CEACAM16

Chr 19ADAR

CEA cell adhesion molecule 16, tectorial membrane component

Also known as: CEAL2, DFNA4B, DFNB113

NCBI Gene: 388551 ENSG00000213892 UniProt: Q2WEN9 OMIM: 614591

CEACAM16 encodes a secreted glycoprotein that maintains the integrity of the tectorial membrane in the inner ear and is essential for proper hearing across an extended frequency range. Mutations cause nonsyndromic hearing loss with both autosomal dominant (DFNA4B) and autosomal recessive (DFNB113) inheritance patterns. The gene shows low constraint to loss-of-function variation (pLI near zero), which is consistent with recessive forms of deafness being tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismAD/ARLOEUF 1.032 OMIM phenotypes

Clinical Summary— CEACAM16

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Gene-Disease Validity (ClinGen)

nonsyndromic genetic hearing loss · ARStrong

Strong evidence — appropriate for clinical testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.52Z-score

OE missense 0.91 (0.82–1.01)

253 obs / 277.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.61 (0.37–1.03)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 10 / 16.4Missense obs/exp: 253 / 277.6Syn Z: 0.04

This gene — mechanism propensity

0.74top 25%

GOF

0.77top 25%

LOF

0.2774th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.