CHP1

calcineurin like EF-hand protein 1, the group of EF-hand domain containing

Basic information

Region (hg38): 15:41230839-41281887

Links

ENSG00000187446

∙ NCBI:11261 ∙ OMIM:606988 ∙ HGNC:17433 ∙ Uniprot:Q99653 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

spastic ataxia 9, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spastic ataxia 9, 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	Musculoskeletal; Neurologic	29379881

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHP1 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				1 clinvar	1 clinvar	2
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	0	1	1

Variants in CHP1

This is a list of pathogenic ClinVar variants found in the CHP1 region.

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

Position	Phenotype	Significance	ClinVar
15-41231433-CAAG-C	Spastic ataxia 9, autosomal recessive	Pathogenic (Feb 25, 2022)	632545
15-41243711-C-T	CHP1-related disorder	Likely benign (Feb 26, 2019)	3046627
15-41278763-C-T		Likely benign (Oct 01, 2023)	2645189
15-41278829-G-A	CHP1-related disorder	Benign (Oct 28, 2019)	3045325

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHP1	protein_coding	protein_coding	ENST00000334660	7	51007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.627	0.372	125740	0	4	125744	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.26	50	119	0.419	0.00000694	1300
Missense in Polyphen		11	41.018	0.26818		438
Synonymous	0.0391	40	40.3	0.992	0.00000197	353
Loss of Function	2.64	2	11.8	0.170	6.50e-7	128

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)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate- phosphorylations in a calcium-dependent manner. {ECO:0000269|PubMed:10593895, ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:8901634}.;
Pathway: Alzheimers Disease;T-Cell antigen Receptor (TCR) pathway during Staphylococcus aureus infection;Hyaluronan uptake and degradation;Hyaluronan metabolism;Metabolism of carbohydrates;Glycosaminoglycan metabolism;Metabolism;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Calcium signaling in the CD4+ TCR pathway (Consensus)

Intolerance Scores

loftool
rvis_EVS: -0.05
rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

pHI
hipred: Y
hipred_score: 0.760
ghis: 0.506

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: H
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Chp1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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);

Zebrafish Information Network

Gene name: chp1
Affected structure: CaP motoneuron
Phenotype tag: abnormal
Phenotype quality: branchiness

Gene ontology

Biological process: microtubule bundle formation;negative regulation of protein phosphorylation;negative regulation of protein kinase activity;protein export from nucleus;potassium ion transport;small GTPase mediated signal transduction;negative regulation of phosphatase activity;calcium ion regulated exocytosis;membrane docking;hyaluronan catabolic process;cytoplasmic microtubule organization;negative regulation of protein ubiquitination;negative regulation of protein autophosphorylation;negative regulation of NF-kappaB transcription factor activity;positive regulation of sodium:proton antiporter activity;negative regulation of protein import into nucleus;protein stabilization;positive regulation of protein transport;protein complex oligomerization;regulation of intracellular pH;positive regulation of protein glycosylation;membrane organization;membrane fusion;negative regulation of calcineurin-NFAT signaling cascade;cellular response to acidic pH;positive regulation of protein targeting to membrane;regulation of neuron death
Cellular component: Golgi membrane;nucleus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum-Golgi intermediate compartment;cytosol;plasma membrane;focal adhesion;microtubule cytoskeleton;transport vesicle;extracellular exosome
Molecular function: protein kinase inhibitor activity;transporter activity;calcium ion binding;protein binding;microtubule binding;potassium channel regulator activity;kinase binding;calcium-dependent protein binding