DCDC2

Chr 6AR

doublecortin domain containing 2

Also known as: DCDC2A, DFNB66, NPHP19, NSC, RU2, RU2S

NCBI Gene: 51473ENSG00000146038UniProt: Q9UHG0

This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

?Deafness, autosomal recessive 66MIM #610212
AR
Nephronophthisis 19MIM #616217
AR
Sclerosing cholangitis, neonatalMIM #617394
AR
UniProtDyslexia 2
403
ClinVar variants
40
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— DCDC2
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 182 VUS of 403 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.16LOEUF
pLI 0.000
Z-score 1.00
OE 0.77 (0.53–1.16)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.43Z-score
OE missense 0.93 (0.83–1.03)
252 obs / 272.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.77 (0.53–1.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.83–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 17 / 22.1Missense obs/exp: 252 / 272.0Syn Z: -0.90

ClinVar Variant Classifications

403 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic20
VUS182
Likely Benign110
Benign47
Conflicting24
20
Pathogenic
20
Likely Pathogenic
182
VUS
110
Likely Benign
47
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
10
0
20
Likely Pathogenic
10
3
7
0
20
VUS
4
150
21
7
182
Likely Benign
0
3
62
45
110
Benign
0
3
42
2
47
Conflicting
—24
Total2216114254403

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DCDC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DCDC2-related renal-hepatic ciliopathy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Deafness, autosomal recessive 66

MIM #610212

Molecular basis of disorder known

Autosomal recessive

Nephronophthisis 19

MIM #616217

Molecular basis of disorder known

Autosomal recessive

Sclerosing cholangitis, neonatal

MIM #617394

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — DCDC2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.
Chen HL et al.·J Biomed Sci
2018Review
Biallelic known and novel DCDC2 variants in cholestatic liver disease: Phenotype-genotype observations in four children.
Azabdaftari A et al.·Liver Int
2023
Two cases of DCDC2-related neonatal sclerosing cholangitis with developmental delay and literature review.
Syryn H et al.·Clin Genet
2021Review
Neonatal Cholestasis: Exploring Genetic Causes and Clinical Outcomes.
Gürcan Kaya N et al.·J Paediatr Child Health
2025
[Neonatal sclerosing cholangitis caused by DCDC2 variations in two siblings and literature review].
Li JQ et al.·Zhonghua Er Ke Za Zhi
2018Review
DCDC2 inhibits hepatic stellate cell activation and ameliorates CCl(4)-induced liver fibrosis by suppressing Wnt/β-catenin signaling.
Liu QQ et al.·Sci Rep
2024
Polymorphisms in DCDC2 and S100B associate with developmental dyslexia.
Matsson H et al.·J Hum Genet
2015
DCDC2 Mutations Cause Neonatal Sclerosing Cholangitis.
Girard M et al.·Hum Mutat
2016
Development of a prognostic model based on the ceRNA network in Triple-Negative Breast cancer.
Zhu Y et al.·PeerJ
2025Functional
A dyslexia-associated variant in DCDC2 changes gene expression.
Meng H et al.·Behav Genet
2011
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Reading Disorder

Gene x Environment Interplay in Developmental Dyslexia Treatment: A Round-trip Translation Between Humans and Animal

RECRUITING
NCT06186882Phase NAIRCCS Eugenio MedeaStarted 2023-04-30
Action Video-Game

External Resources

Links to major genomics databases and tools