PVALB

protein-coding

parvalbumin, the group of EF-hand domain containing

Gene summary

The protein encoded by this gene is a high affinity calcium ion-binding protein that is structurally and functionally similar to calmodulin and troponin C. The encoded protein is thought to be involved in muscle relaxation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

MANE transcript

NM_001315532.2

Inheritance

—

ClinVar variants

U:15B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr22:36,800,684-36,819,479

External References & Databases

Ensembl (ENSG00000100362)

Transcript & Mutation Effects

hg38 • Region Span ~18.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PVALB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 11

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001315532.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			13 clinvar		2 clinvar	15
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	15	0	2	17

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001315532.2	RefSeq	NP_001302461.1	4	MANE Select
ENST00000417718.7	Ensembl	ENSP00000400247.2	4	MANE Select
NM_002854.3	RefSeq	NP_002845.1	4	Standard
ENST00000216200.10	Ensembl	ENSP00000216200.5	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cytosolic calcium ion concentration

Molecular Function

calcium ion binding
protein homodimerization activity
protein heterodimerization activity

Cellular Component

nucleus
cytoplasm
axon
protein-containing complex
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216200
Coding exons: 4
Length: 18796
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0360	61	61.8	0.987	0.00000308	743
Missense (PolyPhen)		24	25.809	0.9299		306
Synonymous	0.424	23	25.7	0.894	0.00000160	192
Loss of Function	1.10	2	4.52	0.443	1.89e-7	63

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.;

Recessive Scores

pRec: 0.363

Intolerance Scores

LoFtool: 0.556
RVIS EVS: 0.26
RVIS percentile EVS: 70.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.164

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium