PARD3B

Chr 2

par-3 family cell polarity regulator beta

Also known as: ALS2CR19, PAR3B, PAR3L, PAR3beta

NCBI Gene: 117583 ENSG00000116117 UniProt: Q8TEW8 OMIM: 619353

The protein functions as an adapter involved in asymmetrical cell division and cell polarization processes, including establishment of epithelial tight junctions. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delays. The gene is not highly constrained against loss-of-function variants, which is consistent with the recessive inheritance pattern observed in affected individuals.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.72

Clinical Summary— PARD3B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 202 VUS of 240 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 3.22

OE 0.53 (0.39–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.56Z-score

OE missense 1.06 (1.00–1.13)

688 obs / 647.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.53 (0.39–0.72)

0≤0.351.4

Missense OE?1.06 (1.00–1.13)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 29 / 54.7Missense obs/exp: 688 / 647.6Syn Z: 0.12

This gene — mechanism propensity

0.7327th %ile

GOF

0.6247th %ile

LOF

0.4628th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

240 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic3

VUS202

Likely Benign9

Benign1

Likely Pathogenic

202

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	2	0	3
VUS	1	200	0	1	202
Likely Benign	0	7	0	2	9
Benign	0	0	0	1	1
Total	2	207	2	4	215

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap PARD3B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →