ADGRB3

Summary

ADGRB3 (adhesion G protein-coupled receptor B3, HGNC:945) is a protein-coding gene on chromosome 6q12-q13, encoding Adhesion G protein-coupled receptor B3 (O60242). Receptor that plays a role in the regulation of synaptogenesis and dendritic spine formation at least partly via interaction with ELMO1 and RAC1 activity.

This p53-target gene encodes a brain-specific angiogenesis inhibitor, a seven-span transmembrane protein, and is thought to be a member of the secretin receptor family. Brain-specific angiogenesis proteins BAI2 and BAI3 are similar to BAI1 in structure, have similar tissue specificities, and may also play a role in angiogenesis.

Source: NCBI Gene 577 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 192 total — 7 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_001704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:945
Approved symbol	ADGRB3
Name	adhesion G protein-coupled receptor B3
Location	6q12-q13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0550
Ensembl gene	ENSG00000135298
Ensembl biotype	protein_coding
OMIM	602684
Entrez	577

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000238918, ENST00000370598, ENST00000546190, ENST00000603207, ENST00000604969, ENST00000684661

RefSeq mRNA: 1 — MANE Select: NM_001704 NM_001704

CCDS: CCDS4968

Canonical transcript exons

ENST00000370598 — 32 exons

Exon	Start	End
ENSE00001153557	69075995	69076038
ENSE00001153562	69062934	69063036
ENSE00001153580	69018391	69018499
ENSE00001279979	69049271	69049346
ENSE00001279986	69048185	69048334
ENSE00001292206	69339333	69339504
ENSE00001292517	69372406	69372441
ENSE00001293856	69355821	69355860
ENSE00001294222	68943830	68943994
ENSE00001298438	68993768	68993962
ENSE00001302551	69327820	69327889
ENSE00001302827	68974763	68974864
ENSE00001305452	69382831	69382935
ENSE00001310733	69354233	69354328
ENSE00001311308	68936519	68936680
ENSE00001312299	68930559	68930669
ENSE00001312709	68956024	68956188
ENSE00001314198	69338916	69339014
ENSE00001314728	69360869	69361512
ENSE00001316429	68975234	68975340
ENSE00001320259	69324872	69325022
ENSE00001320372	68956645	68956809
ENSE00001321295	69233290	69233416
ENSE00001323809	69014038	69014106
ENSE00001330082	69388703	69389506
ENSE00001453148	68638661	68639432
ENSE00001453149	68637391	68637562
ENSE00001453150	68635282	68636000
ENSE00001760981	69330506	69330572
ENSE00003510737	69235032	69235135
ENSE00003727794	69332923	69333008
ENSE00003785650	69239124	69239226

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 98.14.

FANTOM5 (CAGE): breadth broad, TPM avg 14.3125 / max 876.8945, expressed in 587 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68429	10.9337	539
68431	0.7443	136
68434	0.3682	93
68450	0.3547	90
68430	0.3492	108
68451	0.2459	84
68452	0.1918	82
68428	0.1679	84
68449	0.1560	65
204045	0.1555	69

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	98.14	gold quality
endothelial cell	CL:0000115	96.60	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.35	gold quality
cortical plate	UBERON:0005343	95.44	gold quality
ventricular zone	UBERON:0003053	94.85	gold quality
orbitofrontal cortex	UBERON:0004167	94.68	gold quality
superior frontal gyrus	UBERON:0002661	93.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.35	gold quality
postcentral gyrus	UBERON:0002581	93.25	gold quality
entorhinal cortex	UBERON:0002728	92.93	gold quality
parietal lobe	UBERON:0001872	91.61	gold quality
CA1 field of hippocampus	UBERON:0003881	91.50	gold quality
prefrontal cortex	UBERON:0000451	91.18	gold quality
primary visual cortex	UBERON:0002436	91.15	gold quality
frontal cortex	UBERON:0001870	90.74	gold quality
right frontal lobe	UBERON:0002810	90.27	gold quality
ganglionic eminence	UBERON:0004023	90.26	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.02	gold quality
neocortex	UBERON:0001950	89.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.97	gold quality
cerebral cortex	UBERON:0000956	89.93	gold quality
cerebellar hemisphere	UBERON:0002245	89.84	gold quality
cerebellar cortex	UBERON:0002129	89.78	gold quality
nucleus accumbens	UBERON:0001882	89.44	gold quality
occipital lobe	UBERON:0002021	89.26	gold quality
telencephalon	UBERON:0001893	89.10	gold quality
cerebellum	UBERON:0002037	89.07	gold quality
forebrain	UBERON:0001890	88.73	gold quality
temporal lobe	UBERON:0001871	88.49	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	4487.10
E-GEOD-131882	yes	1677.81
E-HCAD-35	yes	88.31
E-ANND-3	yes	5.59
E-MTAB-9543	no	1558.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

