunit / interactions. Interacts with EDC4. Interacts with CCR4-NOT deadenylase complex. Interacts with MAP3K5; the interaction is probably stimulus-dependent.

Subcellular location. Cytoplasm. P-body.

Tissue specificity. Expressed in spleen, testis, ovary and small intestine.

Post-translational modifications. Proteolytically cleaved after Arg-509 and Arg-585 by MALT1 in activated CD4(+) T cells; cleavage at Arg-509 and Arg-585 is critical for promoting RC3H1 degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling Th17 cell differentiation.

Activity regulation. Binding to dsRNA, but not CDE RNA, crosstalks with the E3 ubiquitin ligase activity and may inhibit ubiquitination.

Domain organisation. The RING-type zinc finger is required for proper localization to stress granules, but not to P-bodies. The ROQ region is required for CDE RNA-binding. Has 2 separate RNA-binding sites, one for CDE RNA and the other for dsRNA. It may also be involved in localization to stress granules. HEPN (higher eukaryotes and prokaryotes nucleotide-binding) are observed in both N- and C-terminal sides of ROQ domain with 3D structure even if they are poredcted on the basis of sequence.

Pathway. Protein modification; protein ubiquitination.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9HBD1-1	1	yes
Q9HBD1-2	2
Q9HBD1-3	3
Q9HBD1-4	4
Q9HBD1-5	5
Q9HBD1-6	6

RefSeq proteins (6): NP_001094058, NP_001341407, NP_001341408, NP_001341411, NP_001341415, NP_061323 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR036855	Znf_CCCH_sf	Homologous_superfamily
IPR041523	ROQ_II	Domain
IPR048575	Roquin_1_2-like_ROQ	Domain
IPR052249	Roquin_domain	Family

Pfam: PF00642, PF14634, PF18386, PF21206

UniProt features (55 total): helix 16, splice variant 8, binding site 7, region of interest 5, modified residue 4, mutagenesis site 3, strand 3, zinc finger region 2, site 2, compositionally biased region 2, chain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4ZLD	X-RAY DIFFRACTION	1.6
4Z31	X-RAY DIFFRACTION	2.5
4ZLC	X-RAY DIFFRACTION	2.7
4Z30	X-RAY DIFFRACTION	2.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HBD1-F1	56.50	0.26

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 (2): 509 (cleavage; by malt1); 585 (cleavage; by malt1)

Ligand- & substrate-binding residues (7): 14; 17; 33; 35; 38; 50; 53

Post-translational modifications (4): 549, 808, 983, 1119

Mutagenesis-validated functional residues (3):

Position	Phenotype
33	loss of activity. loss of map3k5 ubiquitination.
244–248	abolishes binding to cde rna but not dsrna.
323	decreases dsrna-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 275 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_B_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_T_CELL_HOMEOSTASIS, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_GROWTH, GOBP_LYMPH_NODE_DEVELOPMENT

GO Biological Process (20): protein polyubiquitination (GO:0000209), nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), B cell homeostasis (GO:0001782), ubiquitin-dependent protein catabolic process (GO:0006511), post-embryonic development (GO:0009791), multicellular organism growth (GO:0035264), T cell proliferation (GO:0042098), T cell homeostasis (GO:0043029), lung alveolus development (GO:0048286), lymph node development (GO:0048535), spleen development (GO:0048536), T cell receptor signaling pathway (GO:0050852), limb development (GO:0060173), T follicular helper cell differentiation (GO:0061470), positive regulation of non-canonical NF-kappaB signal transduction (GO:1901224), negative regulation of T-helper 17 cell differentiation (GO:2000320), regulation of miRNA metabolic process (GO:2000628), regulation of gene expression (GO:0010468), post-transcriptional regulation of gene expression (GO:0010608), protein ubiquitination (GO:0016567)

GO Molecular Function (9): DNA binding (GO:0003677), RNA binding (GO:0003723), double-stranded RNA binding (GO:0003725), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), RNA stem-loop binding (GO:0035613), ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): P-body (GO:0000932), cell surface (GO:0009986), cytoplasmic stress granule (GO:0010494), membrane (GO:0016020), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	3
cellular anatomical structure	3
protein ubiquitination	2
lymphocyte homeostasis	2
multicellular organismal process	2
hematopoietic or lymphoid organ development	2
nucleic acid binding	2
cytoplasmic ribonucleoprotein granule	2
nuclear-transcribed mRNA catabolic process	1
mRNA destabilization	1
modification-dependent protein catabolic process	1
multicellular organism development	1
developmental growth	1
T cell activation	1
lymphocyte proliferation	1
lung development	1
anatomical structure development	1
antigen receptor-mediated signaling pathway	1
appendage development	1
T-helper cell differentiation	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
negative regulation of immune effector process	1
negative regulation of T-helper cell differentiation	1
T-helper 17 cell differentiation	1
negative regulation of T-helper 17 type immune response	1
regulation of T-helper 17 cell differentiation	1
miRNA metabolic process	1
regulation of RNA metabolic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of gene expression	1
protein modification by small protein conjugation	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RC3H2	ZC3H12A	Q5D1E8	674
RC3H2	ZC3H12B	Q5HYM0	538
RC3H2	GPR21	Q99679	527
RC3H2	ICOS	Q9Y6W8	507
RC3H2	ZC3H12D	A2A288	497
RC3H2	MALT1	Q9UDY8	496
RC3H2	NUFIP2	Q7Z417	483
RC3H2	ZC3H12C	Q9C0D7	479
RC3H2	CNOT1	A5YKK6	470
RC3H2	IER3	P46695	449
RC3H2	TNFRSF4	P43489	447
RC3H2	EDC4	Q6P2E9	437
RC3H2	HELZ	P42694	422
RC3H2	NFKBID	Q8NI38	418
RC3H2	ATXN2L	Q8WWM7	412

IntAct

29 interactions, top by confidence:

A	B	Type	Score
PFDN4	PFDN6	psi-mi:“MI:0914”(association)	0.730
CCT2	PPP6C	psi-mi:“MI:0914”(association)	0.640
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
NCKIPSD	GEMIN4	psi-mi:“MI:2364”(proximity)	0.420
UBE2N	RC3H2	psi-mi:“MI:0915”(physical association)	0.370
RC3H2	UBE2I	psi-mi:“MI:0915”(physical association)	0.370
RC3H2	TRIM8	psi-mi:“MI:0915”(physical association)	0.370
Nrip3	ILVBL	psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350
CEP135	WWP2	psi-mi:“MI:0914”(association)	0.350
CEP135	WDR91	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CCT7	PDCD5	psi-mi:“MI:0914”(association)	0.350
RC3H2	CYP19A1	psi-mi:“MI:0914”(association)	0.350
KLHL6	ELF1	psi-mi:“MI:0914”(association)	0.350
MAGEA9	MED19	psi-mi:“MI:0914”(association)	0.350
PFDN4	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
PFDN2	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Rc3h1	CNOT1	psi-mi:“MI:0914”(association)	0.350
Rc3h2	CNOT1	psi-mi:“MI:0914”(association)	0.350
OGT	SMCHD1	psi-mi:“MI:0914”(association)	0.350
SF3B4	MED19	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
RC3H2	TIA1	psi-mi:“MI:0403”(colocalization)	0.270
TIA1	RC3H2	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (765): RC3H2 (Affinity Capture-MS), RC3H2 (Affinity Capture-MS), RC3H2 (Biochemical Activity), UBC (Biochemical Activity), UBE2E2 (Reconstituted Complex), UBE2E3 (Reconstituted Complex), UBE2K (Reconstituted Complex), UBE2Q2 (Reconstituted Complex), UBE2B (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2G2 (Reconstituted Complex), UBE2N (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2V2 (Reconstituted Complex), RC3H2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMF8, A2RSY1, A6QLW9, B1WAV2, B2GV50, O60271, O75069, O77627, P05412, P05627, P0C090, P17325, P22670, P48377, P48378, P48379, P48380, P48381, P56432, Q0V989, Q0V9K5, Q16656, Q32NR3, Q3KR73, Q499B3, Q49GP3, Q4R3I8, Q4R3Z4, Q4V872, Q4VGL6, Q58A65, Q5EAP5, Q5EY87, Q5RDR2, Q5RJA1, Q5TC82, Q62739, Q66IV1, Q6NRE7, Q6NUC6

Diamond homologs: O45962, P0C090, Q4VGL6, Q5TC82, Q6NUC6, Q9HBD1, Q11072, Q13049, Q810I1, Q810I2, Q8CH72, A3BUD2, G5EF15, P47976, Q57W26, Q5VR07, Q84UQ3, Q94131, Q9FWS3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
“CCR4-NOT complex”	“down-regulates quantity by repression”	RC3H2	“post transcriptional regulation”
Ub:E2	“up-regulates activity”	RC3H2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Prefoldin mediated transfer of substrate to CCT/TriC	6	84.4×	9e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	6	18.8×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	114
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2816 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122851079:A:AC	donor_gain	1.0000
9:122851080:C:CC	donor_gain	1.0000
9:122851321:A:AC	donor_gain	1.0000
9:122851322:C:CC	donor_gain	1.0000
9:122853948:TTACC:T	donor_loss	1.0000
9:122853951:CCT:C	donor_gain	1.0000
9:122853951:CCTCT:C	donor_gain	1.0000
9:122853974:T:A	donor_gain	1.0000
9:122854082:TTGGC:T	acceptor_gain	1.0000
9:122854083:TGGC:T	acceptor_gain	1.0000
9:122854083:TGGCC:T	acceptor_gain	1.0000
9:122854084:GGC:G	acceptor_gain	1.0000
9:122854084:GGCCT:G	acceptor_gain	1.0000
9:122854085:GC:G	acceptor_gain	1.0000
9:122854085:GCCTA:G	acceptor_gain	1.0000
9:122854086:CC:C	acceptor_gain	1.0000
9:122854086:CCTAT:C	acceptor_gain	1.0000
9:122854087:C:CA	acceptor_loss	1.0000
9:122854087:C:CC	acceptor_gain	1.0000
9:122854087:C:T	acceptor_gain	1.0000
9:122854089:A:AC	acceptor_gain	1.0000
9:122854089:A:C	acceptor_gain	1.0000
9:122854091:A:AC	acceptor_gain	1.0000
9:122854091:A:C	acceptor_gain	1.0000
9:122854525:CGTTA:C	donor_loss	1.0000
9:122854529:ACCT:A	donor_loss	1.0000
9:122854530:C:CA	donor_loss	1.0000
9:122854612:TAAT:T	acceptor_gain	1.0000
9:122854624:A:C	acceptor_gain	1.0000
9:122854626:G:C	acceptor_gain	1.0000

AlphaMissense

7775 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122877477:A:G	L440P	1.000
9:122877491:A:C	H435Q	1.000
9:122877491:A:T	H435Q	1.000
9:122877493:G:C	H435D	1.000
9:122877495:G:T	A434D	1.000
9:122877497:A:C	F433L	1.000
9:122877497:A:T	F433L	1.000
9:122877498:A:C	F433C	1.000
9:122877498:A:G	F433S	1.000
9:122877499:A:G	F433L	1.000
9:122877499:A:T	F433I	1.000
9:122877503:A:C	C431W	1.000
9:122877504:C:A	C431F	1.000
9:122877504:C:G	C431S	1.000
9:122877504:C:T	C431Y	1.000
9:122877505:A:C	C431G	1.000
9:122877505:A:G	C431R	1.000
9:122877505:A:T	C431S	1.000
9:122877521:A:C	C425W	1.000
9:122877522:C:G	C425S	1.000
9:122877522:C:T	C425Y	1.000
9:122877523:A:C	C425G	1.000
9:122877523:A:G	C425R	1.000
9:122877523:A:T	C425S	1.000
9:122877548:G:C	C416W	1.000
9:122877549:C:A	C416F	1.000
9:122877549:C:G	C416S	1.000
9:122877549:C:T	C416Y	1.000
9:122877550:A:G	C416R	1.000
9:122877550:A:T	C416S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001891 (9:122866810 C>T), RS1000060992 (9:122860606 G>A), RS1000076948 (9:122865888 C>T), RS1000097789 (9:122882231 T>G), RS1000111555 (9:122886286 T>C,G), RS1000186985 (9:122886090 A>G), RS1000527722 (9:122884761 G>A,C), RS1000554531 (9:122865488 C>T), RS1000645652 (9:122878581 C>T), RS1000679394 (9:122860398 A>C,T), RS1000719622 (9:122891504 T>C), RS1000729287 (9:122878416 G>A,C), RS1000754463 (9:122849999 C>T), RS1000793870 (9:122879640 G>T), RS1000898279 (9:122884987 G>A,T)

Disease associations

OMIM: gene MIM:615231 | 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
GCST005951_64	Body mass index	2.000000e-10
GCST010703_296	Brain morphology (MOSTest)	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
coumarin	increases phosphorylation	1
bazedoxifene	decreases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Caffeine	affects phosphorylation	1
Succimer	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Isotretinoin	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Magnetite Nanoparticles	affects cotreatment, increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7ZB	Ubigene A-549 RC3H2 KO	Cancer cell line	Male
CVCL_E2IU	HAP1 RC3H2 (-) 1	Cancer cell line	Male
CVCL_E2IV	HAP1 RC3H2 (-) 2	Cancer cell line	Male
CVCL_E2IW	HAP1 RC3H2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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