LLGL2

Summary

LLGL2 (LLGL scribble cell polarity complex component 2, HGNC:6629) is a protein-coding gene on chromosome 17q25.1, encoding LLGL scribble cell polarity complex component 2 (Q6P1M3). Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division.

The lethal (2) giant larvae protein of Drosophila plays a role in asymmetric cell division, epithelial cell polarity, and cell migration. This human gene encodes a protein similar to lethal (2) giant larvae of Drosophila. In fly, the protein’s ability to localize cell fate determinants is regulated by the atypical protein kinase C (aPKC). In human, this protein interacts with aPKC-containing complexes and is cortically localized in mitotic cells. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 3993 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 294 total
• MANE Select transcript: NM_001031803

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6629
Approved symbol	LLGL2
Name	LLGL scribble cell polarity complex component 2
Location	17q25.1
Locus type	gene with protein product
Status	Approved
Aliases	HGL, Hugl-2
Ensembl gene	ENSG00000073350
Ensembl biotype	protein_coding
OMIM	618483
Entrez	3993

Gene structure

Transcript identifiers

Ensembl transcripts: 54 — 43 protein_coding, 8 retained_intron, 3 nonsense_mediated_decay

ENST00000167462, ENST00000375227, ENST00000392550, ENST00000545227, ENST00000577200, ENST00000577211, ENST00000577500, ENST00000578034, ENST00000578363, ENST00000578536, ENST00000578638, ENST00000578719, ENST00000579092, ENST00000579392, ENST00000580027, ENST00000580578, ENST00000580925, ENST00000581713, ENST00000582393, ENST00000582860, ENST00000583514, ENST00000583658, ENST00000910106, ENST00000910107, ENST00000910108, ENST00000910109, ENST00000910110, ENST00000910111, ENST00000910112, ENST00000910113, ENST00000910114, ENST00000910115, ENST00000910116, ENST00000910117, ENST00000933826, ENST00000933827, ENST00000933828, ENST00000933829, ENST00000933830, ENST00000933831, ENST00000933832, ENST00000933833, ENST00000933834, ENST00000956281, ENST00000956282, ENST00000956283, ENST00000956284, ENST00000956285, ENST00000956286, ENST00000956287, ENST00000956288, ENST00000956289, ENST00000956290, ENST00000956291

RefSeq mRNA: 3 — MANE Select: NM_001031803 NM_001015002, NM_001031803, NM_004524

CCDS: CCDS11725, CCDS32733, CCDS45776

Canonical transcript exons

ENST00000392550 — 26 exons

Exon	Start	End
ENSE00001169985	75558155	75558236
ENSE00001687800	75543397	75543501
ENSE00002336748	75556046	75556143
ENSE00002728334	75525697	75525825
ENSE00003460242	75564353	75564507
ENSE00003463308	75570950	75571100
ENSE00003463735	75573014	75573278
ENSE00003472988	75568978	75569131
ENSE00003499921	75563752	75563806
ENSE00003532798	75571667	75571783
ENSE00003541691	75574610	75574668
ENSE00003542824	75574213	75574260
ENSE00003556939	75563016	75563178
ENSE00003589923	75574453	75574495
ENSE00003596609	75571898	75572064
ENSE00003602153	75570348	75570498
ENSE00003603408	75569221	75569325
ENSE00003605850	75569963	75570255
ENSE00003608298	75563331	75563463
ENSE00003621851	75568772	75568839
ENSE00003638094	75573481	75573631
ENSE00003640043	75573952	75573980
ENSE00003642123	75559252	75559410
ENSE00003650538	75568476	75568693
ENSE00003671736	75574871	75575209
ENSE00003671803	75558512	75558627

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.5001 / max 310.7435, expressed in 1170 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162733	20.3597	1169
162739	0.0573	24
162738	0.0301	15
162740	0.0187	6
162736	0.0146	6
162735	0.0106	5
162734	0.0092	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.15	gold quality
metanephros cortex	UBERON:0010533	98.56	gold quality
lower esophagus mucosa	UBERON:0035834	98.56	gold quality
right uterine tube	UBERON:0001302	98.32	gold quality
body of pancreas	UBERON:0001150	98.13	gold quality
endometrium epithelium	UBERON:0004811	96.68	gold quality
granulocyte	CL:0000094	96.38	gold quality
minor salivary gland	UBERON:0001830	96.24	gold quality
right lobe of liver	UBERON:0001114	96.08	gold quality
esophagus mucosa	UBERON:0002469	95.93	gold quality
upper lobe of left lung	UBERON:0008952	95.86	gold quality
skin of abdomen	UBERON:0001416	95.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.09	gold quality
saliva-secreting gland	UBERON:0001044	95.02	gold quality
upper lobe of lung	UBERON:0008948	95.00	gold quality
skin of leg	UBERON:0001511	94.86	gold quality
right lung	UBERON:0002167	94.75	gold quality
mouth mucosa	UBERON:0003729	94.60	gold quality
right lobe of thyroid gland	UBERON:0001119	94.35	gold quality
transverse colon	UBERON:0001157	94.07	gold quality
left lobe of thyroid gland	UBERON:0001120	93.94	gold quality
rectum	UBERON:0001052	93.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.75	gold quality
spleen	UBERON:0002106	93.33	gold quality
adult mammalian kidney	UBERON:0000082	93.01	gold quality
body of stomach	UBERON:0001161	92.91	gold quality
gall bladder	UBERON:0002110	92.71	gold quality
thyroid gland	UBERON:0002046	92.68	gold quality
small intestine	UBERON:0002108	92.39	gold quality
pancreas	UBERON:0001264	92.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.37
E-MTAB-7606	no	763.22
E-CURD-89	no	46.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZEB1

miRNA regulators (miRDB)

29 targeting LLGL2, 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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-222-5P	98.75	69.17	1242
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-4301	95.00	65.22	554

Literature-anchored findings (GeneRIF, showing 17)

• binding between Lgl2 and LGN play a role in mitotic spindle organization through regulating formation of the LGN.NuMA complex; Lgl2 forms a Lgl2.Par-6.aPKC.LGN complex, which responds to mitotic signaling to establish normal cell division (PMID:15632202)
• The identification and functional characterization of the promoter region ( approximately 1.2kb) of the Hugl-2 gene are reported. (PMID:18155665)
• Retention of Lgl2 expression is critical for the epithelial phenotype;its loss might be involved in metastasis. (PMID:18199550)
• We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. (PMID:19407852)
• Lgl2 differentiates pancreatic intraepithelial neoplasia-3 and ductal adenocarcinoma of the pancreas from lower-grade pancreatic intraepithelial neoplasias. (PMID:20233622)
• There is a role of Lgl2 immunohistochemistry as an adjunct in the diagnosis of foveolar-type gastric dysplasia. (PMID:20941506)
• Hugl-2 induces MET and suppresses Snail tumorigenesis. (PMID:22580609)
• Hugl1 and Hugl2 play an essential role in the maintenance of breast epithelial polarity and differentiated cell morphology, as well as growth control. (PMID:23110097)
• Loss or aberrant Lgl2 staining was useful in identifying Barrett gastric foveolar dysplasia (PMID:23332925)
• It is correlated with lymphatic invasion and lymph node metastasis. (PMID:24318287)
• The crystal structures of the Dlg4 GK domain in complex with two phosphor-Lgl2 peptides reveal the molecular mechanism underlying the specific and phosphorylation-dependent Dlg/Lgl complex formation. (PMID:24513855)
• LLGL2 functions as a promoter of tumour growth and not as a tumour suppressor in ER(+) breast cancer; beyond breast cancer, adaptation to nutrient stress is critically important, and findings identify an unexpected role for LLGL2 in this process (PMID:30996345)
• The crystal structures of human lethal giant larvae homolog 2 (Lgl2) in both its unphosphorylated and atypical protein kinase C(aPKC) phosphorylated states are presented and investigated in this article. (PMID:31088962)
• Study and determination of the crystal structure of lethal giant larvae homolog 2 (Lgl2). (PMID:31088964)
• A human cell polarity protein Lgl2 regulates influenza A virus nucleoprotein exportation from nucleus in MDCK cells. (PMID:32385218)
• Co-expression effect of LLGL2 and SLC7A5 to predict prognosis in ERalpha-positive breast cancer. (PMID:36192404)
• Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer. (PMID:38720397)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	llgl2	ENSDARG00000023920
mus_musculus	Llgl2	ENSMUSG00000020782
rattus_norvegicus	Llgl2	ENSRNOG00000004834
drosophila_melanogaster	l(2)gl	FBGN0002121
caenorhabditis_elegans		WBGENE00018987

Paralogs (3): LLGL1 (ENSG00000131899), STXBP5L (ENSG00000145087), STXBP5 (ENSG00000164506)

Protein

Protein identifiers

LLGL scribble cell polarity complex component 2 — Q6P1M3 (reviewed: Q6P1M3)

Alternative names: HGL, Lethal(2) giant larvae protein homolog 2

All UniProt accessions (11): Q6P1M3, J3KRE1, J3KSD5, J3QKM6, J3QL58, J3QLD8, J3QLV4, J3QRV5, J3QRZ8, J3QS20, J3QSA6

UniProt curated annotations — full annotation on UniProt →

Function. Part of a complex with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6, which may ensure the correct organization and orientation of bipolar spindles for normal cell division. This complex plays roles in the initial phase of the establishment of epithelial cell polarity.

Subunit / interactions. Interacts with GPSM2/LGN, PRKCI/aPKC and PARD6B/Par-6. The complex is enhanced during mitosis. Interacts with DCAF1.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated at Ser-653 by PRKCI. Phosphorylation is enhanced during cell polarization induced by calcium. Phosphorylation may occur during the cell-cell contact-induced cell polarization and may contribute to the segregation of LLGL2 from the PRKCI/aPKC and PARD6B/Par-6 complex.

Miscellaneous. Overexpression of LLGL2 inhibits the tight junction formation.

Similarity. Belongs to the WD repeat L(2)GL family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P1M3-1	C	yes
Q6P1M3-2	A
Q6P1M3-3	B

RefSeq proteins (3): NP_001015002, NP_001026973, NP_004515 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000664	Lethal2_giant	Family
IPR001680	WD40_rpt	Repeat
IPR013577	LLGL2	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF08366

UniProt features (126 total): strand 61, helix 16, repeat 14, turn 10, sequence variant 8, mutagenesis site 6, region of interest 3, modified residue 3, splice variant 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6N8R	X-RAY DIFFRACTION	1.91
3WP0	X-RAY DIFFRACTION	2.04
6N8Q	X-RAY DIFFRACTION	2.2
8R3X	X-RAY DIFFRACTION	2.59
3WP1	X-RAY DIFFRACTION	2.8
9EJK	ELECTRON MICROSCOPY	3.08
6N8P	X-RAY DIFFRACTION	3.19
9EJM	ELECTRON MICROSCOPY	3.33
9EJL	ELECTRON MICROSCOPY	3.48
6N8S	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1M3-F1	85.23	0.75

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): 653, 965, 1015

Mutagenesis-validated functional residues (6):

Position	Phenotype
641	no effect on phosphorylation.
645	decrease of phosphorylation.
649	decrease of phosphorylation.
653	loss of phosphorylation.
660	decrease of phosphorylation.
663	no effect on phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (15): exocytosis (GO:0006887), Golgi to plasma membrane transport (GO:0006893), regulation of Notch signaling pathway (GO:0008593), post-embryonic development (GO:0009791), L-leucine transport (GO:0015820), establishment or maintenance of polarity of embryonic epithelium (GO:0016332), cortical actin cytoskeleton organization (GO:0030866), regulation of establishment or maintenance of cell polarity (GO:0032878), multicellular organism growth (GO:0035264), establishment or maintenance of epithelial cell apical/basal polarity (GO:0045197), establishment of spindle orientation (GO:0051294), cell division (GO:0051301), branching involved in labyrinthine layer morphogenesis (GO:0060670), labyrinthine layer blood vessel development (GO:0060716), placenta development (GO:0001890)

GO Molecular Function (4): GTPase activator activity (GO:0005096), PDZ domain binding (GO:0030165), myosin II binding (GO:0045159), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), cortical actin cytoskeleton (GO:0030864)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
multicellular organismal process	2
establishment or maintenance of cell polarity	2
cellular anatomical structure	2
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
Notch signaling pathway	1
regulation of signal transduction	1
multicellular organism development	1
branched-chain amino acid transport	1
neutral amino acid transport	1
L-amino acid transport	1
morphogenesis of embryonic epithelium	1
actin cytoskeleton organization	1
cortical cytoskeleton organization	1
regulation of cellular process	1
developmental growth	1
establishment or maintenance of apical/basal cell polarity	1
establishment of cell polarity	1
establishment of spindle localization	1
cellular process	1
embryonic morphogenesis	1
labyrinthine layer morphogenesis	1
morphogenesis of a branching epithelium	1
embryonic organ development	1
placenta blood vessel development	1
labyrinthine layer development	1
animal organ development	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
protein domain specific binding	1
myosin binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LLGL2	SLC7A5	Q01650	883
LLGL2	YKT6	O15498	737
LLGL2	PARD3	Q8TEW0	734
LLGL2	CRB3	Q9BUF7	724
LLGL2	NSUN6	Q8TEA1	700
LLGL2	PATJ	Q8NI35	609
LLGL2	PARD6B	Q9BYG5	590
LLGL2	SCRIB	Q14160	585
LLGL2	ALG11	Q2TAA5	522
LLGL2	MARVELD2	Q8N4S9	505
LLGL2	ERBB3	P21860	499
LLGL2	PALS1	Q8N3R9	496
LLGL2	CLDN7	O95471	487
LLGL2	PARD6G	Q9BYG4	473
LLGL2	PRKCI	P41743	466

IntAct

56 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
PRKCZ	PRKCI	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0915”(physical association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
PRKCI	LLGL1	psi-mi:“MI:0914”(association)	0.790
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
PRKCZ	NIPSNAP2	psi-mi:“MI:0914”(association)	0.730
IFI30	DAPK1	psi-mi:“MI:0914”(association)	0.730
PARD6G	PRKCI	psi-mi:“MI:0914”(association)	0.720
LLGL1	DNAJA2	psi-mi:“MI:0914”(association)	0.640
PRKCI	NIPSNAP2	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
KBTBD7	PLD2	psi-mi:“MI:0914”(association)	0.530
PARD6B	ZZEF1	psi-mi:“MI:0914”(association)	0.530
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
RAB30	UBB	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PARD6B	PARD3	psi-mi:“MI:0914”(association)	0.350
PARD6A		psi-mi:“MI:0914”(association)	0.350
LLGL2	RBBP6	psi-mi:“MI:0914”(association)	0.350
Pard6b	PARD3	psi-mi:“MI:0914”(association)	0.350
SPHK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
PRKAR1A	RBFOX3	psi-mi:“MI:0914”(association)	0.350
RAC1		psi-mi:“MI:0914”(association)	0.350
PRKCI	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (205): LLGL2 (Affinity Capture-MS), LLGL2 (Affinity Capture-MS), LLGL2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA2 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), KBTBD7 (Affinity Capture-MS), PRKCI (Affinity Capture-MS), PRKCZ (Affinity Capture-MS), LLGL2 (Affinity Capture-MS), NUDC (Affinity Capture-MS), PARD6B (Affinity Capture-MS), PARD6G (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A0A1L8HX76, A6QR40, O08764, O60294, O95382, P10938, P70218, P97452, Q12851, Q14137, Q15334, Q16586, Q28686, Q32P44, Q3TJ91, Q499N3, Q499U2, Q4KLI9, Q561R2, Q562C2, Q5RBH8, Q5RCX2, Q61161, Q6AY79, Q6F5E8, Q6P1M3, Q6V7V2, Q7SZE3, Q7TMC8, Q80Y17, Q8BYZ7, Q8C3I8, Q8C6B2, Q8CHW4, Q8K4K5, Q8MKF0, Q8N0W3, Q8VC03, Q91WI7

Diamond homologs: P08111, Q08470, Q15334, Q3TJ91, Q5RCX2, Q6P1M3, Q7SZE3, Q80Y17, Q8K4K5, Q8MKF0

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
LLGL2	“form complex”	Scribble_complex_DLG2-LLGL2_variant	binding
LLGL2	“form complex”	Scribble_complex_DLG3-LLGL2_variant	binding
LLGL2	“form complex”	Scribble_complex_DLG4-LLGL2_variant	binding
LLGL2	“form complex”	Scribble_complex_DLG5-LLGL2_variant	binding
PRKCI	“up-regulates activity”	LLGL2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 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
Tight junction interactions	5	55.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	7	90.4×	3e-10
establishment or maintenance of cell polarity	5	44.6×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	220
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

5284 predictions. Top by Δscore:

Variant	Effect	Δscore
17:75556141:GCT:G	donor_gain	1.0000
17:75558510:A:AG	acceptor_gain	1.0000
17:75558511:G:GG	acceptor_gain	1.0000
17:75558625:AGGGT:A	donor_loss	1.0000
17:75558626:GG:G	donor_gain	1.0000
17:75558627:GG:G	donor_gain	1.0000
17:75558627:GGTAA:G	donor_loss	1.0000
17:75558628:G:GG	donor_gain	1.0000
17:75558629:T:A	donor_loss	1.0000
17:75559247:CACAG:C	acceptor_loss	1.0000
17:75559249:CA:C	acceptor_loss	1.0000
17:75559250:A:AG	acceptor_gain	1.0000
17:75559250:A:C	acceptor_loss	1.0000
17:75559250:AG:A	acceptor_gain	1.0000
17:75559251:G:GC	acceptor_loss	1.0000
17:75559251:G:GG	acceptor_gain	1.0000
17:75559251:GG:G	acceptor_gain	1.0000
17:75559251:GGGCT:G	acceptor_gain	1.0000
17:75559408:GCG:G	donor_gain	1.0000
17:75559409:CGGT:C	donor_loss	1.0000
17:75559411:G:GG	donor_gain	1.0000
17:75559411:G:T	donor_loss	1.0000
17:75559412:T:A	donor_loss	1.0000
17:75559413:GA:G	donor_loss	1.0000
17:75559453:T:G	donor_gain	1.0000
17:75563011:CCCA:C	acceptor_loss	1.0000
17:75563014:A:AG	acceptor_gain	1.0000
17:75563014:AG:A	acceptor_gain	1.0000
17:75563015:G:GG	acceptor_gain	1.0000
17:75563015:GG:G	acceptor_gain	1.0000

AlphaMissense

6599 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:75570210:G:A	G610D	1.000
17:75571062:T:A	V713D	1.000
17:75568839:G:A	G441E	0.999
17:75568989:G:A	G445D	0.999
17:75568989:G:T	G445V	0.999
17:75569003:T:A	W450R	0.999
17:75569003:T:C	W450R	0.999
17:75569320:G:T	G526W	0.999
17:75569321:G:A	G526E	0.999
17:75570053:T:A	W558R	0.999
17:75570053:T:C	W558R	0.999
17:75570055:G:C	W558C	0.999
17:75570055:G:T	W558C	0.999
17:75570197:G:C	G606R	0.999
17:75570198:G:A	G606D	0.999
17:75570209:G:C	G610R	0.999
17:75571690:T:A	W734R	0.999
17:75571690:T:C	W734R	0.999
17:75571697:G:A	G736D	0.999
17:75571709:G:A	G740D	0.999
17:75568827:T:C	L437P	0.998
17:75568830:T:C	L438P	0.998
17:75568838:G:T	G441W	0.998
17:75569230:T:C	F496L	0.998
17:75569232:T:A	F496L	0.998
17:75569232:T:G	F496L	0.998
17:75569249:A:G	D502G	0.998
17:75569255:G:C	R504P	0.998
17:75569300:T:C	L519P	0.998
17:75569309:C:A	A522E	0.998

dbSNP variants (sampled 300 via entrez): RS1000014367 (17:75551865 A>G), RS1000031067 (17:75529903 C>G,T), RS1000032968 (17:75535655 A>G), RS1000101001 (17:75563873 G>A), RS1000156013 (17:75530541 T>C), RS1000159107 (17:75525372 C>A,T), RS1000205272 (17:75566389 C>T), RS1000305124 (17:75524960 G>A,C), RS1000309490 (17:75566374 C>G,T), RS1000405618 (17:75535931 C>T), RS1000440720 (17:75525173 A>G), RS1000501066 (17:75531583 C>G,T), RS1000521961 (17:75568284 C>T), RS1000598354 (17:75566713 C>A), RS1000678163 (17:75526528 C>A)

Disease associations

OMIM: gene MIM:618483 | 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
GCST002938_38	Copper levels	8.000000e-06
GCST003042_1	Sight-threatening diabetic retinopathy in type 2 diabetes	7.000000e-07
GCST006979_252	Heel bone mineral density	5.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression, affects expression	4
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	4
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression	4
Estradiol	affects binding, affects reaction, increases reaction, affects cotreatment, decreases expression	3
Arsenic Trioxide	decreases expression, decreases response to substance, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, affects methylation, decreases expression	2
Smoke	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
afuresertib	increases expression	1
alpha phellandrene	decreases expression	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
nickel sulfate	increases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pien tze huang	decreases expression	1
apatinib	decreases expression, affects cotreatment	1
MT19c compound	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1

Clinical trials (associated diseases)

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