RING1

Summary

RING1 (ring finger protein 1, HGNC:10018) is a protein-coding gene on chromosome 6p21.32, encoding E3 ubiquitin-protein ligase RING1 (Q06587). Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of ‘Lys-119’ of histone H2A, thereby playing a central role in histone code and gene regulation.

This gene belongs to the RING finger family, members of which encode proteins characterized by a RING domain, a zinc-binding motif related to the zinc finger domain. The gene product can bind DNA and can act as a transcriptional repressor. It is associated with the multimeric polycomb group protein complex. The gene product interacts with the polycomb group proteins BMI1, EDR1, and CBX4, and colocalizes with these proteins in large nuclear domains. It interacts with the CBX4 protein via its glycine-rich C-terminal domain. The gene maps to the HLA class II region, where it is contiguous with the RING finger genes FABGL and HKE4.

Source: NCBI Gene 6015 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 51 total
• Druggable target: yes
• MANE Select transcript: NM_002931

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10018
Approved symbol	RING1
Name	ring finger protein 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	RNF1
Ensembl gene	ENSG00000204227
Ensembl biotype	protein_coding
OMIM	602045
Entrez	6015

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374656, ENST00000478431, ENST00000869799, ENST00000869800, ENST00000869801, ENST00000869802, ENST00000930482, ENST00000930483, ENST00000961973

RefSeq mRNA: 1 — MANE Select: NM_002931 NM_002931

CCDS: CCDS34424

Canonical transcript exons

ENST00000374656 — 7 exons

Exon	Start	End
ENSE00001634262	33209626	33209786
ENSE00001658072	33208765	33208900
ENSE00001881557	33208500	33208644
ENSE00003492119	33211158	33211547
ENSE00003533249	33209915	33210130
ENSE00003633044	33212298	33212716
ENSE00003685143	33211729	33212002

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 97.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.3602 / max 476.6859, expressed in 1822 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67257	40.0805	1821
67259	0.9124	646
67258	0.3674	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	97.00	gold quality
adenohypophysis	UBERON:0002196	96.95	gold quality
right lobe of thyroid gland	UBERON:0001119	96.10	gold quality
left lobe of thyroid gland	UBERON:0001120	95.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.83	gold quality
thyroid gland	UBERON:0002046	95.71	gold quality
cerebellar hemisphere	UBERON:0002245	95.49	gold quality
cerebellar cortex	UBERON:0002129	95.47	gold quality
cerebellum	UBERON:0002037	95.46	gold quality
right uterine tube	UBERON:0001302	95.37	gold quality
endocervix	UBERON:0000458	95.10	gold quality
left ovary	UBERON:0002119	95.07	gold quality
body of uterus	UBERON:0009853	94.98	gold quality
right ovary	UBERON:0002118	94.75	gold quality
left uterine tube	UBERON:0001303	94.61	gold quality
ovary	UBERON:0000992	94.54	gold quality
right frontal lobe	UBERON:0002810	94.36	gold quality
prostate gland	UBERON:0002367	94.32	gold quality
ectocervix	UBERON:0012249	94.10	gold quality
apex of heart	UBERON:0002098	94.09	gold quality
primary visual cortex	UBERON:0002436	94.09	gold quality
nucleus accumbens	UBERON:0001882	94.02	gold quality
putamen	UBERON:0001874	93.93	gold quality
hypothalamus	UBERON:0001898	93.92	gold quality
caudate nucleus	UBERON:0001873	93.87	gold quality
myometrium	UBERON:0001296	93.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.77	gold quality
fallopian tube	UBERON:0003889	93.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.56	gold quality
right testis	UBERON:0004534	93.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.53

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

miRNA regulators (miRDB)

45 targeting RING1, 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-6870-5P	99.99	68.55	2115
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-6754-3P	98.84	66.60	889

Literature-anchored findings (GeneRIF, showing 22)

