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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DCDC2
doublecortin domain containing 2
Chromosome 6 Β· 6p22.3
NCBI Gene: 51473Ensembl: ENSG00000146038.13HGNC: HGNC:18141UniProt: Q9UHG0
90PubMed Papers
24Diseases
0Drugs
33Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsensory perception of soundregulation of Wnt signaling pathwaypositive regulation of smoothened signaling pathwaysclerosing cholangitisSenior-Boichis syndromehearing loss, autosomal recessivedeafness
✦AI Summary

DCDC2 (doublecortin domain containing 2) is a ciliary protein with pleiotropic functions across multiple biological systems. Primary function: DCDC2 regulates ciliogenesis and ciliary length 12 and inhibits canonical Wnt signaling 3. In the nervous system, DCDC2 supports neuronal migration during neocortex development and maintains episodic memory through dorsolateral prefrontal cortex expression 4. Mechanism: DCDC2 stabilizes ENO1 protein, enhancing AKT phosphorylation and promoting FGL1 expression, which facilitates immune evasion via the FGL1-LAG3 checkpoint 5. Disease relevance: Biallelic DCDC2 variants cause neonatal sclerosing cholangitis (NSC), a progressive biliary fibrosis requiring early intervention 678. Variants also associate with nephronophthisis, autosomal recessive deafness, and developmental delay 78. Common polymorphisms (rs807701) contribute to dyslexia risk 9, correlating with visuo-spatial memory and long-term memory deficits in animal models 10. Clinical significance: DCDC2 protein-truncating variants cause severe early-onset hepatobiliary disease, while missense variants present milder childhood-onset phenotypes 7. Anti-DCDC2 autoantibodies represent potential diagnostic biomarkers for intrahepatic cholangiocarcinoma 5.

Sources cited
1
DCDC2 controls ciliogenesis and ciliary length
PMID: 25601850
2
DCDC2 involved in regulation of ciliary length
PMID: 27319779
3
DCDC2 inhibits canonical Wnt signaling pathway
PMID: 25557784
4
DCDC2 associated with episodic memory maintenance through dorsolateral prefrontal cortex expression
PMID: 34873813
5
DCDC2 stabilizes ENO1 and promotes FGL1-LAG3 immune checkpoint activation in cancer
PMID: 40533767
6
DCDC2 mutations cause neonatal sclerosing cholangitis
PMID: 30367658
7
Protein-truncating DCDC2 variants cause severe hepatobiliary disease; missense variants cause milder phenotypes; associated with nephronophthisis and learning disability
PMID: 36938759
8
DCDC2 ciliopathy causes neonatal sclerosing cholangitis with developmental delay, microcephaly, and risk for arterial aneurysms
PMID: 34155636
9
DCDC2 rs807701 polymorphism contributes to dyslexia risk
PMID: 23229871
10
Dcdc2 mutation impairs visuo-spatial memory and long-term memory in mice
PMID: 21883923
Disease Associationsβ“˜24
sclerosing cholangitisOpen Targets
0.77Strong
Senior-Boichis syndromeOpen Targets
0.71Strong
hearing loss, autosomal recessiveOpen Targets
0.64Moderate
deafnessOpen Targets
0.55Moderate
dyslexiaOpen Targets
0.46Moderate
ciliopathyOpen Targets
0.38Weak
neurodegenerative diseaseOpen Targets
0.37Weak
chylomicron retention diseaseOpen Targets
0.34Weak
autosomal dominant nonsyndromic hearing lossOpen Targets
0.33Weak
nonsyndromic deafnessOpen Targets
0.33Weak
nervous system benign neoplasmOpen Targets
0.31Weak
sialadenitisOpen Targets
0.27Weak
major depressive disorderOpen Targets
0.25Weak
hypertrophic cardiomyopathyOpen Targets
0.25Weak
hypersomniaOpen Targets
0.24Weak
polycystic ovary syndromeOpen Targets
0.23Weak
Sacroiliac arthritisOpen Targets
0.22Weak
inherited retinal dystrophyOpen Targets
0.21Weak
mental or behavioural disorderOpen Targets
0.21Weak
genetic disorderOpen Targets
0.19Weak
Deafness, autosomal recessive, 66UniProt
Dyslexia 2UniProt
Nephronophthisis 19UniProt
Sclerosing cholangitis, neonatalUniProt
Pathogenic Variants33
NM_016356.5(DCDC2):c.349-2A>GPathogenic
Nephronophthisis 19|not provided|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|Autosomal recessive nonsyndromic hearing loss 66;Nephronophthisis 19;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2025
NM_016356.5(DCDC2):c.890T>A (p.Leu297Ter)Pathogenic
Isolated neonatal sclerosing cholangitis|Autosomal recessive nonsyndromic hearing loss 66;Nephronophthisis 19;Isolated neonatal sclerosing cholangitis|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2025β†’ Residue 297
NM_016356.5(DCDC2):c.383C>G (p.Ser128Ter)Pathogenic
not provided|Nephronophthisis 19|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis;Nephronophthisis 19|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2025β†’ Residue 128
NM_016356.5(DCDC2):c.705-2A>GPathogenic
DCDC2-related disorder|Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66|Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66
β˜…β˜…β˜†β˜†2025
NM_016356.5(DCDC2):c.294-2A>GPathogenic
not provided|Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2024
NM_016356.5(DCDC2):c.529dup (p.Ile177fs)Pathogenic
Isolated neonatal sclerosing cholangitis|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|not provided|Autosomal recessive nonsyndromic hearing loss 66;Nephronophthisis 19;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2024β†’ Residue 177
NM_016356.5(DCDC2):c.942del (p.Gly315fs)Pathogenic
not provided|Isolated neonatal sclerosing cholangitis|Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|DCDC2-related disorder|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜…β˜†β˜†2024β†’ Residue 315
NM_016356.5(DCDC2):c.123_124del (p.Ser42fs)Pathogenic
Nephronophthisis 19|Isolated neonatal sclerosing cholangitis|Dyslexia, susceptibility to, 2|Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 42
NM_016356.5(DCDC2):c.970dup (p.Ala324fs)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis|DCDC2-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 324
NM_016356.5(DCDC2):c.1023+2T>CLikely pathogenic
Isolated neonatal sclerosing cholangitis;Autosomal recessive nonsyndromic hearing loss 66
β˜…β˜†β˜†β˜†2025
NM_016356.5(DCDC2):c.2T>G (p.Met1Arg)Likely pathogenic
Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_016356.5(DCDC2):c.558G>C (p.Arg186Ser)Likely pathogenic
DCDC2-related disorder|Nephronophthisis 19
β˜…β˜†β˜†β˜†2024β†’ Residue 186
NM_016356.5(DCDC2):c.557+1G>TPathogenic
DCDC2-related disorder
β˜…β˜†β˜†β˜†2024
NM_016356.5(DCDC2):c.38dup (p.Pro14fs)Likely pathogenic
Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2024β†’ Residue 14
NM_016356.5(DCDC2):c.604G>T (p.Glu202Ter)Likely pathogenic
Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2024β†’ Residue 202
NM_016356.5(DCDC2):c.901C>T (p.Gln301Ter)Likely pathogenic
Nephronophthisis 19
β˜…β˜†β˜†β˜†2024β†’ Residue 301
NM_016356.5(DCDC2):c.76G>C (p.Asp26His)Likely pathogenic
Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2024β†’ Residue 26
NM_016356.5(DCDC2):c.289_292del (p.Leu97fs)Likely pathogenic
Nephronophthisis 19;Autosomal recessive nonsyndromic hearing loss 66;Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2024β†’ Residue 97
NM_016356.5(DCDC2):c.1045G>T (p.Glu349Ter)Likely pathogenic
Isolated neonatal sclerosing cholangitis
β˜…β˜†β˜†β˜†2024β†’ Residue 349
NM_016356.5(DCDC2):c.1155del (p.Glu386fs)Likely pathogenic
DCDC2-related disorder
β˜…β˜†β˜†β˜†2023β†’ Residue 386
View on ClinVar β†—
Related Genes
ROBO1Protein interaction98%ATP2C2Protein interaction98%TDP2Protein interaction94%KIAA0319Protein interaction92%ACOT13Protein interaction92%MRPL19Protein interaction79%
Tissue Expression6 tissues
Liver
100%
Lung
46%
Brain
42%
Ovary
7%
Bone Marrow
1%
Heart
0%
Gene Interaction Network
Click a node to explore
DCDC2ROBO1ATP2C2TDP2KIAA0319ACOT13MRPL19
PROTEIN STRUCTURE
Preparing viewer…
PDB2DNF Β· NMR
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.06LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.79 [0.60–1.06]
RankingsWhere DCDC2 stands among ~20K protein-coding genes
  • #5,300of 20,598
    Most Researched90
  • #1,726of 5,498
    Most Pathogenic Variants33
  • #10,686of 17,882
    Most Constrained (LOEUF)1.06
Genes detectedDCDC2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 27336129
1.00
2
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.
PMID: 30367658
J Biomed Sci Β· 2018
0.90
3
Integration of GWAS and brain transcriptomic analyses in a multiethnic sample of 35,245 older adults identifies DCDC2 gene as predictor of episodic memory maintenance.
PMID: 34873813
Alzheimers Dement Β· 2022
0.80
4
The DCDC2/ENO1 axis promotes tumor progression and immune evasion in intrahepatic cholangiocarcinoma via activating FGL1-LAG3 checkpoint.
PMID: 40533767
J Exp Clin Cancer Res Β· 2025
0.70
5
[Genetics of dyslexia].
PMID: 17094062
Z Kinder Jugendpsychiatr Psychother Β· 2006
0.60