CIB2

Summary

CIB2 (calcium and integrin binding family member 2, HGNC:24579) is a protein-coding gene on chromosome 15q25.1, encoding Calcium and integrin-binding family member 2 (O75838). Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis.

The protein encoded by this gene is similar to that of KIP/CIB, calcineurin B, and calmodulin. The encoded protein is a calcium-binding regulatory protein that interacts with DNA-dependent protein kinase catalytic subunits (DNA-PKcs), and it is involved in photoreceptor cell maintenance. Mutations in this gene cause deafness, autosomal recessive, 48 (DFNB48), and also Usher syndrome 1J (USH1J). Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10518 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic genetic hearing loss (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 270 total — 14 pathogenic, 10 likely-pathogenic
• GTEx eGene: eQTL in 48 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 3
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.27 (unconstrained)
• MANE Select transcript: NM_006383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24579
Approved symbol	CIB2
Name	calcium and integrin binding family member 2
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIP2
Ensembl gene	ENSG00000136425
Ensembl biotype	protein_coding
OMIM	605564
Entrez	10518

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 7 nonsense_mediated_decay

MANE Select: ENST00000258930

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 4, TSL 5: 1

ENST00000258930, ENST00000539011, ENST00000557818, ENST00000557846, ENST00000557917, ENST00000559054, ENST00000559645, ENST00000560618, ENST00000561190, ENST00000643268, ENST00000935334, ENST00000958911, ENST00001016135, ENST00001016136, ENST00001080820, ENST00001080821, ENST00001125687, ENST00001136738

RefSeq mRNA: 4 — MANE Select: NM_006383 NM_001271888, NM_001271889, NM_001301224, NM_006383

CCDS: CCDS10296, CCDS61722, CCDS61723

Canonical transcript exons

ENST00000258930 — 6 exons

Exon	Start	End
ENSE00001284128	78104606	78105332
ENSE00001322417	78131165	78131445
ENSE00003476144	78105739	78105934
ENSE00003629140	78109235	78109382
ENSE00003655126	78111165	78111276
ENSE00003682818	78123705	78123739

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 94.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5103 / max 128.4859, expressed in 1297 samples.

Highest expression (Bgee): atrium auricular region, cardiac atrium, apex of heart, sperm, cervix squamous epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CIB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 48 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	1.2e-128	+0.89	15:78131254:A:C
Muscle Skeletal	eqtl	2.4e-75	+0.69	15:78131254:A:C
Cells Cultured fibroblasts	eqtl	4.4e-61	+0.67	15:78131254:A:C
Esophagus Mucosa	eqtl	7.0e-51	+0.70	15:78131254:A:C
Artery Tibial	eqtl	2.4e-49	+0.56	15:78131254:A:C
Colon Transverse	eqtl	1.4e-48	+0.81	15:78131254:A:C
Heart Left Ventricle	eqtl	8.2e-48	+0.85	15:78131254:A:C
Brain Cortex	eqtl	2.8e-37	+0.74	15:78131254:A:C
Esophagus Muscularis	eqtl	1.5e-36	+0.47	15:78131254:A:C
Brain Frontal Cortex BA9	eqtl	2.9e-36	+0.75	15:78131254:A:C
Skin Sun Exposed Lower leg	eqtl	1.6e-35	+0.49	15:78131254:A:C
Pancreas	eqtl	8.4e-33	+0.82	15:78131254:A:C
Pituitary	eqtl	2.5e-32	+0.76	15:78131254:A:C
Lung	eqtl	5.1e-32	+0.43	15:78131254:A:C
Brain Caudate basal ganglia	eqtl	5.2e-30	+0.60	15:78131254:A:C
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-29	+0.40	15:78131254:A:C
Colon Sigmoid	eqtl	4.3e-27	+0.58	15:78131254:A:C
Artery Aorta	eqtl	4.3e-26	+0.50	15:78131254:A:C
Whole Blood	eqtl	5.2e-25	+0.32	15:78131254:A:C
Liver	eqtl	1.4e-23	+0.85	15:78131254:A:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
151098	4.0528	1130
151096	1.9260	653
151100	0.5323	264
151099	0.4591	259
151097	0.4285	240
207600	0.1116	40

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	94.26	gold quality
cardiac atrium	UBERON:0002081	93.83	gold quality
apex of heart	UBERON:0002098	93.67	gold quality
sperm	CL:0000019	93.34	gold quality
cervix squamous epithelium	UBERON:0006922	92.49	silver quality
ganglionic eminence	UBERON:0004023	91.94	gold quality
male germ cell	CL:0000015	91.67	gold quality
jejunal mucosa	UBERON:0000399	91.29	gold quality
embryo	UBERON:0000922	90.43	gold quality
ventricular zone	UBERON:0003053	89.87	gold quality
left testis	UBERON:0004533	88.95	gold quality
right testis	UBERON:0004534	88.78	gold quality
duodenum	UBERON:0002114	87.88	gold quality
testis	UBERON:0000473	87.77	gold quality
cortical plate	UBERON:0005343	87.40	gold quality
cardiac muscle of right atrium	UBERON:0003379	86.90	gold quality
hair follicle	UBERON:0002073	86.62	gold quality
cranial nerve II	UBERON:0000941	85.84	gold quality
jejunum	UBERON:0002115	85.70	gold quality
myocardium	UBERON:0002349	85.49	gold quality
dorsal root ganglion	UBERON:0000044	85.47	gold quality
heart	UBERON:0000948	85.45	gold quality
cingulate cortex	UBERON:0003027	84.88	gold quality
vena cava	UBERON:0004087	84.83	gold quality
anterior cingulate cortex	UBERON:0009835	84.76	gold quality
thymus	UBERON:0002370	84.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.54	gold quality
stromal cell of endometrium	CL:0002255	84.49	gold quality
right adrenal gland cortex	UBERON:0035827	84.33	gold quality
amygdala	UBERON:0001876	84.17	gold quality
pancreatic ductal cell	CL:0002079	83.78	silver quality
right adrenal gland	UBERON:0001233	83.76	gold quality
left adrenal gland cortex	UBERON:0035825	83.75	gold quality
left adrenal gland	UBERON:0001234	83.42	gold quality
adrenal cortex	UBERON:0001235	83.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.36	gold quality
heart left ventricle	UBERON:0002084	83.36	gold quality
cardiac ventricle	UBERON:0002082	83.21	gold quality
small intestine	UBERON:0002108	82.99	gold quality
ectocervix	UBERON:0012249	82.79	gold quality
endocervix	UBERON:0000458	82.54	gold quality
adrenal gland	UBERON:0002369	82.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.41	gold quality
lower esophagus	UBERON:0013473	82.38	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.27	gold quality
gastrocnemius	UBERON:0001388	82.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.99	gold quality
prefrontal cortex	UBERON:0000451	81.96	gold quality
muscle of leg	UBERON:0001383	81.80	gold quality
trigeminal ganglion	UBERON:0001675	81.60	gold quality
adenohypophysis	UBERON:0002196	81.49	gold quality
neocortex	UBERON:0001950	81.46	gold quality
uterine cervix	UBERON:0000002	81.38	gold quality
right frontal lobe	UBERON:0002810	81.36	gold quality
muscle organ	UBERON:0001630	81.35	gold quality
skeletal muscle organ	UBERON:0014892	81.35	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.34	gold quality
temporal lobe	UBERON:0001871	81.27	gold quality
hypothalamus	UBERON:0001898	81.23	gold quality
mucosa of transverse colon	UBERON:0004991	81.09	gold quality
ileal mucosa	UBERON:0000331	81.07	gold quality
pituitary gland	UBERON:0000007	81.02	gold quality
quadriceps femoris	UBERON:0001377	80.99	silver quality
amniotic fluid	UBERON:0000173	80.98	gold quality
mucosa of stomach	UBERON:0001199	80.97	gold quality
vastus lateralis	UBERON:0001379	80.94	silver quality
body of uterus	UBERON:0009853	80.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.86	gold quality
nucleus accumbens	UBERON:0001882	80.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	80.78	gold quality
frontal cortex	UBERON:0001870	80.61	gold quality
frontal lobe	UBERON:0016525	80.61	gold quality
muscle tissue	UBERON:0002385	80.57	gold quality
ventral tegmental area	UBERON:0002691	80.54	gold quality
metanephros cortex	UBERON:0010533	80.45	gold quality
cerebral cortex	UBERON:0000956	80.28	gold quality
intestine	UBERON:0000160	80.19	gold quality
prostate gland	UBERON:0002367	80.13	gold quality
cervix epithelium	UBERON:0004801	79.99	gold quality
superior vestibular nucleus	UBERON:0007227	79.98	gold quality
midbrain	UBERON:0001891	79.95	gold quality
substantia nigra	UBERON:0002038	79.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.91	gold quality
forebrain	UBERON:0001890	79.86	gold quality
transverse colon	UBERON:0001157	79.85	gold quality
telencephalon	UBERON:0001893	79.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.68	gold quality
sigmoid colon	UBERON:0001159	79.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.57	gold quality
Ammon’s horn	UBERON:0001954	79.56	gold quality
brain	UBERON:0000955	79.39	gold quality
central nervous system	UBERON:0001017	79.34	gold quality
skeletal muscle tissue	UBERON:0001134	79.29	gold quality
colon	UBERON:0001155	79.28	gold quality
large intestine	UBERON:0000059	79.15	gold quality
inferior vagus X ganglion	UBERON:0005363	78.81	gold quality
biceps brachii	UBERON:0001507	78.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.68	gold quality
rectum	UBERON:0001052	78.62	gold quality
descending thoracic aorta	UBERON:0002345	78.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.60

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	227.2
Medulla oblongata	tissue	171.5
Pons	tissue	142.4
Periaqueductal gray	tissue	128.1
Thalamus	tissue	113.7
Substantia nigra	tissue	113.1
Midbrain	tissue	108.0
Superior colliculi	tissue	94.3
Hippocampal formation	tissue	86.0
Hypothalamus	tissue	83.0
Cerebral cortex	tissue	72.5	low
Motor cortex	tissue	72.5
Somatosensory cortex	tissue	60.8
Putamen	tissue	60.5
Septum	tissue	59.6
Retrosplenial cortex	tissue	58.7
Ventral forebrain	tissue	58.4
Prefrontal cortex	tissue	57.1
Retrosplenial and cingulate cortex	tissue	55.7
Temporal cortex	tissue	55.6
Insular cortex	tissue	55.5
Occipital cortex	tissue	55.2
Entorhinal cortex	tissue	55.1
Amygdala	tissue	53.9
Basal ganglia	tissue	45.1	medium
Thymus	tissue	44.7
Cerebellum	tissue	40.7	low
Olfactory bulb	tissue	33.1
Frontal cortex	tissue	32.1
Corpus callosum	tissue	29.8
Small intestine	tissue	23.3	low
Locus coeruleus	tissue	20.8
Heart muscle	tissue	18.3	medium
Duodenum	tissue	18.0	medium
Hippocampus	tissue	16.2	not detected
Caudate putamen	tissue	13.9
Parathyroid gland	tissue	12.7	low
Testis	tissue	12.0	medium
Postcentral gyrus	tissue	10.0
Pituitary gland	tissue	9.9
Cervix	tissue	9.4	not detected
Adrenal gland	tissue	8.5	low
Seminal vesicle	tissue	8.2	low
Colon	tissue	8.1	low
Prostate	tissue	8.0	low
Nucleus accumbens	tissue	7.8
Salivary gland	tissue	7.6	not detected
Vagina	tissue	7.4	low
Ovary	tissue	7.3	low
Choroid plexus	tissue	7.1
Skeletal muscle	tissue	6.9	medium
Rectum	tissue	6.7	medium
Adipose tissue	tissue	6.5	not detected
Smooth muscle	tissue	6.2	medium
Tonsil	tissue	6.1	low
Urinary bladder	tissue	5.9	low
Endometrium 1	tissue	5.8	low
Pancreas	tissue	5.1	medium
Retina	tissue	4.7
Skin 1	tissue	4.4	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Ventral spinal cord (227.2), Dorsal spinal cord (126.7), Dorsal hippocampus (86.0), Ventral hippocampus (84.6), Subiculum (56.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

Targeting CIB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 39 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-660-3P	98.14	66.04	1434
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6757-5P	98.08	65.50	724

Functional genomics

gnomAD constraint: pLI 1.59e-06, LOEUF 1.27, missense Z 0.643 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000258930 — one region, missense o/e 0.91.

Literature-anchored findings (GeneRIF, showing 13)

• CIB2, as binding partners for the integrin alphaIIb subunit, which suggests that they are potentially involved in regulating integrin alphaIIb subunit activation. (PMID:22779914)
• Consistent with molecular modeling predictions of calcium binding, CIB2 significantly decreased the ATP-induced calcium responses in heterologous cells, whereas mutations in deafness DFNB48 altered CIB2 effects on calcium responses (PMID:23023331)
• Data indicate that that CIB2 localizes to stereocilia and interacts with the USH proteins myosin VIIa and whirlin, suggesting CIB2 is a Ca2+-buffering protein essential for calcium homeostasis in the mechanosensory stereocilia of inner ear hair cells. (PMID:24022220)
• Novel homozygous missense variant c.196C>T and compound heterozygous variants, c.[97C>T];[196C>T], were associated with nonsyndromic deafness. (PMID:26173970)
• We identified a novel variant (rs7164338) on chromosome 15q25.1 in the CIB2 associated with lower pulse wave velocity. (PMID:26378684)
• CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family (PMID:26426422)
• this study identifies CIB1 and CIB2 as host helper factors for HIV-1 replication that are required for optimal receptor-mediated viral entry (PMID:27489023)
• High CIB2 expression is associated with ovarian Cancer. (PMID:28729416)
• results suggest that GJB2 and CIB2 are common cause of hearing loss in different Pakistani ethnicities (PMID:29086887)
• This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients (PMID:29112224)
• Oligomeric state, hydrodynamic properties and target recognition of human Calcium and Integrin Binding protein 2 (CIB2). (PMID:31636333)
• CIB2 and CIB3 are auxiliary subunits of the mechanotransduction channel of hair cells. (PMID:34089643)
• Calcium- and Integrin-Binding Protein 2 (CIB2) in Physiology and Disease: Bright and Dark Sides. (PMID:35408910)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	cib2	ENSDARG00000102820
mus_musculus	Cib2	ENSMUSG00000037493
rattus_norvegicus	Cib2	ENSRNOG00000079672
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), CIB3 (ENSG00000141977), CIB4 (ENSG00000157884), CHP2 (ENSG00000166869), CIB1 (ENSG00000185043), CHP1 (ENSG00000187446), PPP3R2 (ENSG00000188386), PPP3R1 (ENSG00000221823)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1929293) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 30 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal hair cell mechanoelectric transduction	2
increased or absent threshold for auditory brainstem response	2
tremors	1
abnormal startle reflex	1
decreased startle reflex	1
limb grasping	1
impaired balance	1
increased circulating triglyceride level	1
increased circulating HDL cholesterol level	1
abnormal hearing physiology	1
deafness	1
abnormal ear morphology	1
increased basophil cell number	1
abnormal cochlear hair cell morphology	1
abnormal heart left ventricle morphology	1
cochlear hair cell degeneration	1
absent cochlear microphonics	1
abnormal cochlear outer hair cell physiology	1
abnormal vestibular hair cell stereociliary bundle morphology	1
decreased vestibular hair cell stereocilia number	1
abnormal outer hair cell stereociliary bundle morphology	1
decreased outer hair cell stereocilia number	1
abnormal inner hair cell stereociliary bundle morphology	1
absent distortion product otoacoustic emissions	1
abnormal auditory brainstem response	1

+5 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	B1A8Z2	100.0%	Diamond
Cryptococcus deneoformans JEC21	P0CM54	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CM55	100.0%	Diamond
Bos taurus	P63099	100.0%	Diamond
Nakaseomyces glabratus CBS 138	Q6FLU4	93.7%	Diamond
Arabidopsis thaliana	O81445	89.7%	Diamond
Oryza sativa Japonica Group	Q7XC27	79.3%	Diamond
Candidozyma auris	A0A2H0ZYD3	78.2%	Diamond
Neurospora crassa OR74A	P87072	71.4%	Diamond
Schizosaccharomyces pombe 972h-	Q9UU93	70.4%	Diamond
Naegleria gruberi	P42322	62.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DNAJA4-DT	ncRNA	105370911
ACSBG1	protein-coding	23205
IDH3A	protein-coding	3419
SH2D7	protein-coding	646892
TBC1D2B	protein-coding	23102
DNAJA4	protein-coding	55466

Protein

Protein identifiers

Calcium and integrin-binding family member 2 — O75838 (reviewed: O75838)

Alternative names: Kinase-interacting protein 2

All UniProt accessions (8): A0A2R8Y4Y2, H0YKC8, H0YKX8, H0YLL7, H0YLX3, H0YML3, O75838, H0YND4

UniProt curated annotations — full annotation on UniProt →

Function. Calcium- and integrin-binding protein that plays a role in intracellular calcium homeostasis. Acts as an auxiliary subunit of the sensory mechanoelectrical transduction (MET) channel in hair cells. Essential for mechanoelectrical transduction (MET) currents in auditory hair cells and thereby required for hearing. Regulates the function of hair cell mechanotransduction by controlling the distribution of transmembrane channel-like proteins TMC1 and TMC2, and by regulating the function of the MET channels in hair cells. Required for the maintenance of auditory hair cell stereocilia bundle morphology and function and for hair-cell survival in the cochlea. Critical for proper photoreceptor cell maintenance and function. Plays a role in intracellular calcium homeostasis by decreasing ATP-induced calcium release.

Subunit / interactions. Monomer. Homodimer. Interacts with WHRN and MYO7A. Interacts with ITGA2B (via C-terminus cytoplasmic tail region); the interactions are stabilized/increased in a calcium and magnesium-dependent manner. Interacts with ITGA7 (via C-terminus cytoplasmic tail region); the interactions are stabilized/increased in a calcium and magnesium-dependent manner. Interacts with TMC1. Interacts with TMC2.

Subcellular location. Cytoplasm. Cell projection. Stereocilium. Photoreceptor inner segment. Cilium. Photoreceptor outer segment. Cell membrane. Sarcolemma.

Tissue specificity. Widely expressed.

Disease relevance. Deafness, autosomal recessive, 48 (DFNB48) [MIM:609439] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB48 patients have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies. The disease is caused by variants affecting the gene represented in this entry.

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 (4)

UniProt ID	Names	Canonical?
O75838-1	1	yes
O75838-2	2
O75838-3	3
O75838-4	4

RefSeq proteins (4): NP_001258817, NP_001258818, NP_001288153, NP_006374* (*=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 (42 total): helix 10, binding site 9, sequence variant 9, strand 5, domain 3, splice variant 3, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
8XOQ	Human Calcium and Integrin Binding Protein 2 (CIB2) Fusion to TMC1 CBD-1 domain at 2.4 …	X-RAY DIFFRACTION	2.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75838-F1	88.71	0.68

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Potential drug targets, Human disease related genes, Eye disease, Ear disease

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; centrosome; cytosol; primary cilium transition zone

Antibody reliability (HPA): IH approved · IF uncertain

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 (9)

Position	Role
161	Ca(2+)
163	Ca(2+)
168	Ca(2+)
116	Ca(2+)
118	Ca(2+)
120	Ca(2+)
127	Ca(2+)
157	Ca(2+)
159	Ca(2+)

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-9709957	Sensory Perception	—
R-HSA-9659379	Sensory processing of sound	—
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea	electronic
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea	electronic

MSigDB gene sets: 175 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, KYNG_DNA_DAMAGE_DN, CTATGCA_MIR153, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_ATP, MODULE_205, GOBP_PHOTORECEPTOR_CELL_MAINTENANCE, KYNG_DNA_DAMAGE_BY_GAMMA_RADIATION, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_RESPONSE_TO_ATP, LIAO_METASTASIS, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND

GO Biological Process (4): positive regulation of cytosolic calcium ion concentration (GO:0007204), photoreceptor cell maintenance (GO:0045494), calcium ion homeostasis (GO:0055074), cellular response to ATP (GO:0071318)

GO Molecular Function (7): magnesium ion binding (GO:0000287), integrin binding (GO:0005178), calcium ion binding (GO:0005509), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), protein-containing complex binding (GO:0044877), metal ion binding (GO:0046872)

GO Cellular Component (12): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), muscle tendon junction (GO:0005927), neuromuscular junction (GO:0031594), stereocilium (GO:0032420), cuticular plate (GO:0032437), sarcolemma (GO:0042383), cell periphery (GO:0071944), blood microparticle (GO:0072562), plasma membrane (GO:0005886), cilium (GO:0005929)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Sensory processing of sound	2
Sensory Perception	1

GO top-level categories

32 GO namespaces:

Category	Terms
cellular anatomical structure	6
metal ion binding	2
binding	2
regulation of biological quality	1
retina homeostasis	1
multicellular organismal process	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
response to ATP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
identical protein binding	1
protein dimerization activity	1
cation binding	1
photoreceptor cell cilium	1
intracellular anatomical structure	1
cell-substrate junction	1
synapse	1
stereocilium bundle	1
neuron projection	1
actin-based cell projection	1
cortical actin cytoskeleton	1
plasma membrane	1
extracellular region	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to ATP	BP	direct assay
positive regulation of cytosolic calcium ion concentration	BP	direct assay
blood microparticle	CC	high-throughput assay
cuticular plate	CC	direct assay
stereocilium	CC	direct assay
calcium ion binding	MF	direct assay
magnesium ion binding	MF	direct assay
protein homodimerization activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 958 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CIB2	USH1G	Q495M9	824
CIB2	E9PNW1	E9PNW1	814
CIB2	TMC2	Q8TDI7	814
CIB2	CLRN1	P58418	810
CIB2	WHRN	Q9P202	807
CIB2	CDH23	Q9H251	804
CIB2	PCDH15	Q96QU1	803
CIB2	TMC1	Q8TDI8	775
CIB2	MYO7A	P78427	774
CIB2	PDZD7	Q9H5P4	774
CIB2	LHFPL5	Q8TAF8	772
CIB2	USH2A	O75445	751
CIB2	ADGRV1	Q8WXG9	727
CIB2	MYO15A	Q9UKN7	624
CIB2	TMIE	Q8NEW7	622

IntAct

Human interaction partners of CIB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 81 partners by confidence:

Partner	Interaction type	MIscore	Records
PARD3B	direct interaction	0.590	1
PATJ	direct interaction	0.440	8
GRIP2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	5
GRIP1	direct interaction	0.440	4
DLG1	direct interaction	0.440	3
DLG3	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
LNX1	direct interaction	0.440	3
MPDZ	direct interaction	0.440	3
NHERF4	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
DLG4	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
PDZK1	direct interaction	0.440	2
SCRIB	direct interaction	0.440	2
TJP1	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
APBA3	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1
CARD11	direct interaction	0.440	1
CASK	direct interaction	0.440	1
DLG5	direct interaction	0.440	1
ERBIN	direct interaction	0.440	1
FRMPD1	direct interaction	0.440	1

BioGRID (86 interactions; top human partners by supporting records): AAAS (Affinity Capture-MS), ABCF3 (Affinity Capture-MS), ACVR2A (Affinity Capture-MS), ADCY3 (Affinity Capture-MS), ANAPC5 (Affinity Capture-MS), APAF1 (Affinity Capture-MS), ARAP3 (Affinity Capture-MS), ASCC3 (Affinity Capture-MS), ATP13A2 (Affinity Capture-MS), AXL (Affinity Capture-MS), B3GNT2 (Affinity Capture-MS), BANP (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), CHTF18 (Affinity Capture-MS)

SIGNOR signaling

7 signaling interactions:

A	Effect	B	Mechanism
magnesium(2+)	“up-regulates activity”	CIB2	“chemical activation”
calcium(2+)	“up-regulates activity”	CIB2	“chemical activation”
CIB2	“up-regulates activity”	“a7/b1 integrin”	binding
CIB2	“up-regulates activity”	“AIIB/b3 integrin”	binding
CIB2	“down-regulates activity”	mTORC1	binding
CIB2	“up-regulates activity”	TMC1	binding
CIB2	“up-regulates activity”	TMC2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	2e-06
Long-term potentiation	5	44.1×	3e-06
Assembly and cell surface presentation of NMDA receptors	9	42.3×	5e-11
Neurexins and neuroligins	10	36.5×	2e-11
Protein-protein interactions at synapses	6	29.5×	2e-06
RHOA GTPase cycle	5	6.9×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	82.0×	2e-16
protein localization to synapse	6	58.9×	8e-08
receptor clustering	7	56.0×	8e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
protein-containing complex assembly	9	13.1×	2e-06
cell-cell adhesion	10	13.0×	4e-07
chemical synaptic transmission	7	6.9×	2e-03
nervous system development	8	4.7×	6e-03

Disease & clinical

Genetic variants

Variant evidence for CIB2: 270 ClinVar records (24 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	10
Uncertain significance	89
Likely benign	110
Benign	23

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 24 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
816953	NM_006383.4(CIB2):c.97C>T (p.Arg33Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
1058577	NM_006383.4(CIB2):c.542+1G>A	Pathogenic	criteria provided, single submitter	1
1420092	NM_006383.4(CIB2):c.40_47del (p.Asp14fs)	Pathogenic	criteria provided, single submitter	1
1455258	NM_006383.4(CIB2):c.385G>T (p.Glu129Ter)	Pathogenic	criteria provided, single submitter	1
3601861	NM_006383.4(CIB2):c.175del (p.Ile59fs)	Pathogenic	criteria provided, single submitter	1
3601868	NM_006383.4(CIB2):c.286del (p.Ser96fs)	Pathogenic	criteria provided, single submitter	1
3601879	NM_006383.4(CIB2):c.375_381del (p.Lys125fs)	Pathogenic	criteria provided, single submitter	1
3601900	NM_006383.4(CIB2):c.384_385insT (p.Glu129Ter)	Pathogenic	criteria provided, single submitter	1
3601911	NM_006383.4(CIB2):c.530del (p.Pro177fs)	Pathogenic	criteria provided, single submitter	1
3601920	NM_006383.4(CIB2):c.531del (p.Asp178fs)	Pathogenic	criteria provided, single submitter	1
4809535	NM_006383.4(CIB2):c.280_281del (p.Met94fs)	Pathogenic	criteria provided, single submitter	1
39685	NM_006383.4(CIB2):c.272T>C (p.Phe91Ser)	Likely pathogenic	criteria provided, single submitter	3
2501662	NM_006383.4(CIB2):c.199-1G>A	Likely pathogenic	criteria provided, single submitter	2
2430854	NM_006383.4(CIB2):c.347-2A>C	Likely pathogenic	criteria provided, single submitter	1
2635022	NM_006383.4(CIB2):c.199-125G>A	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CIB2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 469):

Position(s)	Effect	Δscore	Sites
15:78105795	donor_gain	1.0000
15:78109383–78109384	acceptor_loss	1.0000	6
15:78111163–78111164	donor_loss	1.0000	3
15:78111278	acceptor_gain	1.0000
15:78123703–78123704	donor_loss	1.0000	4
15:78105737–78105739	donor_loss	0.9900	7
15:78105936	acceptor_loss	0.9900
15:78105937	acceptor_gain	0.9900
15:78109233–78109234	donor_loss	0.9900	5
15:78109258	donor_gain	0.9900

AlphaMissense

806 missense substitutions predicted likely pathogenic (of 1,266 scored), across 165 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D116	8	0.995	0.999
N68	8	0.993	0.999
D127	8	0.992	0.999
D157	8	0.990	0.997
F183	8	0.989	1.000
F70	8	0.988	0.999
F78	8	0.988	0.999
F169	8	0.988	0.999
F179	8	0.988	0.999
F112	8	0.984	0.999
F8	8	0.982	0.999
F91	8	0.966	0.998
H184	8	0.964	0.996
F88	8	0.963	0.998
D168	8	0.961	0.993
F22	8	0.960	0.998
D120	8	0.950	0.998
D159	8	0.948	0.988
D178	8	0.947	0.994
D93	8	0.941	0.981

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:605564 | disease phenotypes: MIM:609439, MIM:614869, MIM:220290, MIM:607197, MIM:276900

GenCC curated gene-disease

4 curated gene-disease records:

Disease	Classification	Inheritance	Records
nonsyndromic genetic hearing loss	Definitive	Autosomal recessive
Usher syndrome type 1J	Definitive	Autosomal recessive	2
autosomal recessive nonsyndromic hearing loss 48	Strong	Autosomal recessive	2
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

2 validity classifications:

Disease	Classification	Inheritance
Usher syndrome type 1	Refuted	AR
nonsyndromic genetic hearing loss	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
DDG2P	green
Monogenic hearing loss	green
Paediatric disorders	green

Mondo (8): hearing loss disorder (MONDO:0005365), autosomal recessive nonsyndromic hearing loss 48 (MONDO:0012273), inherited retinal dystrophy (MONDO:0019118), hearing loss, autosomal recessive (MONDO:0019588), Usher syndrome type 1 (MONDO:0010168), Usher syndrome (MONDO:0019501), nonsyndromic genetic hearing loss (MONDO:0019497), (MONDO:0013935)

Orphanet (6): Usher syndrome type 1 (Orphanet:231169), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Usher syndrome (Orphanet:886), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

3 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001751	Abnormal vestibular function
HP:0011476	Profound sensorineural hearing impairment

GWAS associations

1 associations:

Study	Trait	p-value
GCST003476_8	Eyebrow thickness	1e-6

MeSH disease descriptors

6 disease descriptors:

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D058499	Retinal Dystrophies	C11.768.585.658
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886
C564609	Deafness, Autosomal Recessive *(supp.)*
C563720	Deafness, Autosomal Recessive 48 *(supp.)*
C580334	Nonsyndromic Deafness *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	3
Benzo(a)pyrene	increases expression, increases methylation	2
fluorene-9-bisphenol	decreases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	increases expression	1
Arsenic	increases expression	1
Carbamazepine	affects expression	1
Methapyrilene	increases methylation	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Vitamin E	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UD	Abcam HEK293T CIB2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 301 trials:

NCT	Phase	Status	Title
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	Phase 3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	Phase 3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	Phase 3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	Phase 3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	Phase 2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	Phase 2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	Phase 2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	Phase 2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	Phase 2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	Phase 2	WITHDRAWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	Phase 2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	Phase 2	UNKNOWN	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	Phase 2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	Phase 2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	Phase 2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	Phase 2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	Phase 1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	Phase 1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	Phase 1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	Phase 1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	Phase 1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	Phase 1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	Phase 1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	Phase 1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	Phase 1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT00486577	Phase 2/3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	Phase 2/3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	Phase 2/3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	Phase 2/3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	Phase 1/2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	Phase 1/2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	Phase 1/2	ACTIVE_NOT_RECRUITING	A Phase I/II Clinical Trial With SENS-501 in Children Suffering From Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	Phase 1/2	ACTIVE_NOT_RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	Phase 1/2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	Early Phase 1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss
NCT03300687	Early Phase 1	COMPLETED	First in Human Safety Study of FX-322 in Adults Undergoing Cochlear Implantation
NCT04777669	Early Phase 1	UNKNOWN	Removing Background Talker Noise for Cochlear Implant Users
NCT06025032	Early Phase 1	WITHDRAWN	a Study in Subjects With Otoferlin Mutation-related Hearing Loss Using RNA Base-eDiting Therapy(SOUND)
NCT00001668	Not specified	COMPLETED	Endolymphatic Sac Tumors in a Population of Patients With Von Hippel-Lindau Disease:The Natural History and Pathobiology, and a Prospective Non-Randomized Clinical Trial of Hearing Preservation Surgery in Patients With Early Stage Endolymphatic Sac Tumors
NCT00001782	Not specified	COMPLETED	Areas of Brain Responsible for Understanding American Sign Language
NCT00013468	Not specified	COMPLETED	Early Diagnosis of Steroid-Responsive & No-Responsive Hearing Loss
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00018486	Not specified	COMPLETED	Epidemiology of Hearing Loss in Diabetic and Non-Diabetic Veterans
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT00110604	Not specified	COMPLETED	The Effect of Folic Acid on Atherosclerosis, Cognitive Performance and Hearing
NCT00126113	Not specified	COMPLETED	The Performance-Perceptual Test as a Counseling Tool
NCT00260663	Not specified	COMPLETED	The Hearing Aid Effectiveness After Aural Rehabilitation (HEAR) Trial
NCT00371436	Not specified	COMPLETED	Progressive Intervention Program for Tinnitus Management
NCT00371449	Not specified	COMPLETED	Predicting Success With Hearing Aids
NCT00371839	Not specified	COMPLETED	Clinical Applications for Time-Compressed Speech Tests
NCT00400413	Not specified	COMPLETED	Neuroanatomy of Reading in Congenital Deafness.
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NCT00484224	Not specified	UNKNOWN	Audiological Disturbances in Vitiligo