CCDC154

Chr 16

coiled-coil domain containing 154

Also known as: C16orf29

The protein encoded by this gene is predicted to be involved in bone mineralization during bone maturation and is located in early endosomes. Mutations cause autosomal recessive spondyloepiphyseal dysplasia with hearing loss and intellectual disability, affecting bone development, auditory function, and cognitive development. This gene is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.15
Clinical SummaryCCDC154
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 0.86
OE 0.84 (0.621.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.52Z-score
OE missense 0.93 (0.851.01)
359 obs / 387.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.621.15)
00.351.4
Missense OE0.93 (0.851.01)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 28 / 33.4Missense obs/exp: 359 / 387.7Syn Z: -0.20
DN
0.6550th %ile
GOF
0.6639th %ile
LOF
0.4135th %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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CCDC154 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →