RSPO4

Summary

RSPO4 (R-spondin 4, HGNC:16175) is a protein-coding gene on chromosome 20p13, encoding R-spondin-4 (Q2I0M5). Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors.

This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 343637 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nonsyndromic congenital nail disorder 4 (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 88 total — 11 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001029871

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16175
Approved symbol	RSPO4
Name	R-spondin 4
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	dJ824F16.3
Ensembl gene	ENSG00000101282
Ensembl biotype	protein_coding
OMIM	610573
Entrez	343637

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000217260, ENST00000400634, ENST00000873320, ENST00000873321, ENST00000873322, ENST00000922623, ENST00000922624

RefSeq mRNA: 2 — MANE Select: NM_001029871 NM_001029871, NM_001040007

CCDS: CCDS42845, CCDS42846

Canonical transcript exons

ENST00000217260 — 5 exons

Exon	Start	End
ENSE00000655139	967174	967314
ENSE00000858560	963935	964120
ENSE00000858561	967950	968138
ENSE00000858562	1002086	1002311
ENSE00000990907	958452	960466

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 77.28.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7830 / max 64.0939, expressed in 299 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185996	0.7830	299

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper lobe of left lung	UBERON:0008952	77.28	gold quality
hypothalamus	UBERON:0001898	76.74	gold quality
upper lobe of lung	UBERON:0008948	75.09	gold quality
putamen	UBERON:0001874	73.33	gold quality
caudate nucleus	UBERON:0001873	72.25	gold quality
nucleus accumbens	UBERON:0001882	71.69	gold quality
right uterine tube	UBERON:0001302	69.06	gold quality
cerebellar vermis	UBERON:0004720	68.99	gold quality
right lung	UBERON:0002167	67.93	gold quality
substantia nigra	UBERON:0002038	67.63	gold quality
lung	UBERON:0002048	67.11	gold quality
midbrain	UBERON:0001891	66.62	gold quality
endothelial cell	CL:0000115	66.34	gold quality
right lobe of thyroid gland	UBERON:0001119	65.36	gold quality
amygdala	UBERON:0001876	65.10	gold quality
left lobe of thyroid gland	UBERON:0001120	64.71	gold quality
lower esophagus	UBERON:0013473	64.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	64.38	gold quality
thyroid gland	UBERON:0002046	63.74	gold quality
skin of abdomen	UBERON:0001416	63.72	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	62.76	gold quality
anterior cingulate cortex	UBERON:0009835	62.36	gold quality
pons	UBERON:0000988	62.15	silver quality
spinal cord	UBERON:0002240	62.12	gold quality
temporal lobe	UBERON:0001871	61.97	gold quality
skin of leg	UBERON:0001511	61.90	gold quality
forebrain	UBERON:0001890	61.90	gold quality
zone of skin	UBERON:0000014	61.60	gold quality
sural nerve	UBERON:0015488	61.58	silver quality
Ammon’s horn	UBERON:0001954	61.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting RSPO4, 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-4455	100.00	65.48	1587
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6772-5P	99.94	67.01	577

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 8)

• RSPO4 has a crucial role in nail morphogenesis. (PMID:17041604)
• These findings expand our understanding of the role of RSPO4 in nail development and disease. (PMID:17805348)
• The previously unknown mutations c.190C>T (p.Arg64Cys) in exon 2 and c.301C>T (p.Gln101X) in exon 3 were identified in RSPO4, thereby corroborating R-spondin 4 as the major protein in autosomal-recessive anonychia. (PMID:17914448)
• identification of a missense mutation c.199G > C (p.Gly67Arg) in the RSPO4 gene in a large consanguineous Pakistani family with an autosomal recessive form of anonychia (PMID:18070203)
• A novel nonsense mutation in RSPO4 gene involves in the development of anonychia congenita. (PMID:22300369)
• c.3G>A mutation is not sufficient to cause the congenital hyponychia and could be considered a polymorphism. (PMID:23234511)
• Single-cell RNA sequencing of human nail unit defines RSPO4 onychofibroblasts and SPINK6 nail epithelium. (PMID:34099859)
• RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity. (PMID:36507580)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rspo4	ENSDARG00000038593
mus_musculus	Rspo4	ENSMUSG00000032852
rattus_norvegicus	Rspo4	ENSRNOG00000009662

Paralogs (3): RSPO3 (ENSG00000146374), RSPO2 (ENSG00000147655), RSPO1 (ENSG00000169218)

Protein

Protein identifiers

R-spondin-4 — Q2I0M5 (reviewed: Q2I0M5)

Alternative names: Roof plate-specific spondin-4

All UniProt accessions (1): Q2I0M5

UniProt curated annotations — full annotation on UniProt →

Function. Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway.

Subunit / interactions. Binds heparin. Interacts with LGR4, LGR5 and LGR6.

Subcellular location. Secreted.

Post-translational modifications. Tyr-112 may be phosphorylated; however as this position is probably extracellular, the vivo relevance is not proven.

Disease relevance. Nail disorder, non-syndromic congenital, 4 (NDNC4) [MIM:206800] A nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The FU repeat is required for activation and stabilization of beta-catenin.

Similarity. Belongs to the R-spondin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q2I0M5-1	1	yes
Q2I0M5-2	2

RefSeq proteins (2): NP_001025042, NP_001035096 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR006212	Furin_repeat	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR043601	Rspo_Fu-CRD_dom	Domain
IPR051514	R-spondin	Family

Pfam: PF15913

UniProt features (25 total): disulfide bond 11, sequence variant 5, compositionally biased region 2, signal peptide 1, chain 1, splice variant 1, repeat 1, domain 1, region of interest 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2I0M5-F1	78.46	0.45

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 (11): 50–69, 73–88, 91–98, 95–104, 107–118, 122–135, 139–181, 150–157, 190–196, 35–41, 38–47

Glycosylation sites (1): 34

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-4641263	Regulation of FZD by ubiquitination
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT

MSigDB gene sets: 89 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE45365_NK_CELL_VS_BCELL_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_APPENDAGE_DEVELOPMENT, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_POSITIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_HEPARIN_BINDING, GOMF_SULFUR_COMPOUND_BINDING, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3

GO Biological Process (5): Wnt signaling pathway (GO:0016055), positive regulation of Wnt signaling pathway (GO:0030177), nail development (GO:0035878), positive regulation of canonical Wnt signaling pathway (GO:0090263), limb development (GO:0060173)

GO Molecular Function (3): signaling receptor binding (GO:0005102), heparin binding (GO:0008201), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
TCF dependent signaling in response to WNT	1
Signal Transduction	1
Signaling by WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell surface receptor signaling pathway	1
positive regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
anatomical structure development	1
limb development	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
appendage development	1
protein binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

921 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSPO4	LGR4	Q9BXB1	893
RSPO4	LGR6	Q9HBX8	829
RSPO4	FURIN	P09958	803
RSPO4	ZNRF3	Q9ULT6	740
RSPO4	LGR5	O75473	712
RSPO4	RNF43	Q68DV7	705
RSPO4	CTNNB1	P35222	666
RSPO4	WNT3	P56703	551
RSPO4	THBS1	P07996	512
RSPO4	WNT1	P04628	452
RSPO4	FZD6	O60353	438
RSPO4	HPGD	P15428	428
RSPO4	ASB13	Q8WXK3	425
RSPO4	BMP2	P12643	420
RSPO4	LRP6	O75581	401
RSPO4	EPB41L4B	Q9H329	401

IntAct

46 interactions, top by confidence:

