USP27X

Summary

USP27X (ubiquitin specific peptidase 27 X-linked, HGNC:13486) is a protein-coding gene on chromosome Xp11.23, encoding Ubiquitin carboxyl-terminal hydrolase 27 (A6NNY8). Deubiquitinase involved in innate antiviral immunity by mediating deubiquitination of CGAS and RIGI.

This gene encodes a member of the peptidase protein family. The encoded protein functions as a deubiquitinase that is involved in upregulation of the pro-apoptotic Bim protein. This protein may act as a tumor suppressor by increasing levels of Bim to counteract anti-apoptotic signals in cancer cells. Mutations in this gene have been associated with X-linked cognitive disability.

Source: NCBI Gene 389856 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, X-linked 105 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 80 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes
• MANE Select transcript: NM_001145073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13486
Approved symbol	USP27X
Name	ubiquitin specific peptidase 27 X-linked
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Aliases	USP27
Ensembl gene	ENSG00000273820
Ensembl biotype	protein_coding
OMIM	300975
Entrez	389856

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000621775

RefSeq mRNA: 1 — MANE Select: NM_001145073 NM_001145073

CCDS: CCDS65260

Canonical transcript exons

ENST00000621775 — 1 exons

Exon	Start	End
ENSE00003718369	49879484	49882558

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 93.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4177 / max 267.7466, expressed in 1753 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196337	9.4177	1753

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.79	gold quality
endothelial cell	CL:0000115	93.34	gold quality
cerebellar vermis	UBERON:0004720	91.17	silver quality
placenta	UBERON:0001987	88.95	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.49	gold quality
entorhinal cortex	UBERON:0002728	83.47	gold quality
cerebellar cortex	UBERON:0002129	83.45	gold quality
middle temporal gyrus	UBERON:0002771	83.37	gold quality
cerebellar hemisphere	UBERON:0002245	83.29	gold quality
cerebellum	UBERON:0002037	83.23	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.49	gold quality
substantia nigra pars compacta	UBERON:0001965	82.36	gold quality
superior frontal gyrus	UBERON:0002661	82.14	gold quality
postcentral gyrus	UBERON:0002581	81.44	gold quality
germinal epithelium of ovary	UBERON:0001304	81.33	gold quality
primary visual cortex	UBERON:0002436	80.97	gold quality
medial globus pallidus	UBERON:0002477	80.90	gold quality
parietal lobe	UBERON:0001872	80.88	gold quality
cortical plate	UBERON:0005343	80.54	gold quality
bronchial epithelial cell	CL:0002328	79.24	gold quality
globus pallidus	UBERON:0001875	79.09	gold quality
pons	UBERON:0000988	78.57	gold quality
amniotic fluid	UBERON:0000173	78.51	gold quality
substantia nigra pars reticulata	UBERON:0001966	78.50	gold quality
occipital lobe	UBERON:0002021	78.34	gold quality
ventral tegmental area	UBERON:0002691	77.81	gold quality
superior vestibular nucleus	UBERON:0007227	77.78	gold quality
frontal cortex	UBERON:0001870	77.23	gold quality
neocortex	UBERON:0001950	77.18	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

119 targeting USP27X, 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-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-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-374C-5P	99.80	72.06	2910

Literature-anchored findings (GeneRIF, showing 10)

• Usp27x can trigger via its proteolytic activity the deubiquitination of Bim and enhance its levels, counteracting the anti-apoptotic effects of ERK activity, and therefore acts as a tumour suppressor. (PMID:27013495)
• ATXN7L3 and ENY2 orchestrate activities of multiple deubiquitinating enzymes, including USP27x and USP51, and that imbalances in these activities likely potentiate human diseases including cancer. (PMID:27132940)
• Data found that USP27 promotes Cyclin E stability by negatively regulating its ubiquitination and regulates its abundance to accelerate cell cycle progression, cell proliferation, and hepatocellular carcinoma cell growth as well. (PMID:29497124)
• High USP27X expression is associated with Chemoresistance in breast cancer by Stabilization of Snail1. (PMID:30341066)
• The USP27X is a novel regulator of theCyclic GMP-AMP synthase (cGAS)-STING cytosolic DNA sensing pathway. (PMID:31534008)
• these studies uncover a novel negative regulatory role of USP27X in targeting RIG-I to balance innate immune responses. (PMID:32027733)
• Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression. (PMID:35018513)
• The deubiquitinase Usp27x as a novel regulator of cFLIPL protein expression and sensitizer to death-receptor-induced apoptosis. (PMID:35044632)
• Phosphorylation of USP27X by GSK3beta maintains the stability and oncogenic functions of CBX2. (PMID:38030604)
• USP27X variants underlying X-linked intellectual disability disrupt protein function via distinct mechanisms. (PMID:38182161)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Usp27x	ENSMUSG00000046269
rattus_norvegicus	Usp27x	ENSRNOG00000002844

Paralogs (71): USP2 (ENSG00000036672), USP28 (ENSG00000048028), USP36 (ENSG00000055483), USP13 (ENSG00000058056), USP33 (ENSG00000077254), USP40 (ENSG00000085982), USP48 (ENSG00000090686), USP14 (ENSG00000101557), USP11 (ENSG00000102226), USP10 (ENSG00000103194), USP31 (ENSG00000103404), USP42 (ENSG00000106346), USP5 (ENSG00000111667), USP4 (ENSG00000114316), USP9Y (ENSG00000114374), USP34 (ENSG00000115464), USP35 (ENSG00000118369), USP45 (ENSG00000123552), USP22 (ENSG00000124422), USP9X (ENSG00000124486), USP6 (ENSG00000129204), USP29 (ENSG00000131864), USP26 (ENSG00000134588), USP30 (ENSG00000135093), USP15 (ENSG00000135655), USP37 (ENSG00000135913), USP44 (ENSG00000136014), USP20 (ENSG00000136878), USP8 (ENSG00000138592), USP3 (ENSG00000140455), USP21 (ENSG00000143258), USP43 (ENSG00000154914), USP25 (ENSG00000155313), USP16 (ENSG00000156256), USP24 (ENSG00000162402), USP1 (ENSG00000162607), USP49 (ENSG00000164663), USP38 (ENSG00000170185), USP50 (ENSG00000170236), USP47 (ENSG00000170242)

Protein

Protein identifiers

Ubiquitin carboxyl-terminal hydrolase 27 — A6NNY8 (reviewed: A6NNY8)

Alternative names: Deubiquitinating enzyme 27, Ubiquitin carboxyl-terminal hydrolase 22-like, Ubiquitin thioesterase 27, Ubiquitin-specific-processing protease 27, X-linked ubiquitin carboxyl-terminal hydrolase 27

All UniProt accessions (1): A6NNY8

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinase involved in innate antiviral immunity by mediating deubiquitination of CGAS and RIGI. Negatively regulates RIGI by mediating ‘Lys-63’-linked deubiquitination of RIGI, inhibiting type I interferon signaling. Also regulates ‘Lys-63’-linked ubiquitination level of MDA5/IFIH1. Acts as a positive regulator of the cGAS-STING pathway by catalyzing ‘Lys-48’-linked deubiquitination of CGAS, thereby promoting its stabilization. Can reduce the levels of BCL2L11/BIM ubiquitination and stabilize BCL2L11 in response to the RAF-MAPK-degradation signal. By acting on BCL2L11 levels, may counteract the anti-apoptotic effects of MAPK activity.

Subunit / interactions. Interacts with phosphorylated BCL2L11 isoform BIMEL; this interaction leads to BCL2L11 deubiquitination and stabilization.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Disease relevance. Intellectual developmental disorder, X-linked 105 (XLID105) [MIM:300984] A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase C19 family.

RefSeq proteins (1): NP_001138545* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001394	Peptidase_C19_UCH	Domain
IPR018200	USP_CS	Conserved_site
IPR028889	USP	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR050185	Ub_carboxyl-term_hydrolase	Family

Pfam: PF00443

UniProt features (10 total): mutagenesis site 3, active site 2, sequence conflict 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NNY8-F1	78.52	0.53

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): 87 (nucleophile); 380 (proton acceptor)

Mutagenesis-validated functional residues (3):

Position	Phenotype
87	abolished deubiquitinase activity; impaired ability to mediate deubiquitination of cgas.
87	abolished deubiquitinase activity; impaired ability to mediate deubiquitination of rigi; when associated with a-380.
380	abolished deubiquitinase activity; impaired ability to mediate deubiquitination of rigi; when associated with s-87.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): GOBP_RESPONSE_TO_PEPTIDE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_PROTEIN_STABILIZATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_PROTEIN_K48_LINKED_DEUBIQUITINATION, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_CYTOKINE_STIMULUS, GOBP_DEFENSE_RESPONSE_TO_VIRUS

GO Biological Process (10): proteolysis (GO:0006508), protein deubiquitination (GO:0016579), positive regulation of apoptotic process (GO:0043065), innate immune response (GO:0045087), protein stabilization (GO:0050821), defense response to virus (GO:0051607), positive regulation of type I interferon-mediated signaling pathway (GO:0060340), protein K63-linked deubiquitination (GO:0070536), protein K48-linked deubiquitination (GO:0071108), immune system process (GO:0002376)

GO Molecular Function (7): cysteine-type endopeptidase activity (GO:0004197), cysteine-type deubiquitinase activity (GO:0004843), K63-linked deubiquitinase activity (GO:0061578), K48-linked deubiquitinase activity (GO:1990380), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
deubiquitinase activity	3
protein deubiquitination	2
cysteine-type peptidase activity	2
cellular anatomical structure	2
protein metabolic process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
immune response	1
defense response to symbiont	1
regulation of protein stability	1
defense response	1
response to virus	1
positive regulation of cytokine-mediated signaling pathway	1
positive regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
biological_process	1
endopeptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

917 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
USP27X	ENY2	Q9NPA8	885
USP27X	ATXN7L3	Q14CW9	836
USP27X	ZUP1	Q96AP4	662
USP27X	BCL2L11	O43521	533
USP27X	OTUB1	Q96FW1	504
USP27X	OTUD7A	Q8TE49	479
USP27X	OTUD6A	Q7L8S5	473
USP27X	USP25	Q9UHP3	469
USP27X	USP5	P45974	458
USP27X	FBXL14	Q8N1E6	456
USP27X	ATXN7	O15265	450
USP27X	TRIM40	Q6P9F5	440
USP27X	OTUD1	Q5VV17	438
USP27X	OTUD6B	Q8N6M0	433
USP27X	JOSD1	Q15040	430

IntAct

23 interactions, top by confidence:

A	B	Type	Score
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.350
USP22	CNOT1	psi-mi:“MI:0914”(association)	0.350
SGF29	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
TACSTD2	RIMOC1	psi-mi:“MI:0914”(association)	0.350
ATXN7L1	USP27X	psi-mi:“MI:0914”(association)	0.350
USP51	USP27X	psi-mi:“MI:0914”(association)	0.350
SLC15A3	GXYLT2	psi-mi:“MI:0914”(association)	0.350
KLF8	USP27X	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (429): USP27X (Affinity Capture-MS), USP27X (Affinity Capture-MS), USP27X (Affinity Capture-Western), UBC (Biochemical Activity), BCL2L11 (Co-localization), BCL2L11 (Affinity Capture-Western), USP27X (Affinity Capture-MS), USP27X (Affinity Capture-MS), USP27X (Reconstituted Complex), CCNE1 (Affinity Capture-Western), USP27X (Affinity Capture-Western), USP27X (Affinity Capture-MS), USP27X (Affinity Capture-Western), USP27X (Affinity Capture-MS), ATXN7L3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A4FUN7, A5D9H7, A5WWB0, A6H8I0, A6NNY8, A6QNS3, C0HB46, D0RB01, E1C1R4, F1M625, O24454, O75317, P09851, P0C8Z3, P20936, P50904, P62068, P62069, Q09LZ8, Q12979, Q16288, Q3TIX9, Q52KZ6, Q53GS9, Q5DU02, Q5F415, Q5F450, Q5IFJ9, Q5IS37, Q5IS82, Q5M981, Q5R573, Q5R761, Q5R8I6, Q5RBQ4, Q5RDP3, Q5SSL4, Q60969, Q6DCJ1

Diamond homologs: A0A0R4IB93, A0JM59, A5PMR2, A5PN09, A6NNY8, A6QNM7, A7Z056, B1AY13, B1WBD7, D2HBJ8, D6RBM5, E1C213, E7F6T8, E9Q9U0, F6Z5C0, F8VPU6, F8VPZ3, M9PD06, O00507, O22207, O60079, O74442, O94269, O94966, O96612, P0C7I0, P0C8Z3, P0CAQ1, P35125, P39538, P40453, P51784, P53874, P55824, P70398, Q01988, Q09738, Q0V9G5, Q28CN3, Q2HJE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	58
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
254684	NM_001145073.3(USP27X):c.1026_1030del (p.Ser342fs)	Pathogenic
254685	NM_001145073.3(USP27X):c.1141T>C (p.Tyr381His)	Pathogenic
625216	NM_001145073.3(USP27X):c.310_311del (p.Asp104fs)	Pathogenic
2097077	NM_001145073.3(USP27X):c.221_225delinsAGA (p.Thr74fs)	Likely pathogenic
2499534	NM_001145073.3(USP27X):c.1205dup (p.Ala403fs)	Likely pathogenic
2499535	NM_001145073.3(USP27X):c.937T>G (p.Phe313Val)	Likely pathogenic
2499536	NM_001145073.3(USP27X):c.394G>T (p.Glu132Ter)	Likely pathogenic
2684394	NM_001145073.3(USP27X):c.954del (p.Lys318fs)	Likely pathogenic

SpliceAI

59 predictions. Top by Δscore:

Variant	Effect	Δscore
X:49880543:G:GT	donor_gain	0.9100
X:49880534:GTT:G	donor_gain	0.9000
X:49880535:TTT:T	donor_gain	0.9000
X:49881238:AAAC:A	acceptor_gain	0.7700
X:49881241:C:CA	acceptor_gain	0.5900
X:49880291:G:GT	donor_gain	0.5800
X:49880533:GGTT:G	donor_gain	0.5700
X:49881238:A:AG	acceptor_gain	0.5400
X:49880559:C:T	donor_gain	0.5100
X:49881239:A:G	acceptor_gain	0.5000
X:49881238:AAACG:A	acceptor_gain	0.4700
X:49880530:A:G	donor_gain	0.4600
X:49880214:T:TA	acceptor_gain	0.4400
X:49880141:C:T	donor_gain	0.4300
X:49880507:G:GT	donor_gain	0.3800
X:49880536:T:G	donor_gain	0.3800
X:49881484:TTC:T	donor_gain	0.3800
X:49880442:G:GT	donor_gain	0.3600
X:49880131:A:T	donor_gain	0.3500
X:49880635:A:AG	acceptor_gain	0.3500
X:49880636:G:GG	acceptor_gain	0.3500
X:49881239:AAC:A	acceptor_gain	0.3500
X:49880060:G:GT	donor_gain	0.3400
X:49881526:G:GT	donor_gain	0.3100
X:49880057:TGG:T	donor_gain	0.3000
X:49880058:GGG:G	donor_gain	0.3000
X:49880059:G:A	donor_gain	0.3000
X:49880218:T:A	acceptor_gain	0.3000
X:49880298:A:G	donor_gain	0.2900
X:49880278:GACCT:G	donor_gain	0.2800

AlphaMissense

2925 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:49880543:G:A	G79E	1.000
X:49880553:T:A	N82K	1.000
X:49880553:T:G	N82K	1.000
X:49880568:C:G	C87W	1.000
X:49880569:T:C	F88L	1.000
X:49880571:T:A	F88L	1.000
X:49880571:T:G	F88L	1.000
X:49880580:C:G	C91W	1.000
X:49880758:T:A	W151R	1.000
X:49880758:T:C	W151R	1.000
X:49880797:G:C	D164H	1.000
X:49880798:A:C	D164A	1.000
X:49880798:A:G	D164G	1.000
X:49880798:A:T	D164V	1.000
X:49880799:T:A	D164E	1.000
X:49880799:T:G	D164E	1.000
X:49880809:T:C	F168L	1.000
X:49880811:C:A	F168L	1.000
X:49880811:C:G	F168L	1.000
X:49880914:T:C	F203L	1.000
X:49880915:T:C	F203S	1.000
X:49880916:C:A	F203L	1.000
X:49880916:C:G	F203L	1.000
X:49880927:T:C	L207P	1.000
X:49880932:T:C	S209P	1.000
X:49880939:T:A	V211D	1.000
X:49880944:T:C	C213R	1.000
X:49880995:A:C	S230R	1.000
X:49880997:T:A	S230R	1.000
X:49880997:T:G	S230R	1.000

dbSNP variants (sampled 300 via entrez): RS1000953971 (X:49882827 G>T), RS1003791734 (X:49877662 G>A), RS1004076272 (X:49881701 C>T), RS1009716353 (X:49882882 C>T), RS1011889871 (X:49877706 G>A), RS1012823883 (X:49882771 G>A), RS1012898195 (X:49879329 G>A,T), RS1013980376 (X:49882439 C>T), RS1014914522 (X:49881736 T>C,G), RS1018507321 (X:49879618 G>A), RS1019777637 (X:49882906 C>G,T), RS1021992528 (X:49879354 A>G), RS1022357901 (X:49878955 G>A,C), RS1024110461 (X:49881792 G>T), RS1027285297 (X:49881120 G>A)

Disease associations

OMIM: gene MIM:300975 | disease phenotypes: MIM:300984

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, X-linked 105	Strong	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked intellectual disability	Limited	XL

Mondo (4): intellectual disability, X-linked 105 (MONDO:0010510), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), non-syndromic X-linked intellectual disability (MONDO:0019181)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000708	Atypical behavior
HP:0001249	Intellectual disability
HP:0001344	Absent speech
HP:0001419	X-linked recessive inheritance

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630801 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	4
Benzo(a)pyrene	affects methylation, decreases expression	2
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Malathion	increases expression	1
Rotenone	decreases expression	1
Silver	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4605972	Binding	Inhibition of human DAC-tagged USP27X expressed in Escherichia coli assessed as cleavage of KI63-linked di-ubiquitin to mono-ubiquitin using di-ubiquitin as substrate by mass spectrometry	Discovery of Potent, Selective, and Orally Bioavailable Inhibitors of USP7 with In Vivo Antitumor Activity. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TW80	HAP1 USP27X (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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,
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
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
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
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
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
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
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)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays