OTUD6B

Summary

OTUD6B (OTU deubiquitinase 6B, HGNC:24281) is a protein-coding gene on chromosome 8q21.3, encoding Deubiquitinase OTUD6B (Q8N6M0). Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1.

This gene encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Deubiquitinating enzymes are primarily involved in removing ubiquitin from proteins targeted for degradation. This protein may function as a negative regulator of the cell cycle in B cells.

Source: NCBI Gene 51633 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 104 total — 11 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• MANE Select transcript: NM_016023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24281
Approved symbol	OTUD6B
Name	OTU deubiquitinase 6B
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Aliases	CGI-77, DUBA5
Ensembl gene	ENSG00000155100
Ensembl biotype	protein_coding
OMIM	612021
Entrez	51633

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000285420, ENST00000404789, ENST00000522894, ENST00000524027, ENST00000615618, ENST00000617869, ENST00000910621, ENST00000910622, ENST00000921578

RefSeq mRNA: 3 — MANE Select: NM_016023 NM_001286745, NM_001416022, NM_016023

CCDS: CCDS6253, CCDS69513

Canonical transcript exons

ENST00000404789 — 7 exons

Exon	Start	End
ENSE00003467366	91073831	91073911
ENSE00003499512	91084008	91084114
ENSE00003520911	91071138	91071289
ENSE00003522048	91070344	91070466
ENSE00003588115	91084784	91087093
ENSE00003631677	91078356	91078668
ENSE00003682163	91080669	91080730

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 92.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.3238 / max 475.7342, expressed in 1775 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89733	18.8973	1771
89734	0.4265	237

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	92.44	gold quality
epithelial cell of pancreas	CL:0000083	89.77	silver quality
calcaneal tendon	UBERON:0003701	87.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.25	gold quality
cortical plate	UBERON:0005343	84.61	gold quality
corpus callosum	UBERON:0002336	84.06	gold quality
oviduct epithelium	UBERON:0004804	84.04	gold quality
adrenal tissue	UBERON:0018303	83.70	gold quality
colonic epithelium	UBERON:0000397	83.08	gold quality
ventricular zone	UBERON:0003053	83.01	gold quality
gastrocnemius	UBERON:0001388	82.90	gold quality
muscle of leg	UBERON:0001383	82.69	gold quality
deltoid	UBERON:0001476	82.52	gold quality
embryo	UBERON:0000922	82.45	gold quality
ganglionic eminence	UBERON:0004023	82.45	gold quality
skeletal muscle organ	UBERON:0014892	82.14	gold quality
superficial temporal artery	UBERON:0001614	81.99	gold quality
monocyte	CL:0000576	81.92	gold quality
endothelial cell	CL:0000115	81.89	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.74	gold quality
skin of hip	UBERON:0001554	81.55	gold quality
leukocyte	CL:0000738	81.43	gold quality
vastus lateralis	UBERON:0001379	81.40	gold quality
spinal cord	UBERON:0002240	81.14	gold quality
epithelium of nasopharynx	UBERON:0001951	81.07	gold quality
smooth muscle tissue	UBERON:0001135	81.06	gold quality
nasopharynx	UBERON:0001728	81.05	gold quality
tonsil	UBERON:0002372	81.03	gold quality
germinal epithelium of ovary	UBERON:0001304	80.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting OTUD6B, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
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-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-32-5P	99.98	75.21	1964

Literature-anchored findings (GeneRIF, showing 15)

• down-regulation of Otud-6b expression after prolonged cytokine stimulation may be required for cell proliferation in B lymphocytes (PMID:21267069)
• The global OTUD6B expression level does not change significantly between nonneoplastic and malignant tissues, suggesting that modifications of splicing factors during the process of transformation are responsible for this isoform switch. (PMID:27864334)
• OTUD6B encodes a deubiquitinating enzyme; study reports biallelic pathogenic variants in OTUD6B in 12 individuals from 6 families with intellectual disability syndrome associated with seizures & dysmorphic features; other features include developmental delay, microcephaly, absent speech, hypotonia, growth retardation, feeding difficulties, structural brain abnormalities, malformations of heart & musculoskeleton. (PMID:28343629)
• OTUD6B-AS1 Might Be a Novel Regulator of Apoptosis in Systemic Sclerosis. (PMID:31156645)
• DUB-independent regulation of pVHL by OTUD6B suppresses hepatocellular carcinoma. (PMID:32323143)
• OTUD6B-associated intellectual disability: novel variants and genetic exclusion of retinal degeneration as part of a refined phenotype. (PMID:34354232)
• Compound Heterozygote of Point Mutation and Chromosomal Microdeletion Involving OTUD6B Coinciding with ZMIZ1 Variant in Syndromic Intellectual Disability. (PMID:34680978)
• Deubiquitylase OTUD6B stabilizes the mutated pVHL and suppresses cell migration in clear cell renal cell carcinoma. (PMID:35110537)
• Novel biallelic variants affecting the OTU domain of the gene OTUD6B associate with severe intellectual disability syndrome and molecular dynamics simulations. (PMID:35430327)
• The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma. (PMID:36059274)
• MCTS1 enhances the proliferation of laryngeal squamous cell carcinoma via promoting OTUD6B-1 mediated LIN28B deubiquitination. (PMID:37634410)
• Human OTUD6B positively regulates type I IFN antiviral innate immune responses by deubiquitinating and stabilizing IRF3. (PMID:37650650)
• Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1alpha signaling pathway. (PMID:38878112)
• The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1. (PMID:38880876)
• OTUD6B promotes cholangiocarcinoma growth by regulating STAT3 phosphorylation through deubiquitination of PTK2. (PMID:39192576)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	otud6b	ENSDARG00000102705
mus_musculus	Otud6b	ENSMUSG00000040550
rattus_norvegicus	Otud6b	ENSRNOG00000006636
drosophila_melanogaster	otu	FBGN0003023
drosophila_melanogaster	CG7857	FBGN0026738
drosophila_melanogaster	CG3251	FBGN0031622
caenorhabditis_elegans		WBGENE00009007

Paralogs (5): OTUD5 (ENSG00000068308), OTUD4 (ENSG00000164164), OTUD1 (ENSG00000165312), OTUD3 (ENSG00000169914), OTUD6A (ENSG00000189401)

Protein

Protein identifiers

Deubiquitinase OTUD6B — Q8N6M0 (reviewed: Q8N6M0)

Alternative names: DUBA-5, OTU domain-containing protein 6B

All UniProt accessions (3): Q8N6M0, A0A087X0W9, A0A0C4DH76

UniProt curated annotations — full annotation on UniProt →

Function. Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1. May associate with the protein synthesis initiation complex and modify its ubiquitination to repress translation. May also repress DNA synthesis and modify different cellular targets thereby regulating cell growth and proliferation. May also play a role in proteasome assembly and function. Stimulates protein synthesis. Influences the expression of CCND1/cyclin D1 by promoting its translation and regulates MYC/c-Myc protein stability.

Subunit / interactions. Interacts with the eukaryotic translation initiation factor 4F complex.

Disease relevance. Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (IDDFSDA) [MIM:617452] An autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early-onset seizures, intellectual disability, and dysmorphic features. Additional features include microcephaly, absent speech, hypotonia, feeding difficulties, structural brain abnormalities, congenital malformations including congenital heart disease, and musculoskeletal features. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N6M0-1	1, OTUD6B-1	yes
Q8N6M0-2	2, OTUD6B-2

RefSeq proteins (3): NP_001273674, NP_001402951, NP_057107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003323	OTU_dom	Domain
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR049772	OTU_OTUD6	Domain
IPR050704	Peptidase_C85-like	Family

Pfam: PF02338

UniProt features (15 total): sequence variant 3, region of interest 3, active site 3, chain 1, domain 1, mutagenesis site 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6M0-F1	85.27	0.61

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 (3): 155; 158 (nucleophile); 277

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (1):

Position	Phenotype
158	abolishes the deubiquitinating enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): GCM_GSPT1, GOBP_PROTEASOME_ASSEMBLY, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_REMOVAL, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GARY_CD5_TARGETS_DN, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GCM_NF2, GOBP_POSITIVE_REGULATION_OF_TRANSLATION

GO Biological Process (6): proteolysis (GO:0006508), cell population proliferation (GO:0008283), protein deubiquitination (GO:0016579), negative regulation of translation (GO:0017148), proteasome assembly (GO:0043248), positive regulation of translation (GO:0045727)

GO Molecular Function (5): cysteine-type deubiquitinase activity (GO:0004843), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (1): eukaryotic translation initiation factor 4F complex (GO:0016281)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translation	2
regulation of translation	2
protein metabolic process	1
cellular process	1
cysteine-type deubiquitinase activity	1
protein modification by small protein removal	1
negative regulation of gene expression	1
negative regulation of protein metabolic process	1
protein-containing complex assembly	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
cysteine-type peptidase activity	1
deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
cytoplasm	1
RNA cap binding complex	1

Protein interactions and networks

STRING

1198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OTUD6B	ZUP1	Q96AP4	916
OTUD6B	OTUD5	Q96G74	650
OTUD6B	YOD1	Q5VVQ6	643
OTUD6B	OTUD7A	Q8TE49	630
OTUD6B	OTUD4	Q01804	613
OTUD6B	VCPIP1	Q96JH7	609
OTUD6B	OTUB1	Q96FW1	603
OTUD6B	OTUD7B	Q6GQQ9	598
OTUD6B	OTUD1	Q5VV17	586
OTUD6B	OTUB2	Q96DC9	577
OTUD6B	USP7	Q93009	541
OTUD6B	USP5	P45974	535
OTUD6B	USP36	Q9P275	504
OTUD6B	USP8	P40818	500
OTUD6B	COPS5	Q92905	500

IntAct

19 interactions, top by confidence:

A	B	Type	Score
OTUD6B	BTBD1	psi-mi:“MI:0915”(physical association)	0.620
OTUD6B	OTUB1	psi-mi:“MI:0915”(physical association)	0.540
OTUD6B	OTUB1	psi-mi:“MI:0407”(direct interaction)	0.540
OTUD6B	H3-4	psi-mi:“MI:0915”(physical association)	0.400
OTUD6B	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
Pip4k2c	LAMA5	psi-mi:“MI:0914”(association)	0.350
Oxnad1	KPNA6	psi-mi:“MI:0914”(association)	0.350
Ttll12	TPM1	psi-mi:“MI:0914”(association)	0.350
Rmdn3	DERL1	psi-mi:“MI:0914”(association)	0.350
AKAP5	MRPL43	psi-mi:“MI:0914”(association)	0.350
Kif13b	TCF3	psi-mi:“MI:0914”(association)	0.350
Syce2	DNAJA2	psi-mi:“MI:0914”(association)	0.350
OTUD6B	GALC	psi-mi:“MI:0914”(association)	0.350
OTUD6B		psi-mi:“MI:0914”(association)	0.350
OTUD6B	SULT1A3	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (162): METAP2 (Affinity Capture-MS), LIMCH1 (Affinity Capture-MS), GALC (Affinity Capture-MS), BTBD1 (Affinity Capture-MS), AP2M1 (Co-fractionation), APEX1 (Co-fractionation), BASP1 (Co-fractionation), CHD3 (Co-fractionation), HDDC2 (Co-fractionation), MCTS1 (Co-fractionation), OTUB1 (Co-fractionation), PTK2 (Co-fractionation), OTUD6B (Affinity Capture-MS), OTUD6B (Affinity Capture-MS), OTUD6B (Affinity Capture-MS)

ESM2 similar proteins: A0A3L6DPG1, A1A4I9, A9UMG5, O00233, O60870, O94874, P27612, P45974, P54731, P56399, Q05B57, Q0IH43, Q0JL44, Q2T9S3, Q32Q05, Q4R367, Q567B1, Q5GFD9, Q5M8G6, Q5M8L0, Q5R407, Q5VVQ6, Q5ZIN1, Q5ZIP6, Q642J4, Q642Q1, Q6GM06, Q6GM65, Q6IE21, Q7L8S5, Q7ZV00, Q7ZY60, Q86U44, Q8C3P7, Q8CB27, Q8CCJ3, Q8K2H2, Q8K339, Q8N6M0, Q8VZM1

Diamond homologs: P38747, Q5ZIP6, Q6GM06, Q6IE21, Q7L8S5, Q8K2H2, Q8N6M0, Q9UUK3, Q5M8L0, Q7ZV00, Q9LYC7, F4K3M6, Q8LBZ4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	OTUD6B	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	6
Uncertain significance	59
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (17)

Variant ID	HGVS	Classification
1029424	NM_016023.5(OTUD6B):c.631G>T (p.Glu211Ter)	Pathogenic
1072997	NM_016023.5(OTUD6B):c.521dup (p.Thr175fs)	Pathogenic
2627380	NM_016023.5(OTUD6B):c.381_388del (p.Leu127fs)	Pathogenic
3341105	NM_016023.5(OTUD6B):c.83-1del	Pathogenic
3342804	NM_016023.5(OTUD6B):c.776C>G (p.Ser259Ter)	Pathogenic
375701	NM_016023.5(OTUD6B):c.343C>T (p.Arg115Ter)	Pathogenic
375702	NM_016023.5(OTUD6B):c.379_383del (p.Leu127fs)	Pathogenic
375703	NM_016023.5(OTUD6B):c.83-2A>G	Pathogenic
4687388	NM_016023.5(OTUD6B):c.287del (p.Pro96fs)	Pathogenic
488709	NM_016023.5(OTUD6B):c.797+1G>A	Pathogenic
967815	NM_016023.5(OTUD6B):c.189_190del (p.His63fs)	Pathogenic
1216417	NM_016023.5(OTUD6B):c.205C>T (p.Gln69Ter)	Likely pathogenic
1324839	NM_016023.5(OTUD6B):c.481A>T (p.Lys161Ter)	Likely pathogenic
1335813	NM_016023.5(OTUD6B):c.731T>G (p.Ile244Arg)	Likely pathogenic
1810274	NM_016023.5(OTUD6B):c.401A>G (p.Glu134Gly)	Likely pathogenic
375704	NM_016023.5(OTUD6B):c.557A>G (p.Tyr186Cys)	Likely pathogenic
559925	NM_016023.5(OTUD6B):c.686T>C (p.Leu229Pro)	Likely pathogenic

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
8:91070466:GGTGA:G	donor_loss	1.0000
8:91070467:G:GA	donor_loss	1.0000
8:91070468:T:G	donor_loss	1.0000
8:91070479:G:GT	donor_gain	1.0000
8:91071136:A:AG	acceptor_gain	1.0000
8:91071137:G:GA	acceptor_gain	1.0000
8:91071137:GC:G	acceptor_gain	1.0000
8:91071137:GCC:G	acceptor_gain	1.0000
8:91071137:GCCA:G	acceptor_gain	1.0000
8:91071137:GCCAA:G	acceptor_gain	1.0000
8:91071281:GAGAA:G	donor_gain	1.0000
8:91071285:ATAAG:A	donor_gain	1.0000
8:91071286:TAAG:T	donor_gain	1.0000
8:91071287:AAG:A	donor_gain	1.0000
8:91071288:AG:A	donor_gain	1.0000
8:91071289:GG:G	donor_gain	1.0000
8:91071290:G:GG	donor_gain	1.0000
8:91073146:GCCT:G	donor_gain	1.0000
8:91073941:G:GG	donor_gain	1.0000
8:91078351:CTTA:C	acceptor_loss	1.0000
8:91078352:TTA:T	acceptor_loss	1.0000
8:91078353:TA:T	acceptor_loss	1.0000
8:91078354:A:AC	acceptor_loss	1.0000
8:91078354:A:AG	acceptor_gain	1.0000
8:91078354:AG:A	acceptor_gain	1.0000
8:91078355:G:GT	acceptor_gain	1.0000
8:91078355:GG:G	acceptor_gain	1.0000
8:91078355:GGA:G	acceptor_gain	1.0000
8:91078355:GGAA:G	acceptor_gain	1.0000
8:91078355:GGAAA:G	acceptor_gain	1.0000

AlphaMissense

1933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:91080713:T:A	W225R	0.999
8:91080713:T:C	W225R	0.999
8:91073908:A:C	R104S	0.998
8:91073908:A:T	R104S	0.998
8:91080715:G:C	W225C	0.998
8:91080715:G:T	W225C	0.998
8:91073910:G:C	R105P	0.997
8:91078404:G:C	A122P	0.997
8:91078512:T:C	C158R	0.997
8:91078514:T:G	C158W	0.997
8:91078579:G:C	R180T	0.997
8:91078629:T:C	F197L	0.997
8:91078631:T:A	F197L	0.997
8:91078631:T:G	F197L	0.997
8:91071165:T:A	V37D	0.996
8:91078513:G:A	C158Y	0.996
8:91078524:G:C	A162P	0.996
8:91078580:A:C	R180S	0.996
8:91078580:A:T	R180S	0.996
8:91084015:C:A	A233D	0.996
8:91084817:T:A	H277Q	0.996
8:91084817:T:G	H277Q	0.996
8:91073907:G:C	R104T	0.995
8:91078384:G:C	R115P	0.995
8:91078393:G:C	R118P	0.995
8:91078507:G:A	G156D	0.995
8:91080717:G:A	G226E	0.995
8:91084810:G:A	G275E	0.994
8:91084815:C:G	H277D	0.994
8:91071190:G:C	R45S	0.993

dbSNP variants (sampled 300 via entrez): RS1000181339 (8:91072140 G>A), RS1000250368 (8:91081103 C>G), RS1000411720 (8:91074781 T>C), RS1000689138 (8:91082876 T>A), RS1000747520 (8:91076093 A>G), RS1000803987 (8:91074482 G>A), RS1000839286 (8:91069685 C>G), RS1000843440 (8:91069765 G>A), RS1000897296 (8:91070058 C>A,G,T), RS1001158571 (8:91076283 A>G), RS1001180079 (8:91070924 C>G,T), RS1001197805 (8:91071066 C>G), RS1001232461 (8:91071364 C>A,G,T), RS1001250906 (8:91081674 G>A,C), RS1001305353 (8:91082021 TC>T)

Disease associations

OMIM: gene MIM:612021 | disease phenotypes: MIM:617452

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AR

Mondo (3): intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (MONDO:0044319), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027)

Orphanet (2): Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome (Orphanet:505237), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000278	Retrognathia
HP:0000343	Long philtrum
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000527	Long eyelashes
HP:0000637	Long palpebral fissure
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000960	Sacral dimple
HP:0001166	Arachnodactyly
HP:0001182	Tapered finger
HP:0001187	Hyperextensibility of the finger joints
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630843 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
clothianidin	increases expression	1
MT19c compound	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Endosulfan	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Thimerosal	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4606000	Binding	Inhibition of human GST-tagged OTUD6B expressed in Escherichia coli assessed as cleavage of Ubiquitin-Rhodamine110-glycine to Ubiquitin and Rhodamine110-glycine using Ubiquitin-Rhodamine110-glycine as substrate by fluorescence based analysi	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_TB77	HAP1 OTUD6B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

197 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
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
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
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)
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
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders