PVALB

Chr 22

myoglobin

Also known as: MYOSB, PVALB

NCBI Gene: 4151ENSG00000100362UniProt: P20472

This gene encodes a member of the globin superfamily and is predominantly expressed in skeletal and cardiac muscles. The encoded protein forms a monomeric globular haemoprotein that is primarily responsible for the storage and facilitated transfer of oxygen from the cell membrane to the mitochondria. This protein also plays a role in regulating physiological levels of nitric oxide. Multiple transcript variants encoding distinct isoforms exist for this gene. [provided by RefSeq, May 2020]

42
ClinVar variants
17
Pathogenic / LP
0.09
pLI score
3
Active trials
Clinical Summary— PVALB
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 18 VUS of 42 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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.
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?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.
0.04Z-score
OE missense 0.99 (0.80–1.22)
61 obs / 61.8 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.0.44 (0.18–1.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.80–1.22)
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.0.89
0≤1.21.6
LoF obs/exp: 2 / 4.5Missense obs/exp: 61 / 61.8Syn Z: 0.42

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PARVALBUMIN; PVALB
MIM #168890 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis.
Pfisterer U et al.·Nat Commun
2020
Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects.
Walsh RM et al.·Neuron
2025
Cerebrospinal fluid biomarkers as predictors of multiple sclerosis severity.
Tolentino M et al.·Mult Scler Relat Disord
2025
Neurobiology of ARID1B haploinsufficiency related to neurodevelopmental and psychiatric disorders.
Moffat JJ et al.·Mol Psychiatry
2022Review
Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.
Moujaes F et al.·Elife
2024Functional
Brain connectivity and transcriptional changes induced by rTMS in first-episode major depressive disorder.
Guan M et al.·Transl Psychiatry
2025
Cell-class-specific electric field entrainment of neural activity.
Lee SY et al.·Neuron
2024
Evaluating PVALB as a candidate gene for SLC12A3-negative cases of Gitelman's syndrome.
Riveira-Munoz E et al.·Nephrol Dial Transplant
2008Cohort
Cytomegalic parvalbumin neurons in fetal cases of hemimegalencephaly.
Gelot AB et al.·Epilepsia
2025Cohort
Genes associated with bowel metastases in ovarian cancer.
Mariani A et al.·Gynecol Oncol
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Schizophrenia and Related DisordersMitochondrial AlterationCognitive Impairment

MitoQ for Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction

RECRUITING
NCT06191965Phase PHASE2, PHASE3Mclean HospitalStarted 2024-06-01
MitoQPlacebo
SupplementationSports NutritionErgogenic Support

Caffeine Kinetics and CrossFit®-Specific Performance

RECRUITING
NCT05516212Phase PHASE2, PHASE3Poznan University of Physical EducationStarted 2022-06-29
CAFMONO supplementationCAFMIPS_1 supplementationCAFMIPS_2 supplementation
Muscular DystrophyDuchenne Muscular DystrophyBecker Muscular Dystrophy

Follow-up Study on Female Carriers With DMD Gene Variants

ENROLLING BY INVITATION
NCT05715957Rigshospitalet, DenmarkStarted 2023-05-18
No intervention

External Resources

Links to major genomics databases and tools