ACTL6A

Chr 3

actin like 6A

Also known as: ACTL6, ARPN-BETA, Arp4, BAF53A, INO80K, SMARCN1

This gene encodes ACTL6A, a 53 kDa subunit of the BAF chromatin remodeling complex that is essential for transcriptional regulation during neural development, specifically required for neural progenitor proliferation and the transition to postmitotic neurons. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and epilepsy, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (pLI 0.997), indicating intolerance to protein-disrupting mutations.

Summary from RefSeq, UniProt
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0
Active trials
15
Pubs (1 yr)
28
P/LP submissions
0%
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryACTL6A
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Gene-Disease Validity (ClinGen)
ACTL6A-related BAFopathy · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
28 unique Pathogenic / Likely Pathogenic· 51 VUS of 114 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.997
Z-score 4.32
OE 0.08 (0.030.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.94Z-score
OE missense 0.46 (0.400.54)
110 obs / 237.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.030.25)
00.351.4
Missense OE0.46 (0.400.54)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 2 / 25.6Missense obs/exp: 110 / 237.5Syn Z: 0.28
DN
0.4090th %ile
GOF
0.4579th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

114 submitted variants in ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic4
VUS51
Likely Benign9
Benign2
Conflicting2
24
Pathogenic
4
Likely Pathogenic
51
VUS
9
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
4
0
4
VUS
4
43
4
0
51
Likely Benign
0
3
1
5
9
Benign
0
1
0
1
2
Conflicting
2
Total44733692

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

View in ClinVar →

Protein Context — Lollipop Plot

ACTL6A · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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