ACTL6B

Chr 7ARAD

actin like 6B

Also known as: ACTL6, BAF53B, DEE76, EIEE76, IDDSSAD, SMARCN2, arpNalpha

NCBI Gene: 51412ENSG00000077080UniProt: O94805

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. [provided by RefSeq, Dec 2015]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 76MIM #618468
AR
Intellectual developmental disorder with severe speech and ambulation defectsMIM #618470
AD
185
ClinVar variants
75
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— ACTL6B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
75 Pathogenic / Likely Pathogenic· 86 VUS of 185 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.65LOEUF
pLI 0.000
Z-score 3.00
OE 0.39 (0.24–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.27Z-score
OE missense 0.44 (0.38–0.51)
120 obs / 271.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.39 (0.24–0.65)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.38–0.51)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 11 / 28.2Missense obs/exp: 120 / 271.9Syn Z: 0.08

ClinVar Variant Classifications

185 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic40
VUS86
Likely Benign19
Benign1
Conflicting4
35
Pathogenic
40
Likely Pathogenic
86
VUS
19
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
5
25
0
35
Likely Pathogenic
10
17
13
0
40
VUS
5
70
11
0
86
Likely Benign
0
1
3
15
19
Benign
0
0
1
0
1
Conflicting
—4
Total20935315185

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ACTL6B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ACTL6B-related epileptic encephalopathy, early infantile

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

ACTL6B-related intellectual developmental disorder with severe speech and ambulation defects

limited
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ACTIN-LIKE 6B; ACTL6B
MIM #612458 · *

Developmental and epileptic encephalopathy 76

MIM #618468

Molecular basis of disorder known

Autosomal recessive

Intellectual developmental disorder with severe speech and ambulation defects

MIM #618470

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autozygome and high throughput confirmation of disease genes candidacy.
Maddirevula S et al.·Genet Med
2019
Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.
Cali E et al.·Genet Med
2025
An epilepsy-associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model.
Ahn LY et al.·J Neurosci Res
2021Functional
Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epileptic encephalopathy with brain hypomyelination and cerebellar atrophy.
Fichera M et al.·Hum Genet
2019Clinical trial
Pathogenic homozygous variations in ACTL6B cause DECAM syndrome: Developmental delay, Epileptic encephalopathy, Cerebral Atrophy, and abnormal Myelination.
Yüksel Z et al.·Am J Med Genet A
2019Case report
A global profile of gene promoter methylation in treatment-naïve urothelial cancer.
Ibragimova I et al.·Epigenetics
2014
SWI/SNF complex heterogeneity is related to polyphenotypic differentiation, prognosis, and immune response in rhabdoid tumors.
Panwalkar P et al.·Neuro Oncol
2020
Variant recurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense variants.
Lecoquierre F et al.·Genet Med
2019
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder.
Krupp DR et al.·Am J Hum Genet
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools