CIB2

calcium and integrin binding family member 2, the group of EF-hand domain containing

Basic information

Region (hg38): 15:78104606-78131535

Previous symbols: [ "DFNB48", "USH1J" ]

Links

ENSG00000136425

∙ NCBI:10518 ∙ OMIM:605564 ∙ HGNC:24579 ∙ Uniprot:O75838 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive nonsyndromic hearing loss 48 (Strong), mode of inheritance: AR
Usher syndrome type 1J (Definitive), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 48 (Strong), mode of inheritance: AR
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
Usher syndrome type 1 (Supportive), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 48 (Strong), mode of inheritance: AR
Usher syndrome type 1J (Limited), mode of inheritance: Unknown
Usher syndrome type 1 (Refuted Evidence), mode of inheritance: AR
nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 48; Usher syndrome type IJ	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Ophthalmologic	18505454; 23023331

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CIB2 gene.

not_provided (176 variants)
Inborn_genetic_diseases (21 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_48 (20 variants)
not_specified (11 variants)
Usher_syndrome_type_1J (9 variants)
CIB2-related_disorder (7 variants)
Retinal_dystrophy (3 variants)
Hearing_loss,_autosomal_recessive (3 variants)
Usher_syndrome (2 variants)
Rare_genetic_deafness (1 variants)
Hearing_impairment (1 variants)
Childhood_onset_hearing_loss (1 variants)
Usher_syndrome_type_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CIB2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006383.4. 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			2 clinvar	42 clinvar		44
missense	1 clinvar	5 clinvar	75 clinvar	3 clinvar		84
nonsense	4 clinvar					4
start loss						0
frameshift	10 clinvar	2 clinvar				12
splice donor/acceptor (+/-2bp)	1 clinvar	2 clinvar				3
Total	16	9	77	45	0

Highest pathogenic variant AF is 0.0000806773

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CIB2	protein_coding	protein_coding	ENST00000258930	6	26939

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00145	0.883	125706	0	42	125748	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.519	98	114	0.863	0.00000685	1258
Missense in Polyphen		26	35.345	0.7356		416
Synonymous	0.379	43	46.3	0.929	0.00000320	324
Loss of Function	1.37	6	10.9	0.553	6.30e-7	116

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000328	0.000325
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Calcium-binding protein critical for proper photoreceptor cell maintenance and function. Plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release (PubMed:23023331, PubMed:26173970, PubMed:26426422). May be involved in the mechanotransduction process (By similarity). {ECO:0000250, ECO:0000269|PubMed:23023331, ECO:0000269|PubMed:26173970, ECO:0000269|PubMed:26426422}.;
Disease: DISEASE: Usher syndrome 1J (USH1J) [MIM:614869]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. {ECO:0000269|PubMed:23023331}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.136

Intolerance Scores

loftool: 0.623
rvis_EVS: -0.29
rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

pHI: 0.409
hipred: N
hipred_score: 0.466
ghis: 0.510

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.577

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Cib2
Phenotype: hearing/vestibular/ear 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); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name: cib2
Affected structure: neuromast hair cell
Phenotype tag: abnormal
Phenotype quality: mislocalised

Gene ontology

Biological process: positive regulation of cytosolic calcium ion concentration;photoreceptor cell maintenance;calcium ion homeostasis;cellular response to ATP
Cellular component: photoreceptor outer segment;photoreceptor inner segment;cytoplasm;muscle tendon junction;neuromuscular junction;stereocilium;cuticular plate;sarcolemma;blood microparticle
Molecular function: magnesium ion binding;integrin binding;calcium ion binding;protein binding;protein homodimerization activity