CDRT4

Chr 17ADAR

CMT1A duplicated region transcript 4

NCBI Gene: 284040 ENSG00000239704 UniProt: Q8N9R6 OMIM: 601097

CDRT4 encodes a protein involved in peripheral nerve myelination and maintenance. Mutations cause various forms of Charcot-Marie-Tooth disease (types 1A and 1E), Dejerine-Sottas disease, recurrent neuropathy with pressure palsies, and Roussy-Levy syndrome, primarily affecting peripheral nerves with demyelinating features. The inheritance pattern is typically autosomal dominant, though autosomal recessive forms have been reported.

OMIM ResearchSummary from OMIM

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

?Neuropathy, inflammatory demyelinatingMIM #139393

Charcot-Marie-Tooth disease, type 1AMIM #118220

Charcot-Marie-Tooth disease, type 1EMIM #118300

Dejerine-Sottas diseaseMIM #145900

ADAR

Neuropathy, recurrent, with pressure palsiesMIM #162500

Roussy-Levy syndromeMIM #180800

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Charcot-Marie-Tooth disease, type 1A; Charcot-Marie-Tooth disease, type 1E (+3); no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.096

Z-score 0.08

OE 0.92 (0.25–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.99 (0.83–1.18)

87 obs / 87.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.92 (0.25–1.88)

0≤0.351.4

Missense OE?0.99 (0.83–1.18)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 1 / 1.1Missense obs/exp: 87 / 87.9Syn Z: -0.11

Background carrier burden — how many people carry a rare variant somewhere in CDRT4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

179 rare PASS variants

Rare truncating (LoF)

1 in 5,100

25 rare PASS variants

Rare synonymous (reference)

1 in 410

66 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CDRT4. 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 480	1 in 6,500
South Asian	~43k	1 in 130	1 in 2,500
Remaining (unassigned)	~30k	1 in 220	1 in 5,000
European (Finnish)	~27k	1 in 1,200	none seen
Admixed American	~22k	1 in 220	≈ 1 in 7,500
African / African American	~21k	1 in 270	1 in 2,900
East Asian	~20k	1 in 230	none seen
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 130	none seen

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