PVALB

Summary

PVALB (parvalbumin, HGNC:9704) is a protein-coding gene on chromosome 22q12.3, encoding Parvalbumin alpha (P20472). In muscle, parvalbumin is thought to be involved in relaxation after contraction.

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.

Source: NCBI Gene 5816 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001315532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9704
Approved symbol	PVALB
Name	parvalbumin
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	D22S749
Ensembl gene	ENSG00000100362
Ensembl biotype	protein_coding
OMIM	168890
Entrez	5816

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000216200, ENST00000404171, ENST00000406910, ENST00000417718, ENST00000443735, ENST00000467935, ENST00000912200, ENST00000912201, ENST00000912202, ENST00000912203

RefSeq mRNA: 2 — MANE Select: NM_001315532 NM_001315532, NM_002854

CCDS: CCDS13933

Canonical transcript exons

ENST00000417718 — 4 exons

Exon	Start	End
ENSE00003656494	36816945	36817035
ENSE00003685025	36815103	36815235
ENSE00003786367	36813646	36813755
ENSE00003843949	36800703	36800918

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 99.39.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9177 / max 1550.3953, expressed in 904 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193974	6.1937	243
193973	1.0946	707
193977	0.3495	28
193975	0.2192	67
193976	0.0608	25

Top tissues by expression

135 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.39	gold quality
primary visual cortex	UBERON:0002436	99.35	gold quality
cerebellum	UBERON:0002037	99.27	gold quality
cerebellar cortex	UBERON:0002129	99.26	gold quality
cerebellar hemisphere	UBERON:0002245	99.24	gold quality
superior frontal gyrus	UBERON:0002661	96.21	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.37	gold quality
right frontal lobe	UBERON:0002810	94.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.75	gold quality
adult mammalian kidney	UBERON:0000082	93.47	gold quality
substantia nigra	UBERON:0002038	93.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.97	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.88	gold quality
frontal cortex	UBERON:0001870	92.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.33	gold quality
prefrontal cortex	UBERON:0000451	90.37	gold quality
cerebral cortex	UBERON:0000956	89.77	gold quality
anterior cingulate cortex	UBERON:0009835	89.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.15	gold quality
kidney	UBERON:0002113	89.12	gold quality
metanephros cortex	UBERON:0010533	88.54	gold quality
monocyte	CL:0000576	88.09	gold quality
leukocyte	CL:0000738	86.84	gold quality
cortex of kidney	UBERON:0001225	86.00	gold quality
brain	UBERON:0000955	81.22	gold quality
Ammon’s horn	UBERON:0001954	80.98	gold quality
putamen	UBERON:0001874	79.16	gold quality
hypothalamus	UBERON:0001898	74.89	gold quality
granulocyte	CL:0000094	71.29	gold quality
blood	UBERON:0000178	69.03	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	3634.74
E-GEOD-137537	yes	1071.94
E-HCAD-10	yes	14.91
E-HCAD-30	no	56.72
E-ANND-3	no	1.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting PVALB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4724-5P	98.87	67.75	1324
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4436B-3P	98.25	65.26	1494
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-338-3P	98.14	67.38	1137

Literature-anchored findings (GeneRIF, showing 35)

• In subjects with schizophrenia a reduction in parvalbumin [PV] and GAD67 mRNA expression in prefrontal cortex neurons was noted (PMID:12867516)
• Slow relaxation caused by alpha-Tm mutants can be corrected by modifying calcium handling with parvalbumin. (PMID:15059934)
• In dopaminergic cells of the substantia nigra in Parkinson disease an increased parvalbumin content is detected reflecting a natural protective mechanism against putative increase of intracellular calcium caused by excitotoxic injury and oxidative stress. (PMID:15257133)
• demonstration of a reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia (PMID:17405923)
• There is no correlation between total neuronal loss and PV-ir neuronal loss in any of the hippocampal fields in epileptic patient. (PMID:17850980)
• The results of this study indicate a significant reduction in the number of PV interneurons within layer 2 of the multiple sclerosis primary motor cortex (PMID:18297277)
• sequencing of PVALB was performed in 132 cases of Gitelman’s syndrome in whom only one or no (N = 79) mutant SLC12A3 allele was found (PMID:18469313)
• parvalbumin has a role in calcium handling in cardiac diastolic dysfunction [review] (PMID:20093724)
• PVALB is a novel diagnostic marker for Hurthle ademonas of the thyroid. (PMID:20926528)
• Data show calbindin (CB)- and tyrosine hydroxylase (TH)-cells were distributed in the three striatal territories, and the density of calretinin (CR) and parvalbumin (PV) interneurons were more abundant in the associative and sensorimotor striatum. (PMID:22272358)
• A subpopulation of projection neurons containing calcium-binding protein parvalbumin (PV) is identified in a precise mapping of the GABAergic cortical distribution. (PMID:23254904)
• This study demonistrated that loss of parvalbium immunoreactive axons in anterolateral columns of spinal cord in patient of lateral sclerosis spinal cords (PMID:23764361)
• Parvalbumin neurons decrease the drive of the input to the visual cortex in contrast sensitivity. (PMID:23825418)
• mRNA labeling at the single cell level shows a significant decrease in parvalbumin expression in Parkinson’s (PD) cases; however, neuronal density of parvalbumin-positive neurons was not significantly different between PD patients and controls. (PMID:23891794)
• This study showed that the parvalbumin basket cell inputs in the dorsolateral prefrontal cortex were lower in patient with schizophrenia. (PMID:24217255)
• This study demonistrated that differentially expressed in PV neurons in subjects with schizophrenia, including genes associated with WNT (wingless-type), NOTCH, and PGE2 (prostaglandin E2) signaling. (PMID:24628518)
• TRPV1-, TRPV2-, P2X3-, and parvalbumin-immunoreactivity neurons in the human nodose ganglion innervate the pharynx and epiglottis through the pharyngeal branch and superior laryngeal nerve (PMID:24764033)
• Increased numbers of PVALB neurons and fiber labeling in focal cortical dysplasia compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation. (PMID:26081613)
• This study demonstrated that A reduction of PV-positive cells and PV-immunoreactivity was observed exclusively in FCD type I/III specimens compared with cryptogenic tissue from control patients with a poor postsurgical outcome. (PMID:27173597)
• excitatory synapse density is lower selectively on parvalbumin interneurons in schizophrenia and predicts the activity-dependent down-regulation of parvalbumin and GAD67 (PMID:27444795)
• Our data support the hypothesis that the loss of PVALB plays a role in the pathogenesis of thyroid tumors. (PMID:27458244)
• The results of this study suggested that innervation from PV-containing thalamic nuclei extends across superficial and middle layers of the human dorsolateral prefrontal cortex. (PMID:28074478)
• These results demonstrate a specific association between elevated PVALB methylation and METH-induced psychosis. (PMID:28835159)
• This study showed that the density of parvalbumin was significantly diminished in the basolateral complex in patients with Parkinson Disease. (PMID:28859333)
• These results provide the first evidence that PVALB promoter methylation is abnormal in schizophrenia and suggest that this epigenetic finding may relate to the reduction of PV expression seen in the disease. (PMID:29688033)
• the Calreticulin deficiency-mediated increase in cell death was not prevented by calbindin-D28k or Parvalbumin. (PMID:30545133)
• PVALB promoter methylation in major depressive disorder and its correlation with major depressive disorder severity indicating a role for epigenetics in this psychiatric disorder. (PMID:31588185)
• Age-related changes in the number of cresyl-violet-stained, parvalbumin and NMDAR 2B expressing neurons in the human spiral ganglion. (PMID:31981822)
• GluN2D-mediated excitatory drive onto medial prefrontal cortical PV+ fast-spiking inhibitory interneurons. (PMID:32497062)
• Transcriptional and imaging-genetic association of cortical interneurons, brain function, and schizophrenia risk. (PMID:32514083)
• Parvalbumin immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney. (PMID:32524185)
• Propofol sedation-induced alterations in brain connectivity reflect parvalbumin interneurone distribution in human cerebral cortex. (PMID:33386125)
• Strontium Binding to alpha-Parvalbumin, a Canonical Calcium-Binding Protein of the ““EF-Hand”” Family. (PMID:34439824)
• The Nature of Prefrontal Cortical GABA Neuron Alterations in Schizophrenia: Markedly Lower Somatostatin and Parvalbumin Gene Expression Without Missing Neurons. (PMID:37073488)
• Elevations in the Mitochondrial Matrix Protein Cyclophilin D Correlate With Reduced Parvalbumin Expression in the Prefrontal Cortex of Patients With Schizophrenia. (PMID:38412332)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pvalb6	ENSDARG00000009311
danio_rerio	pvalb7	ENSDARG00000034705
mus_musculus	Pvalb	ENSMUSG00000005716
rattus_norvegicus	Pvalb	ENSRNOG00000006471

