CIB3

Summary

CIB3 (calcium and integrin binding family member 3, HGNC:24580) is a protein-coding gene on chromosome 19p13.11, encoding Calcium and integrin-binding family member 3 (Q96Q77). Acts a an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells.

This gene product shares a high degree of sequence similarity with DNA-dependent protein kinase catalytic subunit-interacting protein 2 in human and mouse, and like them may bind the catalytic subunit of DNA-dependent protein kinases. The exact function of this gene is not known. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 117286 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_054113

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24580
Approved symbol	CIB3
Name	calcium and integrin binding family member 3
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	KIP3
Ensembl gene	ENSG00000141977
Ensembl biotype	protein_coding
OMIM	610645
Entrez	117286

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000269878, ENST00000379859, ENST00000541493, ENST00000597251

RefSeq mRNA: 2 — MANE Select: NM_054113 NM_001300922, NM_054113

CCDS: CCDS12340, CCDS74305

Canonical transcript exons

ENST00000269878 — 6 exons

Exon	Start	End
ENSE00000951603	16169630	16169741
ENSE00002235916	16161368	16161486
ENSE00003170869	16173425	16173525
ENSE00003459602	16168137	16168284
ENSE00003590101	16164718	16164913
ENSE00003594558	16173162	16173196

Expression profiles

Bgee: expression breadth broad, 81 present calls, max score 90.21.

Top tissues by expression

209 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.21	gold quality
buccal mucosa cell	CL:0002336	74.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	66.04	gold quality
granulocyte	CL:0000094	62.94	gold quality
parotid gland	UBERON:0001831	61.86	gold quality
heart right ventricle	UBERON:0002080	60.36	gold quality
lower lobe of lung	UBERON:0008949	60.36	silver quality
nasal cavity epithelium	UBERON:0005384	60.26	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.05	gold quality
amniotic fluid	UBERON:0000173	59.27	gold quality
vena cava	UBERON:0004087	58.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	57.77	gold quality
cartilage tissue	UBERON:0002418	57.53	gold quality
Brodmann (1909) area 46	UBERON:0006483	56.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	56.65	gold quality
saphenous vein	UBERON:0007318	56.19	gold quality
middle temporal gyrus	UBERON:0002771	56.18	gold quality
pericardium	UBERON:0002407	56.12	gold quality
urethra	UBERON:0000057	56.01	gold quality
subthalamic nucleus	UBERON:0001906	55.99	gold quality
layer of synovial tissue	UBERON:0007616	55.99	gold quality
inferior vagus X ganglion	UBERON:0005363	55.76	gold quality
nipple	UBERON:0002030	55.74	gold quality
dorsal root ganglion	UBERON:0000044	55.73	gold quality
trigeminal ganglion	UBERON:0001675	55.73	gold quality
synovial joint	UBERON:0002217	55.68	gold quality
dorsal plus ventral thalamus	UBERON:0001897	55.65	gold quality
gingival epithelium	UBERON:0001949	55.55	gold quality
pylorus	UBERON:0001166	55.54	gold quality
medulla oblongata	UBERON:0001896	55.53	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.13

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• CIB3, as binding partners for the integrin alphaIIb subunit, which suggests that they are potentially involved in regulating integrin alphaIIb subunit activation. (PMID:22779914)
• CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells. (PMID:34089643)
• Atomic force microscopy reveals distinct protofilament-scale structural dynamics in depolymerizing microtubule arrays. (PMID:35101922)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	cib3	ENSDARG00000091072
mus_musculus	Cib3	ENSMUSG00000074240
rattus_norvegicus	Cib3	ENSRNOG00000014600
drosophila_melanogaster	CG32812	FBGN0025642
drosophila_melanogaster	Cib2	FBGN0034558
drosophila_melanogaster	elm	FBGN0037358
drosophila_melanogaster	CG14362	FBGN0038186
caenorhabditis_elegans	calm-1	WBGENE00009260
caenorhabditis_elegans		WBGENE00014109
caenorhabditis_elegans		WBGENE00019108

Paralogs (8): TESC (ENSG00000088992), CIB2 (ENSG00000136425), CIB4 (ENSG00000157884), CHP2 (ENSG00000166869), CIB1 (ENSG00000185043), CHP1 (ENSG00000187446), PPP3R2 (ENSG00000188386), PPP3R1 (ENSG00000221823)

Protein

Protein identifiers

Calcium and integrin-binding family member 3 — Q96Q77 (reviewed: Q96Q77)

Alternative names: Kinase-interacting protein 3

All UniProt accessions (2): Q96Q77, M0QZ29

UniProt curated annotations — full annotation on UniProt →

Function. Acts a an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells. Plays a role in regulating hair cell MET channel localization and function.