• cpo has a role in regulating proper nervous system function, including seizure susceptibility (PMID:15687283)
• variation for the diapause phenotype is caused by a single Lys/Ile substitution in one of the six cpo transcripts (PMID:18852464)
• There is no evidence for an association between the cpo I462K polymorphism and ovarian dormancy in Australian fruit flies. (PMID:21689187)
• The results reveal that the downstream cpo SNP does not seem to play any role in diapause induction in European Drosophila populations in contrast to the upstream coding cpo SNP. (PMID:27598401)
• Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family has been reported (PMID:28003515)
• PcG protein RING1 is associated with adverse pathological features and clinical PSA recurrence in prostate cancer. (PMID:17134822)
• Studies in mammalian cells have found a multiplicity of protein complexes containing Ring1A and Ring1B, suggesting an expanded regulatory role for Ring1A, Ring1B proteins in the epigenetic regulation of gene expression. (PMID:19412891)
• USP7 was identified as a deubiquitinating enzyme that regulates the ubiquitination state of RING1B. (PMID:20800574)
• Overexpression of the EZH2, RING1, and BMI1 genes is common in MDS and indicate poor prognosis. The products of these genes might participate in epigenetic regulation of Myelodysplastic syndromes. (PMID:21125401)
• High RING1 expression is associated with non-small cell lung cancer. (PMID:24414991)
• HSCARG interacts with RING1 and inhibits RING1 ubiquitination. (PMID:24711370)
• On the basis of these results, we proposed that the expression of Ring1 protein may be a novel indicator of hepatocellular carcinoma prognosis. (PMID:26141041)
• The polycomb complex proteins BMI1 and RING1A regulate the ubiquitination of chromatin associated proteins bound to promoters. (PMID:26578590)
• The release of epigenetic repression by nitrosylation of RING1A is critical for effective cell transdifferentiation. (PMID:27623813)
• study identified novel interactions between CD147 and RING1, recovered CD147 nuclear envelope distribution in melanoma cells, and suggested a new mechanism underlying how cytoplasmic CD147 promotes melanoma development (PMID:28832687)
• High RING1 expression is associated with hepatocellular carcinoma. (PMID:29187402)
• Mutation of RING1 is associated with neurodevelopmental abnormalities (PMID:29386386)
• LncRNA C5orf66-AS1, as a competitive endogenous RNA, regulated the effect of RING1 on the proliferation, apoptosis and cell cycle of cervical cancer cells through adsorbing miR-637. (PMID:30518760)
• Essential role of MESP1-RING1A complex in cardiac differentiation. (PMID:36413948)
• RING induces cell cycle arrest and apoptosis in human breast cancer cells by regulating the HSF1/MT2A axis. (PMID:37797799)
• RING1 Inhibition Has a Cell-Specific Antitumoral Role by Promoting Autophagy in Endometrial Cancer Cells. (PMID:38219048)
• RING1 missense variants reveal sensitivity of DNA damage repair to H2A monoubiquitination dosage during neurogenesis. (PMID:39256363)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ring1	ENSMUSG00000024325
rattus_norvegicus	Ring1	ENSRNOG00000000467
drosophila_melanogaster	Psc	FBGN0005624
drosophila_melanogaster	Su(z)2	FBGN0265623

Paralogs (7): PCGF1 (ENSG00000115289), RNF2 (ENSG00000121481), PCGF6 (ENSG00000156374), BMI1 (ENSG00000168283), PCGF5 (ENSG00000180628), PCGF3 (ENSG00000185619), PCGF2 (ENSG00000277258)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RING1 — Q06587 (reviewed: Q06587)

Alternative names: Polycomb complex protein RING1, RING finger protein 1, RING-type E3 ubiquitin transferase RING1, Really interesting new gene 1 protein

All UniProt accessions (2): Q06587, A0A1U9X8F2

UniProt curated annotations — full annotation on UniProt →

Function. Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of ‘Lys-119’ of histone H2A, thereby playing a central role in histone code and gene regulation. H2A ‘Lys-119’ ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. Compared to RNF2/RING2, it does not have the main E3 ubiquitin ligase activity on histone H2A, and it may rather act as a modulator of RNF2/RING2 activity.

Subunit / interactions. Component of chromatin-associated Polycomb (PcG) complexes. Interacts with BMI1. Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2/RING2 MBLR, L3MBTL2 and YAF2. Interacts with CBX2 and PCGF6. Component of a PRC1-like complex. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of RYBP, PCGF1, BCOR and RNF2/RING2. Interacts with PCGF2, RNF2; CBX6, CBX7 and CBX8. Interacts with PHC2. Interacts with MN1. Interacts with USP26.

Subcellular location. Nucleus. Nucleus speckle.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. The hPRC-H complex purification reported by PubMed:12167701 probably presents a mixture of different PRC1-like complexes.

Isoforms (2)

UniProt ID	Names	Canonical?
Q06587-1	1	yes
Q06587-2	2

RefSeq proteins (1): NP_002922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR032443	RAWUL	Domain
IPR043540	RING1/RING2	Family

Pfam: PF13923, PF16207

UniProt features (25 total): modified residue 11, compositionally biased region 5, region of interest 4, chain 1, zinc finger region 1, splice variant 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06587-F1	72.69	0.28

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 (11): 24, 38, 140, 187, 190, 215, 220, 229, 232, 248, 254

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4655427	SUMOylation of DNA methylation proteins
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 193 (showing top): ATF_B, GGGACCA_MIR133A_MIR133B, PAX4_01, CREBP1_Q2, GCM_PRKCG, CREB_Q4, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GCM_RING1, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GCM_DPF2, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, ATF3_Q6, GCM_TEC, NGUYEN_NOTCH1_TARGETS_DN

GO Biological Process (6): chromatin remodeling (GO:0006338), anterior/posterior pattern specification (GO:0009952), protein ubiquitination (GO:0016567), negative regulation of DNA-templated transcription (GO:0045892), camera-type eye morphogenesis (GO:0048593), chromatin organization (GO:0006325)

GO Molecular Function (7): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), ubiquitin-protein transferase activator activity (GO:0097027), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (9): ubiquitin ligase complex (GO:0000151), sex chromatin (GO:0001739), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), nuclear speck (GO:0016607), PcG protein complex (GO:0031519), PRC1 complex (GO:0035102), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	5
Cellular Senescence	1
Transcriptional regulation by RUNX1	1
PTEN Regulation	1
Generic Transcription Pathway	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
ubiquitin-protein transferase activity	2
cellular anatomical structure	2
chromatin organization	1
regionalization	1
protein modification by small protein conjugation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
camera-type eye development	1
eye morphogenesis	1
cellular component organization	1
transition metal ion binding	1
ubiquitin-like protein ligase activity	1
enzyme activator activity	1
ubiquitin-protein transferase regulator activity	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
heterochromatin	1
sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
nuclear protein-containing complex	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RING1	BMI1	P35226	999
RING1	CBX2	Q14781	998
RING1	YAF2	Q8IY57	998
RING1	RYBP	Q8N488	998
RING1	PCGF1	Q9BSM1	997
RING1	PCGF6	Q9BYE7	997
RING1	PHC1	P78364	996
RING1	R4GMX3	R4GMX3	993
RING1	PCGF2	P35227	991
RING1	KDM2B	Q8NHM5	990
RING1	CBX7	O95931	989
RING1	CBX1	P23197	989
RING1	CBX8	Q9HC52	987
RING1	SLC25A3	Q00325	984
RING1	RNF2	Q99496	983

IntAct

316 interactions, top by confidence:

A	B	Type	Score
RING1	BMI1	psi-mi:“MI:0915”(physical association)	0.960
BMI1	RING1	psi-mi:“MI:0915”(physical association)	0.960
RING1	BMI1	psi-mi:“MI:0914”(association)	0.960
BMI1	RING1	psi-mi:“MI:0914”(association)	0.960
RYBP	RING1	psi-mi:“MI:0915”(physical association)	0.950
RING1	RYBP	psi-mi:“MI:0915”(physical association)	0.950
PCGF2	RING1	psi-mi:“MI:0915”(physical association)	0.940
RING1	PCGF2	psi-mi:“MI:0915”(physical association)	0.940
RING1	CBX8	psi-mi:“MI:0915”(physical association)	0.920
CBX8	RING1	psi-mi:“MI:0915”(physical association)	0.920
RING1	CBX8	psi-mi:“MI:0407”(direct interaction)	0.920
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
YAF2	RING1	psi-mi:“MI:0915”(physical association)	0.880
RING1	YAF2	psi-mi:“MI:0915”(physical association)	0.880
RING1	PCGF5	psi-mi:“MI:0915”(physical association)	0.860
RNF2	RING1	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (504): RING1 (Two-hybrid), YAF2 (Two-hybrid), RYBP (Two-hybrid), CBX8 (Two-hybrid), RING1 (Protein-peptide), RING1 (Affinity Capture-MS), RING1 (Affinity Capture-MS), RING1 (Affinity Capture-MS), RING1 (Co-localization), RING1 (Affinity Capture-Western), RING1 (Biochemical Activity), UBE2D1 (Reconstituted Complex), RING1 (Affinity Capture-MS), RING1 (Affinity Capture-MS), RING1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JUG7, A1YER5, A1YFY1, A2T6X5, B2DD29, C0HBT3, O08629, O15156, O15169, O35730, O60307, O95343, P0C0T2, P28702, P28704, P29353, P50241, P98083, Q06587, Q0IHB0, Q13263, Q2V2M9, Q2YDU3, Q3U1V8, Q3U2S4, Q4KMP7, Q5DU25, Q5JU85, Q5PRF9, Q5R7W7, Q5RBI7, Q5RJI5, Q5TJF3, Q5TJF7, Q62233, Q62318, Q66J69, Q68DC2, Q6MGB6, Q6ZRS2

Diamond homologs: A1YER5, A1YFY1, A2T6X5, H2KYH3, O35730, O94264, Q06587, Q0WX00, Q4KLY4, Q5R9J5, Q5TJF3, Q66J69, Q6MGB6, Q7ZWM8, Q803I4, Q8WMN5, Q94AY3, Q99496, Q9CQJ4, Q9FKW0, Q9M9Y4, Q9VB08, P78317, Q9QZS2, A0A3B3IT33, B8B5U8, G2Q0E2, O19085, O35445, O70418, O74747, O77666, P10862, P14373, P18892, P19474, P62603, P93030, Q00940, Q03605

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RING1	up-regulates	FHL1	binding
Ub:E2	“up-regulates activity”	RING1	ubiquitination
RING1	“down-regulates activity”	“Histone H2A”	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 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
SUMOylation of DNA methylation proteins	5	44.8×	5e-06
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	11	44.1×	2e-13
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	7	34.4×	2e-07
Transcriptional Regulation by E2F6	7	27.3×	7e-07
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	10	19.5×	2e-08
SUMOylation of transcription cofactors	6	19.4×	3e-05
Regulation of PTEN gene transcription	8	19.0×	7e-07
PTEN Regulation	6	18.3×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	20.1×	5e-04
protein K48-linked ubiquitination	11	18.5×	6e-09
positive regulation of miRNA transcription	6	17.4×	2e-04
protein monoubiquitination	5	17.2×	1e-03
anatomical structure morphogenesis	6	8.4×	5e-03
chromatin remodeling	11	8.0×	3e-05
transcription by RNA polymerase II	11	7.8×	3e-05
protein polyubiquitination	6	6.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

904 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33208640:GCTGG:G	donor_gain	1.0000
6:33208641:C:G	donor_gain	1.0000
6:33209614:T:A	acceptor_gain	1.0000
6:33209910:CCCA:C	acceptor_loss	1.0000
6:33209911:CCA:C	acceptor_loss	1.0000
6:33209912:CAGG:C	acceptor_loss	1.0000
6:33209913:A:AG	acceptor_gain	1.0000
6:33209914:G:GG	acceptor_gain	1.0000
6:33209914:G:GT	acceptor_loss	1.0000
6:33210102:G:GT	donor_gain	1.0000
6:33210105:GGGC:G	donor_gain	1.0000
6:33210106:GGC:G	donor_gain	1.0000
6:33210126:CACAG:C	donor_loss	1.0000
6:33210127:ACAGG:A	donor_loss	1.0000
6:33210128:CAG:C	donor_loss	1.0000
6:33210130:GG:G	donor_loss	1.0000
6:33210131:GT:G	donor_gain	1.0000
6:33211724:TCCA:T	acceptor_loss	1.0000
6:33211725:CCAG:C	acceptor_loss	1.0000
6:33211726:CAG:C	acceptor_loss	1.0000
6:33211728:GGT:G	acceptor_gain	1.0000
6:33211817:G:GT	donor_gain	1.0000
6:33211825:G:T	donor_gain	1.0000
6:33211833:G:GT	donor_gain	1.0000
6:33212286:C:G	acceptor_gain	1.0000
6:33208641:CTGGG:C	donor_loss	0.9900
6:33208642:TGGGT:T	donor_loss	0.9900
6:33208643:GG:G	donor_gain	0.9900
6:33208643:GGGTG:G	donor_loss	0.9900
6:33208644:GG:G	donor_gain	0.9900

