RNF11

Summary

RNF11 (ring finger protein 11, HGNC:10056) is a protein-coding gene on chromosome 1p32.3, encoding RING finger protein 11 (Q9Y3C5). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways.

The protein encoded by this gene contains a RING-H2 finger motif, which is known to be important for protein-protein interactions. The expression of this gene has been shown to be induced by mutant RET proteins (MEN2A/MEN2B). The germline mutations in RET gene are known to be responsible for the development of multiple endocrine neoplasia (MEN).

Source: NCBI Gene 26994 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_014372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10056
Approved symbol	RNF11
Name	ring finger protein 11
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-123, Sid1669p, MGC51169
Ensembl gene	ENSG00000123091
Ensembl biotype	protein_coding
OMIM	612598
Entrez	26994

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000242719, ENST00000486691, ENST00000494873, ENST00000856527, ENST00000856528, ENST00000856529, ENST00000963612

RefSeq mRNA: 1 — MANE Select: NM_014372 NM_014372

CCDS: CCDS556

Canonical transcript exons

ENST00000242719 — 3 exons

Exon	Start	End
ENSE00000772030	51269956	51270125
ENSE00000835622	51271151	51273447
ENSE00001244768	51236273	51236879

Expression profiles

Bgee: expression breadth ubiquitous, 303 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 104.5329 / max 1384.5025, expressed in 1819 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2837	83.2755	1819
2838	11.2420	1719
2840	6.6712	1671
2839	2.0042	921
2841	0.5833	305
2842	0.3454	83
2843	0.3393	151
2836	0.0721	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.02	gold quality
endothelial cell	CL:0000115	98.96	gold quality
prefrontal cortex	UBERON:0000451	98.78	gold quality
substantia nigra pars compacta	UBERON:0001965	98.75	gold quality
lateral globus pallidus	UBERON:0002476	98.49	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.42	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.39	gold quality
superior vestibular nucleus	UBERON:0007227	98.25	gold quality
monocyte	CL:0000576	98.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.23	gold quality
penis	UBERON:0000989	98.20	gold quality
CA1 field of hippocampus	UBERON:0003881	98.19	gold quality
pons	UBERON:0000988	98.18	gold quality
oral cavity	UBERON:0000167	98.13	gold quality
primary visual cortex	UBERON:0002436	98.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.10	gold quality
mononuclear cell	CL:0000842	98.09	gold quality
blood vessel layer	UBERON:0004797	98.09	gold quality
occipital lobe	UBERON:0002021	98.08	gold quality
frontal cortex	UBERON:0001870	98.06	gold quality
frontal lobe	UBERON:0016525	98.06	gold quality
neocortex	UBERON:0001950	98.03	gold quality
cingulate cortex	UBERON:0003027	98.01	gold quality
cerebral cortex	UBERON:0000956	98.00	gold quality
germinal epithelium of ovary	UBERON:0001304	98.00	gold quality
postcentral gyrus	UBERON:0002581	97.99	gold quality
anterior cingulate cortex	UBERON:0009835	97.98	gold quality
parietal lobe	UBERON:0001872	97.97	gold quality
amygdala	UBERON:0001876	97.97	gold quality
orbitofrontal cortex	UBERON:0004167	97.94	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	801.91
E-ANND-3	yes	13.53
E-GEOD-111727	no	312.37
E-MTAB-6524	no	77.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

158 targeting RNF11, 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-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
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-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562

Literature-anchored findings (GeneRIF, showing 22)

• overexpression of RNF11, through its interaction with Smurf2, can restore TGFbeta responsiveness in transfected tumor cells (PMID:14562029)
• characterization of ring finger protein 11 (PMID:16123141)
• RNF11 is a small RING E3 ligase that affects transforming growth factorbeta and EGF-R signaling and is overexpressed in invasive breast cancers (PMID:16925951)
• these findings identify RNF11 as a strong candidate gene at the PARK10 locus and highlight its potential significance in the development of the common form of Parkinson disease (PMID:17917589)
• Analysis reveals that the main determinants of selectivity between ubiquitin ligases RNF11 and E2 ubiquitin-conjugating enzymes resides on ring domains, rather than on the E2s. (PMID:18615712)
• WWP1 may promote cell proliferation and survival partially through suppressing RNF11-mediated ErbB2 and EGFR downregulation in human cancer cells. (PMID:18724389)
• RNF11, together with TAX1BP1 and Itch, is an essential component of an A20 ubiquitin-editing protein complex that ensures transient activation of inflammatory signalling pathways. (PMID:19131965)
• Data show that membrane anchoring through acylation is necessary for RNF11 to be post-translationally modified by the addition of several ubiquitin moieties. (PMID:20676133)
• RNF11 negatively regulates canonical NF-kappaB signaling in the nervous system. (PMID:22507528)
• Microglial RNF11 is a negative regulator of NF-kappaB signalling pathway and could be a strong potential target for modulating inflammatory responses in neurodegenerative diseases. (PMID:22975135)
• The negative influence that perturbation of RNF11 and SARA levels exerts on the lysosomal degradation of EGFRs could underscore the significance of overexpression of RNF11 in certain cancers. (PMID:23222715)
• RNF11 functions together with TAX1BP1 to restrict antiviral signaling and IFN-beta production. (PMID:23308279)
• Our data exemplifies the relevance of RNF11 and persistent NF-kappaB activation in Parkinson’s disease (PMID:23669642)
• RNF11 is at the center of a finally regulated system where it acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. (PMID:25195858)
• Up-regulation of COPII components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. (PMID:27872256)
• data suggest for the first time that the choice of binding partners for SMURF2 can sustain or repress TGFbeta signaling, and RNF11 may promote TGFbeta-induced cell migration. (PMID:28292929)
• RNF11 may regulate the activity of E3s that rely on Ubc13 for ubiquitin chain assembly by limiting the availability of Ubc13 and its conjugate. (PMID:29537486)
• Ring Finger Protein 11 acts on ligand-activated EGFR via the direct interaction with the UIM region of ANKRD13 protein family. (PMID:31985874)
• miR-425-5p Acts as a Molecular Marker and Promoted Proliferation, Migration by Targeting RNF11 in Hepatocellular Carcinoma. (PMID:33123581)
• RNF11 at the Crossroads of Protein Ubiquitination. (PMID:33187263)
• Endurance exercise training-responsive miR-19b-3p improves skeletal muscle glucose metabolism. (PMID:34642330)
• [Mechanism of ring finger protein 11 regulating Akt signaling pathway to promote osteogenic differentiation of bone marrow mesenchymal stem cells]. (PMID:35038807)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf11b	ENSDARG00000040635
mus_musculus	Rnf11	ENSMUSG00000028557
rattus_norvegicus	Rnf11l2	ENSRNOG00000048819
rattus_norvegicus		ENSRNOG00000074831
caenorhabditis_elegans		WBGENE00007226

Paralogs (2): ZNRF2 (ENSG00000180233), ZNRF1 (ENSG00000186187)

Protein

Protein identifiers

RING finger protein 11 — Q9Y3C5 (reviewed: Q9Y3C5)

All UniProt accessions (1): Q9Y3C5

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. Promotes the association of TNFAIP3 to RIPK1 after TNF stimulation. TNFAIP3 deubiquitinates ‘Lys-63’ polyubiquitin chains on RIPK1 and catalyzes the formation of ‘Lys-48’-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Recruits STAMBP to the E3 ubiquitin-ligase SMURF2 for ubiquitination, leading to its degradation by the 26S proteasome.

Subunit / interactions. Interacts (when phosphorylated) with 14-3-3. Interacts with the E3 ubiquitin-ligases NEDD4, ITCH, SMURF2 and WWP1. Also interacts with the E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2N, but neither with CDC34, nor with UBE2L3. Interacts with ZNF350, EPS15 and STAMBP. After TNF stimulation, interacts with TAX1BP1, TNFAIP3 and RIPK1; these interactions are transient and they are lost after 1 hour of stimulation with TNF. Interacts with GGA1.

Subcellular location. Early endosome. Recycling endosome. Cytoplasm. Nucleus.

Tissue specificity. Expressed at low levels in the lung, liver, kidney, pancreas, spleen, prostate, thymus, ovary, small intestine, colon, and peripheral blood lymphocytes, and, at intermediate levels, in the testis, heart, brain and placenta. Highest expression in the skeletal muscle. In the brain, expressed at different levels in several regions: high levels in the amygdala, moderate in the hippocampus and thalamus, low in the caudate and extremely low levels in the corpus callosum (at protein level). Restricted to neurons, enriched in somatodendritic compartments and excluded from white matter (at protein level). In substantia nigra, present in cell bodies and processes of dopaminergic and nondopaminergic cells (at protein level). In Parkinson disease, sequestered in Lewy bodies and neurites. Overexpressed in breast cancer cells, but not detected in the surrounding stroma and weakly, if at all, in normal breast epithelial cells (at protein level). Also expressed in several tumor cell lines.

Post-translational modifications. Ubiquitinated in the presence of ITCH, or SMURF2, and UBE2D1, as well as WWP1. Phosphorylation by PKB/AKT1 may accelerate degradation by the proteasome. Acylation at both Gly-2 and Cys-4 is required for proper localization to the endosomes.

Domain organisation. The PPxY motif mediates interaction with NEDD4.

RefSeq proteins (1): NP_055187* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR042981	RNF11_RING-H2	Domain
IPR052804	UEC_component	Family

Pfam: PF13639

UniProt features (28 total): mutagenesis site 14, modified residue 3, lipid moiety-binding region 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence variant 1, zinc finger region 1, sequence conflict 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3C5-F1	78.98	0.45

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 (5): 2, 4, 14, 25, 135

Mutagenesis-validated functional residues (14):

Position	Phenotype
2	loss of myristoylation. change in subcellular location: becomes diffused throughout the cytosol. strong reduction of ubi
4	change in subcellular location: becomes partially cytosolic and retained in association with the golgi apparatus. partia
12	loss of gga1-binding.
15	loss of gga1-binding.
16	loss of gga1-binding.
40	loss of itch-, smurf2- and wwp1-binding. partial loss of ubiquitination by itch. no effect on stambp-binding; when assoc
99	no effect on stambp- and smurf2-binding; when associated with s-102. persistent tnf-mediated nfkbia phosphorylation. no
102	no effect on stambp- and smurf2-binding; when associated with s-99. no effect on ubiquitination by itch; when associated
103	loss of ube2n-binding. no gain of ube2l3-binding.
103	no effect on ube2n-binding. no gain of ube2l3-binding; when associated with l-127 and l-128.
103	no effect on ube2n-binding. gain of ube2l3-binding.
127	no effect on ube2n-binding. no gain of ube2l3-binding; when associated with l-128.
128	no effect on ube2n-binding. no gain of ube2l3-binding.
135	loss of phosphorylation and of 14-3-3-binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 234 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, HORIUCHI_WTAP_TARGETS_DN, NKX25_02, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, RIZKI_TUMOR_INVASIVENESS_3D_DN, GGGTGGRR_PAX4_03, MODULE_503, ATGTTAA_MIR302C, MODULE_195, OCT1_03, GOBP_PROTEIN_AUTOUBIQUITINATION, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, ATTCTTT_MIR186, TGACATY_UNKNOWN

GO Biological Process (2): ubiquitin-dependent protein catabolic process (GO:0006511), protein autoubiquitination (GO:0051865)

GO Molecular Function (5): DNA binding (GO:0003677), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), early endosome (GO:0005769), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
endosome	2
modification-dependent protein catabolic process	1
nucleic acid binding	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
extracellular vesicle	1
intracellular anatomical structure	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1316 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF11	TAX1BP1	Q86VP1	994
RNF11	ITCH	Q96J02	978
RNF11	SMURF2	Q9HAU4	921
RNF11	TNFAIP3	P21580	905
RNF11	STAMBP	O95630	827
RNF11	EPS15	P42566	681
RNF11	UBE2N	P61088	667
RNF11	WWP1	Q9H0M0	642
RNF11	STAM2	O75886	612
RNF11	TNIP1	Q15025	606
RNF11	SMURF1	Q9HCE7	599
RNF11	CDC34	P49427	596
RNF11	UBE2D1	P51668	581
RNF11	NEDD4L	Q96PU5	531
RNF11	OPTN	Q96CV9	528

IntAct

815 interactions, top by confidence:

A	B	Type	Score
RNF11	UBE2D4	psi-mi:“MI:0915”(physical association)	0.880
UBE2D4	RNF11	psi-mi:“MI:0915”(physical association)	0.880
RNF11	UBE2D2	psi-mi:“MI:0915”(physical association)	0.840
UBE2D2	RNF11	psi-mi:“MI:0220”(ubiquitination reaction)	0.840
UBE2D2	RNF11	psi-mi:“MI:0915”(physical association)	0.840
QARS1	RNF11	psi-mi:“MI:0915”(physical association)	0.830
RNF11	UBE2D1	psi-mi:“MI:0915”(physical association)	0.790
UBE2D1	RNF11	psi-mi:“MI:0915”(physical association)	0.790
RNF11	UBE2D1	psi-mi:“MI:0220”(ubiquitination reaction)	0.790
UBE2N	RNF11	psi-mi:“MI:0915”(physical association)	0.730
RNF11	UBE2N	psi-mi:“MI:0915”(physical association)	0.730
RNF11	UBE2N	psi-mi:“MI:0220”(ubiquitination reaction)	0.730
STAMBP	RNF11	psi-mi:“MI:0915”(physical association)	0.700
UBE2V1	RNF11	psi-mi:“MI:0915”(physical association)	0.680
RNF11	UBE2E3	psi-mi:“MI:0915”(physical association)	0.670
RPS27A	RNF11	psi-mi:“MI:0915”(physical association)	0.670
RNF11	UBA52	psi-mi:“MI:0915”(physical association)	0.670
STAM2	RNF11	psi-mi:“MI:0915”(physical association)	0.670
UBE2E3	RNF11	psi-mi:“MI:0915”(physical association)	0.670
WWP2	RNF11	psi-mi:“MI:0915”(physical association)	0.670
RNF11	WWP2	psi-mi:“MI:0915”(physical association)	0.670
RNF11	UBQLN2	psi-mi:“MI:0915”(physical association)	0.670
RNF11	UBE2D3	psi-mi:“MI:0915”(physical association)	0.650

BioGRID (271): RNF11 (Affinity Capture-Western), RNF11 (Reconstituted Complex), RNF11 (Protein-peptide), RNF11 (Protein-peptide), RNF11 (Protein-peptide), RNF11 (Reconstituted Complex), RNF11 (Biochemical Activity), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D3 (Reconstituted Complex), UBE2E1 (Reconstituted Complex), RNF11 (Two-hybrid), STAM2 (Reconstituted Complex), RNF11 (Co-localization), UBE2D4 (Two-hybrid)

ESM2 similar proteins: A7TSJ7, C5DZR8, O22255, O49691, O64762, O64763, O80927, P0C041, P22161, P48002, P87119, Q08DI6, Q12157, Q38Q40, Q570X5, Q6NKR1, Q6NML0, Q6NQG7, Q84W40, Q8L9T5, Q8LFY8, Q8LGA5, Q8RXX9, Q93Z92, Q9C7I1, Q9C9X7, Q9FG21, Q9FHG8, Q9FIR0, Q9FX67, Q9LQM2, Q9LS99, Q9LUL6, Q9LX93, Q9LZJ6, Q9M0R4, Q9M0R5, Q9M0R6, Q9QYK7, Q9SJJ7

Diamond homologs: A0A0D1E015, A5WWA0, A8Y4B2, E9QAU8, F1MM41, F1QB30, F7EP40, G3X9R7, O49691, O54965, P0C035, P0DPR2, Q06651, Q07G42, Q08CN9, Q08D68, Q08DI6, Q0V9R0, Q20798, Q29RU0, Q3U2C5, Q4KLR8, Q4R6Y5, Q5DTZ6, Q5M974, Q5NCP0, Q5R476, Q5RF74, Q5SSZ7, Q5XHH7, Q5XIL0, Q641J8, Q66HG0, Q66J97, Q66KG7, Q6AY01, Q6NKR1, Q6NRL6, Q6NRV8, Q6NRX0

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
RNF11	“up-regulates activity”	ITCH	binding
AKT	“down-regulates quantity”	RNF11	phosphorylation
AKT1	“down-regulates quantity”	RNF11	phosphorylation
Ub:E2	“up-regulates activity”	RNF11	ubiquitination
RNF11	“up-regulates activity”	SMURF2	binding
RNF11	“down-regulates quantity by destabilization”	STAMBP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
TICAM1, RIP1-mediated IKK complex recruitment	7	35.1×	2e-07
InlB-mediated entry of Listeria monocytogenes into host cell	5	31.7×	4e-05
IKK complex recruitment mediated by RIP1	7	29.0×	4e-07
PINK1-PRKN Mediated Mitophagy	8	23.8×	3e-07
Negative regulation of MET activity	5	21.6×	2e-04
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	6	18.4×	8e-05
Inactivation of CSF3 (G-CSF) signaling	5	18.3×	4e-04
Regulation of TNFR1 signaling	9	16.8×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
protein K6-linked ubiquitination	5	34.4×	3e-05
protein monoubiquitination	9	21.5×	1e-07
protein K63-linked ubiquitination	8	14.9×	1e-05
protein K11-linked ubiquitination	5	13.6×	3e-03
negative regulation of TORC1 signaling	6	13.5×	5e-04
protein autoubiquitination	7	11.4×	3e-04
protein K48-linked ubiquitination	9	10.5×	3e-05
regulation of macroautophagy	5	10.3×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

540 predictions. Top by Δscore:

Variant	Effect	Δscore
1:51236881:T:A	donor_loss	1.0000
1:51269946:A:AG	acceptor_gain	1.0000
1:51269947:A:G	acceptor_gain	1.0000
1:51269948:T:G	acceptor_gain	1.0000
1:51269949:A:AG	acceptor_gain	1.0000
1:51269953:TAGG:T	acceptor_loss	1.0000
1:51269954:A:AG	acceptor_gain	1.0000
1:51269954:AG:A	acceptor_gain	1.0000
1:51269955:G:GC	acceptor_gain	1.0000
1:51269955:GG:G	acceptor_gain	1.0000
1:51269955:GGA:G	acceptor_gain	1.0000
1:51269955:GGAA:G	acceptor_gain	1.0000
1:51269955:GGAAC:G	acceptor_gain	1.0000
1:51270121:CGGGA:C	donor_gain	1.0000
1:51270122:GGGA:G	donor_gain	1.0000
1:51270122:GGGAG:G	donor_gain	1.0000
1:51270123:GGA:G	donor_gain	1.0000
1:51270123:GGAG:G	donor_gain	1.0000
1:51270124:GA:G	donor_gain	1.0000
1:51270124:GAG:G	donor_gain	1.0000
1:51270124:GAGT:G	donor_loss	1.0000
1:51270125:AGTA:A	donor_loss	1.0000
1:51270126:G:GG	donor_gain	1.0000
1:51270126:G:T	donor_loss	1.0000
1:51270127:T:A	donor_loss	1.0000
1:51271137:ATT:A	acceptor_gain	1.0000
1:51271139:T:A	acceptor_gain	1.0000
1:51271145:CAACA:C	acceptor_loss	1.0000
1:51271148:CAG:C	acceptor_loss	1.0000
1:51271149:A:T	acceptor_loss	1.0000

AlphaMissense

1007 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:51270017:T:C	L62P	1.000
1:51270032:A:C	Q67P	1.000
1:51270043:G:C	A71P	1.000
1:51270044:C:A	A71D	1.000
1:51270047:A:C	Q72P	1.000
1:51270051:A:C	R73S	1.000
1:51270051:A:T	R73S	1.000
1:51270055:G:C	G75R	1.000
1:51270056:G:A	G75D	1.000
1:51270059:T:C	L76P	1.000
1:51270071:T:A	L80Q	1.000
1:51270071:T:C	L80P	1.000
1:51270073:C:T	P81S	1.000
1:51270074:C:A	P81H	1.000
1:51271152:T:A	C99S	1.000
1:51271152:T:C	C99R	1.000
1:51271153:G:A	C99Y	1.000
1:51271153:G:C	C99S	1.000
1:51271153:G:T	C99F	1.000
1:51271154:T:G	C99W	1.000
1:51271158:A:T	I101F	1.000
1:51271159:T:A	I101N	1.000
1:51271159:T:C	I101T	1.000
1:51271159:T:G	I101S	1.000
1:51271161:T:A	C102S	1.000
1:51271161:T:C	C102R	1.000
1:51271162:G:A	C102Y	1.000
1:51271162:G:C	C102S	1.000
1:51271162:G:T	C102F	1.000
1:51271163:T:G	C102W	1.000

dbSNP variants (sampled 300 via entrez): RS1000118742 (1:51255605 C>A), RS1000189442 (1:51256855 G>C,T), RS1000198532 (1:51252164 C>G), RS1000238762 (1:51255351 C>G), RS1000697467 (1:51265084 T>G), RS1000708210 (1:51234291 CTTTCTTTCTTTCTTTCT>C,CTTTCTTTCTTTCTTTCTTTTCTTTCTTTCTTTCT), RS1000897075 (1:51242506 C>A), RS1001167462 (1:51268557 C>T), RS1001257384 (1:51242591 G>A,C), RS1001318689 (1:51243840 G>A,T), RS1001368179 (1:51236177 A>G,T), RS1001437218 (1:51255215 T>C), RS1001509149 (1:51239271 C>A,G), RS1001519636 (1:51254013 A>T), RS1001733519 (1:51248877 A>C,G)

Disease associations

OMIM: gene MIM:612598 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000872_3	QRS duration	3.000000e-10
GCST005306_4	Atrial fibrillation	2.000000e-11
GCST006661_54	Male-pattern baldness	2.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation	2
Tretinoin	increases expression	2
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	increases expression	1
jinfukang	decreases expression	1
Bortezomib	increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases oxidation	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	increases expression	1
Gold	decreases expression	1
Ozone	affects cotreatment, increases oxidation	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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