Subunit / interactions. Monomer and homodimer. Interacts with ITGA2B (via C-terminus cytoplasmic tail region); the interaction is stabilized/increased in a calcium and magnesium-dependent manner. Interacts with TMC1.

Miscellaneous. The binding of either calcium or magnesium significantly increases the structural stability of the protein in comparison to apo-CIB (calcium- and magnesium-free form).

Isoforms (2)

UniProt ID	Names	Canonical?
Q96Q77-1	1	yes
Q96Q77-2	2

RefSeq proteins (2): NP_001287851, NP_473454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR051433	CIBP	Family

Pfam: PF13499

UniProt features (33 total): helix 11, binding site 10, domain 3, turn 3, strand 3, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6WU7	X-RAY DIFFRACTION	1.84
6WUD	X-RAY DIFFRACTION	1.84
6WU5	X-RAY DIFFRACTION	1.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96Q77-F1	85.17	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 159; 161; 163; 168; 116; 118; 120; 122; 127; 157

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): CDP_01, BRN2_01, GOBP_MONOATOMIC_ION_HOMEOSTASIS, CDPCR3HD_01, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, chr19p13, GOMF_MAGNESIUM_ION_BINDING, CDPCR1_01, ZNF768_TARGET_GENES, GSE8685_IL2_STARVED_VS_IL15_ACT_IL2_STARVED_CD4_TCELL_UP, GSE13493_DP_VS_CD8POS_THYMOCYTE_DN, GSE14350_IL2RB_KO_VS_WT_TREG_UP, PBX1_01, GOBP_CALCIUM_ION_HOMEOSTASIS

GO Biological Process (1): calcium ion homeostasis (GO:0055074)

GO Molecular Function (4): magnesium ion binding (GO:0000287), calcium ion binding (GO:0005509), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	2
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
binding	1
cation binding	1

Protein interactions and networks

STRING

1792 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIB3	KIF18A	Q8NI77	825
CIB3	KIF19	Q2TAC6	695
CIB3	KIF2C	Q99661	666
CIB3	KIF18B	Q86Y91	653
CIB3	TMC2	Q8TDI7	607
CIB3	BRICD5	Q6PL45	544
CIB3	KIF4A	O95239	529
CIB3	KIF11	P52732	522
CIB3	MAPK8IP3	Q9UPT6	517
CIB3	KLHL26	Q53HC5	516
CIB3	CIMAP1D	Q3SX64	515
CIB3	CENPE	Q02224	507
CIB3	KLC2	Q9H0B6	495
CIB3	NR2C2AP	Q86WQ0	494
CIB3	KLC1	Q07866	492

IntAct

198 interactions, top by confidence:

A	B	Type	Score
SP4	CIB3	psi-mi:“MI:0915”(physical association)	0.720
KLF17	CIB3	psi-mi:“MI:0915”(physical association)	0.720
ZNF398	CIB3	psi-mi:“MI:0915”(physical association)	0.720
TRIM2	CIB3	psi-mi:“MI:0915”(physical association)	0.720
CIB3	TACC3	psi-mi:“MI:0915”(physical association)	0.720
CIB3	ZNF398	psi-mi:“MI:0915”(physical association)	0.720
CIB3	TRIM2	psi-mi:“MI:0915”(physical association)	0.720
TACC3	CIB3	psi-mi:“MI:0915”(physical association)	0.720
CIB3	KLF17	psi-mi:“MI:0915”(physical association)	0.720
CIB3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MEOX1	CIB3	psi-mi:“MI:0915”(physical association)	0.560
REL	CIB3	psi-mi:“MI:0915”(physical association)	0.560
CIB3	TLE5	psi-mi:“MI:0915”(physical association)	0.560
ENOX2	CIB3	psi-mi:“MI:0915”(physical association)	0.560
CIB3	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
FLJ13057	CIB3	psi-mi:“MI:0915”(physical association)	0.560
CIB3	KASH5	psi-mi:“MI:0915”(physical association)	0.560
BEND7	CIB3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (75): CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), CIB3 (Two-hybrid), KLF17 (Two-hybrid), CCDC155 (Two-hybrid)

ESM2 similar proteins: C7A276, O73763, O75838, O81445, P06814, P06815, P28782, P29104, P35332, P36608, P43367, P62166, P62167, P62168, P62760, P62761, P62762, P62763, P62764, P80363, Q06389, Q09711, Q0P523, Q0VFG3, Q16981, Q2V8Y7, Q3YLA4, Q4R5F7, Q54MF3, Q568Z7, Q5R6S5, Q5RC90, Q5RD22, Q5XJX1, Q63ZJ3, Q6PC72, Q75K28, Q75KU4, Q874T7, Q8BGZ1

Diamond homologs: A0PJX0, B1A8Z2, C7A276, C7A278, O75838, Q0IQB6, Q0IUU4, Q0P523, Q17QE5, Q3KQ77, Q568Z7, Q6PC72, Q96Q77, Q99828, Q9D9N5, Q9R010, Q9W2Q5, Q9Y6T7, Q9Z0F4, Q9Z309, G5EDN6, P28470, P63098, P63099, P63100, Q2TBI5, Q3HRN8, Q3HRN9, Q63810, Q63811, Q6CGE6, Q7XC27, Q96LZ3, Q9LTB8, O81223, O81445, P06707, P06708, P0CM54, P0CM55

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1033 predictions. Top by Δscore:

Variant	Effect	Δscore
19:16168158:AAG:A	donor_gain	1.0000
19:16168284:CCTGG:C	acceptor_loss	1.0000
19:16161487:C:CC	acceptor_gain	0.9900
19:16164712:CATCA:C	donor_loss	0.9900
19:16164713:ATCAC:A	donor_loss	0.9900
19:16164714:TCA:T	donor_loss	0.9900
19:16164715:CA:C	donor_loss	0.9900
19:16164716:A:AG	donor_loss	0.9900
19:16164717:CCTGA:C	donor_loss	0.9900
19:16168133:GCAC:G	donor_loss	0.9900
19:16168134:CA:C	donor_loss	0.9900
19:16168135:A:AT	donor_loss	0.9900
19:16168159:AG:A	donor_gain	0.9900
19:16168191:T:C	donor_gain	0.9900
19:16168280:TTGTC:T	acceptor_gain	0.9900
19:16168281:TGTC:T	acceptor_gain	0.9900
19:16168282:GTC:G	acceptor_gain	0.9900
19:16168283:TC:T	acceptor_gain	0.9900
19:16168284:CC:C	acceptor_gain	0.9900
19:16168285:C:CC	acceptor_gain	0.9900
19:16169627:TACCT:T	donor_loss	0.9900
19:16169628:A:C	donor_loss	0.9900
19:16169629:C:CG	donor_loss	0.9900
19:16169741:CCTGA:C	acceptor_gain	0.9900
19:16173435:T:TA	donor_gain	0.9900
19:16161483:GGTG:G	acceptor_gain	0.9800
19:16161484:GTG:G	acceptor_gain	0.9800
19:16161485:TG:T	acceptor_gain	0.9800
19:16161487:CTGT:C	acceptor_loss	0.9800
19:16161489:G:C	acceptor_gain	0.9800

AlphaMissense

1262 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:16161480:G:C	F183L	0.998
19:16161480:G:T	F183L	0.998
19:16161482:A:G	F183L	0.998
19:16168147:A:C	F112L	0.998
19:16168147:A:T	F112L	0.998
19:16168149:A:G	F112L	0.998
19:16168162:C:A	K107N	0.998
19:16168162:C:G	K107N	0.998
19:16168249:G:C	F78L	0.997
19:16168249:G:T	F78L	0.997
19:16168251:A:G	F78L	0.997
19:16164753:G:C	F169L	0.996
19:16164753:G:T	F169L	0.996
19:16164755:A:G	F169L	0.996
19:16168151:G:T	A111D	0.996
19:16168279:G:C	N68K	0.996
19:16168279:G:T	N68K	0.996
19:16164754:A:G	F169S	0.995
19:16168148:A:G	F112S	0.995
19:16168274:A:G	F70S	0.995
19:16169634:A:G	L65P	0.995
19:16169728:A:C	Y34D	0.995
19:16164723:G:C	F179L	0.994
19:16164723:G:T	F179L	0.994
19:16164725:A:G	F179L	0.994
19:16164880:T:G	D127A	0.994
19:16168178:G:T	A102D	0.994
19:16168186:A:C	S99R	0.994
19:16168186:A:T	S99R	0.994
19:16168188:T:G	S99R	0.994

dbSNP variants (sampled 300 via entrez): RS1000117430 (19:16172298 G>A), RS1000593074 (19:16164405 G>C), RS1000840016 (19:16165512 C>T), RS1000951871 (19:16171710 C>A), RS1001394981 (19:16170704 C>G), RS1001659552 (19:16170370 A>G), RS1001872742 (19:16165535 C>A,T), RS1002221396 (19:16170762 C>T), RS1002345722 (19:16164964 C>A,T), RS1002892056 (19:16167948 G>A), RS1002926765 (19:16171739 C>T), RS1003229160 (19:16169516 G>A), RS1003385792 (19:16163327 G>A), RS1003409419 (19:16173681 T>C), RS1003458268 (19:16162065 T>G)

Disease associations

OMIM: gene MIM:610645 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002388_47	Lymphocyte count	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression	1
Tobacco Smoke Pollution	increases methylation	1
Sodium Selenite	decreases expression	1
Antirheumatic Agents	decreases expression	1
Zinc Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.