CDRT4

Summary

CDRT4 (CMT1A duplicated region transcript 4, HGNC:14383) is a protein-coding gene on chromosome 17p12, encoding CMT1A duplicated region transcript 4 protein (Q8N9R6).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 29 total — 4 pathogenic
• MANE Select transcript: NM_001204477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14383
Approved symbol	CDRT4
Name	CMT1A duplicated region transcript 4
Location	17p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36674
Ensembl gene	ENSG00000239704
Ensembl biotype	protein_coding
Entrez	284040

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000519354, ENST00000520956, ENST00000619038, ENST00000885788, ENST00000885789, ENST00000885790, ENST00000963509

RefSeq mRNA: 1 — MANE Select: NM_001204477 NM_001204477

CCDS: CCDS73995

Canonical transcript exons

ENST00000619038 — 4 exons

Exon	Start	End
ENSE00001329632	15436015	15438200
ENSE00001416960	15467460	15467621
ENSE00001422824	15453004	15453085
ENSE00004474589	15440208	15440285

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0210 / max 12.6304, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164690	0.0210	4

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.77	gold quality
pituitary gland	UBERON:0000007	94.50	gold quality
adenohypophysis	UBERON:0002196	93.98	gold quality
right testis	UBERON:0004534	90.04	gold quality
left testis	UBERON:0004533	89.88	gold quality
lower esophagus mucosa	UBERON:0035834	89.28	gold quality
testis	UBERON:0000473	88.69	gold quality
right lobe of thyroid gland	UBERON:0001119	88.60	gold quality
left lobe of thyroid gland	UBERON:0001120	88.36	gold quality
thyroid gland	UBERON:0002046	88.21	gold quality
body of pancreas	UBERON:0001150	87.39	gold quality
right adrenal gland cortex	UBERON:0035827	86.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.51	gold quality
cerebellar hemisphere	UBERON:0002245	86.19	gold quality
cerebellar cortex	UBERON:0002129	86.09	gold quality
left ovary	UBERON:0002119	85.87	gold quality
cerebellum	UBERON:0002037	85.85	gold quality
endocervix	UBERON:0000458	85.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.28	gold quality
ovary	UBERON:0000992	84.84	gold quality
right ovary	UBERON:0002118	84.78	gold quality
right adrenal gland	UBERON:0001233	84.77	gold quality
prostate gland	UBERON:0002367	84.61	gold quality
hypothalamus	UBERON:0001898	84.55	gold quality
minor salivary gland	UBERON:0001830	84.48	gold quality
nucleus accumbens	UBERON:0001882	84.12	gold quality
sural nerve	UBERON:0015488	83.95	gold quality
left adrenal gland cortex	UBERON:0035825	83.90	gold quality
saliva-secreting gland	UBERON:0001044	83.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.48

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cdrt4	ENSMUSG00000042200
rattus_norvegicus	Cdrt4	ENSRNOG00000003294

Protein

Protein identifiers

CMT1A duplicated region transcript 4 protein — Q8N9R6 (reviewed: Q8N9R6)

All UniProt accessions (1): Q8N9R6

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Expressed in fetal skeletal muscle and kidney.

RefSeq proteins (1): NP_001191406* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029185	CDRT4	Family

Pfam: PF15213

UniProt features (7 total): region of interest 2, compositionally biased region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9R6-F1	66.42	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): chr17p12, TGACATY_UNKNOWN, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, CSR_EARLY_UP.V1_DN, PRC2_EED_DN.V1_UP, JAK2_DN.V1_DN, CBX7_TARGET_GENES, HAND1_TARGET_GENES, HES2_TARGET_GENES, ZNF92_TARGET_GENES, MIR4288, MIR4666B, GSE11057_CD4_CENT_MEM_VS_PBMC_UP, MIR3675_3P, GSE12366_PLASMA_CELL_VS_NAIVE_BCELL_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

166 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDRT4	TVP23C	Q96ET8	728
CDRT4	A0A0A6YYB9	A0A0A6YYB9	720
CDRT4	TVP23B	Q9NYZ1	658
CDRT4	CDRT15	Q96T59	621
CDRT4	TEKT3	Q9BXF9	571
CDRT4	H0YIS7	H0YIS7	571
CDRT4	SMCO2	A6NFE2	507
CDRT4	LRRC9	Q6ZRR7	479
CDRT4	HS3ST3B1	Q9Y662	433
CDRT4	ITFG1	Q8TB96	355
CDRT4	GPR146	Q96CH1	349
CDRT4	TMEM176A	Q96HP8	332
CDRT4	TEKT2	Q9UIF3	330
CDRT4	FOCAD	Q5VW36	325
CDRT4	MANSC4	A6NHS7	324

IntAct

8 interactions, top by confidence:

A	B	Type	Score
VAC14	CDRT4	psi-mi:“MI:0915”(physical association)	0.780
CDRT4	VAC14	psi-mi:“MI:0915”(physical association)	0.780
CDRT4	VAC14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): CDRT4 (Two-hybrid), CDRT4 (Affinity Capture-MS), CDRT4 (Two-hybrid), CDRT4 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUI7, A1DL98, A1L1K4, A4V8B4, A6QLJ4, A6ZMG4, A6ZR60, A7NVJ4, A9JR56, B3LLZ8, C5E1C7, C7GWA2, C8ZEW0, O13916, O60153, P0C2W9, P15130, P16135, P20486, P27271, P28974, P35198, P40063, P84395, Q04438, Q28EW5, Q28GG3, Q4V853, Q5FVD7, Q5R4F8, Q5R977, Q5RD94, Q5U550, Q66657, Q68EK9, Q68FR5, Q6AX78, Q6C3T0, Q751I6, Q7T2A3

Diamond homologs: Q2YDL7, Q8N9R6, Q9DA64

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	20
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2498728	GRCh37/hg19 17p12(chr17:14095306-15466762)x3	Pathogenic
4820236	Single allele	Pathogenic
523238	GRCh37/hg19 17p12(chr17:14215739-15422582)	Pathogenic
815906	GRCh37/hg19 17p12(chr17:14195642-15545880)x3	Pathogenic

SpliceAI

530 predictions. Top by Δscore:

Variant	Effect	Δscore
17:15438201:C:CA	acceptor_loss	0.9900
17:15438201:C:CC	acceptor_gain	0.9900
17:15438202:T:G	acceptor_loss	0.9900
17:15438206:A:T	acceptor_gain	0.9900
17:15438205:C:CT	acceptor_gain	0.9800
17:15438199:TC:T	acceptor_gain	0.9700
17:15438200:CC:C	acceptor_gain	0.9700
17:15453002:A:C	donor_gain	0.9700
17:15438196:GAGTC:G	acceptor_gain	0.9600
17:15438198:GTC:G	acceptor_gain	0.9600
17:15438197:AGTC:A	acceptor_gain	0.9500
17:15438205:C:T	acceptor_gain	0.9400
17:15438208:C:CT	acceptor_gain	0.9400
17:15438198:GTCCT:G	acceptor_gain	0.9300
17:15438197:AGTCC:A	acceptor_gain	0.9200
17:15438199:TCCTA:T	acceptor_gain	0.9200
17:15438200:CCTAC:C	acceptor_gain	0.9200
17:15438201:CTACC:C	acceptor_gain	0.9200
17:15439736:A:T	donor_gain	0.9200
17:15467488:T:TA	donor_gain	0.9100
17:15475375:G:C	donor_gain	0.9100
17:15438202:T:A	acceptor_gain	0.8800
17:15441782:T:TA	donor_gain	0.8600
17:15443826:TGC:T	donor_gain	0.8400
17:15440202:CCCTA:C	donor_loss	0.8200
17:15440203:CCTA:C	donor_loss	0.8200
17:15440203:CCTAC:C	donor_loss	0.8200
17:15440204:CTACC:C	donor_loss	0.8200
17:15440205:TACC:T	donor_loss	0.8200
17:15440205:TACCT:T	donor_loss	0.8200

AlphaMissense

992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:15437818:A:C	F138L	0.965
17:15437818:A:T	F138L	0.965
17:15437820:A:G	F138L	0.965
17:15437825:A:G	I136T	0.896
17:15437825:A:C	I136S	0.873
17:15438134:A:T	V33D	0.869
17:15437827:C:A	K135N	0.855
17:15437827:C:G	K135N	0.855
17:15437819:A:G	F138S	0.853
17:15438104:A:G	L43P	0.842
17:15437831:T:A	N134I	0.822
17:15438140:G:T	A31D	0.814
17:15437819:A:C	F138C	0.802
17:15438147:A:G	W29R	0.801
17:15438147:A:T	W29R	0.801
17:15437830:G:C	N134K	0.787
17:15437830:G:T	N134K	0.787
17:15438145:C:A	W29C	0.769
17:15438145:C:G	W29C	0.769
17:15438091:G:C	S47R	0.750
17:15438091:G:T	S47R	0.750
17:15438093:T:G	S47R	0.750
17:15438114:C:A	V40L	0.724
17:15438114:C:G	V40L	0.724
17:15438113:A:T	V40E	0.723
17:15437820:A:T	F138I	0.722
17:15437820:A:C	F138V	0.720
17:15437822:A:T	I137N	0.718
17:15438135:C:G	V33L	0.715
17:15438134:A:C	V33G	0.700

dbSNP variants (sampled 300 via entrez): RS1000158031 (17:15439509 A>G), RS1000226932 (17:15453979 A>G), RS1000489409 (17:15441101 C>T), RS1000490720 (17:15457580 A>G), RS1000530934 (17:15445803 A>C), RS1000542570 (17:15457250 T>C), RS1000564326 (17:15464719 T>C), RS1000595052 (17:15449316 A>G), RS1000604517 (17:15446122 G>A), RS1000830934 (17:15452565 G>A), RS1000951313 (17:15452934 C>A), RS1001032557 (17:15445184 T>C), RS1001241876 (17:15439275 A>G,T), RS1001287308 (17:15440954 G>A), RS1001429698 (17:15446815 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:118220

GenCC curated gene-disease

Mondo (3): Charcot-Marie-Tooth disease type 1A (MONDO:0007309), axonal neuropathy (MONDO:0004183), hearing loss disorder (MONDO:0005365)

Orphanet (1): Charcot-Marie-Tooth disease type 1A (Orphanet:101081)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000106_6	Pulmonary function	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
Valproic Acid	decreases expression, increases methylation	2
fluorene-9-bisphenol	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	affects cotreatment, affects expression	1
Colforsin	affects cotreatment, affects expression	1
Hydrogen Peroxide	affects expression	1
Iron	increases expression	1
Quercetin	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT02579759	PHASE3	COMPLETED	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT02600286	PHASE2	TERMINATED	Ulipristal Acetate In Disease Charcot-Marie-Tooth Type of 1A
NCT02967679	PHASE2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT07140614	PHASE1	RECRUITING	A First in Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of EDK060 in Adults With CMT1A.
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT01289704	PHASE2/PHASE3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT06328712	PHASE1/PHASE2	RECRUITING	Evaluate the Safety and Efficacy of EN001 in Patients With Charcot-Marie-Tooth Disease Type 1A(CMT1A) (Phase 1b: Open-label, Dose-escalation, Single-center; Phase 2a: Randomized, Double-blind, Placebo-controlled, Multicenter)
NCT02357355	Not specified	COMPLETED	Driving Ability in Patients With CMT 1A
NCT02596191	Not specified	ACTIVE_NOT_RECRUITING	Tools for Therapeutic Evaluation in Charcot-Marie-Tooth Disease Type 1A: Outcome Measures and Biomarkers
NCT03278093	Not specified	UNKNOWN	Effect of Orthoses and Underfoot Vibration on Balance in Neuropathy
NCT06794489	Not specified	RECRUITING	Longitudinal Biomarkers With Selected Outcome Measures In CMT