CCDC54

Chr 3

coiled-coil domain containing 54

Also known as: NYD-SP17, SP17

NCBI Gene: 84692 ENSG00000138483 UniProt: Q8NEL0

The protein localizes to the cytoplasm and is involved in cellular processes, though its specific molecular function remains unclear. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and developmental delays, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

Research

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.91

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.91LOEUF

pLI 0.000

Z-score -1.20

OE 1.43 (0.91–1.91)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.17Z-score

OE missense 0.96 (0.85–1.10)

160 obs / 166.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.43 (0.91–1.91)

0≤0.351.4

Missense OE?0.96 (0.85–1.10)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 13 / 9.1Missense obs/exp: 160 / 166.0Syn Z: 0.17

Background carrier burden — how many people carry a rare variant somewhere in CCDC54?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 87

409 rare PASS variants

Rare truncating (LoF)

1 in 310

59 rare PASS variants

Rare synonymous (reference)

1 in 350

135 rare PASS variants

Rare missense and truncating variants are carried at similar rates in CCDC54; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 1,400
South Asian	~43k	1 in 130	1 in 640
Remaining (unassigned)	~30k	1 in 120	1 in 410
European (Finnish)	~27k	1 in 330	1 in 520
Admixed American	~22k	1 in 94	1 in 550
African / African American	~21k	1 in 150	1 in 1,700
East Asian	~20k	1 in 130	1 in 2,100
Ashkenazi Jewish	~13k	1 in 1,500	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 100	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