PVALB

Chr 22

parvalbumin

Also known as: D22S749

NCBI Gene: 5816ENSG00000100362UniProt: P20472OMIM: 168890

This gene encodes parvalbumin, a high-affinity calcium-binding protein involved in muscle relaxation after contraction. Mutations cause autosomal recessive congenital myopathy with cores and rods, presenting in infancy with hypotonia and muscle weakness. The gene shows tolerance to loss-of-function variants, consistent with the recessive inheritance pattern observed in affected patients.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.36
Clinical Summary— PVALB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 18 VUS of 42 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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
1.36LOEUF
pLI 0.087
Z-score 1.10
OE 0.44 (0.18–1.36)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.04Z-score
OE missense 0.99 (0.80–1.22)
61 obs / 61.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.18–1.36)
0≤0.351.4
Missense OE0.99 (0.80–1.22)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 2 / 4.5Missense obs/exp: 61 / 61.8Syn Z: 0.42
DN
0.80top 25%
GOF
0.7027th %ile
LOF
0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

42 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS18
Benign3
Conflicting1
16
Pathogenic
1
Likely Pathogenic
18
VUS
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
12
6
0
18
Likely Benign
0
0
0
0
0
Benign
0
2
1
0
3
Conflicting
—1
Total01424039

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

View in ClinVar →

Protein Context — Lollipop Plot

PVALB · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients