ADGRL2

Summary

ADGRL2 (adhesion G protein-coupled receptor L2, HGNC:18582) is a protein-coding gene on chromosome 1p31.1, encoding Adhesion G protein-coupled receptor L2 (O95490). Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity.

This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors. The encoded protein participates in the regulation of exocytosis. The proprotein is thought to be further cleaved within a cysteine-rich G-protein-coupled receptor proteolysis site into two chains that are non-covalently bound at the cell membrane. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23266 — RefSeq curated summary.

At a glance

• GWAS associations: 33
• Clinical variants (ClinVar): 208 total — 2 pathogenic
• MANE Select transcript: NM_001366006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18582
Approved symbol	ADGRL2
Name	adhesion G protein-coupled receptor L2
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0786, LEC1, CIRL2
Ensembl gene	ENSG00000117114
Ensembl biotype	protein_coding
OMIM	607018
Entrez	23266

Gene structure

Transcript identifiers

Ensembl transcripts: 85 — 67 protein_coding, 9 protein_coding_CDS_not_defined, 7 retained_intron, 2 nonsense_mediated_decay

ENST00000319517, ENST00000359929, ENST00000370713, ENST00000370715, ENST00000370717, ENST00000370721, ENST00000370723, ENST00000370725, ENST00000370727, ENST00000370728, ENST00000370730, ENST00000402328, ENST00000449420, ENST00000464551, ENST00000464775, ENST00000468283, ENST00000469377, ENST00000472424, ENST00000473719, ENST00000492666, ENST00000498776, ENST00000627151, ENST00000674168, ENST00000674198, ENST00000674208, ENST00000674209, ENST00000674307, ENST00000674333, ENST00000674367, ENST00000674373, ENST00000674378, ENST00000674386, ENST00000674393, ENST00000674407, ENST00000674410, ENST00000674419, ENST00000674442, ENST00000674458, ENST00000674464, ENST00000674489, ENST00000674492, ENST00000686636, ENST00000855565, ENST00000855566, ENST00000855567, ENST00000855568, ENST00000855569, ENST00000855570, ENST00000855571, ENST00000855572, ENST00000855573, ENST00000855574, ENST00000855575, ENST00000855576, ENST00000855577, ENST00000926499, ENST00000926500, ENST00000926501, ENST00000926502, ENST00000926503, ENST00000926504, ENST00000926505, ENST00000926506, ENST00000926507, ENST00000941333, ENST00000941334, ENST00000941335, ENST00000941336, ENST00000941337, ENST00000941338, ENST00000941339, ENST00000941340, ENST00000941341, ENST00000941342, ENST00000941343, ENST00000941344, ENST00000941345, ENST00000941346, ENST00000941347, ENST00000941348, ENST00000941349, ENST00000941350, ENST00000941351, ENST00000941352, ENST00000941353

RefSeq mRNA: 21 — MANE Select: NM_001366006 NM_001297704, NM_001297705, NM_001297706, NM_001330645, NM_001350698, NM_001350699, NM_001366002, NM_001366003, NM_001366004, NM_001366005, NM_001366006, NM_001366007, NM_001366008, NM_001366009, NM_001393349, NM_001393350, NM_001393351, NM_001393352, NM_001393353, NM_001393354, NM_012302

CCDS: CCDS689, CCDS72811, CCDS76174, CCDS81345, CCDS90986, CCDS90988, CCDS90990

Canonical transcript exons

ENST00000686636 — 24 exons

Exon	Start	End
ENSE00000775497	81966404	81966609
ENSE00000775537	81969178	81969387
ENSE00000775540	81970314	81970534
ENSE00000775550	81979869	81979960
ENSE00000830796	81951018	81951121
ENSE00000830798	81951957	81952142
ENSE00000830799	81952987	81953025
ENSE00000830807	81968026	81968199
ENSE00000830813	81971852	81971918
ENSE00001240159	81955877	81956060
ENSE00001240179	81950189	81950482
ENSE00001240189	81942969	81943769
ENSE00001624881	81986901	81987029
ENSE00001769170	81987869	81987886
ENSE00001784145	81942034	81942045
ENSE00003462296	81966058	81966183
ENSE00003494247	81936728	81936837
ENSE00003519156	81984583	81984711
ENSE00003549590	81907017	81907230
ENSE00003552990	81836885	81837057
ENSE00003615826	81985259	81985355
ENSE00003675846	81981808	81981976
ENSE00003925184	81800934	81801068
ENSE00003931679	81990391	81993932

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8586 / max 758.0055, expressed in 1388 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3730	15.2502	1313
3727	4.9624	1130
3703	1.0716	218
3726	0.8788	318
3729	0.7944	408
3725	0.7051	392
3707	0.4273	163
3728	0.3814	174
3709	0.3652	108
3704	0.3267	114

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.59	gold quality
right lung	UBERON:0002167	97.34	gold quality
upper lobe of left lung	UBERON:0008952	96.21	gold quality
upper lobe of lung	UBERON:0008948	96.16	gold quality
ventricular zone	UBERON:0003053	94.51	gold quality
lung	UBERON:0002048	94.09	gold quality
left lobe of thyroid gland	UBERON:0001120	94.00	gold quality
right lobe of thyroid gland	UBERON:0001119	93.97	gold quality
thyroid gland	UBERON:0002046	93.85	gold quality
lower esophagus mucosa	UBERON:0035834	93.42	gold quality
left ovary	UBERON:0002119	92.94	gold quality
mucosa of stomach	UBERON:0001199	92.83	gold quality
lower lobe of lung	UBERON:0008949	92.65	gold quality
ganglionic eminence	UBERON:0004023	92.60	gold quality
right ovary	UBERON:0002118	92.56	gold quality
embryo	UBERON:0000922	92.52	gold quality
calcaneal tendon	UBERON:0003701	91.78	gold quality
gall bladder	UBERON:0002110	91.23	gold quality
ovary	UBERON:0000992	91.13	gold quality
right atrium auricular region	UBERON:0006631	90.83	gold quality
lower esophagus	UBERON:0013473	90.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.52	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.50	gold quality
minor salivary gland	UBERON:0001830	90.46	gold quality
cardiac atrium	UBERON:0002081	90.38	gold quality
colonic epithelium	UBERON:0000397	90.34	gold quality
adenohypophysis	UBERON:0002196	90.32	gold quality
right uterine tube	UBERON:0001302	90.29	gold quality
right lobe of liver	UBERON:0001114	89.97	gold quality
heart left ventricle	UBERON:0002084	89.92	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	1366.60
E-ENAD-27	yes	178.07
E-HCAD-25	yes	80.61
E-MTAB-5061	yes	13.44
E-ANND-3	yes	11.96
E-GEOD-81608	yes	8.56
E-MTAB-9067	yes	7.18
E-GEOD-83139	no	2.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

179 targeting ADGRL2, 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-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 4)

• The results of this study suggest that this ADGRL2 variation impedes the proper development of the cerebellum resulting in RES which is thought to occur when the cerebellar primordium develops and probably results from abnormal function of genes expressed during initial patterning of the mesencephalon-rhombencephalon (PMID:30340542)
• Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK. (PMID:33798451)
• LPHN2 inhibits vascular permeability by differential control of endothelial cell adhesion. (PMID:34581723)
• Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. (PMID:38886581)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrl2a	ENSDARG00000069356
danio_rerio	ADGRL2	ENSDARG00000075899
danio_rerio	adgrl2b.1	ENSDARG00000111712
mus_musculus	Adgrl2	ENSMUSG00000028184
rattus_norvegicus	Adgrl2	ENSRNOG00000065347

Paralogs (42): CALCR (ENSG00000004948), GIPR (ENSG00000010310), ADGRA2 (ENSG00000020181), CALCRL (ENSG00000064989), GLP2R (ENSG00000065325), ADGRF5 (ENSG00000069122), ADGRL1 (ENSG00000072071), ADCYAP1R1 (ENSG00000078549), SCTR (ENSG00000080293), VIPR2 (ENSG00000106018), CRHR2 (ENSG00000106113), GHRHR (ENSG00000106128), ADGRD1 (ENSG00000111452), GLP1R (ENSG00000112164), ADGRG6 (ENSG00000112414), VIPR1 (ENSG00000114812), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), ADGRB3 (ENSG00000135298), PTH2R (ENSG00000144407), ADGRG7 (ENSG00000144820), ADGRL3 (ENSG00000150471), ADGRA3 (ENSG00000152990), ADGRF1 (ENSG00000153292), ADGRF4 (ENSG00000153294), ADGRG4 (ENSG00000156920), ADGRG5 (ENSG00000159618), PTH1R (ENSG00000160801), ADGRL4 (ENSG00000162618), EVA1C (ENSG00000166979), ADGRF3 (ENSG00000173567), ADGRG2 (ENSG00000173698), ADGRE1 (ENSG00000174837), ADGRD2 (ENSG00000180264), ADGRB1 (ENSG00000181790), ADGRG3 (ENSG00000182885), ADGRA1 (ENSG00000197177)

Protein

Protein identifiers

Adhesion G protein-coupled receptor L2 — O95490 (reviewed: O95490)

Alternative names: Calcium-independent alpha-latrotoxin receptor 2, Latrophilin homolog 1, Latrophilin-2, Lectomedin-1

All UniProt accessions (14): O95490, A0A6I8PIV6, A0A6I8PLG0, A0A6I8PRJ0, A0A6I8PRM6, A0A6I8PRQ0, A0A6I8PTT2, A0A6I8PU30, A0A6I8PUE4, A0A8I5KUX3, B1ALU1, B1ALU3, H0Y3V3, H0Y5C0

UniProt curated annotations — full annotation on UniProt →

Function. Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. Following G-protein coupled receptor activation, associates with cell adhesion molecules that are expressed at the surface of adjacent cells to direct synapse specificity. Specifically mediates the establishment of perforant-path synapses on CA1-region pyramidal neurons in the hippocampus. Localizes to postsynaptic spines in excitatory synapses in the S.lacunosum-moleculare and interacts with presynaptic cell adhesion molecules, such as teneurins, promoting synapse formation.

Subunit / interactions. Heterodimer of 2 chains generated by proteolytic processing; the large extracellular N-terminal fragment and the membrane-bound C-terminal fragment predominantly remain associated and non-covalently linked.

Subcellular location. Postsynaptic cell membrane.

Tissue specificity. Expressed very widely in all normal tissues tested. Expression is variable in tumor cell lines, apparently elevated in some lines and absent or markedly reduced in others.

Post-translational modifications. Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity.

Activity regulation. Forms a heterodimer of 2 chains generated by proteolytic processing that remain associated through non-covalent interactions mediated by the GAIN-B domain. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling. The cleaved GAIN-B and N-terminal domains can then dissociate from the rest of the receptor.

Domain organisation. The Stachel sequence (also named stalk) in the C-terminal part of the extracellular domain (ECD) functions as a tethered agonist. In the inactivated receptor, the Stachel sequence (also named stalk) is embedded in the GAIN-B domain, where it adopts a beta-strand conformation. On activation, the Stachel moves into the 7 transmembrane region and adopts a twisted hook-shaped configuration that forms contacts within the receptor, leading to coupling of a G-alpha protein, which activates signaling.

Similarity. Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
O95490-1	1	yes
O95490-2	2, Lectomedin-1 gamma
O95490-3	3, Lectomedin-1 beta
O95490-4	4, Lectomedin-1 alpha
O95490-5	5
O95490-6	6
O95490-7	7

RefSeq proteins (21): NP_001284633, NP_001284634, NP_001284635, NP_001317574, NP_001337627, NP_001337628, NP_001352931, NP_001352932, NP_001352933, NP_001352934, NP_001352935, NP_001352936, NP_001352937, NP_001352938, NP_001380278, NP_001380279, NP_001380280, NP_001380281, NP_001380282, NP_001380283, NP_036434 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR000922	Lectin_gal-bd_dom	Domain
IPR001879	GPCR_2_extracellular_dom	Domain
IPR003112	Olfac-like_dom	Domain
IPR003334	GPCR_2_latrophilin_rcpt_C	Domain
IPR003924	GPCR_2_latrophilin	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR032471	AGRL2-4_GAIN_subdom_A	Domain
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR043159	Lectin_gal-bd_sf	Homologous_superfamily
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF01825, PF02140, PF02191, PF02354, PF02793, PF16489

UniProt features (50 total): glycosylation site 9, topological domain 8, transmembrane region 7, splice variant 7, domain 3, region of interest 3, modified residue 3, disulfide bond 3, compositionally biased region 2, signal peptide 1, chain 1, site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9E51	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95490-F1	69.66	0.31

Functional residue map

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

Catalytic / active sites (1): 824–825 (cleavage; by autolysis)

Post-translational modifications (3): 1374, 1409, 1430

Disulfide bonds (3): 136–318, 788–819, 807–821

Glycosylation sites (9): 99, 331, 520, 629, 731, 744, 787, 792, 813

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 236 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, NKX25_02, TATTATA_MIR374, MAHADEVAN_IMATINIB_RESISTANCE_DN, TAL1ALPHAE47_01, FOXO4_01, FOXO1_01, MORF_RAD51L3, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, AACWWCAANK_UNKNOWN, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_289, FOSTER_TOLERANT_MACROPHAGE_UP

GO Biological Process (4): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), excitatory synapse assembly (GO:1904861), signal transduction (GO:0007165)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), latrotoxin receptor activity (GO:0016524), carbohydrate binding (GO:0030246), transmembrane signaling receptor activity (GO:0004888)

GO Cellular Component (4): plasma membrane (GO:0005886), membrane (GO:0016020), postsynaptic membrane (GO:0045211), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
transmembrane signaling receptor activity	2
G protein-coupled receptor activity	1
synapse assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
synaptic membrane	1
postsynapse	1
cell junction	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRL2	TENM2	Q9NT68	943
ADGRL2	MGAT1	P26572	925
ADGRL2	TENM4	Q6N022	822
ADGRL2	POMGNT1	Q8WZA1	773
ADGRL2	FLRT3	Q9NZU0	732
ADGRL2	GCNT2	Q8N0V5	613
ADGRL2	TENM1	Q9UKZ4	611
ADGRL2	NRXN1	Q9ULB1	603
ADGRL2	ABI3	Q9P2A4	581
ADGRL2	NRXN2	Q9P2S2	544
ADGRL2	CNTN6	Q9UQ52	538
ADGRL2	SHANK1	Q9Y566	523
ADGRL2	GNAQ	P50148	509
ADGRL2	NFYB	P25208	505
ADGRL2	ROBO1	Q9Y6N7	493

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FLRT1	TCAF2	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
ADGRL2	Shank2	psi-mi:“MI:0407”(direct interaction)	0.440
ADGRL2	NCK1	psi-mi:“MI:0915”(physical association)	0.370
SHANK1	ADGRL2	psi-mi:“MI:0915”(physical association)	0.370
IRF3	ESYT2	psi-mi:“MI:0914”(association)	0.350
M2	AGPS	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
SLC15A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
	CCN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
CACNA1C	CACNB4	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	ADAM10	psi-mi:“MI:0914”(association)	0.350
UCHL1	SNAP23	psi-mi:“MI:0914”(association)	0.350
BSCL2	QSOX1	psi-mi:“MI:0914”(association)	0.350
MFSD5	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (131): LPHN2 (Affinity Capture-MS), LPHN2 (Proximity Label-MS), LPHN2 (Proximity Label-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Proximity Label-MS), LPHN2 (Proximity Label-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Affinity Capture-RNA), LPHN2 (Proximity Label-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Affinity Capture-MS), LPHN2 (Proximity Label-MS), LPHN2 (Affinity Capture-MS)

ESM2 similar proteins: A0A6J2ATK2, A5HUI5, A6QPT7, D3UW23, M3XFH7, O57579, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P15144, P15145, P15541, P15684, P16406, P42658, P42659, P46101, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10737, Q22523, Q2KHK3, Q2M2H8, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q7TT41, Q80TR1, Q80TS3

Diamond homologs: A2BD09, A4IIT5, A6QLD2, B0BNI5, B5MFE9, O70624, O88917, O88923, O88998, O94910, O95490, O95897, O97817, O97827, O97831, P63056, P63057, Q0P3W2, Q0V9V5, Q0VCP3, Q25C36, Q2PT31, Q3UZZ4, Q3V1G4, Q568Y7, Q594P2, Q62609, Q66H86, Q68BL7, Q68BL8, Q6UWY5, Q6UX06, Q80TR1, Q80TS3, Q863A3, Q866N2, Q8BHP7, Q8BK62, Q8BM13, Q8JZZ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 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
R-HSA-425393	6	14.2×	1e-03
SLC-mediated transmembrane transport	9	9.7×	2e-04
Transport of small molecules	10	4.6×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
amino acid transport	5	22.3×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	150
Likely benign	22
Benign	15

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
150045	GRCh38/hg38 1p31.1-22.2(chr1:76419302-88628464)x1	Pathogenic
3391870	GRCh37/hg19 1p31.1-22.2(chr1:76492334-91166951)x1	Pathogenic

SpliceAI

6437 predictions. Top by Δscore:

Variant	Effect	Δscore
1:81445016:TCTA:T	acceptor_loss	1.0000
1:81445017:CTAG:C	acceptor_loss	1.0000
1:81445018:TAGG:T	acceptor_loss	1.0000
1:81445019:A:C	acceptor_loss	1.0000
1:81445020:G:GC	acceptor_loss	1.0000
1:81675125:G:GT	donor_gain	1.0000
1:81761805:TTCCA:T	acceptor_loss	1.0000
1:81761806:TCCA:T	acceptor_loss	1.0000
1:81761807:CCA:C	acceptor_loss	1.0000
1:81761808:CAG:C	acceptor_loss	1.0000
1:81761809:A:AG	acceptor_gain	1.0000
1:81761809:A:T	acceptor_loss	1.0000
1:81761809:AG:A	acceptor_gain	1.0000
1:81761810:G:GG	acceptor_gain	1.0000
1:81761810:G:T	acceptor_loss	1.0000
1:81761810:GG:G	acceptor_gain	1.0000
1:81761810:GGGT:G	acceptor_gain	1.0000
1:81837054:GAAG:G	donor_gain	1.0000
1:81837057:GGTAA:G	donor_loss	1.0000
1:81837058:G:C	donor_loss	1.0000
1:81837059:T:G	donor_loss	1.0000
1:81445017:CTAGG:C	acceptor_gain	0.9900
1:81445018:TAGGT:T	acceptor_gain	0.9900
1:81445019:A:AG	acceptor_gain	0.9900
1:81445020:G:GG	acceptor_gain	0.9900
1:81445085:ATAAG:A	donor_loss	0.9900
1:81445087:AAGG:A	donor_loss	0.9900
1:81445088:AGGTA:A	donor_loss	0.9900
1:81445089:GGT:G	donor_loss	0.9900
1:81445091:T:A	donor_loss	0.9900

AlphaMissense

9686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:81907067:T:A	C42S	1.000
1:81907067:T:C	C42R	1.000
1:81907068:G:A	C42Y	1.000
1:81907068:G:C	C42S	1.000
1:81907069:T:G	C42W	1.000
1:81907089:T:C	L49P	1.000
1:81907094:T:A	C51S	1.000
1:81907094:T:C	C51R	1.000
1:81907095:G:A	C51Y	1.000
1:81907095:G:C	C51S	1.000
1:81907096:C:G	C51W	1.000
1:81907157:T:A	C72S	1.000
1:81907157:T:C	C72R	1.000
1:81907158:G:A	C72Y	1.000
1:81907158:G:C	C72S	1.000
1:81907159:T:G	C72W	1.000
1:81907193:T:A	C84S	1.000
1:81907193:T:C	C84R	1.000
1:81907194:G:C	C84S	1.000
1:81907195:C:G	C84W	1.000
1:81936729:T:A	C97S	1.000
1:81936729:T:C	C97R	1.000
1:81936730:G:C	C97S	1.000
1:81936731:C:G	C97W	1.000
1:81936739:G:C	R100P	1.000
1:81936747:T:A	C103S	1.000
1:81936747:T:C	C103R	1.000
1:81936748:G:A	C103Y	1.000
1:81936748:G:C	C103S	1.000
1:81936749:T:G	C103W	1.000

dbSNP variants (sampled 300 via entrez): RS1000000975 (1:81537759 T>G), RS1000002418 (1:81640112 A>C), RS1000007605 (1:81887106 G>C), RS1000008170 (1:81927969 AT>A), RS1000012970 (1:81618067 T>C), RS1000014082 (1:81745986 T>A), RS1000016429 (1:81971189 A>G), RS1000017808 (1:81792574 A>T), RS1000021035 (1:81876423 T>G), RS1000022461 (1:81702835 A>C), RS1000030569 (1:81537510 T>G), RS1000031259 (1:81595405 A>G), RS1000033005 (1:81452390 A>C,G), RS1000035451 (1:81856769 T>G), RS1000041153 (1:81787663 A>G)

Disease associations

OMIM: gene MIM:607018 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

33 associations (top):

Study	Trait	p-value
GCST001531_6	Temperament	3.000000e-06
GCST001762_835	Obesity-related traits	7.000000e-06
GCST002119_7	Metabolite levels (X-11787)	6.000000e-06
GCST002671_1	Toenail selenium levels	9.000000e-06
GCST002751_2	Spontaneous preterm birth (preterm birth)	7.000000e-07
GCST002829_2	Urate levels in overweight individuals	9.000000e-06
GCST003071_2	Cerebrospinal P-tau181p levels	4.000000e-07
GCST003097_35	Pediatric autoimmune diseases	8.000000e-11
GCST003124_13	Mild influenza (H1N1) infection	1.000000e-09
GCST003210_8	Low vWF levels	4.000000e-07
GCST003485_8	Response to fenofibrate (HDL cholesterol levels)	9.000000e-06
GCST003628_3	Clozapine-induced agranulocytosis/granulocytopenia in treatment-resistant schizophrenia	8.000000e-07
GCST003830_23	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	3.000000e-07
GCST004068_24	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	4.000000e-07
GCST004292_41	Glomerular filtration rate (creatinine)	2.000000e-08
GCST004639_28	Prudent dietary pattern	5.000000e-06
GCST005352_22	Paclitaxel disposition in epithelial ovarian cancer	7.000000e-06
GCST006069_68	Time-dependent creatinine clearance change response to tenofovir treatment in HIV infection (time and treatment arm interaction)	2.000000e-06
GCST006073_10	Tenofovir clearance in HIV infection	8.000000e-06
GCST006904_14	Cerebral amyloid deposition (PET imaging)	8.000000e-06
GCST007204_1	Low density lipoprotein cholesterol levels	2.000000e-06
GCST007576_109	Chronotype	5.000000e-10
GCST007649_1	Estimated glomerular filtration rate after 5 years in renal transplantation (recipient effect)	4.000000e-06
GCST009385_2	Cocaine use disorder	2.000000e-07
GCST009390_1	Cocaine use disorder x household tobacco use interaction	4.000000e-08
GCST009462_19	Optic disc size	9.000000e-11
GCST009642_1	Impaired insulin sensitivity in response to n-3 PUFA supplementation	8.000000e-06
GCST010988_242	Adult body size	3.000000e-09
GCST010988_243	Adult body size	6.000000e-09
GCST012095_17	Major depressive episode treated with electroconvulsive therapy	4.000000e-06

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004825	temperament and character inventory
EFO:0005276	hydroxy-leucine measurement
EFO:0006917	spontaneous preterm birth
EFO:0006921	birth measurement
EFO:0004531	urate measurement
EFO:0004763	p-tau measurement
EFO:1001488	influenza A (H1N1)
EFO:0007805	HDL cholesterol change measurement
EFO:0005921	FEV change measurement
EFO:0008111	diet measurement
EFO:0007934	creatinine clearance measurement
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008328	chronotype measurement
EFO:0005199	renal transplant outcome measurement
EFO:0010445	cocaine use disorder
EFO:0010552	social environment measurement
EFO:0004471	insulin sensitivity measurement
EFO:0009131	response to polyunsaturated fatty acid supplementation
EFO:0007634	major depressive episode
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Adhesion Class GPCRs

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
α-latrotoxin	Full agonist	8.85	pKd
AJ-292	Antagonist	7.68	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
bisphenol A	increases expression, increases methylation, decreases expression, affects cotreatment, affects methylation	3
sodium arsenite	increases abundance, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
terbufos	increases methylation	1
arsenite	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, affects methylation, decreases methylation	1
Vorinostat	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Chromium	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression, affects cotreatment	1

Clinical trials (associated diseases)

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