165 targeting ADGRB3, 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-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
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-1184	99.99	68.19	1458
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964

Literature-anchored findings (GeneRIF, showing 9)

• Level of disorganized symptoms was significantly (P < 6.00 x 10(-5)) associated 2 SNPs within the brain-specific angiogenesis inhibitor 3 (BAI3) gene, which is highly expressed in brain during development. (PMID:18628273)
• The BAI3 locus where the rs9363864 maps is a new candidate for venous thromboembolism risk (PMID:20946148)
• C1ql proteins are secreted signaling molecules that bind to BAI3 and act, at least in part, to regulate synapse formation and/or maintenance. (PMID:21262840)
• Discriminated small-cell lung carcinoma from large-cell neuroendocrine lung carcinoma with immunohistochemical markers BAI3, CDX2 and VIL1. (PMID:24266897)
• BAI3 has the potential to act as target for pharmaceutical intervention inline with developing trends in molecular pathology aiming to provide personalized, treatment regimes based on tumor-specific mutation profiles. (PMID:28537194)
• BAI3 mediates the inhibitory effects of C1ql3 on insulin secretion from pancreatic beta-cells. (PMID:30228187)
• These findings further support this association and also suggest that biallelic variants affecting the function of the ADGRB3 gene may also cause cognitive impairments and ataxia. (PMID:30659260)
• Tethered agonist exposure in intact adhesion/class B2 GPCRs through intrinsic structural flexibility of the GAIN domain. (PMID:33497605)
• Genetic underpinnings of affective temperaments: a pilot GWAS investigation identifies a new genome-wide significant SNP for anxious temperament in ADGRB3 gene. (PMID:34075027)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrb3	ENSDARG00000059832
mus_musculus	Adgrb3	ENSMUSG00000033569
rattus_norvegicus	Adgrb3	ENSRNOG00000012045

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), ADGRL2 (ENSG00000117114), CRHR1 (ENSG00000120088), ADGRB2 (ENSG00000121753), ADGRE5 (ENSG00000123146), ADGRE2 (ENSG00000127507), ADGRE3 (ENSG00000131355), 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 B3 — O60242 (reviewed: O60242)

Alternative names: Brain-specific angiogenesis inhibitor 3

All UniProt accessions (5): A0A804HJR2, O60242, J3KMY8, S4R307, S4R3D0

UniProt curated annotations — full annotation on UniProt →

Function. Receptor that plays a role in the regulation of synaptogenesis and dendritic spine formation at least partly via interaction with ELMO1 and RAC1 activity. Promotes myoblast fusion through ELMO/DOCK1.

Subunit / interactions. Forms a heterodimer, consisting of a large extracellular region non-covalently linked to a seven-transmembrane moiety. Interacts (via TSP N-terminal domains) with C1QL1, C1QL2, C1QL3 and C1QL4. Interacts with ELMO1, ELMO2 and ELMO3.

Subcellular location. Cell membrane.

Tissue specificity. Strongly expressed in brain. Also detected in heart. Reduced expression in some glioblastoma cell lines.

Post-translational modifications. The endogenous protein is proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit.

Miscellaneous. Autoproteolysis appears to be cell specific, does not readily undergo proteolytic cleavage in HEK293T cells.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O60242-1	1	yes
O60242-2	2

RefSeq proteins (1): NP_001695* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR000859	CUB_dom	Domain
IPR000884	TSP1_rpt	Repeat
IPR001879	GPCR_2_extracellular_dom	Domain
IPR008077	GPCR_2_brain_angio_inhib	Family
IPR017981	GPCR_2-like_7TM	Domain
IPR017983	GPCR_2_secretin-like_CS	Conserved_site
IPR032471	AGRL2-4_GAIN_subdom_A	Domain
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR036445	GPCR_2_extracell_dom_sf	Homologous_superfamily
IPR043838	AGRB_N	Domain
IPR046338	GAIN_dom_sf	Homologous_superfamily
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF00090, PF01825, PF02793, PF16489, PF19188

UniProt features (89 total): disulfide bond 17, strand 17, glycosylation site 13, helix 10, topological domain 8, transmembrane region 7, domain 6, modified residue 3, turn 3, signal peptide 1, chain 1, region of interest 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4DLO	X-RAY DIFFRACTION	2.3
9LKM	ELECTRON MICROSCOPY	3.34
9LKL	ELECTRON MICROSCOPY	3.48

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60242-F1	63.85	0.18

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): 619, 1220, 1411

Disulfide bonds (17): 30–55, 303–336, 307–342, 318–326, 357–392, 361–397, 372–382, 412–447, 416–452, 427–437, 467–502, 471–507, 482–492, 514–549, 537–567, 819–851, 839–853

Glycosylation sites (13): 51, 54, 82, 105, 241, 337, 418, 540, 625, 779, 812, 828, 937

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 291 (showing top): GOBP_DENDRITE_DEVELOPMENT, GNF2_RTN1, TAATAAT_MIR126, GOBP_COGNITION, GOBP_BEHAVIOR, TGCGCANK_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, chr6q12, GOBP_NEURON_MATURATION, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY

GO Biological Process (13): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), myoblast fusion (GO:0007520), neuron remodeling (GO:0016322), negative regulation of angiogenesis (GO:0016525), regulation of dendrite morphogenesis (GO:0048814), positive regulation of synapse assembly (GO:0051965), motor learning (GO:0061743), regulation of synapse maturation (GO:0090128), maintenance of synapse structure (GO:0099558), regulation of synapse pruning (GO:1905806), signal transduction (GO:0007165), cell differentiation (GO:0030154)

GO Molecular Function (4): G protein-coupled receptor activity (GO:0004930), GTPase activator activity (GO:0005096), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (7): plasma membrane (GO:0005886), membrane (GO:0016020), synaptic cleft (GO:0043083), postsynapse (GO:0098794), postsynaptic density membrane (GO:0098839), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signal transduction	2
regulation of synapse organization	2
G protein-coupled receptor activity	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
neuron maturation	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
learning	1
regulation of developmental process	1
synapse maturation	1
cell junction maintenance	1
synapse organization	1
synapse pruning	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cellular developmental process	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
extracellular region	1
synapse	1

Protein interactions and networks

STRING

1958 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRB3	C1QL1	O75973	798
ADGRB3	C1QL3	Q5VWW1	768
ADGRB3	GRM8	O00222	717
ADGRB3	DOCK1	Q14185	683
ADGRB3	STAB2	Q8WWQ8	665
ADGRB3	ELMO1	Q92556	634
ADGRB3	CBLN1	P02682	574
ADGRB3	GNAO1	P09471	566
ADGRB3	APLNR	P35414	549
ADGRB3	PTPRD	P23468	545
ADGRB3	ADGRG1	Q9Y653	513
ADGRB3	C1QL2	Q7Z5L3	502
ADGRB3	LRP1B	Q9NZR2	501
ADGRB3	GNAS	Q5JWF2	495
ADGRB3	MYMK	A6NI61	493

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ADGRB3	C1ql3	psi-mi:“MI:0407”(direct interaction)	0.600
GPATCH11	ADGRB3	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	GPATCH11	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	GPR37L1	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	SLC7A1	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	MUC1	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
ADGRB3	OXCT1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB3	C1ql2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ADGRB3	SLC7A1	psi-mi:“MI:0915”(physical association)	0.000
ADGRB3	MUC1	psi-mi:“MI:0915”(physical association)	0.000
ADGRB3	TLCD4	psi-mi:“MI:0915”(physical association)	0.000
ADGRB3	GPR37L1	psi-mi:“MI:0915”(physical association)	0.000
ADGRB3	ZNF24	psi-mi:“MI:0915”(physical association)	0.000
DSCR9	ADGRB3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): GPATCH11 (Two-hybrid), BAI3 (Two-hybrid), SLC7A1 (Two-hybrid), TMEM56 (Two-hybrid), GPR37L1 (Two-hybrid), MUC1 (Two-hybrid), C1QL3 (Affinity Capture-MS), C1QL2 (Affinity Capture-MS), BAI3 (Reconstituted Complex), C1QL3 (Reconstituted Complex), OXCT1 (Proximity Label-MS), BAI3 (Affinity Capture-MS), BAI3 (Two-hybrid), HSP90AB1 (Cross-Linking-MS (XL-MS)), HSP90AB1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A259, A2AIR5, H2Q5A1, O00222, O15399, O60242, O75077, O75882, O97741, P15209, P24786, P31423, P35400, P37088, P47743, P55270, P70579, Q00961, Q01098, Q03351, Q03391, Q13507, Q14833, Q14957, Q16288, Q1ZZH0, Q4R766, Q5IS37, Q5RDQ8, Q62645, Q63604, Q68ED2, Q68EF4, Q6AYT7, Q80ZF8, Q8CIW5, Q8TCU5, Q8VHN2, Q91044, Q91YD4

Diamond homologs: A2ATD1, A2VEC9, B1AKI9, B3EWY9, O60242, P07996, P35441, P35448, Q19204, Q28178, Q58T08, Q5EGE1, Q6H9L7, Q80ZF8, Q8CG65, Q8CGM1, Q8QFV1, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O75173, O88783, O95185, O95450, P04275, P07358, P27918, P35442

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	158
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
148991	GRCh38/hg38 6p11.2-q12(chr6:57466921-68712228)x3	Pathogenic
148992	GRCh38/hg38 6q12-13(chr6:68735649-70794393)x4	Pathogenic
1527249	GRCh37/hg19 6q12-16.1(chr6:69938252-94379210)	Pathogenic
154460	GRCh38/hg38 6q12-14.2(chr6:64549655-83426791)x1	Pathogenic
1703664	GRCh37/hg19 6q12-14.1(chr6:64954687-79581678)	Pathogenic
3391890	GRCh37/hg19 6q12-14.1(chr6:66523005-81798980)x1	Pathogenic
687049	GRCh37/hg19 6q12-13(chr6:69481460-73185349)x1	Pathogenic
4076077	GRCh37/hg19 6q12-13(chr6:68357758-74447347)x1	Likely pathogenic
599565	NM_001704.3(ADGRB3):c.4298G>A (p.Arg1433Lys)	Likely pathogenic
599566	NM_001704.3(ADGRB3):c.2294T>C (p.Val765Ala)	Likely pathogenic

SpliceAI

5187 predictions. Top by Δscore:

Variant	Effect	Δscore
6:68890080:T:G	acceptor_gain	1.0000
6:68930557:A:AG	acceptor_gain	1.0000
6:68930558:G:GG	acceptor_gain	1.0000
6:68930558:GA:G	acceptor_gain	1.0000
6:68930677:G:GG	donor_gain	1.0000
6:68943826:ACAGT:A	acceptor_loss	1.0000
6:68943827:CAGT:C	acceptor_loss	1.0000
6:68943828:A:AC	acceptor_loss	1.0000
6:68943828:A:AG	acceptor_gain	1.0000
6:68943829:G:A	acceptor_loss	1.0000
6:68943829:G:GA	acceptor_gain	1.0000
6:68943829:GTA:G	acceptor_gain	1.0000
6:68943829:GTAC:G	acceptor_gain	1.0000
6:68943969:GCCTT:G	donor_gain	1.0000
6:68943977:A:AG	donor_gain	1.0000
6:68943993:AGG:A	donor_loss	1.0000
6:68943994:GG:G	donor_loss	1.0000
6:68943996:T:A	donor_loss	1.0000
6:68956018:T:A	acceptor_gain	1.0000
6:68956019:GGTA:G	acceptor_loss	1.0000
6:68956020:GTAGT:G	acceptor_loss	1.0000
6:68956021:TAGTT:T	acceptor_loss	1.0000
6:68956022:A:AG	acceptor_gain	1.0000
6:68956022:A:G	acceptor_loss	1.0000
6:68956022:AGTT:A	acceptor_gain	1.0000
6:68956023:G:GA	acceptor_gain	1.0000
6:68956023:GTT:G	acceptor_gain	1.0000
6:68956023:GTTG:G	acceptor_gain	1.0000
6:68956644:GCCA:G	acceptor_gain	1.0000
6:68975341:G:GG	donor_gain	1.0000

AlphaMissense

10049 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:68638851:T:C	L59P	1.000
6:68639189:T:C	C172R	1.000
6:68639191:T:G	C172W	1.000
6:68639195:T:A	W174R	1.000
6:68639195:T:C	W174R	1.000
6:68639197:G:C	W174C	1.000
6:68639197:G:T	W174C	1.000
6:68936541:G:C	W297C	1.000
6:68936541:G:T	W297C	1.000
6:68936548:T:A	W300R	1.000
6:68936548:T:C	W300R	1.000
6:68936550:G:C	W300C	1.000
6:68936550:G:T	W300C	1.000
6:68936591:G:C	R314P	1.000
6:68936656:T:C	C336R	1.000
6:68943850:T:A	W351R	1.000
6:68943850:T:C	W351R	1.000
6:68943852:G:C	W351C	1.000
6:68943852:G:T	W351C	1.000
6:68943859:T:A	W354R	1.000
6:68943859:T:C	W354R	1.000
6:68943861:G:C	W354C	1.000
6:68943861:G:T	W354C	1.000
6:68943868:T:A	C357S	1.000
6:68943868:T:C	C357R	1.000
6:68943869:G:A	C357Y	1.000
6:68943869:G:C	C357S	1.000
6:68943870:T:G	C357W	1.000
6:68943880:T:A	C361S	1.000
6:68943880:T:C	C361R	1.000

dbSNP variants (sampled 300 via entrez): RS1000000843 (6:69068519 T>C), RS1000000873 (6:68783161 G>T), RS1000002902 (6:68682572 A>C), RS1000005636 (6:68900050 A>C), RS1000012128 (6:69145132 C>T), RS1000018802 (6:69025209 G>A), RS1000026208 (6:68703194 A>G), RS1000026209 (6:69189490 G>A,T), RS1000030796 (6:69336879 C>T), RS1000033190 (6:69304866 G>T), RS1000033732 (6:69221218 A>G), RS1000038568 (6:68783323 A>C,G,T), RS1000039154 (6:69246340 G>A,C), RS1000044552 (6:69145476 G>A), RS1000044975 (6:69071105 G>A)

Disease associations

OMIM: gene MIM:602684 | disease phenotypes: MIM:613544

GenCC curated gene-disease

Mondo (1): chromosome 6q11-q14 deletion syndrome (MONDO:0013299)

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST000635_7	Response to statin therapy	4.000000e-06
GCST001178_8	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	6.000000e-07
GCST001350_6	Pancreatic cancer	1.000000e-06
GCST005666_3	Fractional excretion of metabolites in chronic kidney disease	4.000000e-08
GCST006482_37	Lung function (FEV1/FVC)	3.000000e-08
GCST007325_147	General risk tolerance (MTAG)	3.000000e-12
GCST007625_3	Negative urgency	7.000000e-07
GCST009265_2	Superior parietal cortex volume	7.000000e-06
GCST009391_1294	Metabolite levels	7.000000e-07
GCST009391_1963	Metabolite levels	1.000000e-06
GCST009391_2098	Metabolite levels	4.000000e-06
GCST010134_2	Non-oily fish consumption	3.000000e-09
GCST010721_1	Body mass index	1.000000e-08
GCST010732_16	Sensory peripheral neuropathy in microtubule targeting agent-treated breast cancer	8.000000e-06
GCST010988_367	Adult body size	4.000000e-11
GCST012164_2	Adiponectin levels	5.000000e-07
GCST012191_8	Body mass index and systolic blood pressure (bivariate analysis)	2.000000e-06
GCST012490_166	Femur bone mineral density x serum urate levels interaction	6.000000e-11

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0007760	eicosapentaenoic acid measurement
EFO:0005116	urinary metabolite measurement
EFO:0004713	FEV/FVC ratio
EFO:0008579	risk-taking behaviour
EFO:0006946	behavioural disinhibition measurement
EFO:0010549	xanthosine measurement
EFO:0008392	triiodothyronine measurement
EFO:0010374	phosphatidylcholine 32:2 measurement
EFO:0008111	diet measurement
EFO:0004340	body mass index
EFO:0005260	response to antimicrotubule agent
EFO:0004502	adiponectin measurement
EFO:0006335	systolic blood pressure
EFO:0004531	urate 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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
aristolochic acid I	decreases expression	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
tobacco tar	decreases reaction, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects methylation	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Allergens	increases expression	1
Atrazine	decreases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cytarabine	increases expression	1
Rotenone	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	decreases methylation	1
Uranium Compounds	increases expression	1
Lithium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_KW39	PathHunter CHO-K1 BAI3 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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