ARPC1B

Chr 7AR

actin related protein 2/3 complex subunit 1B

Also known as: ARC41, IMD71, PLTEID, p40-ARC, p41-ARC

NCBI Gene: 10095 ENSG00000130429 UniProt: O15143

This gene encodes one of seven subunits of the human Arp2/3 protein complex. This subunit is a member of the SOP2 family of proteins and is most similar to the protein encoded by gene ARPC1A. The similarity between these two proteins suggests that they both may function as p41 subunit of the human Arp2/3 complex that has been implicated in the control of actin polymerization in cells. It is possible that the p41 subunit is involved in assembling and maintaining the structure of the Arp2/3 complex. Multiple versions of the p41 subunit may adapt the functions of the complex to different cell types or developmental stages. This protein also has a role in centrosomal homeostasis by being an activator and substrate of the Aurora A kinase. [provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Immunodeficiency 71 with inflammatory disease and congenital thrombocytopeniaMIM #617718

403

ClinVar variants

Pathogenic / LP

0.01

pLI score

Active trials

Clinical Summary— ARPC1B

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Gene-Disease Validity (ClinGen)

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

46 Pathogenic / Likely Pathogenic· 149 VUS of 403 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

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 0.011

Z-score 2.75

OE 0.34 (0.19–0.65)

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.

1.18Z-score

OE missense 0.79 (0.70–0.89)

200 obs / 252.8 exp

Tolerant

Mild missense constraint

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.0.34 (0.19–0.65)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.70–0.89)

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.0.98

0≤1.21.6

LoF obs/exp: 7 / 20.4Missense obs/exp: 200 / 252.8Syn Z: 0.15