CBLL1

Summary

CBLL1 (Cbl proto-oncogene like 1, HGNC:21225) is a protein-coding gene on chromosome 7q22.3, encoding E3 ubiquitin-protein ligase Hakai (Q75N03). E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1. It is a selective cancer dependency (DepMap: 31.0% of cell lines).

This gene encodes an E3 ubiquitin-ligase for the E-cadherin complex and mediates its ubiquitination, endocytosis, and degradation in the lysosomes. The encoded protein contains a RING-finger domain and is also thought to have a role in control of cell proliferation. A related pseudogene has been identified on chromosome X. Alternative splicing results in a non-coding transcript variant.

Source: NCBI Gene 79872 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 50 total
• Cancer dependency (DepMap): dependent in 31.0% of screened cell lines
• MANE Select transcript: NM_024814

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21225
Approved symbol	CBLL1
Name	Cbl proto-oncogene like 1
Location	7q22.3
Locus type	gene with protein product
Status	Approved
Aliases	HAKAI, FLJ23109, RNF188
Ensembl gene	ENSG00000105879
Ensembl biotype	protein_coding
OMIM	606872
Entrez	79872

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000222597, ENST00000415884, ENST00000420796, ENST00000432748, ENST00000440859, ENST00000479443, ENST00000487517, ENST00000493361, ENST00000698938

RefSeq mRNA: 2 — MANE Select: NM_024814 NM_001284291, NM_024814

CCDS: CCDS5747, CCDS64754

Canonical transcript exons

ENST00000440859 — 6 exons

Exon	Start	End
ENSE00001686409	107758143	107761667
ENSE00003574735	107748880	107749047
ENSE00003607077	107753895	107753978
ENSE00003617994	107755418	107755491
ENSE00003692483	107753411	107753511
ENSE00003975247	107744142	107744176

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 92.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.8094 / max 460.9967, expressed in 1814 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80475	25.0883	1811
80474	1.2042	669
80473	0.9196	569
80472	0.4220	187
80471	0.1754	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.26	gold quality
colonic epithelium	UBERON:0000397	90.16	gold quality
cortical plate	UBERON:0005343	89.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.33	gold quality
endothelial cell	CL:0000115	89.28	gold quality
bone marrow	UBERON:0002371	88.54	gold quality
germinal epithelium of ovary	UBERON:0001304	88.50	gold quality
bone marrow cell	CL:0002092	88.29	gold quality
muscle of leg	UBERON:0001383	88.19	gold quality
oocyte	CL:0000023	88.17	gold quality
gastrocnemius	UBERON:0001388	87.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.80	gold quality
leukocyte	CL:0000738	87.69	gold quality
islet of Langerhans	UBERON:0000006	87.62	gold quality
monocyte	CL:0000576	87.50	gold quality
mononuclear cell	CL:0000842	87.44	gold quality
palpebral conjunctiva	UBERON:0001812	87.32	gold quality
biceps brachii	UBERON:0001507	87.11	gold quality
eye	UBERON:0000970	86.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.27	gold quality
adrenal tissue	UBERON:0018303	86.27	gold quality
ganglionic eminence	UBERON:0004023	86.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.03	gold quality
lower esophagus	UBERON:0013473	85.98	gold quality
amniotic fluid	UBERON:0000173	85.89	gold quality
rectum	UBERON:0001052	85.74	gold quality
endometrium	UBERON:0001295	85.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.27	gold quality
stromal cell of endometrium	CL:0002255	85.19	gold quality
esophagus squamous epithelium	UBERON:0006920	84.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.50
E-HCAD-5	no	2.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

180 targeting CBLL1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• Results suggest that Hakai is an important regulator of cell proliferation and that Hakai may be an oncoprotein and a potential molecular target for cancer treatment. (PMID:19535458)
• Results suggest that Hakai is a novel corepressor of ERalpha and may play a negative role in the development and progression of breast cancers. (PMID:20608937)
• Together, these data do not support a requirement for CBLL1 during flavivirus entry and rather suggest an essential role of the ubiquitin/proteasome pathway for flavivirus genome amplification. (PMID:21191016)
• Hakai mediates E-cadherin ubiquitination and degradation triggered by Slit-Robo signaling during colorectal epithelial cell carcinogenesis. (PMID:21283129)
• Hakai dimerization allows the formation of a phosphotyrosine-binding pocket that recognizes specific phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. (PMID:22252131)
• By lowering Hakai abundance, miR-203 also reduces Hakai-regulated-cell division. (PMID:23285092)
• these observations suggest that the dimeric architecture of the HYB domain is essential for the phosphotyrosine-binding property of Hakai. (PMID:25074933)
• These results suggest that stabilization of delta-catenin by Hakai is dependent on Src. (PMID:28069439)
• findings suggest that the E3 ubiquitin-ligase, such as Hakai, may be a better target than proteasome for using novel specific inhibitors in tumor subtypes that follow EMT. (PMID:28675930)
• we have detected the presence of micrometastasis in the lung mice, further confirming Hakai role during tumour metastasis in vivo. These results lead to the consideration of Hakai as a potential new therapeutic target to block tumour development and metastasis (PMID:29472634)
• The present study demonstrated for the first time that knockdown of Hakai inhibited the proliferation, migration and invasion of nonsmallcell lung cancer cells, and sensitized nonsmallcell lung cancer cells to cisplatin. (PMID:29786107)
• Study have demonstrated that CBLL1 is highly expressed in non-small lung cancer (NSCLC) cancer tissues compared with corresponding normal lung tissues, and correlated with tumor size. Moreover, CBLL1 promotes the cell proliferation by inducing the G0/G1-S transition and cell invasion by increasing degradation of extracellular matrices of NSCLC cells. (PMID:31124298)
• Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells. (PMID:31646569)
• Role of the E3 ubiquitin-ligase Hakai in intestinal inflammation and cancer bowel disease. (PMID:36266428)
• CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment. (PMID:38062063)
• Stratification of Colorectal Patients Based on Survival Analysis Shows the Value of Consensus Molecular Subtypes and Reveals the CBLL1 Gene as a Biomarker of CMS2 Tumours. (PMID:38339195)
• CBLL1 promotes endometrial stromal cell senescence via inhibiting PTEN in recurrent spontaneous abortion. (PMID:39012313)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbll1	ENSDARG00000015222
mus_musculus	Cbll1	ENSMUSG00000020659
rattus_norvegicus	Cbll1	ENSRNOG00000007253
drosophila_melanogaster	Hakai	FBGN0032812

Paralogs (1): CBLL2 (ENSG00000175809)

Protein

Protein identifiers

E3 ubiquitin-protein ligase Hakai — Q75N03 (reviewed: Q75N03)

Alternative names: Casitas B-lineage lymphoma-transforming sequence-like protein 1, RING finger protein 188, RING-type E3 ubiquitin transferase Hakai

All UniProt accessions (5): Q75N03, A0A8V8TMY5, C9J2P9, C9K074, F8WEM5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1. Targets CDH1 for endocytosis and degradation. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing. Its function in the WMM complex is unknown.

Subunit / interactions. Homodimer. Interacts with tyrosine-phosphorylated SRC substrates. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14. The MACOM subcomplex is composed of WTAP, ZC3H13, CBLL1/HAKAI, VIRMA, and, in some cases of RBM15 (RBM15 or RBM15B). Also a component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, VIRMA, RBM15, BCLAF1 and THRAP3.

Subcellular location. Nucleus speckle. Nucleus. Nucleoplasm. Cytoplasm.

Post-translational modifications. Phosphorylated on tyrosine residues.

Domain organisation. The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the Hakai family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q75N03-1	1	yes
Q75N03-2	2

RefSeq proteins (2): NP_001271220, NP_079090* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR040380	HAKAI-like_RING-HC	Domain
IPR040383	HAKAI/CBLL2	Family
IPR041042	Znf_Hakai	Domain

Pfam: PF18408

UniProt features (16 total): compositionally biased region 5, modified residue 3, region of interest 3, zinc finger region 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q75N03-F1	56.68	0.15

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 (3): 201, 285, 290

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8876493	InlA-mediated entry of Listeria monocytogenes into host cells
R-HSA-9766229	Degradation of CDH1
R-HSA-9958810	SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)

MSigDB gene sets: 196 (showing top): GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_VESICLE_MEDIATED_TRANSPORT, AP2_Q3, GGGTGGRR_PAX4_03, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_CELL_ADHESION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, PID_AJDISS_2PATHWAY, GOBP_REGULATION_OF_ENDOCYTOSIS, DING_LUNG_CANCER_EXPRESSION_BY_COPY_NUMBER, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_TRANSPORT, GOBP_IMPORT_INTO_CELL

GO Biological Process (7): mRNA processing (GO:0006397), negative regulation of cell adhesion (GO:0007162), protein ubiquitination (GO:0016567), regulation of cell adhesion (GO:0030155), positive regulation of cell migration (GO:0030335), positive regulation of endocytosis (GO:0045807), cell-cell adhesion (GO:0098609)

GO Molecular Function (7): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), RNA N6-methyladenosine methyltransferase complex (GO:0036396), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Listeria monocytogenes entry into host cells	1
Regulation of CDH1 Function	1
Activation of STAT3 by cadherin engagement	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell adhesion	3
cellular anatomical structure	3
RNA processing	1
mRNA metabolic process	1
regulation of cell adhesion	1
negative regulation of cellular process	1
protein modification by small protein conjugation	1
regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
endocytosis	1
regulation of endocytosis	1
positive regulation of transport	1
positive regulation of cellular component organization	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular protein-containing complex	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
methyltransferase complex	1
nuclear lumen	1

Protein interactions and networks

STRING

972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBLL1	ZC3H13	Q5T200	998
CBLL1	VIRMA	Q69YN4	997
CBLL1	WTAP	Q15007	997
CBLL1	RBM15	Q96T37	997
CBLL1	METTL14	Q9HCE5	997
CBLL1	METTL3	Q86U44	996
CBLL1	RBM15B	Q8NDT2	990
CBLL1	CDH1	P12830	950
CBLL1	METTL16	Q86W50	926
CBLL1	SLC16A4	O15374	874
CBLL1	SLC16A3	O15427	834
CBLL1	YTHDC1	Q96MU7	773
CBLL1	YTHDC2	Q9H6S0	754
CBLL1	ALKBH5	Q6P6C2	742
CBLL1	YTHDF1	Q9BYJ9	738

IntAct

35 interactions, top by confidence:

A	B	Type	Score
RBM10	CBLL1	psi-mi:“MI:0915”(physical association)	0.560
SRC	CDH1	psi-mi:“MI:0914”(association)	0.500
CDH1	CBLL1	psi-mi:“MI:0915”(physical association)	0.400
CBLL1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
DGCR6	CBLL1	psi-mi:“MI:0915”(physical association)	0.370
KIF26B	CASK	psi-mi:“MI:0914”(association)	0.350
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
METTL14	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
METTL3	TRIM28	psi-mi:“MI:0914”(association)	0.350
METTL14	TRIM28	psi-mi:“MI:0914”(association)	0.350
WTAP	TRIM28	psi-mi:“MI:0914”(association)	0.350
VIRMA	WTAP	psi-mi:“MI:0914”(association)	0.350
VIRMA	TRIM28	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
CBLL1	DDX3X	psi-mi:“MI:0914”(association)	0.350
	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
CPSF6	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SRSF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
U2AF2	NACA	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (123): CBLL1 (Affinity Capture-MS), KIAA1429 (Co-fractionation), WTAP (Co-fractionation), CBLL1 (Affinity Capture-MS), CBLL1 (Two-hybrid), CDH1 (Affinity Capture-Western), SRC (Affinity Capture-Western), CBLL1 (Affinity Capture-MS), CBLL1 (Affinity Capture-MS), CBLL1 (Two-hybrid), CBLL1 (Affinity Capture-MS), CBLL1 (Affinity Capture-MS), CBLL1 (Affinity Capture-MS), CBLL1 (Affinity Capture-Western), CBLL1 (Affinity Capture-MS)

ESM2 similar proteins: A2AJK6, A2VDB3, A5PJN8, C5XYW4, F1R5H6, F4NYQ2, G3CHK5, O55000, O60885, O95104, P0CB49, P49750, P51532, P75330, Q06A37, Q08D75, Q10124, Q15428, Q3TKT4, Q4R7I8, Q4V7X9, Q5TM61, Q5ZHZ4, Q62203, Q63623, Q63627, Q66KL9, Q6AXT8, Q6DFF2, Q6DID3, Q6DRG1, Q75N03, Q767K9, Q7TSH6, Q7YR38, Q80W00, Q8CFT2, Q8CGZ0, Q8IWX8, Q8K1P7

Diamond homologs: M9PBE2, Q4R361, Q4R7I8, Q4V7X9, Q5ZHZ4, Q75N03, Q8N7E2, Q9JIY2, Q9LFC0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	CBLL1	ubiquitination
CBLL1	“down-regulates quantity by destabilization”	ANXA2	ubiquitination
HSP90AA1	“up-regulates quantity”	CBLL1	binding
HSP90AB1	“up-regulates quantity”	CBLL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 39 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
mRNA 3’-end processing	6	39.4×	1e-06
Transport of Mature mRNA derived from an Intron-Containing Transcript	5	25.4×	1e-04
Processing of Capped Intron-Containing Pre-mRNA	8	21.9×	7e-07
mRNA Polyadenylation	7	20.5×	4e-06
mRNA Splicing - Major Pathway	7	12.8×	8e-05
Dengue Virus-Host Interactions	7	10.7×	2e-04
Metabolism of RNA	6	8.3×	4e-03
Infectious disease	7	5.8×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	5	106.4×	1e-07
regulation of alternative mRNA splicing, via spliceosome	5	33.9×	3e-05
mRNA splicing, via spliceosome	9	22.9×	5e-08
mRNA processing	9	19.7×	1e-07
RNA splicing	5	12.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

777 predictions. Top by Δscore:

Variant	Effect	Δscore
7:107748873:A:AG	acceptor_gain	1.0000
7:107748874:A:G	acceptor_gain	1.0000
7:107748875:CACA:C	acceptor_loss	1.0000
7:107748876:A:AG	acceptor_gain	1.0000
7:107748876:ACAGA:A	acceptor_loss	1.0000
7:107748877:CA:C	acceptor_loss	1.0000
7:107748878:A:AG	acceptor_gain	1.0000
7:107748878:A:T	acceptor_loss	1.0000
7:107748879:G:GC	acceptor_gain	1.0000
7:107748879:GA:G	acceptor_gain	1.0000
7:107748879:GAC:G	acceptor_gain	1.0000
7:107748879:GACA:G	acceptor_gain	1.0000
7:107749043:TGAAG:T	donor_loss	1.0000
7:107749045:AAG:A	donor_loss	1.0000
7:107749048:G:T	donor_loss	1.0000
7:107749049:T:A	donor_loss	1.0000
7:107753405:TCTCA:T	acceptor_loss	1.0000
7:107753406:CTCA:C	acceptor_loss	1.0000
7:107753407:TCAG:T	acceptor_loss	1.0000
7:107753408:CAG:C	acceptor_loss	1.0000
7:107753409:A:AG	acceptor_gain	1.0000
7:107753409:AG:A	acceptor_loss	1.0000
7:107753409:AGAAG:A	acceptor_gain	1.0000
7:107753410:G:GA	acceptor_gain	1.0000
7:107753410:GA:G	acceptor_gain	1.0000
7:107753410:GAA:G	acceptor_gain	1.0000
7:107753410:GAAGG:G	acceptor_gain	1.0000
7:107753507:TTCAG:T	donor_loss	1.0000
7:107753508:TCAG:T	donor_loss	1.0000
7:107753509:CAGGT:C	donor_loss	1.0000

AlphaMissense

3236 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:107753937:T:A	C109S	1.000
7:107753937:T:C	C109R	1.000
7:107753938:G:A	C109Y	1.000
7:107753938:G:C	C109S	1.000
7:107753938:G:T	C109F	1.000
7:107753939:T:G	C109W	1.000
7:107753946:T:A	C112S	1.000
7:107753946:T:C	C112R	1.000
7:107753947:G:A	C112Y	1.000
7:107753947:G:C	C112S	1.000
7:107753947:G:T	C112F	1.000
7:107753948:T:G	C112W	1.000
7:107753956:C:A	P115H	1.000
7:107753959:T:A	I116N	1.000
7:107753970:G:A	G120R	1.000
7:107753970:G:C	G120R	1.000
7:107753970:G:T	G120W	1.000
7:107753971:G:A	G120E	1.000
7:107753971:G:T	G120V	1.000
7:107753973:A:G	R121G	1.000
7:107753974:G:C	R121T	1.000
7:107753974:G:T	R121I	1.000
7:107753975:A:C	R121S	1.000
7:107753975:A:T	R121S	1.000
7:107755419:T:A	I123N	1.000
7:107755419:T:C	I123T	1.000
7:107755421:C:T	P124S	1.000
7:107755422:C:A	P124Q	1.000
7:107755424:T:A	C125S	1.000
7:107755424:T:C	C125R	1.000

dbSNP variants (sampled 300 via entrez): RS1000065847 (7:107746372 A>G), RS1000362527 (7:107760339 CTT>C,CT), RS1000388321 (7:107760694 ATAGT>A), RS1000642205 (7:107747595 GT>G), RS1000696201 (7:107747986 C>T), RS1000852124 (7:107752822 G>A), RS1000853143 (7:107746107 T>C), RS1001135291 (7:107759728 G>C,T), RS1001155390 (7:107756375 A>G), RS1001363367 (7:107752460 G>C,T), RS1001482106 (7:107750339 G>A,T), RS1001519281 (7:107744831 T>C), RS1001588063 (7:107744558 C>T), RS1002066148 (7:107762054 G>A,C), RS1002118862 (7:107754864 C>T)

Disease associations

OMIM: gene MIM:606872 | 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
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
arsenite	decreases methylation, affects binding, increases reaction	2
cobaltous chloride	increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	increases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Atrazine	increases expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Hydrogen Peroxide	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1MC	Abcam HeLa CBLL1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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