HPCA

hippocalcin, the group of EF-hand domain containing

Basic information

Region (hg38): 1:32885993-32898441

Previous symbols: [ "DYT2" ]

Links

ENSG00000121905 ∙ NCBI:3208 ∙ OMIM:142622 ∙ HGNC:5144 ∙ Uniprot:P84074 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• torsion dystonia 2 (Strong), mode of inheritance: AR
• torsion dystonia 2 (Strong), mode of inheritance: AR
• torsion dystonia 2 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 2, torsion, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	14694054; 25799108

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HPCA gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HPCA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				18		18
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding				7	3	10
Total	0	0	14	26	3

Variants in HPCA

This is a list of pathogenic ClinVar variants found in the HPCA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-32888923-C-T		not specified	Uncertain significance (Dec 15, 2023)
1-32888924-G-A			Uncertain significance (May 06, 2022)
1-32888948-G-A		not specified	Uncertain significance (Aug 12, 2021)
1-32889021-A-G			Likely benign (Aug 27, 2023)
1-32889054-C-T			Likely benign (Oct 14, 2022)
1-32889057-C-T			Likely benign (May 15, 2023)
1-32889063-C-A		not specified	Uncertain significance (May 30, 2024)
1-32889078-C-T			Likely benign (Oct 28, 2021)
1-32889093-C-T		HPCA-related disorder	Likely benign (Nov 27, 2023)
1-32889099-C-T			Likely benign (Nov 16, 2023)
1-32889110-C-A		Torsion dystonia 2	Pathogenic (Apr 02, 2015)
1-32889123-C-A		Torsion dystonia 2	Pathogenic (Apr 02, 2015)
1-32889126-C-T			Likely benign (Nov 01, 2022)
1-32889157-A-G		not specified	Uncertain significance (Jan 31, 2022)
1-32889177-G-A			Likely benign (Aug 10, 2022)
1-32889180-C-G			Likely benign (Dec 11, 2023)
1-32889180-C-T		HPCA-related disorder	Likely benign (Aug 13, 2019)
1-32889185-G-A			Uncertain significance (Apr 20, 2022)
1-32889192-G-A			Likely benign (Nov 27, 2023)
1-32889198-G-A			Likely benign (Dec 25, 2022)
1-32889202-A-C			Uncertain significance (May 16, 2022)
1-32889231-C-T			Likely benign (Nov 27, 2023)
1-32889233-G-C		not specified	Uncertain significance (Jul 14, 2023)
1-32889237-C-T		HPCA-related disorder	Likely benign (Apr 18, 2023)
1-32889238-G-A			Uncertain significance (Oct 26, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HPCA	protein_coding	protein_coding	ENST00000373467	3	12448

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.678	0.318	125713	0	2	125715	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	57	127	0.450	0.00000765	1291
Missense in Polyphen		12	45.756	0.26226		472
Synonymous	1.10	43	53.2	0.808	0.00000353	347
Loss of Function	2.29	1	7.99	0.125	4.23e-7	89

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Calcium-binding protein that may play a role in the regulation of voltage-dependent calcium channels (PubMed:28398555). May also play a role in cyclic-nucleotide- mediated signaling through the regulation of adenylate and guanylate cyclases (By similarity). {ECO:0000250|UniProtKB:P84076, ECO:0000269|PubMed:28398555}.
• Disease: DISEASE: Dystonia 2, torsion, autosomal recessive (DYT2) [MIM:224500]: A form of torsion dystonia, a disease defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. 'Torsion' refers to the twisting nature of body movements, often affecting the trunk. DYT2 is a slowly progressive form that first affects distal limbs and later involves the neck, orofacial, and craniocervical regions. {ECO:0000269|PubMed:25799108, ECO:0000269|PubMed:28398555}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.150
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.448
• hipred: Y
• hipred_score: 0.736
• ghis: 0.622

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hpca
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: brain development;calcium-mediated signaling;negative regulation of guanylate cyclase activity;activation of phospholipase D activity;positive regulation of adenylate cyclase activity;inner ear development;retina development in camera-type eye;cellular response to electrical stimulus;cellular response to calcium ion;positive regulation of protein targeting to membrane;regulation of postsynaptic neurotransmitter receptor internalization;regulation of voltage-gated calcium channel activity;response to ketamine;response to L-glutamate;cellular response to monosodium glutamate;response to Aroclor 1254
• Cellular component: cytoplasm;cytosol;extrinsic component of membrane;axon;dendrite membrane;neuronal cell body membrane;dendrite cytoplasm;perikaryon;dendritic spine head;glutamatergic synapse
• Molecular function: actin binding;calcium ion binding;kinase binding;identical protein binding