CDNF

Summary

CDNF (cerebral dopamine neurotrophic factor, HGNC:24913) is a protein-coding gene on chromosome 10p13, encoding Cerebral dopamine neurotrophic factor (Q49AH0). Trophic factor for dopamine neurons.

Predicted to enable growth factor activity. Predicted to be involved in dopaminergic neuron differentiation and neuron projection development. Predicted to be located in extracellular region. Predicted to be active in endoplasmic reticulum and extracellular space.

Source: NCBI Gene 441549 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001029954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24913
Approved symbol	CDNF
Name	cerebral dopamine neurotrophic factor
Location	10p13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185267
Ensembl biotype	protein_coding
OMIM	611233
Entrez	441549

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000378441, ENST00000378442, ENST00000465530, ENST00000466269, ENST00000467405, ENST00000861566

RefSeq mRNA: 1 — MANE Select: NM_001029954 NM_001029954

CCDS: CCDS31148

Canonical transcript exons

ENST00000465530 — 4 exons

Exon	Start	End
ENSE00001383386	14837832	14838037
ENSE00001856994	14819245	14820158
ENSE00003513001	14825479	14825620
ENSE00003669152	14828145	14828272

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 89.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.1722 / max 40.2989, expressed in 1134 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108398	2.1612	1133
108399	0.0110	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	89.48	gold quality
muscle of leg	UBERON:0001383	87.92	gold quality
gastrocnemius	UBERON:0001388	87.54	gold quality
left testis	UBERON:0004533	87.01	gold quality
right testis	UBERON:0004534	86.55	gold quality
sperm	CL:0000019	85.90	gold quality
right uterine tube	UBERON:0001302	83.51	gold quality
testis	UBERON:0000473	83.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.10	gold quality
calcaneal tendon	UBERON:0003701	80.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.73	gold quality
body of pancreas	UBERON:0001150	78.80	gold quality
right lobe of liver	UBERON:0001114	77.38	gold quality
skeletal muscle tissue	UBERON:0001134	76.77	gold quality
muscle tissue	UBERON:0002385	75.75	gold quality
pancreas	UBERON:0001264	74.95	gold quality
biceps brachii	UBERON:0001507	74.93	gold quality
vastus lateralis	UBERON:0001379	74.33	gold quality
quadriceps femoris	UBERON:0001377	74.28	gold quality
skin of leg	UBERON:0001511	72.73	gold quality
islet of Langerhans	UBERON:0000006	72.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	72.18	silver quality
right adrenal gland cortex	UBERON:0035827	72.02	gold quality
mucosa of stomach	UBERON:0001199	71.92	gold quality
right adrenal gland	UBERON:0001233	71.73	gold quality
skin of abdomen	UBERON:0001416	71.61	gold quality
stromal cell of endometrium	CL:0002255	71.26	gold quality
left adrenal gland cortex	UBERON:0035825	71.24	gold quality
left adrenal gland	UBERON:0001234	70.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting CDNF, 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-6873-3P	100.00	71.42	2626
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-4711-3P	98.97	66.87	1020
HSA-MIR-374A-3P	98.87	67.82	1531
HSA-MIR-936	98.87	70.51	1124

Literature-anchored findings (GeneRIF, showing 16)

• expressed in several tissues; might be beneficial for the treatment of Parkinson’s disease (PMID:17611540)
• structures of MANF and CDNF were solved; structure explains why MANF and CDNF are bifunctional; neurotrophic activity may reside in the N-terminal domain and ER stress response in the C-terminal domain (PMID:19258449)
• Study suggests that there is no association between variants in the CDNF gene and cocaine dependence. (PMID:19429035)
• Although no CDNF mutations are found in early-onset Parkinson’s disease patient samples, a trend towards increased risk for Parkinson’s in carriers of the C allele of rs7094179 single nucleotide polymorphism (SNP) is found. (PMID:21320571)
• Expression of CDNF in the substantia nigra has an anti-inflammatory effect on experimental Parkinson’s disease. (PMID:25511018)
• Results suggest that CDNF treatment selectively enhances long-term memory consolidation (PMID:25975173)
• showed that CDNF was able to protect dopaminergic neurons against injury caused by alpha-synuclein oligomers. This advises its use against physiological damages caused by alpha-synuclein oligomers (PMID:26149686)
• In various animal models of Parkinson Disease, CDNF is efficient in protecting and repairing dopaminergic neurons, and it inhibits endoplasmic reticulum stress, euroinflammation, and apoptosis. (PMID:28337696)
• The results showed that AAV8-CDNF administration significantly improved the motor function and increased the tyrosine hydroxylase (TH) levels in Parkinson’s disease rats with mild lesions (2 weeks post lesion), but it had limited therapeutic effects in rats with severe lesions (5 weeks post lesion). (PMID:28622392)
• Polymorphisms in CDN,F identified in a Han Chinese population, were associated with increased susceptibility to schizophrenia. (PMID:29298719)
• Cerebral dopamine neurotrophic factor gene expression was significantly reduced in stroke patients relative to control subjects. (PMID:31744764)
• Protection of dopamine neurons by CDNF and neurturin variant N4 against MPP+ in dissociated cultures from rat mesencephalon. (PMID:33534843)
• Cerebral dopamine neurotrophic factor reduces alpha-synuclein aggregation and propagation and alleviates behavioral alterations in vivo. (PMID:33940158)
• Cerebral Dopamine Neurotrophic Factor (CDNF): Structure, Functions, and Therapeutic Potential. (PMID:34284712)
• Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs. (PMID:34575854)
• Delivery of CDNF by AAV-mediated gene transfer protects dopamine neurons and regulates ER stress and inflammation in an acute MPTP mouse model of Parkinson’s disease. (PMID:39019902)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdnf	ENSDARG00000075501
mus_musculus	Cdnf	ENSMUSG00000039496
rattus_norvegicus	Cdnf	ENSRNOG00000026493
drosophila_melanogaster	Manf	FBGN0027095
caenorhabditis_elegans		WBGENE00021888