AlphaMissense

2586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33208880:G:A	E20K	1.000
6:33209657:T:A	V37D	1.000
6:33209672:T:A	L42Q	1.000
6:33209672:T:C	L42P	1.000
6:33209680:G:A	E45K	1.000
6:33209684:T:A	L46H	1.000
6:33209684:T:C	L46P	1.000
6:33209689:T:A	C48S	1.000
6:33209689:T:C	C48R	1.000
6:33209689:T:G	C48G	1.000
6:33209690:G:A	C48Y	1.000
6:33209690:G:C	C48S	1.000
6:33209690:G:T	C48F	1.000
6:33209691:C:G	C48W	1.000
6:33209693:C:A	P49H	1.000
6:33209693:C:T	P49L	1.000
6:33209695:A:T	I50F	1.000
6:33209696:T:A	I50N	1.000
6:33209696:T:C	I50T	1.000
6:33209696:T:G	I50S	1.000
6:33209698:T:A	C51S	1.000
6:33209698:T:C	C51R	1.000
6:33209698:T:G	C51G	1.000
6:33209699:G:A	C51Y	1.000
6:33209699:G:C	C51S	1.000
6:33209699:G:T	C51F	1.000
6:33209700:C:G	C51W	1.000
6:33209702:T:A	L52Q	1.000
6:33209702:T:C	L52P	1.000
6:33209705:A:T	D53V	1.000

dbSNP variants (sampled 300 via entrez): RS1000132732 (6:33209242 C>G,T), RS1000187009 (6:33209649 G>T), RS1001766461 (6:33210753 A>C,G,T), RS1002021746 (6:33208717 C>A,G,T), RS1002260040 (6:33210496 G>C), RS1002478531 (6:33213176 C>T), RS1002539674 (6:33208469 C>A,G), RS1002924466 (6:33206914 C>T), RS1003134062 (6:33206897 G>GA), RS1003429229 (6:33207193 C>T), RS1003519389 (6:33208664 C>T), RS1003546270 (6:33212464 C>T), RS1003854171 (6:33208888 C>T), RS1004770328 (6:33211635 A>G), RS1005370806 (6:33208092 C>G,T)

Disease associations

OMIM: gene MIM:602045 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002160_5	Wegener’s granulomatosis	2.000000e-50
GCST010043_141	Asthma	8.000000e-14

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066043 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
lead acetate	increases expression	1
cobaltous chloride	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Venlafaxine Hydrochloride	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Cadmium	increases expression	1
Caffeine	increases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases phosphorylation	1
Selenium	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5548055	Binding	PROTAC activity at CRBN/RING1A in human K562 cells assessed as degradation of RING1A protein expression at 1 to 10 uM incubated for 24 hrs by Western blotting analysis	Discovery and Characterization of a Novel Cereblon-Recruiting PRC1 Bridged PROTAC Degrader. — J Med Chem

Cellosaurus cell lines

10 cell lines: 8 cancer cell line, 2 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B5QP	WAe001-A-76	Embryonic stem cell	Male
CVCL_B7Z5	Abcam Raji RING1 KO	Cancer cell line	Male
CVCL_B9ZW	Abcam THP-1 RING1 KO	Cancer cell line	Male
CVCL_C0JV	GIBHe013-A	Embryonic stem cell	Male
CVCL_C7BK	Abcam PC-3 RING1 KO	Cancer cell line	Male
CVCL_DX52	HAP1 RING1 (-) RNF2 (-) 1	Cancer cell line	Male
CVCL_E1NP	HAP1 RING1 (-) RNF2 (-) 2	Cancer cell line	Male
CVCL_TJ06	HAP1 RING1 (-) 1	Cancer cell line	Male
CVCL_TJ07	HAP1 RING1 (-) 2	Cancer cell line	Male
CVCL_TJ08	HAP1 RING1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism