ACTL6B

Summary

ACTL6B (actin like 6B, HGNC:160) is a protein-coding gene on chromosome 7q22.1, encoding Actin-like protein 6B (O94805). Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).

The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene encodes a subunit of the BAF (BRG1/brm-associated factor) complex in mammals, which is functionally related to SWI/SNF complex in S. cerevisiae and Drosophila; the latter is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. This subunit may be involved in the regulation of genes by structural modulation of their chromatin, specifically in the brain. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51412 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 76 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 210 total — 16 pathogenic, 37 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈14% of expected missense variation)
• GTEx eGene: eQTL in 4 tissues, sQTL in 1 (q < 0.05)
• Phenotypes (HPO): 79
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.95 (unconstrained)
• MANE Select transcript: NM_016188
• Interaction hub: 2,281 STRING partners (top 5% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:160
Approved symbol	ACTL6B
Name	actin like 6B
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	BAF53B, SMARCN2
Ensembl gene	ENSG00000077080
Ensembl biotype	protein_coding
OMIM	612458
Entrez	51412

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

MANE Select: ENST00000160382

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1, TSL 3: 2, TSL 5: 2

ENST00000160382, ENST00000461605, ENST00000485601, ENST00000487125, ENST00000487225, ENST00000489904, ENST00000863236, ENST00000970941, ENST00000970942, ENST00001049638, ENST00001049639, ENST00001093852, ENST00001134679

RefSeq mRNA: 1 — MANE Select: NM_016188 NM_016188

CCDS: CCDS5702

Canonical transcript exons

ENST00000160382 — 14 exons

Exon	Start	End
ENSE00000710648	100647444	100647533
ENSE00000710650	100646971	100647085
ENSE00000824953	100643097	100643326
ENSE00000824961	100648556	100648662
ENSE00001144224	100656330	100656448
ENSE00003470495	100655019	100655119
ENSE00003518444	100655421	100655586
ENSE00003519476	100646249	100646335
ENSE00003521030	100655803	100655879
ENSE00003555416	100646751	100646831
ENSE00003560645	100647223	100647284
ENSE00003577485	100648729	100648823
ENSE00003593746	100650038	100650135
ENSE00003638480	100646551	100646646

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 97.63.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7016 / max 181.6552, expressed in 195 samples.

Highest expression (Bgee): cortical plate, hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACTL6B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 4 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	3.3e-02	+0.24	7:100625434:G:GTC
Brain Putamen basal ganglia	eqtl	3.4e-02	+0.31	7:99968384:G:A
Brain Cerebellum	sqtl	3.5e-02	-0.81	7:100789278:T:C
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-02	+0.10	7:101289194:A:C
Brain Caudate basal ganglia	eqtl	3.8e-02	+0.24	7:100779233:G:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
85237	2.7016	195

Top tissues by expression

showing 100 of 278 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.63	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.29	gold quality
cerebellar hemisphere	UBERON:0002245	97.15	gold quality
cerebellar cortex	UBERON:0002129	97.06	gold quality
cerebellum	UBERON:0002037	95.97	gold quality
right frontal lobe	UBERON:0002810	94.55	gold quality
ganglionic eminence	UBERON:0004023	94.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.33	gold quality
prefrontal cortex	UBERON:0000451	93.10	gold quality
nucleus accumbens	UBERON:0001882	92.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.11	gold quality
frontal cortex	UBERON:0001870	91.72	gold quality
frontal lobe	UBERON:0016525	91.72	gold quality
neocortex	UBERON:0001950	91.39	gold quality
cingulate cortex	UBERON:0003027	91.26	gold quality
anterior cingulate cortex	UBERON:0009835	91.16	gold quality
putamen	UBERON:0001874	90.45	gold quality
diaphragm	UBERON:0001103	90.17	gold quality
cerebral cortex	UBERON:0000956	89.98	gold quality
caudate nucleus	UBERON:0001873	89.90	gold quality
telencephalon	UBERON:0001893	89.32	gold quality
brain	UBERON:0000955	89.18	gold quality
forebrain	UBERON:0001890	88.96	gold quality
pituitary gland	UBERON:0000007	88.85	gold quality
central nervous system	UBERON:0001017	88.55	gold quality
primary visual cortex	UBERON:0002436	88.13	gold quality
middle temporal gyrus	UBERON:0002771	87.81	gold quality
orbitofrontal cortex	UBERON:0004167	87.59	gold quality
adenohypophysis	UBERON:0002196	87.38	gold quality
amygdala	UBERON:0001876	87.29	gold quality
frontal pole	UBERON:0002795	87.22	gold quality
CA1 field of hippocampus	UBERON:0003881	87.04	gold quality
occipital lobe	UBERON:0002021	86.61	gold quality
superior frontal gyrus	UBERON:0002661	86.12	gold quality
hypothalamus	UBERON:0001898	85.93	gold quality
paraflocculus	UBERON:0005351	85.92	gold quality
temporal lobe	UBERON:0001871	85.88	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.50	gold quality
Ammon’s horn	UBERON:0001954	85.26	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.15	gold quality
pons	UBERON:0000988	83.78	gold quality
entorhinal cortex	UBERON:0002728	83.64	gold quality
parietal lobe	UBERON:0001872	83.60	gold quality
postcentral gyrus	UBERON:0002581	83.57	gold quality
cerebellar vermis	UBERON:0004720	83.22	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.77	gold quality
lateral globus pallidus	UBERON:0002476	82.13	gold quality
embryo	UBERON:0000922	81.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	81.55	gold quality
islet of Langerhans	UBERON:0000006	81.50	gold quality
middle frontal gyrus	UBERON:0002702	81.30	silver quality
substantia nigra pars compacta	UBERON:0001965	81.28	gold quality
vastus lateralis	UBERON:0001379	80.51	gold quality
ventral tegmental area	UBERON:0002691	80.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.97	gold quality
midbrain	UBERON:0001891	79.25	gold quality
substantia nigra	UBERON:0002038	79.22	gold quality
triceps brachii	UBERON:0001509	79.13	gold quality
gluteal muscle	UBERON:0002000	79.07	gold quality
quadriceps femoris	UBERON:0001377	78.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.93	gold quality
substantia nigra pars reticulata	UBERON:0001966	77.67	gold quality
superior vestibular nucleus	UBERON:0007227	77.33	gold quality
olfactory bulb	UBERON:0002264	76.72	gold quality
type B pancreatic cell	CL:0000169	76.51	gold quality
endothelial cell	CL:0000115	76.28	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.23	gold quality
dorsal plus ventral thalamus	UBERON:0001897	75.25	silver quality
ventricular zone	UBERON:0003053	74.98	gold quality
tongue squamous epithelium	UBERON:0006919	73.81	gold quality
medulla oblongata	UBERON:0001896	73.80	silver quality
cervix squamous epithelium	UBERON:0006922	73.33	gold quality
dorsal root ganglion	UBERON:0000044	72.89	gold quality
vena cava	UBERON:0004087	72.28	gold quality
body of tongue	UBERON:0011876	71.77	gold quality
inferior vagus X ganglion	UBERON:0005363	71.25	silver quality
biceps brachii	UBERON:0001507	70.94	gold quality
heart right ventricle	UBERON:0002080	70.52	gold quality
tongue	UBERON:0001723	69.67	gold quality
spinal cord	UBERON:0002240	69.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	69.30	gold quality
trigeminal ganglion	UBERON:0001675	69.24	silver quality
pharyngeal mucosa	UBERON:0000355	68.86	gold quality
nasal cavity epithelium	UBERON:0005384	68.56	gold quality
upper arm skin	UBERON:0004263	68.08	gold quality
adult organism	UBERON:0007023	67.44	gold quality
gingival epithelium	UBERON:0001949	67.37	gold quality
cardia of stomach	UBERON:0001162	67.08	gold quality
pericardium	UBERON:0002407	67.08	gold quality
oocyte	CL:0000023	66.84	gold quality
myocardium	UBERON:0002349	66.55	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	66.46	silver quality
thymus	UBERON:0002370	66.30	gold quality
globus pallidus	UBERON:0001875	66.08	silver quality
superior surface of tongue	UBERON:0007371	66.04	gold quality
gingiva	UBERON:0001828	66.03	gold quality
squamous epithelium	UBERON:0006914	65.95	gold quality
inferior olivary complex	UBERON:0002127	65.87	gold quality
cervix epithelium	UBERON:0004801	65.18	gold quality
skeletal muscle tissue	UBERON:0001134	65.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	12.27
E-ANND-3	no	1.46

HPA expression

RNA tissue specificity: Group enriched

39 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Basal ganglia	tissue	87.9
Caudate putamen	tissue	87.9
Amygdala	tissue	86.2
Ventral forebrain	tissue	85.9
Hippocampal formation	tissue	81.0
Cerebral cortex	tissue	75.9
Frontal cortex	tissue	75.9
Occipital cortex	tissue	75.5
Entorhinal cortex	tissue	75.0
Olfactory bulb	tissue	74.7
Retrosplenial and cingulate cortex	tissue	73.5
Somatosensory cortex	tissue	71.8
Cerebellum	tissue	58.7
Postcentral gyrus	tissue	56.7
Septum	tissue	54.6
Corpus callosum	tissue	47.3
Midbrain	tissue	44.3
Hypothalamus	tissue	40.2
Thalamus	tissue	36.4
Pons	tissue	33.9
Nucleus accumbens	tissue	29.5
Retrosplenial cortex	tissue	29.3
Putamen	tissue	28.5
Hippocampus	tissue	24.5
Locus coeruleus	tissue	20.8
Medulla oblongata	tissue	18.7
Pituitary gland	tissue	14.6
Spinal cord	tissue	14.4
Substantia nigra	tissue	10.9
Retina	tissue	4.0
Adrenal gland	tissue	1.7
Choroid plexus	tissue	1.0
Pancreas	tissue	0.7
Stomach 1	tissue	0.5
Testis	tissue	0.4
Parathyroid gland	tissue	0.1
Colon	tissue	0.1
Small intestine	tissue	0.1
Duodenum	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 184; highest nTPM — Precentral gyrus (48.0), White matter (47.3), Postcentral gyrus, middle (43.9), Frontal eye field (43.4), Perirhinal gyrus (43.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ACTL6B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

18 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4475	97.36	66.95	761
HSA-MIR-6835-5P	95.81	64.27	500

Functional genomics

gnomAD constraint: pLI 9.62e-13, LOEUF 0.954, missense Z 3.37 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000160382 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈14% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:100,643,249–100,646,772	76 / 126.1	0.60	no
7:100,646,773–100,647,080	24 / 81.4	0.29	yes (p 2.0e-10)
7:100,647,081–100,656,354	250 / 364.7	0.69	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 7)

• Data suggest that SWI/SNF complexes containing ArpN alpha might regulate certain genes involved in brain development and/or its function differently from SWI/SNF complexes containing ArpN beta/BAF53. (PMID:12565893)
• we identified BAF53b as a neuron-specific subunit of the chromatin remodeling BAF complexes. (PMID:26077106)
• Missense Mutation in ACTL6B gene is associated with Neurodevelopmental Disorders. (PMID:28867141)
• provide additional genetic and clinical data on three new cases that support the pathogenic role of ACTL6B gene mutation in a syndromic form of Developmental and epileptic encephalopathies. (PMID:30656450)
• Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Neurons. (PMID:31031012)
• ACTL6B loss is thus an important cause of recessive ASD, with impaired neuron-specific chromatin repression indicated as a potential mechanism. (PMID:32312822)
• An epilepsy-associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model. (PMID:33141462)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	actl6b	ENSDARG00000034107
mus_musculus	Actl6b	ENSMUSG00000029712
rattus_norvegicus	Actl6b	ENSRNOG00000001408

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1933548) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	2
abnormal myelination	1
female infertility	1
abnormal auditory brainstem response	1
decreased CNS synapse formation	1
abnormal dendrite morphology	1
postnatal lethality, incomplete penetrance	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryza sativa Indica Group	A2YR10	100.0%	Diamond
Bos taurus	A4FUX8	100.0%	Diamond
Oryza sativa Japonica Group	Q6ZJW9	100.0%	Diamond
Macaca fascicularis	Q4R333	99.8%	Diamond
Aspergillus fumigatus Af293	Q4WHA3	87.3%	Diamond
Aspergillus nidulans FGSC A4	Q5AW89	87.3%	Diamond
Fusarium graminearum PH-1	Q4IPI4	72.4%	Diamond
Neurospora crassa OR74A	Q7SHR0	72.3%	Diamond
Arabidopsis thaliana	Q84M92	68.5%	Diamond
Schizosaccharomyces pombe 972h-	Q09849	55.9%	Diamond
Dictyostelium discoideum	Q54KZ7	42.6%	Diamond
Yarrowia lipolytica CLIB122	Q6C061	37.9%	Diamond
Mycosarcoma maydis	Q4P2E8	34.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
GNB2	protein-coding	2783
GIGYF1	protein-coding	64599
TFR2	protein-coding	7036
PCOLCE-AS1	ncRNA	100129845
PCOLCE	protein-coding	5118
MOSPD3	protein-coding	64598
FBXO24	protein-coding	26261
POP7	protein-coding	10248

Protein

Protein identifiers

Actin-like protein 6B — O94805 (reviewed: O94805)

Alternative names: 53 kDa BRG1-associated factor B, Actin-related protein Baf53b, ArpNalpha, BRG1-associated factor 53B

All UniProt accessions (2): C9JQT4, O94805

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex), as such plays a role in remodeling mononucleosomes in an ATP-dependent fashion, and is required for postmitotic neural development and dendritic outgrowth. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. ACTL6B/BAF53B is not essential for assembly of the nBAF complex but is required for targeting the complex and CREST to the promoter of genes essential for dendritic growth. Essential for neuronal maturation and dendrite development.

Subunit / interactions. Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170 and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific. Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1 and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A or SMARCD2/BAF60B or SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (ACTB). Note that the nBAF complex is polymorphic in regard to the ATPase, SMARCA2 and SMARCA4 occupying mutually exclusive positions. May be a component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin.

Subcellular location. Nucleus.

Disease relevance. Developmental and epileptic encephalopathy 76 (DEE76) [MIM:618468] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE76 is an autosomal recessive form that may result in death in childhood. The disease is caused by variants affecting the gene represented in this entry. Intellectual developmental disorder with severe speech and ambulation defects (IDDSSAD) [MIM:618470] An autosomal dominant neurodevelopmental disorder with onset in infancy, and characterized by global developmental delay, intellectual disability, ambulation deficits, severe language impairment, and minor dysmorphic features including a wide mouth, diastema, and bulbous nose. Additional manifestations are spasticity, hypotonia and autistic features including stereotypies. Brain imaging show thin corpus callosum, generalized atrophy, and mild periventricular gliosis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the actin family.

RefSeq proteins (1): NP_057272* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

UniProt features (17 total): sequence variant 15, chain 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94805-F1	91.52	0.88

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Epilepsy, Mental and behavioural disorders

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli rim; mitotic chromosome

Antibody reliability (HPA): IH uncertain · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-3214858	RMTs methylate histone arginines	curated
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	curated
R-HSA-9932444	ATP-dependent chromatin remodelers	—
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9932451	SWI/SNF chromatin remodelers	—
R-HSA-8878171	Transcriptional regulation by RUNX1	—

MSigDB gene sets: 369 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_NEURON_MATURATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, GOBP_NEUROGENESIS, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, AP2_Q3, DARWICHE_PAPILLOMA_PROGRESSION_RISK

GO Biological Process (20): chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), positive regulation of cell population proliferation (GO:0008284), dendrite development (GO:0016358), regulation of mitotic metaphase/anaphase transition (GO:0030071), neuron maturation (GO:0042551), positive regulation of T cell differentiation (GO:0045582), negative regulation of cell differentiation (GO:0045596), positive regulation of cell differentiation (GO:0045597), positive regulation of myoblast differentiation (GO:0045663), regulation of G0 to G1 transition (GO:0070316), positive regulation of stem cell population maintenance (GO:1902459), regulation of G1/S transition of mitotic cell cycle (GO:2000045), positive regulation of double-strand break repair (GO:2000781), regulation of nucleotide-excision repair (GO:2000819), cytoskeleton organization (GO:0007010), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), structural constituent of cytoskeleton (GO:0005200)

GO Cellular Component (7): kinetochore (GO:0000776), chromatin (GO:0000785), nucleus (GO:0005634), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), NuA4 histone acetyltransferase complex (GO:0035267), nBAF complex (GO:0071565)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Chromatin organization	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
SWI/SNF chromatin remodelers	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
ATP-dependent chromatin remodelers	1

GO top-level categories

60 GO namespaces:

Category	Terms
regulation of DNA-templated transcription	2
positive regulation of cellular process	2
regulation of mitotic cell cycle phase transition	2
cell differentiation	2
regulation of cell differentiation	2
positive regulation of developmental process	2
cellular anatomical structure	2
SWI/SNF superfamily-type complex	2
cellular component organization	1
chromatin organization	1
gene expression	1
RNA biosynthetic process	1
transcription by RNA polymerase II	1
system development	1
animal gross anatomical part developmental process	1
cell population proliferation	1
regulation of cell population proliferation	1
neuron projection development	1
anatomical structure development	1
metaphase/anaphase transition of mitotic cell cycle	1
regulation of metaphase/anaphase transition of cell cycle	1
cell maturation	1
neuron development	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1
negative regulation of cellular process	1
negative regulation of developmental process	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
regulation of cell cycle process	1
G0 to G1 transition	1
stem cell population maintenance	1
positive regulation of multicellular organismal process	1
regulation of stem cell population maintenance	1
G1/S transition of mitotic cell cycle	1
regulation of cell cycle G1/S phase transition	1
double-strand break repair	1
positive regulation of DNA repair	1
regulation of double-strand break repair	1
regulation of DNA repair	1
nucleotide-excision repair	1
organelle organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
structural molecule activity	1
cytoskeleton	1
cytoskeleton organization	1
condensed chromosome, centromeric region	1
intracellular membraneless organelle	1
supramolecular complex	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
H4/H2A histone acetyltransferase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
chromatin remodeling	BP	direct assay
dendrite development	BP	mutant phenotype
neuron maturation	BP	mutant phenotype
SWI/SNF complex	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,281 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTL6B	PHF10	Q8WUB8	945
ACTL6B	DPF1	Q92782	942
ACTL6B	BANF1	O75531	903
ACTL6B	SMARCA4	P51532	758
ACTL6B	SMARCC2	Q8TAQ2	686
ACTL6B	SMARCE1	Q969G3	681
ACTL6B	SMARCC1	Q92922	667
ACTL6B	DPF3	Q92784	658
ACTL6B	SMARCD3	Q6STE5	644
ACTL6B	SMARCD1	Q96GM5	644
ACTL6B	SS18L1	O75177	607
ACTL6B	SMARCB1	Q12824	600
ACTL6B	SMARCD2	Q92925	584
ACTL6B	ARID2	Q68CP9	578
ACTL6B	DPF2	Q92785	574

IntAct

Human interaction partners of ACTL6B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

25 partners by confidence:

Partner	Interaction type	MIscore	Records
SLC35A5	association	0.530	2
YEATS4	association	0.530	1
CHRNG	physical association	0.400	1
RIT1	physical association	0.400	1
SMARCA2	physical association	0.400	1
STAG3L1	physical association	0.400	1
ANXA7	physical association	0.370	1
ATM	physical association	0.370	1
CDKN1A	physical association	0.370	1
CSNK2B	physical association	0.370	1
GSK3B	physical association	0.370	1
PLK1	physical association	0.370	1
SMN1	physical association	0.370	1
TK1	physical association	0.370	1
CR1L	association	0.350	1
FRMD5	association	0.350	1
GBP3	association	0.350	1
HSPA8	association	0.350	1
INO80	association	0.350	1
PLEKHA3	association	0.350	1
RECQL4	association	0.350	1
SELENON	association	0.350	1
SLC25A16	association	0.350	1
SLC38A7	association	0.350	1
COQ9	physical association	0.000	1

BioGRID (106 interactions; top human partners by supporting records): SMARCD1 (Affinity Capture-MS; 4 records), CTBP1 (Phenotypic Enhancement; 3 records), DPF2 (Affinity Capture-MS; 3 records), DPF3 (Affinity Capture-MS; 3 records), HIST1H2BA (Affinity Capture-MS; 3 records), SS18 (Affinity Capture-MS; 3 records), YEATS4 (Affinity Capture-MS; 3 records), BCL7A (Affinity Capture-MS; 2 records), BCL7C (Affinity Capture-MS; 2 records), CHRNG (Affinity Capture-MS; 2 records), RUVBL1 (Affinity Capture-MS; 2 records), RUVBL2 (Affinity Capture-MS; 2 records), SLC35A5 (Affinity Capture-MS; 2 records), SMARCA2 (Affinity Capture-Western; 2 records), SMARCB1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
“MYOD1/SWI/SNF complex”	“up-regulates quantity by expression”	ACTL6B	“transcriptional regulation”
ACTL6B	“form complex”	“SWI/SNF ACTL6B varian”	binding
ACTL6B	“form complex”	“Muscle cell-specific SWI/SNF SMARCA4 variant”	binding
ACTL6B	“form complex”	“Brain-specific SWI/SNF SMARCA2 variant”	binding
ACTL6B	“form complex”	“Brain-specific SWI/SNF SMARCA4 variant”	binding

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
BAF complex	13	ARID1A, ARID1B, SMARCA4, SMARCC1, SMARCE1, ACTL6A, ACTL6B, SMARCA2, SMARCB1, SMARCC2, SMARCD1, ACTB, ACTG1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell cycle	5	15.5×	4e-03

Disease & clinical

Genetic variants

Variant evidence for ACTL6B: 210 ClinVar records (53 pathogenic / likely pathogenic); 13 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	37
Uncertain significance	102
Likely benign	44
Benign	1

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 53 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
635101	NM_016188.5(ACTL6B):c.1045G>A (p.Gly349Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
692137	NM_016188.5(ACTL6B):c.289C>T (p.Arg97Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
692142	NM_016188.5(ACTL6B):c.740G>A (p.Trp247Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	4
2500131	NM_016188.5(ACTL6B):c.832C>T (p.Gln278Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
635099	NM_016188.5(ACTL6B):c.999T>A (p.Cys333Ter)	Pathogenic	criteria provided, single submitter	2
1344717	NM_016188.5(ACTL6B):c.892C>T (p.Arg298Ter)	Pathogenic	criteria provided, single submitter	2
2500135	NM_016188.5(ACTL6B):c.1120C>T (p.Arg374Ter)	Pathogenic	criteria provided, single submitter	2
933910	NM_016188.5(ACTL6B):c.407_410dup (p.Met137fs)	Pathogenic	criteria provided, single submitter	1
3376821	NM_016188.5(ACTL6B):c.604C>T (p.Gln202Ter)	Pathogenic	criteria provided, single submitter	1
3602977	NM_016188.5(ACTL6B):c.1112C>G (p.Pro371Arg)	Pathogenic	criteria provided, single submitter	1
4888039	NM_016188.5(ACTL6B):c.2T>C (p.Met1Thr)	Pathogenic	criteria provided, single submitter	1
402140	NM_016188.5(ACTL6B):c.893G>A (p.Arg298Gln)	Likely pathogenic	criteria provided, single submitter	3
635104	NM_016188.5(ACTL6B):c.724C>T (p.Gln242Ter)	Likely pathogenic	criteria provided, single submitter	3
635105	NM_016188.5(ACTL6B):c.617T>C (p.Leu206Pro)	Likely pathogenic	criteria provided, single submitter	3
635100	NM_016188.5(ACTL6B):c.820C>T (p.Gln274Ter)	Likely pathogenic	criteria provided, single submitter	2

Per-variant reference — Sugi Variant

Explore ACTL6B’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,268):

Position(s)	Effect	Δscore	Sites
7:100646647–100646648	acceptor_loss	1.0000	5
7:100646733	donor_gain	1.0000
7:100647285–100647286	acceptor_loss	1.0000	3
7:100648554–100648555	donor_loss	1.0000	3
7:100648663–100648664	acceptor_loss	1.0000	3
7:100655017–100655018	donor_loss	1.0000	4
7:100646240	donor_gain	0.9900
7:100646648	acceptor_loss	0.9900
7:100646832–100646833	acceptor_loss	0.9900	6
7:100646969–100646970	donor_loss	0.9900	5

AlphaMissense

1,869 missense substitutions predicted likely pathogenic (of 2,797 scored), across 389 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M319	9	0.867	0.996
F403	8	0.997	1.000
D17	8	0.995	0.999
D31	8	0.994	1.000
F138	8	0.993	0.999
D9	8	0.992	0.999
H115	8	0.991	1.000
D334	8	0.991	0.999
D258	8	0.987	0.998
D336	8	0.985	0.999
F306	8	0.984	0.999
F157	8	0.983	1.000
D168	8	0.967	0.989
D307	8	0.966	0.997
D197	8	0.959	0.995
F259	8	0.958	1.000
F198	8	0.954	1.000
D293	8	0.954	0.994
F357	8	0.954	0.998
F147	8	0.946	0.999

HPA cancer prognostics

RNA cancer specificity: Group enriched (Glioblastoma Multiforme, Pancreatic Adenocarcinoma)

Disease associations

OMIM: gene MIM:612458 | disease phenotypes: MIM:618468, MIM:618470, MIM:269700, MIM:209850, MIM:308350

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
developmental and epileptic encephalopathy, 76	Definitive	Autosomal recessive	4
intellectual developmental disorder with severe speech and ambulation defects	Strong	Autosomal dominant	4
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 7 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Early onset or syndromic epilepsy	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (9): autism spectrum disorder (MONDO:0005258), developmental and epileptic encephalopathy, 76 (MONDO:0032768), intellectual developmental disorder with severe speech and ambulation defects (MONDO:0032770), congenital generalized lipodystrophy type 2 (MONDO:0010020), intellectual disability (MONDO:0001071), autism (MONDO:0005260), developmental and epileptic encephalopathy, 1 (MONDO:0010632), undetermined early-onset epileptic encephalopathy (MONDO:0018614), syndromic intellectual disability (MONDO:0000508)

Orphanet (4): Congenital generalized lipodystrophy (Orphanet:528), Congenital generalized lipodystrophy type 2 (Orphanet:696289), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

showing 60 of 79 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000252	Microcephaly
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000348	High forehead
HP:0000414	Bulbous nose
HP:0000494	Downslanted palpebral fissures
HP:0000504	Abnormality of vision
HP:0000508	Ptosis
HP:0000546	Retinal degeneration
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000699	Diastema
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001273	Abnormal corpus callosum morphology
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001315	Diminished deep tendon reflex
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0001558	Decreased fetal movement
HP:0001792	Small nail
HP:0002020	Gastroesophageal reflux
HP:0002059	Cerebral atrophy
HP:0002061	Lower limb spasticity
HP:0002063	Rigidity
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002133	Status epilepticus
HP:0002136	Broad-based gait
HP:0002188	Delayed CNS myelination
HP:0002283	Global brain atrophy
HP:0002317	Unsteady gait
HP:0002376	Developmental regression
HP:0002421	Poor head control
HP:0002509	Limb hypertonia
HP:0002521	Hypsarrhythmia
HP:0002540	Inability to walk
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0004305	Involuntary movements
HP:0004322	Short stature

GWAS associations

13 associations:

Study	Trait	p-value
GCST90002390_688	Mean corpuscular hemoglobin	1e-22
GCST001765_1	Red blood cell traits	2e-20
GCST004008_1	Red blood cell count	3e-16
GCST006011_71	Mean corpuscular volume	4e-15
GCST90002392_560	Mean corpuscular volume	5e-15
GCST004006_22	Mean corpuscular hemoglobin	1e-13
GCST004005_3	Hemoglobin levels	3e-12
GCST005994_3	Hematocrit	1e-10
GCST004003_3	Hematocrit	6e-9
GCST004003_12	Hematocrit	1e-8
GCST004004_56	Mean corpuscular volume	1e-8
GCST004005_12	Hemoglobin levels	1e-8
GCST006804_108	Red cell distribution width	1e-8

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
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: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Caffeine	increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Toluene	decreases expression, increases methylation	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7IK	WAe001-A-65	Embryonic stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
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NCT07655115	Phase 3	RECRUITING	Single Dose Double-blind, Placebo-controlled Cross-over (SDDBPCCO) Shiftability Study, Will be Followed by a 10-week Open-label Study With Arbaclofen (4 Weeks of Titration and Then 6 Weeks of Active/Stable Treatment). The Effects of Arbaclofen on Target EEG and ERG Metrics Will be Associated With th
NCT00251303	Phase 2	COMPLETED	Riluzole to Treat Child and Adolescent Obsessive-Compulsive Disorder With or Without Autism Spectrum Disorders
NCT00614198	Phase 2	COMPLETED	ScanBrit Dietary Intervention in Autism
NCT00619190	Phase 2	COMPLETED	Study of Aripiprazole to Treat Children and Adolescents With Autism
NCT00709202	Phase 2	COMPLETED	Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
NCT00846547	Phase 2	COMPLETED	Open-Label Study of the Safety and Tolerability of STX209 in Subjects With Autism Spectrum Disorders
NCT01064973	Phase 2	TERMINATED	An Open Label Extension Study of STX209 in Subjects With Autism Spectrum Disorders
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NCT01205282	Phase 2	COMPLETED	Dose Finding Study of Pioglitazone in Children With Autism Spectrum Disorders (ASD) (PIO)
NCT01248130	Phase 2	TERMINATED	Omega-3 Fatty Acids Monotherapy in Children and Adolescents With Autism Spectrum Disorders
NCT01248728	Phase 2	COMPLETED	Omega-3 Fatty Acids For Treatment Of Young Children With Autism (OMG)
NCT01256060	Phase 2	COMPLETED	Intranasal Oxytocin for the Treatment of Children and Adolescents With ASD (OXY)
NCT01288716	Phase 2	COMPLETED	Study of Arbaclofen for the Treatment of Social Withdrawal in Subjects With Autism Spectrum Disorders
NCT01300923	Phase 2	COMPLETED	Acamprosate in Youth With Fragile X Syndrome
NCT01366859	Phase 2	COMPLETED	Nutritional Intervention in Children With Autism Using Whey Protein (Immunocal): Impact on Core Areas of Behavior
NCT01372449	Phase 2	COMPLETED	A Multi-site Double-blind Placebo-controlled Trial of Memantine Versus Placebo in Children With Autism (MEM)
NCT01395953	Phase 2	WITHDRAWN	Double-blind Trial of Buspirone for the Treatment of Anxiety in Youth With Autism Spectrum Disorders