DCDC2

Summary

DCDC2 (doublecortin domain containing 2, HGNC:18141) is a protein-coding gene on chromosome 6p22.3, encoding Doublecortin domain-containing protein 2 (Q9UHG0). Protein that plays a role in the inhibition of canonical Wnt signaling pathway.

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.

Source: NCBI Gene 51473 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ciliopathy (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 394 total — 13 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 58
• MANE Select transcript: NM_016356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18141
Approved symbol	DCDC2
Name	doublecortin domain containing 2
Location	6p22.3
Locus type	gene with protein product
Status	Approved
Aliases	RU2, KIAA1154, DCDC2A, NPHP19
Ensembl gene	ENSG00000146038
Ensembl biotype	protein_coding
OMIM	605755
Entrez	51473

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000378450, ENST00000378454, ENST00000436313, ENST00000883243

RefSeq mRNA: 2 — MANE Select: NM_016356 NM_001195610, NM_016356

CCDS: CCDS4550

Canonical transcript exons

ENST00000378454 — 10 exons

Exon	Start	End
ENSE00000973593	24278049	24278211
ENSE00000973594	24205002	24205102
ENSE00000973595	24178330	24178632
ENSE00000973598	24301715	24301846
ENSE00000973599	24290932	24291078
ENSE00000973600	24288852	24288906
ENSE00001085339	24353569	24353623
ENSE00001085344	24301968	24302044
ENSE00001477608	24357458	24358059
ENSE00003841950	24171755	24174834

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 97.71.

FANTOM5 (CAGE): breadth broad, TPM avg 5.4794 / max 474.4203, expressed in 354 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72167	3.1458	292
72171	1.4069	229
72170	0.2482	140
72166	0.1973	120
72165	0.1293	81
72168	0.1031	72
72172	0.0862	42
72173	0.0613	29
203908	0.0555	34
72169	0.0457	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.71	gold quality
oocyte	CL:0000023	96.15	gold quality
oviduct epithelium	UBERON:0004804	90.24	gold quality
islet of Langerhans	UBERON:0000006	87.60	gold quality
kidney epithelium	UBERON:0004819	86.95	gold quality
adult mammalian kidney	UBERON:0000082	86.78	gold quality
metanephros cortex	UBERON:0010533	86.43	gold quality
caput epididymis	UBERON:0004358	85.47	gold quality
kidney	UBERON:0002113	85.11	gold quality
pancreas	UBERON:0001264	84.67	gold quality
body of pancreas	UBERON:0001150	84.03	gold quality
buccal mucosa cell	CL:0002336	83.09	gold quality
metanephros	UBERON:0000081	81.46	gold quality
endometrium	UBERON:0001295	80.82	gold quality
bronchial epithelial cell	CL:0002328	80.60	gold quality
epithelial cell of pancreas	CL:0000083	79.71	silver quality
cortex of kidney	UBERON:0001225	79.41	gold quality
right uterine tube	UBERON:0001302	79.20	gold quality
bronchus	UBERON:0002185	78.80	gold quality
pigmented layer of retina	UBERON:0001782	78.79	gold quality
renal medulla	UBERON:0000362	78.59	gold quality
endothelial cell	CL:0000115	77.04	gold quality
fallopian tube	UBERON:0003889	75.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	73.14	gold quality
gall bladder	UBERON:0002110	72.96	gold quality
thyroid gland	UBERON:0002046	69.84	gold quality
left lobe of thyroid gland	UBERON:0001120	69.81	gold quality
corpus epididymis	UBERON:0004359	68.42	gold quality
ventricular zone	UBERON:0003053	67.00	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	730.98
E-GEOD-124472	yes	472.02
E-HCAD-10	yes	370.24
E-GEOD-83139	yes	166.07
E-CURD-119	yes	42.83
E-MTAB-5061	yes	26.21
E-GEOD-81547	yes	21.79
E-MTAB-10553	yes	19.33
E-ANND-3	yes	12.07
E-MTAB-6386	no	16.62

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EHF, FLCN

miRNA regulators (miRDB)

205 targeting DCDC2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 40)

• DCDC2 is proposed as a candidate gene for reading disability. (PMID:16278297)
• Strong genetic evidence of DCDC2 as a susceptibility gene for dyslexia. (PMID:16385449)
• A slight tendency for an intronic deletion in DCDC2 to be associated with worse performance on some quantitative measures of dyslexia in the probands, was observed. (PMID:17450541)
• we found a nominally significant association for the quantitative dimension “word reading” and dcdc2 genotype (PMID:18810304)
• conclude that the causative variant/s in DCDC2 conferring susceptibility to dyslexia in our sample remain/s to be identified (PMID:19018237)
• suspected dyslexia-associated gene (PMID:19238550)
• Our data suggest that the causal variants for ADHD might be found in the VMP/DCDC2 region (PMID:19362708)
• DCDC2 is a risk gene for reading disorder. (PMID:20068590)
• Five alleles displayed strong enhancer activity and increased gene expression, while allele 1 showed no enhancer activity. These studies suggest that the association of BV677278 with RD reflects a role as a modifier of DCDC2 expression. (PMID:21042874)
• No statistically significant associations were found between DCDC2 or DYX1C1 and language phenotypes. Both DCDC2 and DYX1C1 DD susceptibility genes appear to have a pleiotropic role on mathematics but not language phenotypes. (PMID:21046216)
• We identified four rare variants that were significantly associated with the late MMN component. (PMID:21104116)
• At this point, there is no statistical evidence of association between the allelic variation in the three candidate genes and DD in our sample. (PMID:21203818)
• We provide further support for the role of KIAA0319 and DCDC2 in contributing to reading abilities (PMID:21457949)
• This study demonistrated that The superior prefrontal, temporal and occipital networks were positively related to DCDC2 in the schizophrenia, but not the control group. (PMID:21507613)
• DCDC2 overexpression in C. elegans causes an abnormal neuronal phenotype that can only be seen in ciliated neurons. Together our results suggest a potential role for DCDC2 in the structure and function of primary cilia (PMID:21698230)
• DCDC2 influences both reading and memory impairments. (PMID:21881542)
• The DCDC2 gene may not be a susceptibility factor for developmental dyslexia among the Han Chinese. (PMID:22490485)
• Mutations in cilia co-expressed DCDC2, DYX1C1 and KIAA0319 genes are associated with a cognitive neurological disorder, dyslexia. (PMID:22558177)
• The results of this study found that DCDC2 gene contained polymorphisms that were significantly associated with white matter volume in the left temporo-parietal region and that white matter volume influenced reading ability. (PMID:22683091)
• In prostate cancer cells, DCDC2 colocalized with microtubules and promoted cell migration and resistance to the microtubule-targeting drug taxol.DCDC2 is aberrantly expressed in prostate cancers. (PMID:22733135)
• DCDC2 rs807701 might contribute significantly to dyslexia risk. (PMID:23229871)
• This study demonstrated the association of developmental dyslexia with rs4504469 of KIAA0319 and not with any single-nucleotide polymorphisms of DCDC2. (PMID:23677054)
• BV677278 is a regulatory element that influences reading and language skills. (PMID:23746548)
• DCDC2d is associated with altered fractional anisotropy (PMID:24926531)
• Among children exposed to low socioeconomic level, READ1 [regulatory element associated with dyslexia 1 ] genetic variant targets the worst outcome in children’s attention. (PMID:25012462)
• the association of DCDC2 and KIAA0319 with Developmental dyslexia in Chinese population should be further validated (PMID:25230923)
• This study demonstrated that DCDC2 intron 2 deletion impair illusory visual motion perception-specifically processed by the magnocellular-dorsal (M-D) stream-is impaired in children with Developmental dyslexia. (PMID:25270309)
• An SNP in DCDC2 (rs793842) was significantly associated with the thickness of the left temporoparietal cortex. (PMID:25339756)
• DCDC2 interacts with the mediator of Wnt signaling dishevelled, and that DCDC2 overexpression inhibits beta-catenin-dependent Wnt signaling; central role of Wnt signaling in the pathogenesis of nephronophthisis-related ciliopathies (PMID:25557784)
• Our results reveal DCDC2a to be a deafness gene and a player in hair cell kinocilia and supporting cell primary cilia length regulation likely via its role in microtubule formation and stabilization. (PMID:25601850)
• A nonsynonymous polymorphism in DCDC2 (corrected P = 0.002) and a noncoding variant in S100B (corrected P = 0.016) showed a significant association with spelling performance in families of German origin. (PMID:25877001)
• In a population carrying a deletion in the DCDC2 gene, impaired motion perception was identified in subjects with dyslexia. (PMID:26019324)
• off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development (PMID:26331477)
• DCDC2 Polymorphism is associated with reading disability. (PMID:27100778)
• The study corroborates the importance of rs7765678-DCDC2 among others in the aetiology of dyslexia in a German case-control cohort. (PMID:27312598)
• Study identified biallelic missense mutations or in-frame deletion in DCDC2 in children affected with neonatal sclerosi. Mutations involve highly conserved amino acids in the doublecortin domains of the protein. In cholangiocytes, DCDC2 protein is normally located in the cytoplasm and cilia, whereas in patients the mutated protein is accumulated in the cytoplasm, absent from cilia, and associated with ciliogenesis defect. (PMID:27319779)
• that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium (PMID:27451412)
• Neonatal sclerosing cholangitis patients in substantial proportion harbour mutations in DCDC2. (PMID:27469900)
• Developmental dyslexia genetic (DCDC2) and environmental factors (smoke and miscarriage) underlie ADHD traits supporting a potential pleiotropic effect. (PMID:27501527)
• Study concludes that DCDC2 deletion is not a strong risk factor for dyslexia. (PMID:28742079)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dcdc2a	ENSMUSG00000035910
rattus_norvegicus	Dcdc2	ENSRNOG00000017511

