ARK2C

Summary

ARK2C (arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C, HGNC:31696) is a protein-coding gene on chromosome 18q21.1, encoding E3 ubiquitin-protein ligase ARK2C (Q6ZSG1). E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in motor neuron axon guidance and positive regulation of BMP signaling pathway. Predicted to act upstream of or within several processes, including forelimb morphogenesis; nervous system development; and protein polyubiquitination. Predicted to be part of protein-containing complex. Predicted to be active in nucleus.

Source: NCBI Gene 494470 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 40 total — 10 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_152470

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31696
Approved symbol	ARK2C
Name	arkadia (RNF111) C-terminal like ring finger ubiquitin ligase 2C
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ARKL2, RNF111L2, Ark2C, lncAMPC
Ensembl gene	ENSG00000141622
Ensembl biotype	protein_coding
Entrez	494470

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000269439, ENST00000543885, ENST00000586604, ENST00000587853, ENST00000588679, ENST00000590330, ENST00000592777, ENST00000593230, ENST00000956349

RefSeq mRNA: 2 — MANE Select: NM_152470 NM_001256758, NM_152470

CCDS: CCDS32823, CCDS58621

Canonical transcript exons

ENST00000269439 — 8 exons

Exon	Start	End
ENSE00001341449	46435289	46435396
ENSE00003464055	46456519	46463140
ENSE00003485082	46450296	46450400
ENSE00003497174	46447563	46447692
ENSE00003572173	46433190	46433505
ENSE00003576047	46450704	46450799
ENSE00003681661	46455974	46456080
ENSE00003848031	46334018	46334335

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 95.92.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4831 / max 160.9126, expressed in 680 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170165	1.1423	440
170164	0.9368	418
170168	0.7740	257
170166	0.3294	189
170167	0.1974	97
170163	0.1033	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.92	gold quality
ganglionic eminence	UBERON:0004023	94.34	gold quality
cerebellar hemisphere	UBERON:0002245	88.41	gold quality
cerebellar cortex	UBERON:0002129	88.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.11	gold quality
cerebellum	UBERON:0002037	87.80	gold quality
ventricular zone	UBERON:0003053	87.37	gold quality
primary visual cortex	UBERON:0002436	86.12	gold quality
middle temporal gyrus	UBERON:0002771	84.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.68	gold quality
prefrontal cortex	UBERON:0000451	81.67	gold quality
occipital lobe	UBERON:0002021	81.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.03	gold quality
right frontal lobe	UBERON:0002810	79.78	gold quality
neocortex	UBERON:0001950	79.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.62	gold quality
frontal cortex	UBERON:0001870	78.96	gold quality
frontal lobe	UBERON:0016525	78.96	gold quality
anterior cingulate cortex	UBERON:0009835	78.87	gold quality
cerebral cortex	UBERON:0000956	78.39	gold quality
right lobe of liver	UBERON:0001114	77.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.17	silver quality
brain	UBERON:0000955	76.06	gold quality
granulocyte	CL:0000094	75.51	gold quality
forebrain	UBERON:0001890	75.31	gold quality
buccal mucosa cell	CL:0002336	74.96	silver quality
nucleus accumbens	UBERON:0001882	74.92	gold quality
cerebellar vermis	UBERON:0004720	74.45	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.29	gold quality
amygdala	UBERON:0001876	73.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.51
E-MTAB-6379	no	1.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

134 targeting ARK2C, 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-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-613	99.91	71.50	1710

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ark2ca	ENSDARG00000077906
danio_rerio	ark2cb	ENSDARG00000078817
mus_musculus	Ark2c	ENSMUSG00000025427
rattus_norvegicus	Ark2c	ENSRNOG00000048824
drosophila_melanogaster	CG6923	FBGN0037944
caenorhabditis_elegans	toe-4	WBGENE00012194

Paralogs (2): ARK2N (ENSG00000152242), RNF111 (ENSG00000157450)

Protein

Protein identifiers

E3 ubiquitin-protein ligase ARK2C — Q6ZSG1 (reviewed: Q6ZSG1)

Alternative names: RING finger protein 165

All UniProt accessions (6): A0A059NXK6, Q6ZSG1, K7EIS4, K7ELT0, K7EPZ9, K7EQ96

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL.

Subunit / interactions. Monomer; binding to the ubiquitin-conjugating enzyme E2 does not trigger homodimerization.

Subcellular location. Nucleus.

Activity regulation. Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the ‘closed’ conformation and activating ubiquitin transfer.

Domain organisation. The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin. Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the ‘closed’ conformation and stimulates ubiquitin transfer.

Similarity. Belongs to the Arkadia family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZSG1-1	1	yes
Q6ZSG1-2	2

RefSeq proteins (2): NP_001243687, NP_689683* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR011016	Znf_RING-CH	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR045191	MBR1/2-like	Family

Pfam: PF13639

UniProt features (23 total): binding site 4, strand 4, region of interest 4, mutagenesis site 3, helix 2, turn 2, chain 1, zinc finger region 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
5D0I	X-RAY DIFFRACTION	1.9
5D0M	X-RAY DIFFRACTION	1.91
5ULH	X-RAY DIFFRACTION	1.95
9N1F	X-RAY DIFFRACTION	2.1
5ULK	X-RAY DIFFRACTION	2.38
7R70	X-RAY DIFFRACTION	2.5
5D0K	X-RAY DIFFRACTION	2.65
7R71	X-RAY DIFFRACTION	2.8
9QAL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZSG1-F1	57.50	0.19

Functional residue map

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

Ligand- & substrate-binding residues (4): 320; 294; 297; 317

Mutagenesis-validated functional residues (3):

Position	Phenotype
309	reduced binding to free ubiquitin.
313	reduced binding to free ubiquitin and reduced e3 ubiquitin-protein ligase activity.
335	reduced ubiquitin discharge.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GGTGTGT_MIR329, ATACCTC_MIR202, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_FORELIMB_MORPHOGENESIS, CAGGTCC_MIR492, CTATGCA_MIR153, GTGCCTT_MIR506, GOBP_MOTOR_NEURON_AXON_GUIDANCE, GOBP_POSITIVE_REGULATION_OF_BMP_SIGNALING_PATHWAY, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY

GO Biological Process (9): protein polyubiquitination (GO:0000209), motor neuron axon guidance (GO:0008045), protein catabolic process (GO:0030163), positive regulation of BMP signaling pathway (GO:0030513), forelimb morphogenesis (GO:0035136), innervation (GO:0060384), muscle structure development (GO:0061061), axonogenesis (GO:0007409), limb development (GO:0060173)

GO Molecular Function (6): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), ligase activity (GO:0016874), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
protein ubiquitination	1
axon guidance	1
macromolecule catabolic process	1
protein metabolic process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
limb morphogenesis	1
nerve development	1
multicellular organismal process	1
anatomical structure development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
appendage development	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cellular_component	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARK2C	UBE2D2	P51669	729
ARK2C	ARK2N	Q96B23	645
ARK2C	LOXHD1	Q8IVV2	593
ARK2C	PSTPIP2	Q9H939	505
ARK2C	SKOR2	Q2VWA4	466
ARK2C	UBE2E1	P51965	455
ARK2C	TMEM200C	A6NKL6	439
ARK2C	A6NLF2	A6NLF2	420
ARK2C	RNF4	P78317	419
ARK2C	HAUS1	Q96CS2	418
ARK2C	PRKN	O60260	397
ARK2C	SPMAP1	A8MV24	396
ARK2C	SLC39A6	Q13433	394
ARK2C	Q3MI93	Q3MI93	374
ARK2C	ZNF442	Q9H7R0	359

IntAct

14 interactions, top by confidence:

A	B	Type	Score
ARK2C	SKI	psi-mi:“MI:0915”(physical association)	0.500
SKI		psi-mi:“MI:0914”(association)	0.500
ARK2C	SKIL	psi-mi:“MI:0915”(physical association)	0.400
ARK2C	SMAD7	psi-mi:“MI:0915”(physical association)	0.400
ARK2C	SMAD6	psi-mi:“MI:0915”(physical association)	0.400
UBE2D1	ARK2C	psi-mi:“MI:0915”(physical association)	0.370
UBE2D2	ARK2C	psi-mi:“MI:0915”(physical association)	0.370
ARK2C	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
UBE2D4	ARK2C	psi-mi:“MI:0915”(physical association)	0.370
ARK2C	UBE2E1	psi-mi:“MI:0915”(physical association)	0.370
ARK2C	UBE2E3	psi-mi:“MI:0915”(physical association)	0.370
ARK2C	UBE2N	psi-mi:“MI:0915”(physical association)	0.370
ARK2C	UBE2W	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (19): UBC (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2D2 (Co-crystal Structure), UBC (Co-crystal Structure), UBC (Reconstituted Complex), RNF165 (Affinity Capture-RNA), RNF165 (Affinity Capture-RNA), UBE2D2 (Co-crystal Structure), UBXN7 (Affinity Capture-Western), RNF165 (Affinity Capture-MS), RNF165 (Two-hybrid), RNF165 (Two-hybrid), RNF165 (Two-hybrid), RNF165 (Two-hybrid)

ESM2 similar proteins: A0A0A7EPL0, A2X1A1, A2X1N2, A2YG67, B8B3I4, E9QAU8, F4JYG0, F4KHG8, O49500, O82239, Q01K26, Q21126, Q2QM84, Q3UHJ8, Q45GQ7, Q4V3D3, Q4V7B8, Q5QLR5, Q5SML5, Q5XUX6, Q5Z8R1, Q653U3, Q67W50, Q689G9, Q69V10, Q6H6V4, Q6H805, Q6L4L4, Q6LA42, Q6Z0D2, Q6Z0D9, Q6Z2W3, Q6ZSG1, Q7XKC4, Q7XKC5, Q7XRV0, Q7XTV7, Q8GT73, Q8L649, Q8RYC8

Diamond homologs: A5WWA0, E9QAU8, G3X9R7, O22197, O22755, O43567, O54965, O64763, P0C034, P0CH30, P0DPR2, Q06003, Q07G42, Q08D68, Q0II22, Q0VD51, Q10R93, Q14B02, Q29RU0, Q2TA44, Q3U2C5, Q4KLR8, Q4R6Y5, Q5NCP0, Q5RCV8, Q5RF74, Q5SPX3, Q5SSZ7, Q5XF85, Q641J8, Q66HG0, Q68DV7, Q69U49, Q6AY01, Q6DIP3, Q6IRP0, Q6NML0, Q6NQG7, Q6NRX0, Q6Y290

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF165	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downregulation of SMAD2/3:SMAD4 transcriptional activity	5	153.5×	2e-09
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	5	153.5×	2e-09
Signaling by BMP	5	148.7×	2e-09
E3 ubiquitin ligases ubiquitinate target proteins	5	80.7×	3e-08
Antigen processing: Ubiquitination & Proteasome degradation	8	24.8×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of BMP signaling pathway	6	145.3×	1e-10
protein monoubiquitination	5	143.3×	6e-09
protein K48-linked ubiquitination	6	84.3×	2e-09
protein polyubiquitination	6	57.7×	1e-08
ubiquitin-dependent protein catabolic process	5	30.9×	6e-06
protein ubiquitination	5	17.2×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	21
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
147605	GRCh38/hg38 18q12.3-21.1(chr18:42335174-46726460)x1	Pathogenic
154629	GRCh38/hg38 18q12.3-21.1(chr18:41722823-49043887)x1	Pathogenic
2426180	NC_000018.9:g.(?42281312)(44236996_?)del	Pathogenic
3063545	GRCh37/hg19 18q12.2-21.1(chr18:33793283-46823898)x1	Pathogenic
3242804	NC_000018.9:g.(?42281312)(45423127_?)del	Pathogenic
4682933	GRCh37/hg19 18q12.2-21.1(chr18:36435682-44982975)x1	Pathogenic
58781	GRCh38/hg38 18q12.3-21.1(chr18:45541699-46697357)x3	Pathogenic
59960	GRCh38/hg38 18q12.2-21.1(chr18:36859191-47164436)x1	Pathogenic
816010	GRCh37/hg19 18q12.3-21.1(chr18:39800804-44365152)x1	Pathogenic
816011	GRCh37/hg19 18q12.3-21.1(chr18:41630585-45107905)x1	Pathogenic
3063562	GRCh37/hg19 18q12.2-21.1(chr18:36823620-44030870)x1	Likely pathogenic

SpliceAI

1729 predictions. Top by Δscore:

Variant	Effect	Δscore
18:46334332:AGAG:A	donor_loss	1.0000
18:46334333:GAG:G	donor_gain	1.0000
18:46334333:GAGG:G	donor_loss	1.0000
18:46450698:TTCCA:T	acceptor_loss	1.0000
18:46450699:TCCA:T	acceptor_loss	1.0000
18:46450700:CCAG:C	acceptor_loss	1.0000
18:46450701:CAG:C	acceptor_loss	1.0000
18:46450702:A:AT	acceptor_loss	1.0000
18:46450703:G:A	acceptor_loss	1.0000
18:46450795:AGAAG:A	donor_loss	1.0000
18:46450796:GAAGG:G	donor_loss	1.0000
18:46450797:AAG:A	donor_loss	1.0000
18:46450798:AG:A	donor_loss	1.0000
18:46450799:GG:G	donor_loss	1.0000
18:46450800:GT:G	donor_loss	1.0000
18:46450801:T:G	donor_loss	1.0000
18:46456638:G:GT	donor_gain	1.0000
18:46456639:G:T	donor_gain	1.0000
18:46334333:G:GT	donor_gain	0.9900
18:46334337:T:G	donor_loss	0.9900
18:46433189:G:GT	acceptor_loss	0.9900
18:46433471:G:GT	donor_gain	0.9900
18:46433503:CAG:C	donor_loss	0.9900
18:46433504:AG:A	donor_loss	0.9900
18:46433505:GG:G	donor_loss	0.9900
18:46433507:T:G	donor_loss	0.9900
18:46435281:T:TA	acceptor_gain	0.9900
18:46450702:A:AG	acceptor_gain	0.9900
18:46450702:AG:A	acceptor_gain	0.9900
18:46450703:G:GA	acceptor_gain	0.9900

AlphaMissense

2268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:46450708:T:C	L242P	1.000
18:46450765:T:A	I261N	1.000
18:46450791:T:G	Y270D	1.000
18:46456037:T:A	C294S	1.000
18:46456037:T:C	C294R	1.000
18:46456038:G:A	C294Y	1.000
18:46456038:G:C	C294S	1.000
18:46456038:G:T	C294F	1.000
18:46456039:C:G	C294W	1.000
18:46456044:T:A	I296N	1.000
18:46456044:T:C	I296T	1.000
18:46456044:T:G	I296S	1.000
18:46456046:T:A	C297S	1.000
18:46456046:T:C	C297R	1.000
18:46456046:T:G	C297G	1.000
18:46456047:G:A	C297Y	1.000
18:46456047:G:C	C297S	1.000
18:46456047:G:T	C297F	1.000
18:46456048:T:G	C297W	1.000
18:46456050:T:C	L298P	1.000
18:46456080:G:C	R308T	1.000
18:46456519:A:C	R308S	1.000
18:46456519:A:T	R308S	1.000
18:46456524:T:A	L310Q	1.000
18:46456524:T:C	L310P	1.000
18:46456529:T:A	C312S	1.000
18:46456529:T:C	C312R	1.000
18:46456530:G:A	C312Y	1.000
18:46456530:G:C	C312S	1.000
18:46456530:G:T	C312F	1.000

dbSNP variants (sampled 300 via entrez): RS1000004578 (18:46377235 A>C), RS1000018115 (18:46437917 C>T), RS1000018122 (18:46347170 T>G), RS1000039152 (18:46389646 G>C), RS1000062341 (18:46421013 C>T), RS1000124867 (18:46370079 G>C), RS1000125570 (18:46418767 A>G), RS1000157541 (18:46369885 C>A,T), RS1000186051 (18:46346227 C>T), RS1000193843 (18:46404936 A>G), RS1000204651 (18:46411057 C>T), RS1000210635 (18:46358424 C>A), RS1000245778 (18:46338189 G>T), RS1000262762 (18:46450419 T>C), RS1000264058 (18:46362638 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002337_165	Amyotrophic lateral sclerosis (sporadic)	1.000000e-06
GCST006991_3	Cerebrospinal fluid t-tau levels in Alzheimer’s disease dementia	2.000000e-07
GCST006996_3	Cerebrospinal AB1-42 levels in mild cognitive impairment	3.000000e-06
GCST007012_5	Cerebrospinal fluid AB1-42 levels	1.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004760	t-tau measurement
EFO:0004670	beta-amyloid 1-42 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenate	increases expression, increases abundance	1
sodium arsenite	decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects cotreatment	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Estradiol	increases expression	1
Hydrogen Peroxide	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression	1

Clinical trials (associated diseases)

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