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

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 (5 variants)
• Epidermodysplasia verruciformis, susceptibility to, 3 (1 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.

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	32	3	36
missense			62	2	2	66
nonsense	2					2
start loss			1			1
frameshift	3		1			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	8	3	13
non coding			1	25	6	32
Total	5	1	67	59	11

Highest pathogenic variant AF is 0.0000394

Variants in CIB1

This is a list of pathogenic ClinVar variants found in the CIB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-90230490-G-T			Likely benign (May 29, 2022)
15-90230494-A-G		not specified	Uncertain significance (May 30, 2022)
15-90230522-C-T			Likely benign (Sep 07, 2023)
15-90230550-C-T		not specified	Benign (Jan 24, 2024)
15-90230807-C-T		not specified	Benign (Jan 24, 2024)
15-90230917-G-A			Likely benign (Nov 22, 2022)
15-90230920-G-T			Likely benign (Dec 20, 2023)
15-90230921-A-G			Likely benign (Dec 18, 2023)
15-90230938-C-G			Uncertain significance (Sep 17, 2021)
15-90230938-C-CAA		Epidermodysplasia verruciformis, susceptibility to, 3	risk factor (Feb 01, 2019)
15-90230941-A-G			Uncertain significance (Apr 23, 2021)
15-90230942-G-T			Uncertain significance (Sep 16, 2021)
15-90230950-A-T			Uncertain significance (Apr 17, 2021)
15-90230952-C-A			Uncertain significance (Jun 24, 2022)
15-90230952-C-T			Uncertain significance (Jul 19, 2022)
15-90230963-G-A			Likely benign (Jun 13, 2023)
15-90230974-C-CA			Uncertain significance (Dec 18, 2023)
15-90230981-G-T			Uncertain significance (Oct 27, 2021)
15-90230982-T-C			Uncertain significance (Jul 06, 2022)
15-90231012-T-A			Uncertain significance (Jul 18, 2022)
15-90231025-G-A			Uncertain significance (May 17, 2022)
15-90231027-G-C		not specified • CIB1-related disorder	Benign (Feb 01, 2024)
15-90231032-GGA-G			Likely benign (May 12, 2022)
15-90231033-G-A			Likely benign (Dec 18, 2023)
15-90231033-G-C			Likely benign (Oct 25, 2022)

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