CIB1

calcium and integrin binding 1, the group of EF-hand domain containing

Basic information

Region (hg38): 15:90229975-90234047

Links

ENSG00000185043

∙ NCBI:10519 ∙ OMIM:602293 ∙ HGNC:16920 ∙ Uniprot:Q99828 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

epidermodysplasia verruciformis, susceptibility to, 3 (Strong), mode of inheritance: AR
epidermodysplasia verruciformis (Supportive), mode of inheritance: AR
epidermodysplasia verruciformis, susceptibility to, 3 (Strong), mode of inheritance: AR
epidermodysplasia verruciformis, susceptibility to, 3 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermodysplasia verruciformis, susceptibility to, 3	AR	Oncologic	Among other findings, individuals have been described as being at increased risk of nonmelanoma skin cancer (as well as other skin neoplasms), and awareness have allowed increased surveillance and management	Allergy/Immunology/Infectious; Dermatologic; Oncologic	28646613; 30068544

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CIB1 gene.

not_provided (150 variants)
not_specified (28 variants)
CIB1-related_disorder (8 variants)
Epidermodysplasia_verruciformis,_susceptibility_to,_3 (7 variants)
Susceptibility_to_severe_COVID-19 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006384.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	27 clinvar	3 clinvar	31
missense			61 clinvar	3 clinvar	2 clinvar	66
nonsense	1 clinvar					1
start loss			1			1
frameshift	5 clinvar	2 clinvar	3 clinvar			10
splice donor/acceptor (+/-2bp)		2 clinvar	2 clinvar			4
Total	6	4	68	30	5

Highest pathogenic variant AF is 0.00001313767

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIB1	protein_coding	protein_coding	ENST00000328649	7	4073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000326	0.829	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0612	110	112	0.984	0.00000694	1255
Missense in Polyphen		43	46.652	0.92172		592
Synonymous	0.476	42	46.1	0.911	0.00000279	364
Loss of Function	1.22	7	11.5	0.611	6.42e-7	121

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000456	0.000456
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Calcium-binding protein that plays a role in the regulation of numerous cellular processes, such as cell differentiation, cell division, cell proliferation, cell migration, thrombosis, angiogenesis, cardiac hypertrophy and apoptosis. Involved in bone marrow megakaryocyte differentiation by negatively regulating thrombopoietin-mediated signaling pathway. Participates in the endomitotic cell cycle of megakaryocyte, a form of mitosis in which both karyokinesis and cytokinesis are interrupted. Plays a role in integrin signaling by negatively regulating alpha-IIb/beta3 activation in thrombin- stimulated megakaryocytes preventing platelet aggregation. Up- regulates PTK2/FAK1 activity, and is also needed for the recruitment of PTK2/FAK1 to focal adhesions; it thus appears to play an important role in focal adhesion formation. Positively regulates cell migration on fibronectin in a CDC42-dependent manner, the effect being negatively regulated by PAK1. Functions as a negative regulator of stress activated MAP kinase (MAPK) signaling pathways. Down-regulates inositol 1,4,5-trisphosphate receptor-dependent calcium signaling. Involved in sphingosine kinase SPHK1 translocation to the plasma membrane in a N- myristoylation-dependent manner preventing TNF-alpha-induced apoptosis. Regulates serine/threonine-protein kinase PLK3 activity for proper completion of cell division progression. Plays a role in microtubule (MT) dynamics during neuronal development; disrupts the MT depolymerization activity of STMN2 attenuating NGF-induced neurite outgrowth and the MT reorganization at the edge of lamellipodia. Promotes cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway. Stimulates calcineurin PPP3R1 activity by mediating its anchoring to the sarcolemma. In ischemia-induced (pathological or adaptive) angiogenesis, stimulates endothelial cell proliferation, migration and microvessel formation by activating the PAK1 and ERK1/ERK2 signaling pathway. Promotes also cancer cell survival and proliferation. May regulate cell cycle and differentiation of spermatogenic germ cells, and/or differentiation of supporting Sertoli cells.;

Recessive Scores

pRec: 0.271

Intolerance Scores

loftool: 0.629
rvis_EVS: -0.3
rvis_percentile_EVS: 32.62

Haploinsufficiency Scores

pHI: 0.162
hipred: Y
hipred_score: 0.769
ghis: 0.480

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.541

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cib1
Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype;

Gene ontology

Biological process: angiogenesis;negative regulation of protein phosphorylation;positive regulation of protein phosphorylation;positive regulation of cell-matrix adhesion;response to ischemia;double-strand break repair;apoptotic process;cellular response to DNA damage stimulus;negative regulation of microtubule depolymerization;endomitotic cell cycle;cell adhesion;spermatid development;positive regulation of cell population proliferation;negative regulation of cell population proliferation;negative regulation of neuron projection development;platelet formation;positive regulation of cell growth;positive regulation of cell migration;cytoplasmic microtubule organization;positive regulation of cell adhesion mediated by integrin;thrombopoietin-mediated signaling pathway;regulation of cell population proliferation;negative regulation of apoptotic process;positive regulation of catalytic activity;negative regulation of megakaryocyte differentiation;positive regulation of NF-kappaB transcription factor activity;cell division;regulation of cell division;negative regulation of protein kinase B signaling;positive regulation of ERK1 and ERK2 cascade;positive regulation of calcineurin-NFAT signaling cascade;cellular response to tumor necrosis factor;cellular response to growth factor stimulus;negative regulation of protein serine/threonine kinase activity;positive regulation of protein serine/threonine kinase activity;positive regulation of cell migration involved in sprouting angiogenesis;positive regulation of protein targeting to membrane;extrinsic apoptotic signaling pathway;positive regulation of substrate adhesion-dependent cell spreading;positive regulation of protein localization to plasma membrane;cellular response to nerve growth factor stimulus;positive regulation of male germ cell proliferation
Cellular component: nucleus;nucleoplasm;cytoplasm;endoplasmic reticulum;Golgi apparatus;centrosome;plasma membrane;membrane;apical plasma membrane;lamellipodium;dendrite;growth cone;vesicle;filopodium tip;ruffle membrane;sarcolemma;neuron projection;neuronal cell body;perinuclear region of cytoplasm;extracellular exosome;cell periphery
Molecular function: calcium ion binding;protein binding;protein C-terminus binding;calcium-dependent protein kinase inhibitor activity;Ras GTPase binding;protein kinase binding;protein serine/threonine kinase inhibitor activity;protein membrane anchor;ion channel binding