NUB1

Summary

NUB1 (negative regulator of ubiquitin like proteins 1, HGNC:17623) is a protein-coding gene on chromosome 7q36.1, encoding NEDD8 ultimate buster 1 (Q9Y5A7). Specific down-regulator of the NEDD8 conjugation system.

This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson’s disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 51667 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001243351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17623
Approved symbol	NUB1
Name	negative regulator of ubiquitin like proteins 1
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	BS4, NYREN18, NUB1L
Ensembl gene	ENSG00000013374
Ensembl biotype	protein_coding
OMIM	607981
Entrez	51667

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 35 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000413040, ENST00000460712, ENST00000468404, ENST00000470229, ENST00000470316, ENST00000477666, ENST00000480714, ENST00000480907, ENST00000483358, ENST00000493588, ENST00000497987, ENST00000568733, ENST00000866399, ENST00000866400, ENST00000866401, ENST00000866402, ENST00000866403, ENST00000866404, ENST00000866405, ENST00000866406, ENST00000866407, ENST00000866408, ENST00000866409, ENST00000866410, ENST00000866411, ENST00000866412, ENST00000866413, ENST00000866414, ENST00000866415, ENST00000866416, ENST00000866417, ENST00000866418, ENST00000914409, ENST00000914410, ENST00000914411, ENST00000914412, ENST00000959558, ENST00000959559, ENST00000959560, ENST00000959561, ENST00000959562

RefSeq mRNA: 8 — MANE Select: NM_001243351 NM_001243351, NM_001363529, NM_001385353, NM_001385354, NM_001385355, NM_001385356, NM_001385361, NM_016118

CCDS: CCDS47751, CCDS87565

Canonical transcript exons

ENST00000568733 — 15 exons

Exon	Start	End
ENSE00000399908	151349073	151349240
ENSE00000730206	151351424	151351482
ENSE00000730227	151375848	151375943
ENSE00001200646	151377047	151378449
ENSE00001255870	151376634	151376811
ENSE00001256011	151368735	151368887
ENSE00001409814	151374097	151374243
ENSE00001906403	151341812	151341846
ENSE00003485314	151366939	151367125
ENSE00003498143	151352812	151352882
ENSE00003532234	151355768	151355950
ENSE00003539100	151356128	151356222
ENSE00003574007	151345348	151345466
ENSE00003598778	151367861	151367968
ENSE00003679985	151360141	151360247

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.4467 / max 3442.0768, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82076	45.3037	1816
82075	1.1429	631

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	99.06	gold quality
calcaneal tendon	UBERON:0003701	98.55	gold quality
ileal mucosa	UBERON:0000331	97.35	gold quality
tendon	UBERON:0000043	97.33	gold quality
tibia	UBERON:0000979	97.12	gold quality
monocyte	CL:0000576	96.11	gold quality
leukocyte	CL:0000738	96.04	gold quality
visceral pleura	UBERON:0002401	95.97	gold quality
tendon of biceps brachii	UBERON:0008188	95.89	gold quality
vermiform appendix	UBERON:0001154	95.87	gold quality
parietal pleura	UBERON:0002400	95.81	gold quality
islet of Langerhans	UBERON:0000006	95.42	gold quality
rectum	UBERON:0001052	95.37	gold quality
fallopian tube	UBERON:0003889	95.32	gold quality
lymph node	UBERON:0000029	95.31	gold quality
left testis	UBERON:0004533	95.11	gold quality
right uterine tube	UBERON:0001302	95.00	gold quality
tonsil	UBERON:0002372	94.93	gold quality
gall bladder	UBERON:0002110	94.86	gold quality
right testis	UBERON:0004534	94.67	gold quality
smooth muscle tissue	UBERON:0001135	94.58	gold quality
germinal epithelium of ovary	UBERON:0001304	94.55	gold quality
tibial artery	UBERON:0007610	94.49	gold quality
popliteal artery	UBERON:0002250	94.48	gold quality
colonic epithelium	UBERON:0000397	94.47	gold quality
granulocyte	CL:0000094	94.44	gold quality
medial globus pallidus	UBERON:0002477	94.43	gold quality
middle temporal gyrus	UBERON:0002771	94.31	gold quality
parotid gland	UBERON:0001831	94.30	gold quality
muscle of leg	UBERON:0001383	94.26	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	1415.03
E-CURD-46	yes	17.53
E-MTAB-6142	no	128.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting NUB1, 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-4533	100.00	69.48	2758
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3686	99.90	70.53	2432
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-1179	99.71	68.70	1040
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-1-5P	98.70	68.66	1017
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6792-5P	98.39	68.16	1330

Literature-anchored findings (GeneRIF, showing 21)

• The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1 in the retina. (PMID:12374762)
• NUB1 has a splicing variant, NUB1L, which regulates the NEDD8 conjugation system (PMID:12816948)
• These results imply that the ubiquitin precursor UbC1 hydrolysis mediated by NEDD8 ultimate buster-1 (NUB1) is involved in cellular functions in the seminiferous tubules such as spermatogenesis. (PMID:15009209)
• interaction between NUB1 and AIPL1 is affected in patients with Leber congenital amaurosis (PMID:15081406)
• Data show that aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) can modulate protein translocation and act in a chaperone-like manner and suggest that AIPL1 is an important modulator of NEDD8 ultimate buster protein 1 (NUB1) cellular function. (PMID:15347646)
• NUB1L not only acts as a linker between the 26 S proteasome and ubiquitin-like proteins, but also as a facilitator of proteasomal degradation. (PMID:16707496)
• These results suggest that NUB1 indeed targets synphilin-1 to the proteasome for its efficient degradation, which, because of the resultant reduction in synphilin-1, suppresses the formation of synphilin-1-positive inclusions. (PMID:16877356)
• The finding of this study suggested that NUB1 along with abnormal alpha-synuclein is involved in the pathogenesis of Lewy body disease. (PMID:21937912)
• findings show how FAT10 and NUB1L dock with the 26S proteasome to initiate proteolysis; identified the 26S proteasome subunit hRpn10/S5a as the receptor for FAT10, whereas NUB1L can bind to both Rpn10 and Rpn1/S2. (PMID:22434192)
• In the present study, the proportions of intranuclear inclusion positive for NEDD8, NUB1 and SUMO-1 were significantly lower in glial cells than in neurons. (PMID:22612509)
• Data propose that NUB1, by regulating GSK3beta levels, modulates tau phosphorylation and aggregation, and is a key player in neurodegeneration associated with tau pathology. (PMID:22965877)
• This study identified genes modifying endogenous mHTT using high-throughput screening and demonstrate NUB1 as an exemplar entry point for therapeutic intervention of Huntington’s disease. (PMID:23525043)
• In coordination with the P97-UFD1-NPL4 complex (P97(UFD1/NPL4)), NUB1L promotes transfer of NEDD8 to proteasome for degradation. (PMID:24019527)
• Based on biochemical features of the VBM motifs, we also identified NUB1L (NEDD8 ultimate buster-1 long) as a novel VBM-containing protein, which is involved in proteasomal degradation of NEDD8 through the P97 pathway. (PMID:24100225)
• NUB1L suppresses atypical neddylation and promotes the degradation of misfolded proteins by the proteasome (PMID:26260793)
• data suggest that NUB1 participates in telomere maintenance by regulating the levels of TRF1 at telomeres through both NEDD8-dependent and NEDD8-independent pathways. (PMID:27214791)
• Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159. (PMID:28099510)
• Authors created a series of phosphomimic mutants of NUB1 and found that phosphorylation of NUB1 at S46 (P-NUB46) efficiently degrades aggregates using a cell-based assay. (PMID:31006160)
• Overexpression of negative regulator of ubiquitin-like proteins 1 (NUB1) inhibits proliferation and invasion of gastric cancer cells through upregulation of p27Kip1 and inhibition of epithelial-mesenchymal transition. (PMID:32703484)
• SNHG12 regulates biological behaviors of ox-LDL-induced HA-VSMCs through upregulation of SPRY2 and NUB1. (PMID:34847450)
• FAT10 and NUB1L cooperate to activate the 26S proteasome. (PMID:37188463)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nub1	ENSDARG00000061417
mus_musculus	Nub1	ENSMUSG00000028954
rattus_norvegicus	Nub1	ENSRNOG00000009282
drosophila_melanogaster	CG15445	FBGN0031161
drosophila_melanogaster	CG5111	FBGN0039343