Paralogs (1): MANF (ENSG00000145050)

Protein

Protein identifiers

Cerebral dopamine neurotrophic factor — Q49AH0 (reviewed: Q49AH0)

Alternative names: ARMET-like protein 1, Conserved dopamine neurotrophic factor

All UniProt accessions (1): Q49AH0

UniProt curated annotations — full annotation on UniProt →

Function. Trophic factor for dopamine neurons. Prevents the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When administered after 6-OHDA-lesioning, restores the dopaminergic function and prevents the degeneration of dopaminergic neurons in substantia nigra.

Subcellular location. Secreted.

Tissue specificity. Widely expressed in neuronal and non-neuronal tissues. In the brain, highest levels in the optic nerve and corpus callosum.

Induction. Not induced by endoplasmic reticulum stress.

Similarity. Belongs to the ARMET family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q49AH0-1	1	yes
Q49AH0-2	2

RefSeq proteins (1): NP_001025125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019345	ARMET_C	Domain
IPR036361	SAP_dom_sf	Homologous_superfamily
IPR045332	ARMET_N	Domain
IPR045333	ARMET-like	Family

Pfam: PF10208, PF20145

UniProt features (17 total): helix 9, disulfide bond 3, signal peptide 1, chain 1, turn 1, strand 1, splice variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9I5Y	X-RAY DIFFRACTION	1.5
2W50	X-RAY DIFFRACTION	1.6
9H0C	X-RAY DIFFRACTION	1.65
2LPN	SOLUTION NMR
4BIT	SOLUTION NMR
8QAJ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49AH0-F1	80.80	0.54

Functional residue map

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

Disulfide bonds (3): 37–124, 40–113, 71–82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, CHANDRAN_METASTASIS_DN, chr10p13, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_DOPAMINERGIC_NEURON_DIFFERENTIATION, GOMF_SIGNALING_RECEPTOR_BINDING, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, PEDRIOLI_MIR31_TARGETS_UP, CIITA_TARGET_GENES, ELF2_TARGET_GENES, HOXB6_TARGET_GENES, ID2_TARGET_GENES

GO Biological Process (3): neuron projection development (GO:0031175), dopaminergic neuron differentiation (GO:0071542), signal transduction (GO:0007165)

GO Molecular Function (1): growth factor activity (GO:0008083)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron development	1
plasma membrane bounded cell projection organization	1
neuron differentiation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

576 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDNF	GDNF	P39905	855
CDNF	TH	P07101	768
CDNF	NRTN	Q99748	720
CDNF	PSAPL1	Q6NUJ1	690
CDNF	BDNF	P23560	664
CDNF	PSAP	P07292	571
CDNF	PSPN	O60542	568
CDNF	CNTF	P26441	531
CDNF	XBP1	P17861	483
CDNF	NGF	P01138	465
CDNF	RET	P07949	437
CDNF	SNCA	P37840	428
CDNF	NTF3	P20783	419
CDNF	ARTN	Q5T4W7	413
CDNF	SLC6A3	Q01959	389
CDNF	CRELD2	Q6UXH1	389

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CDNF	NFS1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): NFS1 (Affinity Capture-MS), MANF (Affinity Capture-MS), LYRM4 (Affinity Capture-MS), NFS1 (Affinity Capture-MS), NFS1 (Affinity Capture-MS), CDNF (Cross-Linking-MS (XL-MS)), CDNF (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1L188, A2AMZ4, A2XK00, A7YY73, B4FGS2, B4FTR7, B8B624, C0HAV3, C5E268, G2TRP6, O13973, O75012, O95159, O95872, Q0VDN7, Q12894, Q28H71, Q2YDD3, Q3SZA2, Q3SZW4, Q3U0S6, Q3UJV1, Q49AH0, Q4G012, Q5FVV3, Q5U509, Q5U651, Q61858, Q6ASS9, Q6P0I6, Q756Q5, Q7S4Y4, Q7XAM0, Q7XK12, Q8BGD8, Q8BGX2, Q8CC36, Q8VED2, Q96BP2, Q96C34

Diamond homologs: B3M2I7, B3P113, B4GFM7, B4IBX2, B4JT39, B4K5R6, B4LX78, B4NIN8, B4PR07, B4QX46, P0C5H9, P0C5I0, P55145, P80513, Q295V5, Q49AH0, Q8CC36, Q9CXI5, Q9N3B0, Q9XZ63

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

55 predictions. Top by Δscore:

Variant	Effect	Δscore
10:14838303:A:T	donor_gain	0.9700
10:14838455:ATAAG:A	donor_loss	0.9700
10:14838456:TAAGG:T	donor_loss	0.9700
10:14838457:AAGGT:A	donor_loss	0.9700
10:14838458:AGGT:A	donor_loss	0.9700
10:14838459:GGTGA:G	donor_loss	0.9700
10:14838460:G:A	donor_loss	0.9700
10:14838461:T:A	donor_loss	0.9700
10:14838264:G:GT	donor_gain	0.9500
10:14838264:G:T	donor_gain	0.9200
10:14838349:GCT:G	donor_gain	0.9200
10:14838350:C:G	donor_gain	0.9200
10:14838284:G:GT	donor_gain	0.9100
10:14838291:G:GT	donor_gain	0.9100
10:14838347:T:TA	donor_gain	0.8900
10:14838348:A:AA	donor_gain	0.8900
10:14838263:G:GT	donor_gain	0.8500
10:14838267:G:GT	donor_gain	0.8400
10:14838323:C:G	donor_gain	0.7500
10:14838462:GAGGG:G	donor_loss	0.7300
10:14838460:G:GG	donor_gain	0.7100
10:14838531:GCT:G	donor_gain	0.7000
10:14838266:GGCT:G	donor_gain	0.6600
10:14838308:G:GT	donor_gain	0.6600
10:14838271:T:TA	donor_gain	0.6400
10:14838272:A:AA	donor_gain	0.6400
10:14838302:G:GT	donor_gain	0.6400
10:14838439:GCCT:G	donor_gain	0.6300
10:14838307:TG:T	donor_gain	0.6200
10:14838560:G:T	donor_gain	0.6200

AlphaMissense

1219 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:14825619:C:G	C82S	0.971
10:14825620:A:T	C82S	0.971
10:14820104:A:G	L147P	0.968
10:14825517:A:G	L116P	0.965
10:14825620:A:G	C82R	0.965
10:14825568:A:T	V99D	0.958
10:14820082:C:A	W154C	0.956
10:14820082:C:G	W154C	0.956
10:14825610:A:G	L85P	0.955
10:14825604:G:T	A87D	0.953
10:14828259:G:C	F43L	0.953
10:14828259:G:T	F43L	0.953
10:14828261:A:G	F43L	0.953
10:14825593:C:G	A91P	0.952
10:14825526:C:G	C113S	0.951
10:14825526:C:T	C113Y	0.951
10:14825527:A:T	C113S	0.951
10:14820035:A:G	L170P	0.950
10:14825589:G:T	A92D	0.948
10:14820071:C:G	C158S	0.947
10:14820072:A:T	C158S	0.947
10:14820072:A:G	C158R	0.946
10:14825487:A:G	L126P	0.946
10:14825605:C:G	A87P	0.944
10:14820052:T:A	K164N	0.943
10:14820052:T:G	K164N	0.943
10:14820092:A:G	L151P	0.943
10:14828149:C:G	R80P	0.943
10:14820100:C:A	K148N	0.939
10:14820100:C:G	K148N	0.939

dbSNP variants (sampled 300 via entrez): RS1000074989 (10:14819146 C>T), RS1000309553 (10:14837637 G>A), RS1000360658 (10:14829067 G>A,T), RS1000393177 (10:14829376 C>T), RS1000416448 (10:14831528 TAC>T), RS1000574552 (10:14822509 G>A), RS1000700673 (10:14827696 C>G), RS1000731481 (10:14828017 G>C), RS1000794972 (10:14833810 G>A), RS1000865637 (10:14835338 G>A), RS1000869763 (10:14839536 A>C), RS1000906458 (10:14822228 T>G), RS1000942756 (10:14839737 T>C), RS1001097271 (10:14821336 C>T), RS1001187308 (10:14837106 G>A)

Disease associations

OMIM: gene MIM:611233 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_153	Night sleep phenotypes	2.000000e-06
GCST006585_2354	Blood protein levels	1.000000e-09
GCST008359_6	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
ferrous chloride	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	increases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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