PARVB

Chr 22

parvin beta

Also known as: CGI-56

NCBI Gene: 29780 ENSG00000188677 UniProt: Q9HBI1 OMIM: 608121

The protein is an adapter protein that binds actin filaments and regulates integrin signaling, cytoskeleton reorganization, and cell adhesion through interactions with integrin-linked kinase and guanine exchange factors. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delays. This gene is extremely intolerant to loss-of-function variants, suggesting that complete protein loss is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the parvin family of actin-binding proteins, which play a role in cytoskeleton organization and cell adhesion. These proteins are associated with focal contacts and contain calponin homology domains that bind to actin filaments. This family member binds to alphaPIX and alpha-actinin, and it can inhibit the activity of integrin-linked kinase. This protein also functions in tumor suppression. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.28

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.28LOEUF

pLI 0.000

Z-score 0.51

OE 0.89 (0.63–1.28)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.98 (0.88–1.09)

233 obs / 237.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.89 (0.63–1.28)

0≤0.351.4

Missense OE?0.98 (0.88–1.09)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 21 / 23.7Missense obs/exp: 233 / 237.2Syn Z: 0.42

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 87

612 rare PASS variants

Rare truncating (LoF)

1 in 860

133 rare PASS variants

Rare synonymous (reference)

1 in 120

248 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PARVB. 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 130	1 in 980
South Asian	~43k	1 in 66	1 in 860
Remaining (unassigned)	~30k	1 in 64	1 in 1,400
European (Finnish)	~27k	1 in 260	1 in 610
Admixed American	~22k	1 in 99	1 in 1,000
African / African American	~21k	1 in 81	1 in 660
East Asian	~20k	1 in 72	1 in 570
Ashkenazi Jewish	~13k	1 in 450	none seen
Middle Eastern	~2,884	1 in 57	≈ 1 in 940

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: 12 of 13 (exon 8 below).? see exons ↓