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): 166 total — 16 pathogenic, 34 likely-pathogenic
• Phenotypes (HPO): 79
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_016188

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: 9 — 5 protein_coding, 4 retained_intron

ENST00000160382, ENST00000461605, ENST00000485601, ENST00000487125, ENST00000487225, ENST00000489904, ENST00000863236, ENST00000970941, ENST00000970942

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85237	2.7016	195

Top tissues by expression

278 total, 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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting ACTL6B, 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-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

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)

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): O94805, C9JQT4

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214858	RMTs methylate histone arginines
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-9934037	Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
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 (19): chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), 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 (11): kinetochore (GO:0000776), chromatin (GO:0000785), nucleus (GO:0005634), nuclear matrix (GO:0016363), SWI/SNF complex (GO:0016514), RSC-type complex (GO:0016586), brahma complex (GO:0035060), NuA4 histone acetyltransferase complex (GO:0035267), nBAF complex (GO:0071565), bBAF complex (GO:0140092), GBAF complex (GO:0140288)

Reactome top-level categories

Rollup of top-7 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
SWI/SNF superfamily-type complex	6
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
cellular component organization	1
chromatin organization	1
transcription by RNA polymerase II	1
system development	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

Protein interactions and networks

STRING

4365 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTL6B	DPF1	Q92782	999
ACTL6B	DPF3	Q92784	989
ACTL6B	PHF10	Q8WUB8	959
ACTL6B	BANF1	O75531	934
ACTL6B	SMARCC2	Q8TAQ2	909
ACTL6B	SMARCE1	Q969G3	908
ACTL6B	SMARCC1	Q92922	895
ACTL6B	SS18L1	O75177	890
ACTL6B	ARID1A	O14497	888
ACTL6B	SMARCB1	Q12824	880
ACTL6B	SMARCA4	P51532	867
ACTL6B	ARID2	Q68CP9	836
ACTL6B	ARID1B	Q8NFD5	819
ACTL6B	SMARCA2	P51531	816
ACTL6B	SMARCD1	Q96GM5	801

IntAct

74 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
SMARCC2	ARID1A	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
SS18	ARID1A	psi-mi:“MI:0914”(association)	0.760
DPF2	ARID1A	psi-mi:“MI:0914”(association)	0.730
PRELID1	TRIAP1	psi-mi:“MI:0914”(association)	0.730
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
BCL7A	ARID1A	psi-mi:“MI:0914”(association)	0.640
BCL7C	ARID1A	psi-mi:“MI:0914”(association)	0.640
LMO3	ZBTB43	psi-mi:“MI:0914”(association)	0.550
SLC35A5	ACTL6B	psi-mi:“MI:0914”(association)	0.530
DPF3	ARID1A	psi-mi:“MI:0914”(association)	0.530
DPF1	ARID1A	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
YEATS4	ACTL6B	psi-mi:“MI:0914”(association)	0.530
SS18L2	ARID1A	psi-mi:“MI:0914”(association)	0.480

BioGRID (104): ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), MED14 (Co-fractionation), ACTL6B (Two-hybrid), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS), ACTL6B (Affinity Capture-MS)

ESM2 similar proteins: A2WNB0, A2XMK6, A2YUL5, A3ANB5, A4FUX8, A4IFE3, F2Z5G5, O94241, O94630, O94805, O96019, O96621, P02583, P32381, P38673, P42025, P45888, P45889, P45890, P45891, P47117, P51775, P53489, P85515, P86173, Q09443, Q09849, Q0IEG8, Q2TA43, Q4R333, Q4R6J9, Q54I79, Q5BL41, Q5NBI2, Q61JZ2, Q6AY16, Q6C982, Q6Z256, Q74ZV8, Q7ZTP2

Diamond homologs: A2BDB0, A2XNS1, A2YR10, A4FUX8, O16808, O18840, O42161, O65315, O65316, O93400, O94805, O96019, P02576, P02578, P04829, P07830, P0DM41, P0DM42, P10981, P10984, P10986, P10987, P17304, P18600, P18603, P20904, P30162, P30163, P41340, P43239, P45885, P45886, P45887, P48975, P49871, P53463, P53464, P53470, P53478, P53485

SIGNOR signaling

5 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the canonical BAF (cBAF) complex	11	139.6×	2e-20
Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)	12	109.6×	2e-20
Formation of the embryonic stem cell BAF (esBAF) complex	8	96.2×	3e-13
Formation of the non-canonical BAF (ncBAF) complex	6	80.6×	2e-09
Formation of the polybromo-BAF (pBAF) complex	6	76.1×	3e-09
Regulation of endogenous retroelements	9	66.3×	3e-13
Regulation of MITF-M-dependent genes involved in pigmentation	12	63.7×	2e-17
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	8	48.1×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
regulation of G0 to G1 transition	11	114.1×	1e-18
regulation of nucleotide-excision repair	11	101.8×	2e-18
regulation of mitotic metaphase/anaphase transition	12	91.5×	1e-18
positive regulation of double-strand break repair	12	63.5×	3e-17
nucleosome disassembly	5	61.7×	7e-07
regulation of G1/S transition of mitotic cell cycle	13	61.3×	2e-18
positive regulation of stem cell population maintenance	8	42.3×	8e-10
positive regulation of T cell differentiation	6	42.0×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	34
Uncertain significance	88
Likely benign	19
Benign	1

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1344715	NM_016188.5(ACTL6B):c.1177G>A (p.Gly393Arg)	Pathogenic
1344716	NM_016188.5(ACTL6B):c.460C>T (p.Leu154Phe)	Pathogenic
1344717	NM_016188.5(ACTL6B):c.892C>T (p.Arg298Ter)	Pathogenic
1344718	NM_016188.5(ACTL6B):c.523A>C (p.Thr175Pro)	Pathogenic
1344719	NM_016188.5(ACTL6B):c.465del (p.Ala156fs)	Pathogenic
1344720	NM_016188.5(ACTL6B):c.1249G>T (p.Gly417Trp)	Pathogenic
2500134	NM_016188.5(ACTL6B):c.1114-1G>A	Pathogenic
2500135	NM_016188.5(ACTL6B):c.1120C>T (p.Arg374Ter)	Pathogenic
2500136	NM_016188.5(ACTL6B):c.1267C>T (p.Arg423Ter)	Pathogenic
2500138	NM_016188.5(ACTL6B):c.279G>A (p.Trp93Ter)	Pathogenic
2500141	NM_016188.5(ACTL6B):c.628del (p.Met210fs)	Pathogenic
3376821	NM_016188.5(ACTL6B):c.604C>T (p.Gln202Ter)	Pathogenic
3602977	NM_016188.5(ACTL6B):c.1112C>G (p.Pro371Arg)	Pathogenic
4293542	NM_016188.5(ACTL6B):c.149del (p.Gly50fs)	Pathogenic
635099	NM_016188.5(ACTL6B):c.999T>A (p.Cys333Ter)	Pathogenic
933910	NM_016188.5(ACTL6B):c.407_410dup (p.Met137fs)	Pathogenic
1177328	NM_016188.5(ACTL6B):c.1260C>A (p.Cys420Ter)	Likely pathogenic
1335956	NM_016188.5(ACTL6B):c.388C>T (p.Arg130Trp)	Likely pathogenic
1679718	NM_016188.5(ACTL6B):c.1225del (p.Ser409fs)	Likely pathogenic
1695200	NM_016188.5(ACTL6B):c.1121G>A (p.Arg374Gln)	Likely pathogenic
1702533	NM_016188.5(ACTL6B):c.554T>C (p.Leu185Pro)	Likely pathogenic
1705593	NM_016188.5(ACTL6B):c.1027G>T (p.Gly343Trp)	Likely pathogenic
1709092	NM_016188.5(ACTL6B):c.375C>A (p.Asn125Lys)	Likely pathogenic
2429721	NM_016188.5(ACTL6B):c.1111C>G (p.Pro371Ala)	Likely pathogenic
2431410	NM_016188.5(ACTL6B):c.369+1G>C	Likely pathogenic
2500130	NM_016188.5(ACTL6B):c.70C>T (p.Arg24Cys)	Likely pathogenic
2500131	NM_016188.5(ACTL6B):c.832C>T (p.Gln278Ter)	Likely pathogenic
2500132	NM_016188.5(ACTL6B):c.880T>G (p.Tyr294Asp)	Likely pathogenic
2500133	NM_016188.5(ACTL6B):c.884G>A (p.Gly295Asp)	Likely pathogenic
2500137	NM_016188.5(ACTL6B):c.85G>A (p.Gly29Arg)	Likely pathogenic

SpliceAI

2333 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100646490:AGT:A	donor_gain	1.0000
7:100646645:CC:C	acceptor_gain	1.0000
7:100646646:CC:C	acceptor_gain	1.0000
7:100646647:C:CC	acceptor_gain	1.0000
7:100646647:C:G	acceptor_loss	1.0000
7:100646733:G:C	donor_gain	1.0000
7:100647218:CTCA:C	donor_gain	1.0000
7:100647221:A:AC	donor_gain	1.0000
7:100647222:C:CT	donor_gain	1.0000
7:100647222:CT:C	donor_gain	1.0000
7:100647222:CTGTT:C	donor_gain	1.0000
7:100647286:T:C	acceptor_loss	1.0000
7:100647448:CA:C	donor_gain	1.0000
7:100648550:CCCCA:C	donor_loss	1.0000
7:100648551:CCCA:C	donor_loss	1.0000
7:100648552:CCACC:C	donor_loss	1.0000
7:100648553:CAC:C	donor_loss	1.0000
7:100648554:AC:A	donor_loss	1.0000
7:100648555:C:G	donor_loss	1.0000
7:100648660:TGC:T	acceptor_gain	1.0000
7:100648661:GCCTA:G	acceptor_loss	1.0000
7:100648663:C:CC	acceptor_gain	1.0000
7:100648664:T:G	acceptor_loss	1.0000
7:100648844:C:CT	acceptor_gain	1.0000
7:100650024:AGT:A	donor_gain	1.0000
7:100650026:T:TA	donor_gain	1.0000
7:100650132:TCCA:T	acceptor_gain	1.0000
7:100650133:CCAC:C	acceptor_gain	1.0000
7:100650134:CA:C	acceptor_gain	1.0000
7:100650136:C:CC	acceptor_gain	1.0000

AlphaMissense

2797 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100643308:A:G	W407R	1.000
7:100643308:A:T	W407R	1.000
7:100643318:G:C	F403L	1.000
7:100643318:G:T	F403L	1.000
7:100643319:A:G	F403S	1.000
7:100643320:A:G	F403L	1.000
7:100643325:C:T	G401D	1.000
7:100643326:C:G	G401R	1.000
7:100646250:A:G	L400P	1.000
7:100646254:A:G	S399P	1.000
7:100646256:G:T	A398D	1.000
7:100646257:C:G	A398P	1.000
7:100646259:A:G	L397P	1.000
7:100646262:A:T	I396N	1.000
7:100646265:G:A	S395F	1.000
7:100646265:G:T	S395Y	1.000
7:100646266:A:G	S395P	1.000
7:100646268:C:T	G394D	1.000
7:100646269:C:G	G394R	1.000
7:100646271:C:A	G393V	1.000
7:100646271:C:T	G393E	1.000
7:100646272:C:A	G393W	1.000
7:100646272:C:G	G393R	1.000
7:100646272:C:T	G393R	1.000
7:100646276:C:A	W391C	1.000
7:100646276:C:G	W391C	1.000
7:100646278:A:G	W391R	1.000
7:100646278:A:T	W391R	1.000
7:100646323:T:C	K376E	1.000
7:100646570:A:G	L365P	1.000

dbSNP variants (sampled 300 via entrez): RS1000040489 (7:100655308 G>C), RS1000100063 (7:100648790 C>T), RS1000948770 (7:100648022 C>T), RS1000994915 (7:100655222 A>G), RS1001048655 (7:100654623 A>G), RS1001100729 (7:100654282 A>T), RS1001375725 (7:100656464 G>A), RS1001428080 (7:100656307 C>G,T), RS1001680536 (7:100649672 G>C), RS1001686873 (7:100643555 A>G), RS1001976568 (7:100645824 G>A), RS1002020773 (7:100644948 C>A,T), RS1002113712 (7:100645579 G>A), RS1002728121 (7:100657327 T>C), RS1002992810 (7:100644349 C>T)

Disease associations

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

GenCC curated gene-disease

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

Mondo (8): developmental and epileptic encephalopathy, 76 (MONDO:0032768), intellectual developmental disorder with severe speech and ambulation defects (MONDO:0032770), autism spectrum disorder (MONDO:0005258), congenital generalized lipodystrophy type 2 (MONDO:0010020), intellectual disability (MONDO:0001071), autism (MONDO:0005260), 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

79 total (30 of 79 shown, 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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001765_21	Red blood cell traits	2.000000e-20
GCST004003_12	Hematocrit	1.000000e-08
GCST004003_3	Hematocrit	6.000000e-09
GCST004004_56	Mean corpuscular volume	1.000000e-08
GCST004005_12	Hemoglobin levels	1.000000e-08
GCST004005_3	Hemoglobin levels	3.000000e-12
GCST004006_22	Mean corpuscular hemoglobin	1.000000e-13
GCST004008_1	Red blood cell count	3.000000e-16
GCST005994_3	Hematocrit	1.000000e-10
GCST006011_71	Mean corpuscular volume	4.000000e-15
GCST006804_188	Red cell distribution width	1.000000e-08
GCST90002390_257	Mean corpuscular hemoglobin	1.000000e-22
GCST90002392_335	Mean corpuscular volume	5.000000e-15

EFO canonical traits (5, from GWAS)

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)

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 (VIP=true, CPIC=false)

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)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	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	PHASE3	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	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	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	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder