GIPC3

Chr 19AR

GIPC PDZ domain containing family member 3

Also known as: C19orf64, DFNB15, DFNB72, DFNB95

NCBI Gene: 126326ENSG00000179855UniProt: Q8TF64

The protein encoded by this gene belongs to the GIPC family. Studies in mice suggest that this gene is required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion in the ear. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2011]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 15MIM #601869
AR
292
ClinVar variants
47
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— GIPC3
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Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
47 Pathogenic / Likely Pathogenic· 120 VUS of 292 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.93LOEUF
pLI 0.009
Z-score 1.73
OE 0.44 (0.23–0.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.18Z-score
OE missense 0.96 (0.85–1.09)
173 obs / 179.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.23–0.93)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.85–1.09)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 5 / 11.3Missense obs/exp: 173 / 179.7Syn Z: -0.08

ClinVar Variant Classifications

292 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic15
VUS120
Likely Benign90
Benign19
Conflicting16
32
Pathogenic
15
Likely Pathogenic
120
VUS
90
Likely Benign
19
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
5
22
0
32
Likely Pathogenic
9
4
2
0
15
VUS
2
100
15
3
120
Likely Benign
0
8
36
46
90
Benign
0
0
18
1
19
Conflicting
—16
Total161179350292

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GIPC3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal recessive 15

MIM #601869

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Challenges in whole exome sequencing: an example from hereditary deafness.
Sirmaci A et al.·PLoS One
2012
Homozygosity mapping identifies a novel GIPC3 mutation causing congenital nonsyndromic hearing loss in a Saudi family.
Ramzan K et al.·Gene
2013Case report
Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistani families.
Zhou Y et al.·BMC Med Genet
2020
Low incidence of GIPC3 variants among the prelingual hearing impaired from southern India.
Kalaimathi M et al.·J Genet
2020
Genetic Variant c.245A>G (p.Asn82Ser) in GIPC3 Gene Is a Frequent Cause of Hereditary Nonsyndromic Sensorineural Hearing Loss in Chuvash Population.
Petrova NV et al.·Genes (Basel)
2021
Screening Consanguineous Families for Hearing Loss Using the MiamiOtoGenes Panel.
Kannan-Sundhari A et al.·Genet Test Mol Biomarkers
2020
Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss.
Diaz-Horta O et al.·PLoS One
2012
A novel missense mutation in GIPC3 causes sensorineural hearing loss in an Iranian family revealed by targeted next-generation sequencing.
Asgharzade S et al.·Int J Pediatr Otorhinolaryngol
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools