CEACAM16

Chr 19ADAR

CEA cell adhesion molecule 16, tectorial membrane component

Also known as: CEAL2, DFNA4B, DFNB113

NCBI Gene: 388551ENSG00000213892UniProt: Q2WEN9

The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 4BMIM #614614
AD
Deafness, autosomal recessive 113MIM #618410
AR
322
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CEACAM16
🧬
Gene-Disease Validity (ClinGen)
nonsyndromic genetic hearing loss · ARStrong

Strong evidence — appropriate for clinical testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 167 VUS of 322 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

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.
1.03LOEUF
pLI 0.000
Z-score 1.47
OE 0.61 (0.37–1.03)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.52Z-score
OE missense 0.91 (0.82–1.01)
253 obs / 277.6 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.0.61 (0.37–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.82–1.01)
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.1.00
0≤1.21.6
LoF obs/exp: 10 / 16.4Missense obs/exp: 253 / 277.6Syn Z: 0.04

ClinVar Variant Classifications

322 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13
Likely Pathogenic8
VUS167
Likely Benign80
Benign27
Conflicting27
13
Pathogenic
8
Likely Pathogenic
167
VUS
80
Likely Benign
27
Benign
27
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
8
0
13
Likely Pathogenic
2
3
3
0
8
VUS
2
151
7
7
167
Likely Benign
0
10
26
44
80
Benign
0
2
19
6
27
Conflicting
—27
Total61696357322

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

View in ClinVar →

Protein Context — Lollipop Plot

CEACAM16 · 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 dominant 4B

MIM #614614

Molecular basis of disorder known

Autosomal dominant

Deafness, autosomal recessive 113

MIM #618410

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The old CEACAMs find their new role in tumor immunotherapy.
Han ZW et al.·Invest New Drugs
2020Review
Auditory Phenotype of a Novel Missense Variant in the CEACAM16 Gene in a Large Russian Family With Autosomal Dominant Nonsyndromic Hearing Loss.
Markova TG et al.·J Int Adv Otol
2024
Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment.
Booth KT et al.·J Med Genet
2018
A novel missense variant in CEACAM16 gene causes autosomal dominant nonsyndromic hearing loss.
Zhang D et al.·Ann Hum Genet
2022
Loss of mammal-specific tectorial membrane component carcinoembryonic antigen cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies.
Kammerer R et al.·J Biol Chem
2012
Exome sequencing identifies a novel CEACAM16 mutation associated with autosomal dominant nonsyndromic hearing loss DFNA4B in a Chinese family.
Wang H et al.·J Hum Genet
2015
[Identification of a novel mutation of CEACAM16 gene in a Chinese family with autosomal dominant nonsyndromic hearing loss].
Zhang Q et al.·Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
2020
Further evidence for loss-of-function mutations in the CEACAM16 gene causing nonsyndromic autosomal recessive hearing loss in humans.
Dias AMM et al.·J Hum Genet
2019
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