Paralogs (2): OCM (ENSG00000122543), OCM2 (ENSG00000135175)

Protein

Protein identifiers

Parvalbumin alpha — P20472 (reviewed: P20472)

Alternative names: Alpha-parvalbumin

All UniProt accessions (4): P20472, B1AH72, B8ZZ19, H0Y3U0

UniProt curated annotations — full annotation on UniProt →

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

Domain organisation. AB domain, comprising of helices A and B, is involved in structural stabilization, protecting the hydrophobic core of the protein. It is required for high-affinity binding of Ca(2+) and for Mg(2+)-binding.

Similarity. Belongs to the parvalbumin family.

RefSeq proteins (2): NP_001302461, NP_002845 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR008080	Parvalbumin	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Pfam: PF13499

UniProt features (36 total): binding site 11, helix 9, mutagenesis site 4, modified residue 3, strand 3, domain 2, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9BB8	X-RAY DIFFRACTION	2.72
1RJV	SOLUTION NMR
1RK9	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20472-F1	95.82	0.98

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (11): 91; 93; 95; 97; 102; 52; 54; 56; 58; 60; 63

Post-translational modifications (3): 2, 2, 24

Mutagenesis-validated functional residues (4):

Position	Phenotype
52	inactivation.
63	inactivation.
91	inactivation.
102	inactivation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8986944	Transcriptional Regulation by MECP2

MSigDB gene sets: 124 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, AP1_01, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, CAGCTG_AP4_Q5, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_CELL_CELL_SIGNALING, BROWNE_HCMV_INFECTION_48HR_DN, AP1_Q4_01, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_RELAXATION_OF_MUSCLE, BACH2_01, TGANTCA_AP1_C, ATGCTGG_MIR338

GO Biological Process (4): gene expression (GO:0010467), relaxation of muscle (GO:0090075), excitatory chemical synaptic transmission (GO:0098976), inhibitory chemical synaptic transmission (GO:0098977)

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasm (GO:0005737), axon (GO:0030424), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemical synaptic transmission	2
macromolecule biosynthetic process	1
muscle system process	1
excitatory postsynaptic potential	1
inhibitory postsynaptic potential	1
metal ion binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
neuron projection	1
cell junction	1

Protein interactions and networks

STRING

4236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PVALB	CALB2	P22676	966
PVALB	CALB1	P05937	963
PVALB	GAD1	Q99259	963
PVALB	SST	P01166	934
PVALB	S100G	P29377	851
PVALB	SDF4	Q9BRK5	845
PVALB	NPY	P01303	819
PVALB	GAD2	Q05329	801
PVALB	DISC1	Q9NRI5	796
PVALB	TH	P07101	794
PVALB	CCK	P06307	787
PVALB	SLC17A7	Q9P2U7	780
PVALB	SLC6A1	P30531	779
PVALB	VIP	P01282	777
PVALB	CALM1	P02593	776
PVALB	CALML3	P27482	776

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SREBF1	PVALB	psi-mi:“MI:0914”(association)	0.350
ASCC3	PVALB	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): PVALB (Affinity Capture-MS), PVALB (Affinity Capture-MS), PVALB (Affinity Capture-MS), PVALB (Affinity Capture-MS), PVALB (Affinity Capture-MS), PVALB (PCA), PVALB (PCA), SPTAN1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A3F2YLV2, A0A7M4EAX1, O35508, P02614, P02615, P02616, P02617, P02618, P02619, P02623, P02624, P02625, P02626, P02627, P02629, P02630, P02631, P05940, P05941, P09227, P0CE71, P0CE72, P18087, P19753, P20472, P30563, P32848, P43305, P51879, P59747, P80026, P80050, P80079, P80080, P86739, P86742, P86744, P86760, P86768, P86770

Diamond homologs: A0A1B0GWK0, A0A7M4EAX1, D3GME4, P02597, P02614, P02615, P02616, P02617, P02618, P02619, P02620, P02621, P02622, P02623, P02624, P02625, P02628, P02629, P02631, P04464, P05419, P05939, P05940, P05941, P09227, P0CE72, P19753, P20472, P28582, P30187, P30563, P32848, P43305, P49101, P51879, P53683, P56503, P59747, P80026, P80050

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

22 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:36815153:A:C	F48L	0.992
22:36815153:A:T	F48L	0.992
22:36815155:A:G	F48L	0.992
22:36800915:A:G	F103S	0.980
22:36800914:G:C	F103L	0.978
22:36800914:G:T	F103L	0.978
22:36800916:A:G	F103L	0.978
22:36813737:G:C	F71L	0.976
22:36813737:G:T	F71L	0.976
22:36813739:A:G	F71L	0.976
22:36815207:G:C	F30L	0.976
22:36815207:G:T	F30L	0.976
22:36815209:A:G	F30L	0.976
22:36815154:A:G	F48S	0.975
22:36815121:A:T	I59N	0.973
22:36815129:A:C	S56R	0.971
22:36815129:A:T	S56R	0.971
22:36815131:T:G	S56R	0.971
22:36813738:A:G	F71S	0.965
22:36815196:A:T	V34D	0.965
22:36815222:G:C	F25L	0.964
22:36815222:G:T	F25L	0.964
22:36815224:A:G	F25L	0.964
22:36815123:G:C	F58L	0.963
22:36815123:G:T	F58L	0.963
22:36815125:A:G	F58L	0.963
22:36815137:C:G	D54H	0.961
22:36815208:A:G	F30S	0.960
22:36815143:C:G	D52H	0.959
22:36800915:A:C	F103C	0.958

dbSNP variants (sampled 300 via entrez): RS1000104079 (22:36802227 T>A,C), RS1000244147 (22:36811111 A>C), RS1000296575 (22:36810884 C>G,T), RS1000434673 (22:36816250 C>T), RS1000650187 (22:36800235 A>C), RS1000801775 (22:36811338 T>A,C), RS1000807121 (22:36816554 A>C,G), RS1000854715 (22:36811598 G>A), RS1000978600 (22:36801573 G>T), RS1001102706 (22:36816730 G>C), RS1001208362 (22:36817408 C>A,T), RS1001284004 (22:36818923 C>T), RS1001309342 (22:36812537 A>G), RS1001472266 (22:36807013 C>T), RS1001604115 (22:36801894 T>C)

Disease associations

OMIM: gene MIM:168890 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
butyraldehyde	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cocaine	decreases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Valproic Acid	affects expression	1
Uranium Compounds	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.