ADGRB2

Summary

ADGRB2 (adhesion G protein-coupled receptor B2, HGNC:944) is a protein-coding gene on chromosome 1p35.2, encoding Adhesion G protein-coupled receptor B2 (O60241). Orphan G-protein coupled receptor involved in cell adhesion and probably in cell-cell interactions.

This gene encodes a a seven-span transmembrane protein that is thought to be a member of the secretin receptor family. The encoded protein is a brain-specific inhibitor of angiogenesis. The mature peptide may be further cleaved into additional products (PMID:20367554). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 576 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 484 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001364857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:944
Approved symbol	ADGRB2
Name	adhesion G protein-coupled receptor B2
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000121753
Ensembl biotype	protein_coding
OMIM	602683
Entrez	576

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000373655, ENST00000373658, ENST00000398538, ENST00000398542, ENST00000398547, ENST00000398556, ENST00000420125, ENST00000436464, ENST00000465256, ENST00000466109, ENST00000468430, ENST00000527361, ENST00000530134, ENST00000530999, ENST00000533175

RefSeq mRNA: 3 — MANE Select: NM_001364857 NM_001294335, NM_001294336, NM_001364857

CCDS: CCDS346, CCDS72746, CCDS72747

Canonical transcript exons

ENST00000373658 — 33 exons

Exon	Start	End
ENSE00000825312	31740347	31740541
ENSE00000825313	31741373	31741479
ENSE00000956932	31744193	31744357
ENSE00001210765	31740110	31740178
ENSE00001370598	31757382	31757511
ENSE00001533543	31763884	31764340
ENSE00001726064	31736573	31736723
ENSE00001732436	31737429	31737531
ENSE00001759974	31737652	31737755
ENSE00001764949	31739308	31739635
ENSE00001769853	31738832	31738937
ENSE00002263235	31757201	31757281
ENSE00003497439	31741624	31741725
ENSE00003500348	31732972	31733143
ENSE00003511547	31730800	31731419
ENSE00003517314	31738200	31738326
ENSE00003518616	31735827	31735893
ENSE00003518856	31744648	31744731
ENSE00003525470	31738587	31738630
ENSE00003532807	31728025	31728081
ENSE00003551806	31735580	31735665
ENSE00003553389	31755999	31756815
ENSE00003562643	31728182	31728280
ENSE00003582076	31735183	31735281
ENSE00003585335	31742838	31743002
ENSE00003588369	31732115	31732154
ENSE00003614818	31728598	31728633
ENSE00003622067	31727117	31727605
ENSE00003622884	31732517	31732612
ENSE00003665292	31739926	31740034
ENSE00003686368	31742053	31742217
ENSE00003690338	31736321	31736390
ENSE00003786649	31741800	31741967

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 98.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6235 / max 213.0199, expressed in 1144 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11494	6.1704	1071
11491	0.7281	316
11489	0.3270	186
11492	0.1865	81
11493	0.1632	57
11495	0.0258	10
11488	0.0166	5
11490	0.0058	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	98.16	gold quality
cortical plate	UBERON:0005343	98.09	gold quality
prefrontal cortex	UBERON:0000451	97.24	gold quality
anterior cingulate cortex	UBERON:0009835	97.15	gold quality
cingulate cortex	UBERON:0003027	97.13	gold quality
ganglionic eminence	UBERON:0004023	96.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.84	gold quality
nucleus accumbens	UBERON:0001882	96.81	gold quality
caudate nucleus	UBERON:0001873	96.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.47	gold quality
frontal cortex	UBERON:0001870	96.41	gold quality
neocortex	UBERON:0001950	96.33	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.31	gold quality
amygdala	UBERON:0001876	96.14	gold quality
putamen	UBERON:0001874	96.02	gold quality
cerebral cortex	UBERON:0000956	95.76	gold quality
CA1 field of hippocampus	UBERON:0003881	95.75	gold quality
telencephalon	UBERON:0001893	95.33	gold quality
ventricular zone	UBERON:0003053	95.24	gold quality
Ammon’s horn	UBERON:0001954	95.23	gold quality
temporal lobe	UBERON:0001871	94.11	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.00	gold quality
forebrain	UBERON:0001890	93.83	gold quality
frontal pole	UBERON:0002795	93.63	gold quality
superior frontal gyrus	UBERON:0002661	93.60	gold quality
postcentral gyrus	UBERON:0002581	93.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.07	gold quality
brain	UBERON:0000955	92.67	gold quality
central nervous system	UBERON:0001017	92.41	gold quality
parietal lobe	UBERON:0001872	92.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	50.07
E-ANND-3	no	2.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

Literature-anchored findings (GeneRIF, showing 4)

• involvement of BAI2 in the ischemia-induced brain angiogenesis (PMID:12218411)
• BAI2 is a functional GPCR regulated by proteolytic processing and activates the NFAT pathway (PMID:20367554)
• This is the first study reporting BAI2 as an interaction partner of GIP. (PMID:21787750)
• These studies provide new insights into the signaling capabilities of the adhesion GPCR BAI2/ADGRB2 and shed light on how an apparent gain-of-function mutation to the receptor’s C-terminus may lead to human disease. (PMID:28891236)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	adgrb2	ENSDARG00000025667
mus_musculus	Adgrb2	ENSMUSG00000028782
rattus_norvegicus	Adgrb2	ENSRNOG00000014375

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), 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 B2 — O60241 (reviewed: O60241)

Alternative names: Brain-specific angiogenesis inhibitor 2

All UniProt accessions (7): A2A3C1, A2A3C2, A2A3C3, A2A3C4, A2A3C6, E9PND1, O60241

UniProt curated annotations — full annotation on UniProt →

Function. Orphan G-protein coupled receptor involved in cell adhesion and probably in cell-cell interactions. Activates NFAT-signaling pathway, a transcription factor, via the G-protein GNAZ. Involved in angiogenesis inhibition.

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. Interacts with GABPB2. Interacts (via carboxy-terminus) with TAX1BP3. Interacts with GNAZ. Interacts with SH3GL2.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Detected in cerebrospinal fluid (at protein level). Strongly expressed in brain. Also detected in heart, thymus, skeletal muscle, and different cell lines.

Post-translational modifications. Glycosylated. Autoproteolytically processed at the GPS region of the GAIN-B domain; this cleavage modulates receptor activity. Additionally, furin is involved in the cleavage at another site, in the middle of the extracellular domain, generating a soluble fragment.

Activity regulation. Receptor activity is regulated by proteolytic processing. The long N-terminal has a an inhibitory effect on the constitutive signaling activity. Removal of the N-terminal region induces an increase of the receptor activity.

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

Isoforms (4)

UniProt ID	Names	Canonical?
O60241-1	1	yes
O60241-2	2
O60241-3	3
O60241-4	4

RefSeq proteins (3): NP_001281264, NP_001281265, NP_001351786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000203	GPS	Conserved_site
IPR000832	GPCR_2_secretin-like	Family
IPR000884	TSP1_rpt	Repeat
IPR001879	GPCR_2_extracellular_dom	Domain
IPR008077	GPCR_2_brain_angio_inhib	Family
IPR017981	GPCR_2-like_7TM	Domain
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
IPR051867	Angio_Inhib/Adhesion_GPCR	Family
IPR057244	GAIN_B	Domain

Pfam: PF00002, PF00090, PF01825, PF16489, PF19188

UniProt features (99 total): strand 18, disulfide bond 16, helix 11, glycosylation site 9, topological domain 8, transmembrane region 7, region of interest 6, domain 5, compositionally biased region 5, splice variant 3, mutagenesis site 3, site 2, signal peptide 1, chain 1, modified residue 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8OEK	X-RAY DIFFRACTION	2.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60241-F1	62.10	0.13

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 (2): 296–297 (cleavage; by furin); 911–912 (cleavage; by autolysis)

Post-translational modifications (1): 1351

Disulfide bonds (16): 321–355, 325–361, 336–345, 376–411, 380–416, 391–401, 431–466, 435–471, 446–456, 487–522, 491–527, 502–512, 534–569, 557–587, 874–906, 894–908

Glycosylation sites (9): 106, 191, 192, 266, 356, 437, 560, 645, 867

Mutagenesis-validated functional residues (3):

Position	Phenotype
889	inhibits autoproteolytic cleavage.
908	inhibits autoproteolytic cleavage.
912	inhibits autoproteolytic cleavage.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_SYNAPSE_ASSEMBLY, GGGNRMNNYCAT_UNKNOWN, GCANCTGNY_MYOD_Q6, SP3_Q3, MAZ_Q6, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, NFKB_C, CCANNAGRKGGC_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (7): cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), peripheral nervous system development (GO:0007422), negative regulation of angiogenesis (GO:0016525), calcineurin-NFAT signaling cascade (GO:0033173), positive regulation of synapse assembly (GO:0051965), signal transduction (GO:0007165)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
cellular anatomical structure	2
G protein-coupled receptor activity	1
nervous system development	1
system development	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
calcineurin-mediated signaling	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
transmembrane signaling receptor activity	1
G protein-coupled receptor signaling pathway	1
signaling receptor activity	1
binding	1
membrane	1
cell periphery	1
synapse	1
cell junction	1

Protein interactions and networks

STRING

1308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADGRB2	MAGI1	Q96QZ7	689
ADGRB2	DOCK1	Q14185	686
ADGRB2	CNTN5	O94779	429
ADGRB2	ANKRD34A	Q69YU3	429
ADGRB2	ELMO1	Q92556	396
ADGRB2	TMEM221	A6NGB7	390
ADGRB2	GPR153	Q6NV75	368
ADGRB2	GPRC5B	Q9NZH0	363
ADGRB2	GPR162	Q16538	362
ADGRB2	ELMO2	Q96JJ3	348
ADGRB2	MCRIP2	Q9BUT9	331
ADGRB2	GPR62	Q9BZJ7	329
ADGRB2	ADGRL1	O94910	324
ADGRB2	GPR137C	Q8N3F9	320
ADGRB2	LHFPL7	Q6ICI0	317

IntAct

12 interactions, top by confidence:

A	B	Type	Score
ADGRB2	GNAZ	psi-mi:“MI:0915”(physical association)	0.400
ADGRB2	GNAI1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB2	Arrb2	psi-mi:“MI:0915”(physical association)	0.400
SH3GL2	ADGRB2	psi-mi:“MI:0915”(physical association)	0.400
ADGRB2	GABPA	psi-mi:“MI:0915”(physical association)	0.400
ADGRB2	GABPB1	psi-mi:“MI:0915”(physical association)	0.400
ADGRB2	STARD13	psi-mi:“MI:0915”(physical association)	0.370
ADGRB2	DLG4	psi-mi:“MI:0915”(physical association)	0.370
ADGRB2	SHANK1	psi-mi:“MI:0915”(physical association)	0.370
TULP3	PPM1G	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): BAI2 (Two-hybrid), BAI2 (Affinity Capture-RNA), BAI2 (Two-hybrid), BAI2 (FRET), BAI2 (Co-crystal Structure), BAI2 (Affinity Capture-MS), BAI2 (Affinity Capture-MS), BAI2 (Two-hybrid), BAI2 (Affinity Capture-MS), BAI2 (Two-hybrid), BAI2 (Affinity Capture-RNA), BAI2 (Affinity Capture-RNA), BAI2 (Proximity Label-MS), BAI2 (Protein-peptide)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	285
Likely benign	128
Benign	44

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
58058	GRCh38/hg38 1p36.11-35.2(chr1:26963045-32279045)x3	Pathogenic
58059	GRCh38/hg38 1p35.2-35.1(chr1:31122108-32402160)x3	Pathogenic
430853	NM_001364857.2(ADGRB2):c.4393C>T (p.Arg1465Trp)	Likely pathogenic

SpliceAI

5392 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31728176:CCTCA:C	donor_loss	1.0000
1:31728177:CTCAC:C	donor_loss	1.0000
1:31728178:TCACC:T	donor_loss	1.0000
1:31728179:CA:C	donor_loss	1.0000
1:31728180:A:T	donor_loss	1.0000
1:31728181:C:A	donor_loss	1.0000
1:31728276:ACCTT:A	acceptor_gain	1.0000
1:31728277:CCTT:C	acceptor_loss	1.0000
1:31728277:CCTTC:C	acceptor_gain	1.0000
1:31728278:CTT:C	acceptor_gain	1.0000
1:31728278:CTTC:C	acceptor_loss	1.0000
1:31728279:TT:T	acceptor_gain	1.0000
1:31728279:TTCTA:T	acceptor_loss	1.0000
1:31728280:TCTA:T	acceptor_loss	1.0000
1:31728281:C:CC	acceptor_gain	1.0000
1:31728281:CTA:C	acceptor_loss	1.0000
1:31728282:T:A	acceptor_loss	1.0000
1:31728289:C:CT	acceptor_gain	1.0000
1:31732514:CACCA:C	donor_loss	1.0000
1:31732516:C:T	donor_loss	1.0000
1:31735574:CCTTA:C	donor_loss	1.0000
1:31735576:TTAC:T	donor_loss	1.0000
1:31735577:TACC:T	donor_loss	1.0000
1:31735578:A:AC	donor_gain	1.0000
1:31735578:AC:A	donor_gain	1.0000
1:31735579:C:CC	donor_gain	1.0000
1:31735579:C:CT	donor_loss	1.0000
1:31735579:CC:C	donor_gain	1.0000
1:31735579:CCCGG:C	donor_gain	1.0000
1:31735593:T:TA	donor_gain	1.0000

AlphaMissense

10214 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31728234:A:G	L1488P	1.000
1:31728246:A:G	L1484P	1.000
1:31728602:A:C	F1471C	1.000
1:31733094:A:G	W1168R	1.000
1:31733094:A:T	W1168R	1.000
1:31733111:G:C	P1162R	1.000
1:31736576:A:G	W1043R	1.000
1:31736576:A:T	W1043R	1.000
1:31736666:A:G	W1013R	1.000
1:31736666:A:T	W1013R	1.000
1:31736695:A:G	L1003P	1.000
1:31738305:C:A	W889C	1.000
1:31738305:C:G	W889C	1.000
1:31739550:C:A	W751C	1.000
1:31739550:C:G	W751C	1.000
1:31740125:C:A	W681C	1.000
1:31740125:C:G	W681C	1.000
1:31740127:A:G	W681R	1.000
1:31740127:A:T	W681R	1.000
1:31740399:A:T	V646D	1.000
1:31740408:A:G	L643P	1.000
1:31740433:C:G	D635H	1.000
1:31740436:C:A	G634W	1.000
1:31740471:A:G	L622P	1.000
1:31740520:C:A	G606W	1.000
1:31740528:A:G	L603P	1.000
1:31741406:G:C	C587W	1.000
1:31741407:C:G	C587S	1.000
1:31741407:C:T	C587Y	1.000
1:31741408:A:G	C587R	1.000

dbSNP variants (sampled 300 via entrez): RS1000245649 (1:31730894 G>A), RS1000296450 (1:31730637 A>C,G), RS1000296809 (1:31743057 C>A,G,T), RS1000351829 (1:31731497 G>C,T), RS1000491103 (1:31761209 G>C), RS1000567944 (1:31736266 C>G,T), RS1000635356 (1:31732118 T>C), RS1000694421 (1:31730020 G>A), RS1000788249 (1:31737800 G>A,T), RS1000931333 (1:31754787 A>G), RS1001004714 (1:31742453 A>AAGAG), RS1001020293 (1:31735917 G>A,C), RS1001411380 (1:31733265 G>A), RS1001497634 (1:31726714 T>C), RS1001504320 (1:31751259 C>A,T)

Disease associations

OMIM: gene MIM:602683 | disease phenotypes: MIM:303350

GenCC curated gene-disease

Mondo (1): hereditary spastic paraplegia (MONDO:0019064)

Orphanet (1): Hereditary spastic paraplegia (Orphanet:685)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005580_101	Intraocular pressure	3.000000e-09
GCST005951_36	Body mass index	9.000000e-10
GCST006412_8	Intraocular pressure	3.000000e-08
GCST006957_1	Severe aortic features in Marfan syndrome	9.000000e-06
GCST007327_104	Smoking status (ever vs never smokers)	4.000000e-10
GCST009524_50	Household income (MTAG)	1.000000e-09
GCST009798_61	Asthma	3.000000e-08
GCST010988_525	Adult body size	2.000000e-09
GCST011122_26	Walking pace	3.000000e-12
GCST012332_43	Multisite chronic pain	3.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0009695	household income
EFO:0010100	multisite chronic pain

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D015419	Spastic Paraplegia, Hereditary	C10.500.300.820; C10.574.500.495.820; C10.668.829.800.300.820; C16.131.666.300.820; C16.320.400.375.820

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
bisphenol A	increases expression, affects cotreatment, decreases methylation	2
sodium arsenite	decreases expression	2
Benzo(a)pyrene	increases expression, affects methylation	2
Aflatoxin B1	increases expression, increases methylation	2
GSK-J4	decreases expression	1
OTX015	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
zinc chromate	increases abundance, decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
clothianidin	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
prothioconazole	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Catechin	affects cotreatment, decreases expression	1
Gallic Acid	increases expression	1
Lead	affects expression, affects splicing	1
Methapyrilene	increases methylation	1
Oxygen	decreases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8MP	MRIi018-A	Induced pluripotent stem cell	Male
CVCL_KW38	PathHunter CHO-K1 BAI2 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07542548	PHASE4	COMPLETED	D-Cycloserine for Serine Palmitoyltransferase Inhibition
NCT03961906	PHASE2	COMPLETED	Physiotherapy in Hereditary Spastic Paraplegia
NCT04768166	PHASE2	COMPLETED	Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT02604186	PHASE2/PHASE3	COMPLETED	Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT06948019	PHASE1/PHASE2	NOT_YET_RECRUITING	Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)
NCT06478238	EARLY_PHASE1	RECRUITING	Calcium Folinate Treatment of Spastic Paraplegia 56
NCT00023075	Not specified	COMPLETED	Nuclear Magnetic Spectroscopy Imaging to Evaluate Primary Lateral Sclerosis, Hereditary Spastic Paraplegia and Amyotrophic Lateral Sclerosis
NCT00136630	Not specified	COMPLETED	Natural History, Genetic Bases and Phenotype-genotype Correlations in Autosomal Dominant Spinocerebellar Degenerations
NCT00140829	Not specified	COMPLETED	SPATAX: Clinical and Genetic Analysis of Cerebellar Ataxias and Spastic Paraplegias
NCT00677768	Not specified	COMPLETED	Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
NCT01568658	Not specified	ACTIVE_NOT_RECRUITING	Genetic and Physical Study of Childhood Nerve and Muscle Disorders
NCT02327845	Not specified	ENROLLING_BY_INVITATION	Phenotype, Genotype & Biomarkers in ALS and Related Disorders
NCT02852278	Not specified	COMPLETED	A Patient Centric Motor Neuron Disease Activities of Daily Living Scale
NCT02859428	Not specified	TERMINATED	Disease Natural History and Biomarkers of SPG3A, SPG4A, and SPG31
NCT03104088	Not specified	COMPLETED	Studying Cognition in SPG4
NCT03206190	Not specified	RECRUITING	The preSPG4 Study - Studying the Prodromal and Early Phase of SPG4
NCT03627416	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation as Therapy in Hereditary Spastic Paraplegia and Adrenomyeloneuropathy
NCT03981276	Not specified	RECRUITING	Phenotypes, Biomarkers and Pathophysiology in Hereditary Spastic Paraplegias and Related Disorders
NCT04006418	Not specified	RECRUITING	A Registered Cohort Study on Spastic Paraplegia
NCT04180098	Not specified	COMPLETED	Improving Gait Adaptability in Hereditary Spastic Paraplegia
NCT04256681	Not specified	COMPLETED	SNAP: Measurement of the Subjective Perception of the Symptom in Hereditary Spastic Paraparesis (HSP)
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT04875416	Not specified	ACTIVE_NOT_RECRUITING	Phenotype, Genotype and Biomarkers 2
NCT04912609	Not specified	COMPLETED	Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
NCT05354622	Not specified	RECRUITING	Hereditary Spastic Paraplegia Genomic Sequencing Initiative (HSPseq)
NCT05373082	Not specified	COMPLETED	Identification of Modifying Factors in Hereditary Spastic Paraplegia
NCT05411627	Not specified	WITHDRAWN	A Pilot Study of Shockwave Therapy in HSP
NCT05432999	Not specified	COMPLETED	Extracorporeal Shockwave Therapy for Spasticity in People With Spinal Cord Injury
NCT05613114	Not specified	COMPLETED	Effect of Dalfampridine in Patients With Hereditary Spastic Paraplegia
NCT05767268	Not specified	COMPLETED	Assessment of the Psychophysical State During Rehabilitation Treatment With Lokomat
NCT05848271	Not specified	RECRUITING	Natural History Study of Patients with HPDL Mutations
NCT06156813	Not specified	RECRUITING	Turkish Lower-Extremity Motor Activity Log (LE-MAL)
NCT06229626	Not specified	RECRUITING	Evaluation of an Intensive Training Program for Patients with Hereditary Spastic Paraparesis SPG4/Spast
NCT06260982	Not specified	UNKNOWN	Cognitive Disorders in Hereditary Spastic Paraplegia Type 4
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network
NCT06572046	Not specified	RECRUITING	STOP-HSP.Net: a Registry for Hereditary Spastic Paraplegia as an Integration Tool for Future Therapeutic Strategies
NCT06573866	Not specified	RECRUITING	Enhancement of Quality of Work And Life
NCT06680063	Not specified	COMPLETED	Correlation Between Clinical Assessment and Neurophysiological Assessment in Spinal Cord Injury