Protein

Protein identifiers

NEDD8 ultimate buster 1 — Q9Y5A7 (reviewed: Q9Y5A7)

Alternative names: Negative regulator of ubiquitin-like proteins 1, Renal carcinoma antigen NY-REN-18

All UniProt accessions (9): Q9Y5A7, A0A090N8Q5, C9JRT6, F8WDB6, F8WDL9, H3BM14, H3BM74, H7C5E1, H7C5N1

UniProt curated annotations — full annotation on UniProt →

Function. Specific down-regulator of the NEDD8 conjugation system. Recruits NEDD8, UBD, and their conjugates to the proteasome for degradation. Isoform 1 promotes the degradation of NEDD8 more efficiently than isoform 2.

Subunit / interactions. Directly interacts with NEDD8 and PSMD4/S5a, a member of the regulatory subunit of the 26S proteasome. Isoform 1 binds to NEDD8 more efficiently than isoform 2. Interacts with AIPL1. The interaction with UBD via UBA domains facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates UBD degradation and that of its conjugates.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with lowest expression in the pancreas for isoform 1 and in leukocytes, liver, prostate and skeletal muscle for isoform 2.

Induction. By TNF, IFNG/IFN-gamma and IFNB1/IFN-beta.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5A7-1	1, NUB1L	yes
Q9Y5A7-2	2

RefSeq proteins (8): NP_001230280, NP_001350458, NP_001372282, NP_001372283, NP_001372284, NP_001372285, NP_001372290, NP_057202 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009060	UBA-like_sf	Homologous_superfamily
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR015940	UBA	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR039749	NUB1	Family
IPR041207	NUB1_ubiquitin-like_dom	Domain
IPR058666	SASH1/NUB1_homeodomain	Domain

Pfam: PF00627, PF18037, PF26285

UniProt features (32 total): strand 8, mutagenesis site 6, helix 4, domain 3, region of interest 3, compositionally biased region 2, coiled-coil region 2, chain 1, splice variant 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
8USD	ELECTRON MICROSCOPY	2.7
9E8I	ELECTRON MICROSCOPY	2.87
9E8H	ELECTRON MICROSCOPY	2.9
9E8G	ELECTRON MICROSCOPY	3.01
8USC	ELECTRON MICROSCOPY	3.1
9E8J	ELECTRON MICROSCOPY	3.47
9E8L	ELECTRON MICROSCOPY	3.59
9E8N	ELECTRON MICROSCOPY	3.62
1WJU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5A7-F1	83.66	0.48

Functional residue map

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

Mutagenesis-validated functional residues (6):

Position	Phenotype
448	no effect on nedd8-binding.
453	partial inhibition of nedd8-binding.
464	partial inhibition of nedd8-binding.
468	partial inhibition of nedd8-binding.
587	suppression of nedd8-binding; when associated with a-464; a-468 and a-591. suppression of nedd8-buster function; when as
591	suppression of nedd8-binding; when associated with a-464; a-468 and a-587. suppression of nedd8-buster function; when as

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8951664	Neddylation

MSigDB gene sets: 204 (showing top): GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, ROVERSI_GLIOMA_COPY_NUMBER_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FREAC3_01, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, IRF1_Q6, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, LIAO_METASTASIS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, IRF_Q6

GO Biological Process (8): ubiquitin-dependent protein catabolic process (GO:0006511), proteasomal protein catabolic process (GO:0010498), protein ubiquitination (GO:0016567), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), regulation of ubiquitin-dependent protein catabolic process (GO:2000058), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), Lewy body (GO:0097413), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to cytokine	2
nuclear lumen	2
cellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein catabolic process	1
protein modification by small protein conjugation	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
innate immune response	1
ubiquitin-dependent protein catabolic process	1
regulation of protein catabolic process	1
binding	1
intracellular membraneless organelle	1
cytoplasm	1
inclusion body	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1078 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NUB1	NEDD8	Q15843	942
NUB1	AIPL1	Q9NZN9	910
NUB1	PSMD4	P55036	828
NUB1	UBD	O15205	771
NUB1	UBA6	A0AVT1	557
NUB1	AIP	O00170	556
NUB1	SNCAIP	Q9Y6H5	505
NUB1	UBE2K	P27924	492
NUB1	SNCA	P37840	479
NUB1	UBL7	Q96S82	469
NUB1	UBAC1	Q9BSL1	459
NUB1	ADRM1	Q16186	454
NUB1	UBQLN1	Q9UMX0	453
NUB1	GUCY2D	Q02846	447
NUB1	TMEM11	P17152	447

IntAct

37 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TERF1	NUB1	psi-mi:“MI:0915”(physical association)	0.670
NUB1	TERF1	psi-mi:“MI:0915”(physical association)	0.670
NUB1	TERF1	psi-mi:“MI:0407”(direct interaction)	0.670
NUB1	TERF1	psi-mi:“MI:0403”(colocalization)	0.670
CRNKL1	HNRNPC	psi-mi:“MI:0914”(association)	0.610
NUB1	SF3B4	psi-mi:“MI:0915”(physical association)	0.560
NUB1	AIPL1	psi-mi:“MI:0915”(physical association)	0.510
AIPL1	NUB1	psi-mi:“MI:0915”(physical association)	0.510
UBD	NUB1	psi-mi:“MI:0915”(physical association)	0.500
NUB1	COPB1	psi-mi:“MI:0915”(physical association)	0.370
NUB1	HTT	psi-mi:“MI:0915”(physical association)	0.370
PSMC5	PSMD1	psi-mi:“MI:0914”(association)	0.350
UBB	RNF40	psi-mi:“MI:0914”(association)	0.350
SEMA4C	ARVCF	psi-mi:“MI:0914”(association)	0.350
CCDC12	AQR	psi-mi:“MI:0914”(association)	0.350
VAV1	ALOX12B	psi-mi:“MI:0914”(association)	0.350
LCN8	LRRC41	psi-mi:“MI:0914”(association)	0.350
UBD	RABGGTA	psi-mi:“MI:0914”(association)	0.350
SEM1	PSMD9	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (105): NUB1 (Affinity Capture-Western), NUB1 (Two-hybrid), UBC (Reconstituted Complex), UBC (Affinity Capture-Western), NUB1 (Affinity Capture-MS), NUB1 (Two-hybrid), NUB1 (Reconstituted Complex), TERF1 (Reconstituted Complex), NUB1 (Affinity Capture-Western), TERF1 (Affinity Capture-Western), PSMD4 (Affinity Capture-Western), NUB1 (Affinity Capture-Western), NUB1 (Affinity Capture-MS), NUB1 (Affinity Capture-RNA), NUB1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1S4D1D3, A0A1W2PR95, A1D9I5, A5D796, A7SD85, B0W6N3, D2K8N5, E1C760, E7EXT2, F7AEX0, O08836, O57476, P51951, P54729, P78318, P92948, Q0CU99, Q16543, Q16891, Q173M7, Q1DM35, Q2PIU8, Q2QY04, Q3ZC62, Q4V8E4, Q4W9M7, Q5AXH3, Q5EAC6, Q5M990, Q5PQS7, Q61081, Q61249, Q63692, Q6PID6, Q7SYB2, Q8C6E0, Q8CAQ8, Q8LDQ4, Q8R3N6, Q93VM9

Diamond homologs: P54729, Q8MJ87, Q9Y5A7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MDM2	“up-regulates activity”	NUB1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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
Activation of BAD and translocation to mitochondria	7	171.9×	5e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	151.7×	1e-12
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	151.7×	1e-12
Activation of BH3-only proteins	7	112.1×	1e-11
RHO GTPases activate PKNs	7	71.6×	3e-10
Intrinsic Pathway for Apoptosis	7	66.1×	4e-10
FOXO-mediated transcription	5	54.2×	7e-07
G2/M Checkpoints	11	47.7×	7e-14

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	52.3×	6e-06
intracellular protein localization	7	20.9×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2779 predictions. Top by Δscore:

Variant	Effect	Δscore
7:151345342:TTTCA:T	acceptor_loss	1.0000
7:151345343:TTCAG:T	acceptor_loss	1.0000
7:151345344:TCAGG:T	acceptor_loss	1.0000
7:151345345:CAGG:C	acceptor_loss	1.0000
7:151345346:AGG:A	acceptor_gain	1.0000
7:151345346:AGGGA:A	acceptor_loss	1.0000
7:151345347:GGG:G	acceptor_gain	1.0000
7:151345398:G:T	donor_gain	1.0000
7:151345449:G:GG	donor_gain	1.0000
7:151345463:AAAG:A	donor_loss	1.0000
7:151345464:AAG:A	donor_loss	1.0000
7:151345465:AGGTA:A	donor_loss	1.0000
7:151345466:GGT:G	donor_loss	1.0000
7:151345467:G:A	donor_loss	1.0000
7:151345468:T:A	donor_loss	1.0000
7:151349241:G:GG	donor_gain	1.0000
7:151351478:TCC:T	donor_gain	1.0000
7:151351481:AAGT:A	donor_loss	1.0000
7:151351482:AGTA:A	donor_loss	1.0000
7:151351483:G:GG	donor_gain	1.0000
7:151351483:GT:G	donor_loss	1.0000
7:151351484:T:A	donor_loss	1.0000
7:151351485:AA:A	donor_loss	1.0000
7:151351486:AGTA:A	donor_loss	1.0000
7:151352794:ACT:A	acceptor_gain	1.0000
7:151352806:TTACA:T	acceptor_loss	1.0000
7:151352809:CAGAA:C	acceptor_loss	1.0000
7:151352810:A:AC	acceptor_loss	1.0000
7:151352810:A:AG	acceptor_gain	1.0000
7:151352811:G:GC	acceptor_gain	1.0000

AlphaMissense

4193 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:151367912:G:A	G347R	0.999
7:151367912:G:C	G347R	0.999
7:151366986:T:C	L283P	0.998
7:151367907:T:C	L345P	0.998
7:151367912:G:T	G347W	0.998
7:151367913:G:A	G347E	0.998
7:151366971:A:T	D278V	0.997
7:151367003:T:A	W289R	0.997
7:151367003:T:C	W289R	0.997
7:151367898:T:C	L342P	0.997
7:151368833:G:C	R398S	0.997
7:151368833:G:T	R398S	0.997
7:151345416:T:A	W23R	0.996
7:151345416:T:C	W23R	0.996
7:151360231:G:C	A262P	0.996
7:151366970:G:C	D278H	0.996
7:151366975:C:A	N279K	0.996
7:151366975:C:G	N279K	0.996
7:151366980:C:A	A281D	0.996
7:151366992:T:C	L285P	0.996
7:151367961:T:C	L363P	0.996
7:151368816:G:C	A393P	0.996
7:151368829:T:C	L397P	0.996
7:151366983:T:A	V282D	0.995
7:151367067:C:A	A310D	0.995
7:151368820:G:C	R394P	0.995
7:151345418:G:C	W23C	0.994
7:151345418:G:T	W23C	0.994
7:151360223:T:C	L259P	0.994
7:151366971:A:C	D278A	0.994

dbSNP variants (sampled 300 via entrez): RS1000020673 (7:151341773 C>G,T), RS1000288127 (7:151368680 ATTAAGCT>A), RS1000297419 (7:151377656 C>T), RS1000304244 (7:151358522 A>C,G), RS1000342289 (7:151369012 CTTTTT>C,CTTT,CTTTT,CTTTTTT,CTTTTTTT,CTTTTTTTT,CTTTTTTTTTT,CTTTTTTTTTTTTTTTTTT), RS1000459772 (7:151342045 C>A,G), RS1000498669 (7:151345865 A>G), RS1000592070 (7:151374963 C>T), RS1000822513 (7:151352450 A>G), RS1000857620 (7:151343405 A>G), RS1000875464 (7:151365699 G>A), RS1001064733 (7:151340828 C>G), RS1001088494 (7:151373474 A>G), RS1001267955 (7:151376364 G>T), RS1001306911 (7:151357356 T>C)

Disease associations

OMIM: gene MIM:607981 | 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
GCST003476_9	Eyebrow thickness	7.000000e-06
GCST004162_36	Carotid plaque burden	5.000000e-06
GCST008157_37	Body fat mass	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
bisphenol A	increases methylation	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
1,10-phenanthroline	increases expression	1
nickel sulfate	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
avobenzone	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
Bortezomib	increases expression	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Arsenic	affects methylation	1
Cisplatin	affects expression	1
Diethylstilbestrol	increases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Formaldehyde	increases expression	1
Ketoconazole	increases expression	1
Ozone	increases abundance, affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
Zidovudine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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