TSPOAP1

Summary

TSPOAP1 (TSPO associated protein 1, HGNC:16831) is a protein-coding gene on chromosome 17q22, encoding Peripheral-type benzodiazepine receptor-associated protein 1 (O95153). Required for synaptic transmission regulation.

Enables benzodiazepine receptor binding activity. Involved in regulation of neurotransmitter secretion. Located in mitochondrion. Implicated in dystonia 22, adult-onset and dystonia 22, juvenile-onset.

Source: NCBI Gene 9256 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dystonia 22, juvenile-onset (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 94 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 53
• Druggable target: yes
• MANE Select transcript: NM_004758

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16831
Approved symbol	TSPOAP1
Name	TSPO associated protein 1
Location	17q22
Locus type	gene with protein product
Status	Approved
Aliases	PRAX-1, KIAA0612, RIM-BP1, RIMBP1
Ensembl gene	ENSG00000005379
Ensembl biotype	protein_coding
OMIM	610764
Entrez	9256

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 retained_intron, 5 protein_coding

ENST00000268893, ENST00000343736, ENST00000577871, ENST00000578486, ENST00000578511, ENST00000580669, ENST00000581675, ENST00000581692, ENST00000582679, ENST00000583624, ENST00000585149

RefSeq mRNA: 3 — MANE Select: NM_004758 NM_001261835, NM_004758, NM_024418

CCDS: CCDS11605, CCDS45742

Canonical transcript exons

ENST00000343736 — 32 exons

Exon	Start	End
ENSE00000480333	58326293	58326421
ENSE00000480336	58323298	58323381
ENSE00000739401	58306342	58306413
ENSE00000739402	58306800	58306968
ENSE00000739403	58307611	58307762
ENSE00000739406	58308541	58309380
ENSE00000739409	58309967	58310158
ENSE00000739416	58311892	58312722
ENSE00000739418	58316023	58316132
ENSE00000739421	58316425	58316540
ENSE00000739423	58318280	58318452
ENSE00000739425	58319090	58319294
ENSE00000739434	58322654	58322776
ENSE00000739437	58322950	58323039
ENSE00000739441	58323468	58323545
ENSE00000739443	58324811	58325002
ENSE00000739445	58325534	58325713
ENSE00000739447	58326683	58326790
ENSE00000820273	58310512	58310751
ENSE00000820274	58310836	58311213
ENSE00000820275	58320531	58320581
ENSE00001013278	58320109	58320129
ENSE00001343606	58311571	58311722
ENSE00001343611	58322308	58322412
ENSE00002700022	58327588	58328795
ENSE00003476974	58307842	58307941
ENSE00003538760	58305833	58305865
ENSE00003571852	58305387	58305458
ENSE00003578738	58305540	58305643
ENSE00003596872	58301231	58302447
ENSE00003623020	58304338	58304399
ENSE00003784898	58305061	58305171

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.07.

FANTOM5 (CAGE): breadth broad, TPM avg 8.9534 / max 784.6214, expressed in 386 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167235	7.8776	348
167236	0.5818	112
167233	0.1509	63
208283	0.1288	57
167234	0.0958	53
208282	0.0763	33
167231	0.0421	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.07	gold quality
right frontal lobe	UBERON:0002810	98.02	gold quality
granulocyte	CL:0000094	97.28	gold quality
amygdala	UBERON:0001876	97.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.97	gold quality
cingulate cortex	UBERON:0003027	96.82	gold quality
anterior cingulate cortex	UBERON:0009835	96.81	gold quality
cerebellar hemisphere	UBERON:0002245	96.38	gold quality
cerebellar cortex	UBERON:0002129	96.25	gold quality
nucleus accumbens	UBERON:0001882	96.23	gold quality
caudate nucleus	UBERON:0001873	95.46	gold quality
putamen	UBERON:0001874	95.16	gold quality
left ovary	UBERON:0002119	95.10	gold quality
prefrontal cortex	UBERON:0000451	94.74	gold quality
right ovary	UBERON:0002118	94.72	gold quality
adenohypophysis	UBERON:0002196	94.64	gold quality
cerebellum	UBERON:0002037	94.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.51	gold quality
body of uterus	UBERON:0009853	94.42	gold quality
pituitary gland	UBERON:0000007	94.25	gold quality
neocortex	UBERON:0001950	94.17	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.16	gold quality
frontal cortex	UBERON:0001870	93.97	gold quality
left uterine tube	UBERON:0001303	93.41	gold quality
right lobe of thyroid gland	UBERON:0001119	93.27	gold quality
telencephalon	UBERON:0001893	93.20	gold quality
forebrain	UBERON:0001890	93.10	gold quality
cerebral cortex	UBERON:0000956	92.92	gold quality
Ammon’s horn	UBERON:0001954	92.80	gold quality
endocervix	UBERON:0000458	92.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	19.52
E-ANND-3	yes	5.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AIRE, AP1, BMAL1, BMAL2, FOXP4, GFI1, HAND1, HAND2, IRF6, JUND, MAF, NFKB, POU2F2, PRDM1, REL, RELA, STAT5A

miRNA regulators (miRDB)

66 targeting TSPOAP1, 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-4283	100.00	66.42	2097
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-2113	99.58	71.22	1521

Literature-anchored findings (GeneRIF, showing 5)

• RIMBP1 is identified in humans. (PMID:17855024)
• Long noncoding RNA TSPOAP1 antisense RNA 1 negatively modulates type I IFN signaling to facilitate influenza A virus replication. (PMID:30968963)
• NF-kappaB/miR-18a-3p and miR-4286/BZRAP1 axis may mediate carcinogenesis in Helicobacter pylori-Associated gastric cancer. (PMID:33113427)
• Biallelic variants in TSPOAP1, encoding the active-zone protein RIMBP1, cause autosomal recessive dystonia. (PMID:33539324)
• Choroid Plexus Enlargement in Inflammatory Multiple Sclerosis: 3.0-T MRI and Translocator Protein PET Evaluation. (PMID:34254858)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000103792
mus_musculus	Tspoap1	ENSMUSG00000034156
rattus_norvegicus	Tspoap1	ENSRNOG00000007957
drosophila_melanogaster	Rbp	FBGN0262483
caenorhabditis_elegans		WBGENE00006513

Paralogs (4): RIMBP2 (ENSG00000060709), RIMBP3C (ENSG00000183246), RIMBP3B (ENSG00000274600), RIMBP3 (ENSG00000275793)

Protein

Protein identifiers

Peripheral-type benzodiazepine receptor-associated protein 1 — O95153 (reviewed: O95153)

Alternative names: Peripheral benzodiazepine receptor-interacting protein, RIMS-binding protein 1, TSPO-associated protein 1

All UniProt accessions (4): O95153, A0A0C4DGN5, J3KSY4, J3KT64

UniProt curated annotations — full annotation on UniProt →

Function. Required for synaptic transmission regulation. It probably controls the recruitment of voltage-gated calcium channels to the presynaptic membrane, and modulates neurotransmitter release.

Subunit / interactions. Interacts with RIMS1 and RIMS2. Interacts with TSPO. Interacts with CACNA1A.

Subcellular location. Cytoplasm. Mitochondrion.

Tissue specificity. Predominantly expressed in brain, pituitary gland and thymus in adults. In adult brain, highest expression found in temporal lobe and the putamen, followed by amygdala, caudate nucleus, cerebral cortex, occipital and frontal lobe. A high expression level is also observed in fetal tissues like brain, heart, kidney and thymus.

Disease relevance. Dystonia 22, adult-onset (DYT22AO) [MIM:620456] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT22AO is an autosomal recessive form characterized by focal dystonia or tremor and mild cognitive impairment. The disease may be caused by variants affecting the gene represented in this entry. Dystonia 22, juvenile-onset (DYT22JO) [MIM:620453] A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT22JO is an autosomal recessive form characterized by progressive, generalized dystonia associated with intellectual disability, cognitive decline, and cerebellar atrophy. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The SH3 and proline-rich domain is required for the interaction with TSPO and the second SH3 domain mediates binding to a proline-rich motif in RIMS1 and RIMS2.

Similarity. Belongs to the RIMBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
O95153-1	1	yes
O95153-2	2
O95153-3	3

RefSeq proteins (3): NP_001248764, NP_004749, NP_077729 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR035753	RIM-BP_SH3_2	Domain
IPR035755	RIM-BP_SH3_3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR040325	RIMBP1/2/3	Family
IPR057884	FN3_RIM-BP1/2/3	Domain
IPR057950	RIMB1/RIM3A-C-like_N	Domain

Pfam: PF07653, PF14604, PF25523, PF25566

UniProt features (44 total): compositionally biased region 14, sequence variant 11, region of interest 9, domain 6, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95153-F1	57.91	0.20

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-196108	Pregnenolone biosynthesis
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle

MSigDB gene sets: 287 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, CCAWYNNGAAR_UNKNOWN, GOBP_NEUROTRANSMITTER_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, REACTOME_DOPAMINE_NEUROTRANSMITTER_RELEASE_CYCLE, REACTOME_NOREPINEPHRINE_NEUROTRANSMITTER_RELEASE_CYCLE, DELYS_THYROID_CANCER_DN, MODULE_301, JAZAG_TGFB1_SIGNALING_VIA_SMAD4_UP, AAAGACA_MIR511, GOBP_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (2): regulation of neurotransmitter secretion (GO:0046928), regulation of presynaptic cytosolic calcium ion concentration (GO:0099509)

GO Molecular Function (3): benzodiazepine receptor binding (GO:0030156), voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic calcium levels (GO:0099626), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), calyx of Held (GO:0044305), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Neurotransmitter release cycle	5
Metabolism of steroid hormones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	2
cellular anatomical structure	2
cytoplasm	2
neurotransmitter secretion	1
modulation of chemical synaptic transmission	1
regulation of neurotransmitter transport	1
regulation of secretion by cell	1
regulation of cytosolic calcium ion concentration	1
neuron cellular homeostasis	1
signaling receptor binding	1
regulation of presynaptic cytosolic calcium ion concentration	1
voltage-gated calcium channel activity involved in regulation of cytosolic calcium levels	1
binding	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
axon terminus	1
synapse	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPOAP1	RIMS2	Q9UQ26	932
TSPOAP1	TSPO	P30536	881
TSPOAP1	RIMS1	Q86UR5	877
TSPOAP1	RAB3C	Q96E17	809
TSPOAP1	ACBD3	Q9H3P7	713
TSPOAP1	VDAC1	P21796	687
TSPOAP1	RAB3A	P20336	684
TSPOAP1	UNC13B	O14795	675
TSPOAP1	DBI	P07108	588
TSPOAP1	RIMBP2	O15034	495
TSPOAP1	DNMT3B	Q9UBC3	433
TSPOAP1	FN1	P02751	427
TSPOAP1	ERC1	Q8IUD2	422
TSPOAP1	ECHDC3	Q96DC8	419
TSPOAP1	C15orf62	A8K5M9	414

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ADAM19	TSPOAP1	psi-mi:“MI:0407”(direct interaction)	0.560
TSPOAP1	CACNA1A	psi-mi:“MI:0915”(physical association)	0.510
CACNA1A	TSPOAP1	psi-mi:“MI:0915”(physical association)	0.510
TSPOAP1	K15-M	psi-mi:“MI:0407”(direct interaction)	0.440
TSPOAP1	H1-2	psi-mi:“MI:0915”(physical association)	0.400
	TSPOAP1	psi-mi:“MI:0915”(physical association)	0.370
	TUBA4A	psi-mi:“MI:0914”(association)	0.350
CPVL		psi-mi:“MI:0914”(association)	0.350
CEP170	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
CD244	CAND2	psi-mi:“MI:0914”(association)	0.350
ORAI1	IPO5	psi-mi:“MI:0914”(association)	0.350
EPHA4	TSPOAP1	psi-mi:“MI:0915”(physical association)	0.000
CASS4	TSPOAP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): BZRAP1 (Affinity Capture-MS), BZRAP1 (Affinity Capture-MS), HIST1H1C (Proximity Label-MS), HIST1H2BD (Proximity Label-MS), TSPO (Two-hybrid), TSPO (Reconstituted Complex), BZRAP1 (Affinity Capture-MS), BZRAP1 (Cross-Linking-MS (XL-MS)), BZRAP1 (Affinity Capture-RNA), BZRAP1 (Two-hybrid), BZRAP1 (Affinity Capture-Western), BZRAP1 (Protein-peptide), BZRAP1 (Two-hybrid), BZRAP1 (Two-hybrid), BZRAP1 (Two-hybrid)

ESM2 similar proteins: A1L3T7, A2A3L6, A4IFI1, A7E3N7, A8MYJ7, A8VU90, O94761, O94812, O95153, O95382, P97680, Q0P5G1, Q13671, Q14154, Q3UYR4, Q4V896, Q53GL7, Q569K6, Q58CQ5, Q58EX7, Q66H85, Q6DT37, Q6F5E8, Q6ZVH7, Q76MJ5, Q7TNF8, Q7Z3H0, Q80UU1, Q80UW5, Q8BWA8, Q8BXP5, Q8BYG0, Q8CIE4, Q8CJ00, Q8IYJ3, Q8NAG6, Q8TE82, Q91WA6, Q91WE1, Q921Q7

Diamond homologs: A6NJZ7, A6NNM3, O95153, Q3V0F0, Q80U40, Q9JIR1, Q9UFD9, A0A0K3AV08, A1CEK6, A1DFN5, E2RP94, O15034, P19706, Q15811, Q4WHP5, Q557J6, Q5BBL4, Q7TNF8, Q8QFX1, Q8R550, Q925Q9, Q96B97, Q9JIR0, M0R4F8, Q6XJU9, Q6XZF7, A2QW93, Q0CJU8, P29355, Q6TGW5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TSPOAP1	“down-regulates activity”	RIMS1	binding
TSPOAP1	“down-regulates activity”	RIMS2	binding
TSPOAP1	“down-regulates activity”	RIMS3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	31
Likely benign	17
Benign	11

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2498299	NM_004758.4(TSPOAP1):c.1567C>T (p.Gln523Ter)	Pathogenic
2574616	NM_004758.4(TSPOAP1):c.538del (p.Ala180fs)	Pathogenic
2574617	NM_004758.4(TSPOAP1):c.2449_2450inv (p.Gln817Ter)	Pathogenic
2575977	NM_004758.4(TSPOAP1):c.2277del (p.Ser759fs)	Pathogenic
4070522	NM_004758.4(TSPOAP1):c.3172dup (p.Arg1058fs)	Likely pathogenic
4849373	NM_004758.4(TSPOAP1):c.5134_5141dup (p.Glu1715fs)	Likely pathogenic

SpliceAI

5824 predictions. Top by Δscore:

Variant	Effect	Δscore
17:58305385:A:AC	donor_gain	1.0000
17:58305386:C:CC	donor_gain	1.0000
17:58305534:CCTCA:C	donor_loss	1.0000
17:58305535:CTCA:C	donor_loss	1.0000
17:58305536:TCACC:T	donor_loss	1.0000
17:58305537:CACCT:C	donor_loss	1.0000
17:58305539:C:A	donor_loss	1.0000
17:58306420:C:CT	acceptor_gain	1.0000
17:58306421:A:T	acceptor_gain	1.0000
17:58306966:CAC:C	acceptor_gain	1.0000
17:58306968:CCTGG:C	acceptor_loss	1.0000
17:58306969:CTG:C	acceptor_loss	1.0000
17:58306970:T:A	acceptor_loss	1.0000
17:58307569:G:C	donor_gain	1.0000
17:58307588:AGC:A	donor_gain	1.0000
17:58307845:G:C	donor_gain	1.0000
17:58309238:T:TA	donor_gain	1.0000
17:58309981:C:CA	donor_gain	1.0000
17:58310023:T:TA	donor_gain	1.0000
17:58310034:AGCT:A	donor_gain	1.0000
17:58310035:G:C	donor_gain	1.0000
17:58310043:T:TA	donor_gain	1.0000
17:58310046:T:TA	donor_gain	1.0000
17:58310064:T:TA	donor_gain	1.0000
17:58310070:T:TA	donor_gain	1.0000
17:58310154:TCCTT:T	acceptor_gain	1.0000
17:58310155:CCTTC:C	acceptor_gain	1.0000
17:58310156:CTT:C	acceptor_gain	1.0000
17:58310157:TT:T	acceptor_gain	1.0000
17:58310159:C:CC	acceptor_gain	1.0000

AlphaMissense

11923 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:58311654:A:G	W1000R	1.000
17:58311654:A:T	W1000R	1.000
17:58312692:A:T	V710D	1.000
17:58305143:A:T	V1821D	0.999
17:58305393:G:C	F1809L	0.999
17:58305393:G:T	F1809L	0.999
17:58305395:A:G	F1809L	0.999
17:58311707:G:C	P982R	0.999
17:58311707:G:T	P982H	0.999
17:58312699:C:G	G708R	0.999
17:58312722:C:T	G700E	0.999
17:58316023:C:G	G700R	0.999
17:58316023:C:T	G700R	0.999
17:58316030:A:C	F697L	0.999
17:58316030:A:T	F697L	0.999
17:58316032:A:G	F697L	0.999
17:58316082:A:G	L680P	0.999
17:58316082:A:T	L680Q	0.999
17:58316088:A:G	L678P	0.999
17:58305445:A:G	F1792S	0.998
17:58305451:A:G	L1790P	0.998
17:58305589:G:T	A1771D	0.998
17:58306939:G:C	F1671L	0.998
17:58306939:G:T	F1671L	0.998
17:58306941:A:G	F1671L	0.998
17:58311122:C:G	R1058P	0.998
17:58311605:A:T	V1016D	0.998
17:58311652:C:A	W1000C	0.998
17:58311652:C:G	W1000C	0.998
17:58312682:A:C	N713K	0.998

dbSNP variants (sampled 300 via entrez): RS1000021468 (17:58324445 C>A,T), RS1000027554 (17:58313529 T>G), RS1000032783 (17:58322017 A>G), RS1000053220 (17:58315532 C>T), RS1000187115 (17:58302418 T>A,G), RS1000582381 (17:58319922 G>A), RS1000637834 (17:58309527 G>A,C), RS1000668846 (17:58308378 G>A), RS1000809872 (17:58313820 C>A,T), RS1000991103 (17:58326037 G>A), RS1001016978 (17:58304554 C>T), RS1001205141 (17:58322368 C>A), RS1001344431 (17:58305729 CCT>C), RS1001381059 (17:58316150 G>A), RS1001558309 (17:58328679 G>C)

Disease associations

OMIM: gene MIM:610764 | disease phenotypes: MIM:209900, MIM:620453, MIM:620456

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 22, juvenile-onset	Strong	Autosomal recessive
TH-deficient dopa-responsive dystonia	Supportive	Autosomal recessive

Mondo (6): intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), Bardet-Biedl syndrome (MONDO:0015229), dystonia 22, juvenile-onset (MONDO:0957539), dystonia 22, adult-onset (MONDO:0957542), TH-deficient dopa-responsive dystonia (MONDO:0011551)

Orphanet (2): Bardet-Biedl syndrome (Orphanet:110), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000473	Torticollis
HP:0000508	Ptosis
HP:0000514	Slow saccadic eye movements
HP:0000571	Hypometric saccades
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism
HP:0001310	Dysmetria
HP:0001336	Myoclonus
HP:0001348	Brisk reflexes
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001945	Fever
HP:0002019	Constipation
HP:0002061	Lower limb spasticity
HP:0002063	Rigidity
HP:0002066	Gait ataxia
HP:0002067	Bradykinesia
HP:0002069	Bilateral tonic-clonic seizure

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004246_3	Alzheimer’s disease	4.000000e-08
GCST004609_83	Monocyte percentage of white cells	1.000000e-17
GCST004632_8	Lymphocyte percentage of white cells	1.000000e-14
GCST004633_124	Neutrophil percentage of white cells	3.000000e-12
GCST004781_21	Sulfasalazine-induced agranulocytosis	4.000000e-07
GCST009936_5	Venous thromboembolism	8.000000e-06
GCST010002_126	Refractive error	7.000000e-42
GCST90002389_237	Lymphocyte percentage of white cells	2.000000e-26
GCST90002398_306	Neutrophil count	2.000000e-44
GCST90002407_143	White blood cell count	1.000000e-32

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004833	neutrophil count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5169104 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
Benzo(a)pyrene	affects methylation, decreases expression, increases mutagenesis	3
Panobinostat	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	decreases expression	1
ochratoxin A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	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
licochalcone B	increases expression	1
(+)-JQ1 compound	affects expression	1
Arsenic Trioxide	decreases expression	1
Arbutin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Mycophenolic Acid	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5167554	Binding	Inhibition of PBR (unknown origin) at 10 uM relative to control	Discovery and Characterization of the First Nonpeptide Antagonists for the Relaxin-3/RXFP3 System. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study