ACTR3B

Chr 7

actin related protein 3B

Also known as: APR3B, ARP11, ARP3BETA

NCBI Gene: 57180 ENSG00000133627 UniProt: Q9P1U1 OMIM: 621668

The protein encoded by this gene is an ATP-binding component of the Arp2/3 complex that regulates actin polymerization and mediates formation of branched actin networks essential for cell shape and motility. Mutations cause autosomal dominant dystonia with intellectual disability, and the gene is highly constrained against loss-of-function variants. The condition affects the nervous system with movement disorders and cognitive impairment.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the actin-related proteins (ARP), which form multiprotein complexes and share 35-55% amino acid identity with conventional actin. The protein encoded by this gene may have a regulatory role in the actin cytoskeleton and induce cell-shape change and motility. Pseudogenes of this gene are located on chromosomes 2, 4, 10, 16, 22 and Y. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

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Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.42

OE 0.04 (0.01–0.19)

Highly constrained

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

Missense Constraint?

2.97Z-score

OE missense 0.47 (0.40–0.54)

114 obs / 244.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.47 (0.40–0.54)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 1 / 24.7Missense obs/exp: 114 / 244.9Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in ACTR3B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

280 rare PASS variants

Rare truncating (LoF)

1 in 19,000

25 rare PASS variants

Rare synonymous (reference)

1 in 210

162 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACTR3B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 26,000
South Asian	~43k	1 in 300	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 270	≈ 1 in 30,000
European (Finnish)	~27k	1 in 980	≈ 1 in 15,000
Admixed American	~22k	1 in 290	≈ 1 in 7,600
African / African American	~21k	1 in 500	none seen
East Asian	~20k	1 in 360	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 1,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 12 coding exons well covered in gnomAD exomes; exon 4 poorly covered; exons 1, 2 marginal. Genomes: 10 of 12 (exons 4, 6 below).? see exons ↓