Paralogs (2): DCDC2C (ENSG00000214866), DCDC2B (ENSG00000222046)

Protein

Protein identifiers

Doublecortin domain-containing protein 2 — Q9UHG0 (reviewed: Q9UHG0)

Alternative names: Protein RU2S

All UniProt accessions (2): Q9UHG0, H0Y784

UniProt curated annotations — full annotation on UniProt →

Function. Protein that plays a role in the inhibition of canonical Wnt signaling pathway. May be involved in neuronal migration during development of the cerebral neocortex. Involved in the control of ciliogenesis and ciliary length.

Subunit / interactions. Interacts with DVL1, DVL2 and DVL3.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Cilium axoneme. Kinocilium.

Tissue specificity. Ubiquitously expressed. In brain, highly expressed in the entorhinal cortex, inferior temporal cortex, medial temporal cortex, hypothalamus, amygdala and hippocampus. Expressed in liver by cholangiocytes, the epithelial cells of the bile ducts (at protein level).

Disease relevance. Dyslexia 2 (DYX2) [MIM:600202] A relatively common, complex cognitive disorder characterized by an impairment of reading performance despite adequate motivational, educational and intellectual opportunities. It is a multifactorial trait, with evidence for familial clustering and heritability. Disease susceptibility is associated with variants affecting the gene represented in this entry. Nephronophthisis 19 (NPHP19) [MIM:616217] A form of nephronophthisis, an autosomal recessive disorder characterized by chronic tubulointerstitial nephritis resulting in end-stage renal disease. NPHP19 patients also manifest hepatosplenomegaly, hepatic fibrosis, destruction of the bile ducts, focal bile ductal proliferation, ductal plate malformation, and cholestasis. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal recessive, 66 (DFNB66) [MIM:610212] A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry. Sclerosing cholangitis, neonatal (NSC) [MIM:617394] An autosomal recessive form of liver disease with onset in infancy. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis. Cholangiography shows patent biliary ducts, but there are bile duct irregularities. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UHG0-1	1	yes
Q9UHG0-2	2

RefSeq proteins (2): NP_001182539, NP_057440* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003533	Doublecortin_dom	Domain
IPR033036	DCDC2_DCX_dom2	Domain
IPR036572	Doublecortin_dom_sf	Homologous_superfamily

Pfam: PF03607

UniProt features (32 total): sequence variant 7, strand 6, compositionally biased region 6, sequence conflict 3, helix 3, domain 2, splice variant 2, chain 1, modified residue 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DNF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHG0-F1	63.93	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 270

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 297 (showing top): GOBP_DENDRITE_DEVELOPMENT, AAGCAAT_MIR137, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOZGIT_ESR1_TARGETS_DN, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_DENDRITE_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEURON_MIGRATION

GO Biological Process (11): neuron migration (GO:0001764), cellular defense response (GO:0006968), sensory perception of sound (GO:0007605), regulation of Wnt signaling pathway (GO:0030111), intracellular signal transduction (GO:0035556), positive regulation of smoothened signaling pathway (GO:0045880), dendrite morphogenesis (GO:0048813), cilium assembly (GO:0060271), regulation of cilium assembly (GO:1902017), nervous system development (GO:0007399), cell projection organization (GO:0030030)

GO Molecular Function (2): kinesin binding (GO:0019894), protein binding (GO:0005515)

GO Cellular Component (8): cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), microtubule (GO:0005874), cilium (GO:0005929), axoneme (GO:0005930), kinocilium (GO:0060091), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular anatomical structure	2
microtubule cytoskeleton	2
cell migration	1
generation of neurons	1
defense response	1
sensory perception of mechanical stimulus	1
regulation of signal transduction	1
Wnt signaling pathway	1
signal transduction	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
cilium assembly	1
regulation of plasma membrane bounded cell projection assembly	1
regulation of organelle assembly	1
system development	1
cellular component organization	1
cytoskeletal protein binding	1
binding	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
radial spoke	1
stereocilium bundle	1

Protein interactions and networks

STRING

900 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCDC2	KIAA0319	Q5VV43	986
DCDC2	DNAAF4	Q8WXU2	978
DCDC2	ACOT13	Q9NPJ3	921
DCDC2	KAAG1	Q9UBP8	911
DCDC2	TDP2	O95551	863
DCDC2	GCFC2	P16383	766
DCDC2	ATP2C2	O75185	745
DCDC2	ROBO1	Q9Y6N7	741
DCDC2	MRPL19	P49406	703
DCDC2	KIAA0319L	Q8IZA0	649
DCDC2	CMIP	Q8IY22	648
DCDC2	FOXP2	O15409	599
DCDC2	CNTNAP2	Q9UHC6	586
DCDC2	PCNT	O95613	581
DCDC2	NRSN1	Q8IZ57	576

IntAct

87 interactions, top by confidence:

A	B	Type	Score
DCDC2	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
MRFAP1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
NIF3L1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
DCDC2	MRFAP1	psi-mi:“MI:0915”(physical association)	0.560
DYNLT2	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
C5AR2	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
HORMAD1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
TRMT11	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
MYG1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
GNL3L	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
CYTH4	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
OXT	DCDC2	psi-mi:“MI:0915”(physical association)	0.560
MGME1	DCDC2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (38): NIF3L1 (Two-hybrid), MRFAP1 (Two-hybrid), DCDC2 (Proximity Label-MS), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), DCDC2 (Two-hybrid), MICALL2 (Two-hybrid), POP5 (Two-hybrid), CKS1B (Two-hybrid), B3GNT5 (Two-hybrid)

ESM2 similar proteins: A4FV61, A8MYV0, D3ZR10, G9CGD6, M0R2J8, O54828, O60543, O70302, O75916, O88974, P17863, P28715, P35689, P49805, P55265, P55266, Q02040, Q15047, Q3B7M3, Q3UY96, Q5DU00, Q5EAN7, Q5F3L9, Q5R6F3, Q5T848, Q5VT97, Q642B6, Q68D51, Q69Z99, Q6P3Z3, Q6P9P8, Q7TPQ3, Q8C4S8, Q8K0Q5, Q8N392, Q8NE31, Q8TEW8, Q8WY91, Q91VL8, Q95JV5

Diamond homologs: A2VCK2, A8MYV0, D3ZR10, Q5DU00, Q9D1B8, Q9UHG0, Q9VUI3, P56715, P56716, Q550F6, Q69Z08, Q8CGM2, Q8IWN7, Q8MJ03, Q8MJ04, Q8MJ05, Q8MJ06, D2I3C6, O15075, O43602, O88809, Q5MPA9, Q6PGN3, Q8N568, Q95QC4, Q9JLM8, Q9ESI7, B3NKK1, Q7PLI7, B4IMC3, O00423, O95834, Q05BC3, Q26613, Q2TAF3, Q32P44, Q3UMY5, Q4V8C3, Q6DIP5, Q6P6T4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EHF	“down-regulates quantity by repression”	DCDC2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	14
Uncertain significance	177
Likely benign	102
Benign	46

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1162261	NM_016356.5(DCDC2):c.346G>T (p.Glu116Ter)	Pathogenic
161160	NM_016356.5(DCDC2):c.1271A>C (p.Gln424Pro)	Pathogenic
1687288	NM_016356.5(DCDC2):c.536_537del (p.Leu179fs)	Pathogenic
1687593	NM_016356.5(DCDC2):c.557+1G>T	Pathogenic
180687	NM_016356.5(DCDC2):c.649A>T (p.Lys217Ter)	Pathogenic
180689	NM_016356.5(DCDC2):c.349-2A>G	Pathogenic
2634418	NM_016356.5(DCDC2):c.705-2A>G	Pathogenic
417766	NM_016356.5(DCDC2):c.51G>C (p.Lys17Asn)	Pathogenic
417767	NM_016356.4(DCDC2):c.426_557del	Pathogenic
417768	NM_016356.5(DCDC2):c.890T>A (p.Leu297Ter)	Pathogenic
417769	NM_016356.5(DCDC2):c.529dup (p.Ile177fs)	Pathogenic
502281	NM_016356.5(DCDC2):c.294-2A>G	Pathogenic
593986	NM_016356.5(DCDC2):c.293dup (p.Asn98fs)	Pathogenic
1492885	NM_016356.5(DCDC2):c.426-2A>G	Likely pathogenic
2629455	NM_016356.5(DCDC2):c.1155del (p.Glu386fs)	Likely pathogenic
3028896	NM_016356.5(DCDC2):c.76G>C (p.Asp26His)	Likely pathogenic
3064075	NM_016356.5(DCDC2):c.901C>T (p.Gln301Ter)	Likely pathogenic
3352399	NM_016356.5(DCDC2):c.1249C>T (p.Gln417Ter)	Likely pathogenic
3593426	NM_016356.5(DCDC2):c.604G>T (p.Glu202Ter)	Likely pathogenic
3593429	NM_016356.5(DCDC2):c.289_292del (p.Leu97fs)	Likely pathogenic
3897967	NM_016356.5(DCDC2):c.1045G>T (p.Glu349Ter)	Likely pathogenic
4785159	NM_016356.5(DCDC2):c.1023+2T>C	Likely pathogenic
4794554	NM_016356.5(DCDC2):c.2T>G (p.Met1Arg)	Likely pathogenic
802191	NM_016356.5(DCDC2):c.829A>T (p.Lys277Ter)	Likely pathogenic
804454	NM_016356.5(DCDC2):c.549dup (p.Val184fs)	Likely pathogenic
917935	NM_016356.5(DCDC2):c.223_293del (p.Arg75fs)	Likely pathogenic
973531	NM_016356.5(DCDC2):c.923-283_1023+141del	Likely pathogenic

SpliceAI

2671 predictions. Top by Δscore:

Variant	Effect	Δscore
6:24174830:TCAGC:T	acceptor_gain	1.0000
6:24174831:CAGC:C	acceptor_gain	1.0000
6:24174831:CAGCC:C	acceptor_gain	1.0000
6:24174835:C:CC	acceptor_gain	1.0000
6:24174835:CTA:C	acceptor_loss	1.0000
6:24177582:T:TA	donor_gain	1.0000
6:24177608:A:C	donor_gain	1.0000
6:24178331:T:TA	donor_gain	1.0000
6:24178334:T:C	donor_gain	1.0000
6:24178629:GCCT:G	acceptor_gain	1.0000
6:24178630:CCTC:C	acceptor_gain	1.0000
6:24178631:CT:C	acceptor_gain	1.0000
6:24178633:C:CA	acceptor_loss	1.0000
6:24178633:C:CC	acceptor_gain	1.0000
6:24178642:C:CT	acceptor_gain	1.0000
6:24178643:A:T	acceptor_gain	1.0000
6:24184924:A:AC	donor_gain	1.0000
6:24184925:C:CC	donor_gain	1.0000
6:24205000:A:AG	donor_loss	1.0000
6:24205001:CC:C	donor_loss	1.0000
6:24205018:TCA:T	donor_gain	1.0000
6:24205100:CAT:C	acceptor_gain	1.0000
6:24205101:AT:A	acceptor_gain	1.0000
6:24205102:TCTA:T	acceptor_loss	1.0000
6:24205103:C:CC	acceptor_gain	1.0000
6:24205112:C:CT	acceptor_gain	1.0000
6:24278043:ACTT:A	donor_loss	1.0000
6:24278045:TTACC:T	donor_loss	1.0000
6:24278046:TACCA:T	donor_loss	1.0000
6:24278047:A:AC	donor_gain	1.0000

AlphaMissense

3141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:24357488:G:T	A88D	1.000
6:24357566:A:T	V62D	1.000
6:24353622:A:G	Y99H	0.999
6:24357470:A:G	F94S	0.999
6:24357539:C:T	G71D	0.999
6:24357555:A:C	Y66D	0.999
6:24357611:A:G	F47S	0.999
6:24291010:G:T	A209D	0.998
6:24291034:A:G	L201S	0.998
6:24357485:C:T	G89E	0.998
6:24357491:A:T	V87E	0.998
6:24357495:A:C	Y86D	0.998
6:24357557:A:T	I65N	0.998
6:24357608:A:G	L48P	0.998
6:24357678:C:A	G25W	0.998
6:24357687:A:C	Y22D	0.998
6:24357466:C:A	K95N	0.997
6:24357466:C:G	K95N	0.997
6:24357489:C:G	A88P	0.997
6:24357492:C:T	V87M	0.997
6:24357539:C:A	G71V	0.997
6:24357548:G:T	P68Q	0.997
6:24357557:A:C	I65S	0.997
6:24357562:C:A	R63S	0.997
6:24357562:C:G	R63S	0.997
6:24357574:A:C	F59L	0.997
6:24357574:A:T	F59L	0.997
6:24357576:A:G	F59L	0.997
6:24357587:A:T	V55D	0.997
6:24357684:G:T	R23S	0.997

dbSNP variants (sampled 300 via entrez): RS1000003499 (6:24193887 T>C,G), RS1000041282 (6:24376662 T>C), RS1000042914 (6:24216550 T>C), RS1000051602 (6:24293148 C>T), RS1000059221 (6:24355173 A>G), RS1000062307 (6:24210778 C>T), RS1000074045 (6:24216815 T>C), RS1000102279 (6:24318944 T>C), RS1000102464 (6:24334940 C>T), RS1000125923 (6:24326047 G>A), RS1000141593 (6:24253079 T>C), RS1000148555 (6:24190426 G>A), RS1000156257 (6:24238870 A>G), RS1000165169 (6:24278517 T>C), RS1000165237 (6:24195089 T>A)

Disease associations

OMIM: gene MIM:605755 | disease phenotypes: MIM:610212, MIM:616217, MIM:617394, MIM:246700, MIM:607626

GenCC curated gene-disease

Disease	Classification	Inheritance
ciliopathy	Definitive	Autosomal recessive
nephronophthisis 19	Strong	Autosomal recessive
isolated neonatal sclerosing cholangitis	Strong	Autosomal recessive
Senior-Boichis syndrome	Supportive	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 66	Limited	Autosomal recessive
nonsyndromic genetic hearing loss	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
ciliopathy	Definitive	AR
nonsyndromic genetic hearing loss	Limited	AR

Mondo (9): autosomal recessive nonsyndromic hearing loss 66 (MONDO:0012442), nephronophthisis 19 (MONDO:0014537), isolated neonatal sclerosing cholangitis (MONDO:0018816), chylomicron retention disease (MONDO:0009528), neonatal ichthyosis-sclerosing cholangitis syndrome (MONDO:0011874), ciliopathy (MONDO:0005308), nonsyndromic genetic hearing loss (MONDO:0019497), Senior-Boichis syndrome (MONDO:0019394), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (5): Isolated neonatal sclerosing cholangitis (Orphanet:480556), Senior-Boichis syndrome (Orphanet:84081), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Chylomicron retention disease (Orphanet:71), Neonatal ichthyosis-sclerosing cholangitis syndrome (Orphanet:59303)

HPO phenotypes

58 total (30 of 58 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000090	Nephronophthisis
HP:0000108	Renal corticomedullary cysts
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000713	Agitation
HP:0000718	Aggressive behavior
HP:0000822	Hypertension
HP:0000952	Jaundice
HP:0000989	Pruritus
HP:0001256	Mild intellectual disability
HP:0001394	Cirrhosis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001399	Hepatic failure
HP:0001408	Bile duct proliferation
HP:0001409	Portal hypertension
HP:0001433	Hepatosplenomegaly
HP:0001541	Ascites
HP:0001744	Splenomegaly
HP:0001903	Anemia
HP:0001959	Polydipsia
HP:0002040	Esophageal varix
HP:0002240	Hepatomegaly
HP:0002500	Abnormal cerebral white matter morphology
HP:0002506	Diffuse cerebral atrophy
HP:0002612	Congenital hepatic fibrosis
HP:0002613	Biliary cirrhosis

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000905_4	Information processing speed	3.000000e-06
GCST000963_8	Uric acid levels	5.000000e-06
GCST001621_5	Airflow obstruction	8.000000e-07
GCST006269_1109	General cognitive ability	3.000000e-10
GCST007876_3	Estimated glomerular filtration rate	4.000000e-08
GCST008058_258	Estimated glomerular filtration rate	1.000000e-08
GCST008060_17	Estimated glomerular filtration rate	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004363	information processing speed
EFO:0004761	uric acid measurement
EFO:0003892	pulmonary function measurement
EFO:0004337	intelligence

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
C535460	Chylomicron retention disease (supp.)
C564609	Deafness, Autosomal Recessive (supp.)
C565701	Deafness, Autosomal Recessive 66 (supp.)
C564365	Ichthyosis, Leukocyte Vacuoles, Alopecia, And Sclerosing Cholangitis (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation, affects methylation	5
bisphenol A	affects methylation, affects expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
celastrol	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
belinostat	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Leflunomide	affects expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Azathioprine	decreases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methapyrilene	increases methylation	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7NG	Ubigene A-549 DCDC2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00068224	Not specified	COMPLETED	Clinical and Molecular Investigations Into Ciliopathies
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations
NCT05208879	Not specified	COMPLETED	CArotenoid in hypoChOlesterolemia