A	B	Type	Score
MAPK9	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
STK16	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	DHX57	psi-mi:“MI:0915”(physical association)	0.560
HGS	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	PIH1D2	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	GNG13	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	ZNF330	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
USP20	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	GPSM3	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	GUCD1	psi-mi:“MI:0915”(physical association)	0.560
RSPO4	KLHL38	psi-mi:“MI:0915”(physical association)	0.560
ZNF77	RSPO4	psi-mi:“MI:0915”(physical association)	0.560
LGR6	RSPO4	psi-mi:“MI:0915”(physical association)	0.400
LGR4	RSPO4	psi-mi:“MI:0915”(physical association)	0.400
LGR5	RSPO4	psi-mi:“MI:0915”(physical association)	0.400
MAPK9	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
STK16	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
DHX57	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
HGS	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
PIH1D2	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
GUCD1	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
KLHL38	RSPO4	psi-mi:“MI:0915”(physical association)	0.000
RSPO4	DHX57	psi-mi:“MI:0915”(physical association)	0.000
GNG13	RSPO4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): RSPO4 (Reconstituted Complex), RSPO4 (Reconstituted Complex), RSPO4 (Two-hybrid), ZNF330 (Two-hybrid), STK16 (Two-hybrid), GNG13 (Two-hybrid), USP20 (Two-hybrid), GUCD1 (Two-hybrid), PIH1D2 (Two-hybrid), DHX57 (Two-hybrid), ANKRD11 (Two-hybrid), ZNF77 (Two-hybrid), KLHL38 (Two-hybrid), MKRN3 (Two-hybrid), HGS (Two-hybrid)

ESM2 similar proteins: A7MBS7, D3YXF5, F1LW30, O89103, P10643, P11680, P27918, P35446, P82987, P90884, Q29RQ1, Q2I0M5, Q2MKA7, Q3UPR9, Q3UTY6, Q4R7Z5, Q5M7L6, Q5RAD0, Q5RBP1, Q5RBP8, Q5UE90, Q64181, Q66PY1, Q69ZU6, Q6NZL8, Q6P4U0, Q6UXX9, Q6ZMP0, Q7T3Q2, Q7TSK7, Q80YN4, Q86TH1, Q8BFU0, Q8BJ73, Q8BLI0, Q8IUX8, Q8IWY4, Q8IX30, Q8N6G6, Q8VCC9

Diamond homologs: A7MBS7, P41413, Q04592, Q1RMU1, Q2I0M5, Q2MKA7, Q2TJ95, Q5M7L6, Q5R328, Q5UE90, Q69ZU6, Q6DHR0, Q6P4U0, Q6UXX9, Q8BFU0, Q8BJ73, Q92824, Q9BXY4, Q9C0I4, Q9UPZ6, Q9Z132, P35446, P30432, P35447, P51559, Q8BMS2, Q8VCC9, Q9BUD6, Q9GLX9, Q9HCB6, Q9WV75, P24062, P29122, Q63415

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	1
Uncertain significance	63
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1190	NM_001029871.4(RSPO4):c.194A>G (p.Gln65Arg)	Pathogenic
1191	NM_001029871.4(RSPO4):c.319T>C (p.Cys107Arg)	Pathogenic
1192	NM_001029871.4(RSPO4):c.353G>A (p.Cys118Tyr)	Pathogenic
1193	NM_001029871.4(RSPO4):c.218G>A (p.Cys73Tyr)	Pathogenic
2157189	NM_001029871.4(RSPO4):c.145_166dup (p.Leu56fs)	Pathogenic
30845	NM_001029871.4(RSPO4):c.301C>T (p.Gln101Ter)	Pathogenic
30846	NM_001029871.4(RSPO4):c.190C>T (p.Arg64Cys)	Pathogenic
30847	NM_001029871.4(RSPO4):c.199G>C (p.Gly67Arg)	Pathogenic
3256625	NM_001029871.4(RSPO4):c.335_338del (p.Tyr112fs)	Pathogenic
3256888	NM_001029871.4(RSPO4):c.76_79del (p.Gln26fs)	Pathogenic
521270	NM_001029871.4(RSPO4):c.79+1G>A	Pathogenic
4077476	NM_001029871.4(RSPO4):c.64C>T (p.Arg22Ter)	Likely pathogenic

SpliceAI

1211 predictions. Top by Δscore:

Variant	Effect	Δscore
20:1002080:TTGTA:T	donor_loss	1.0000
20:1002081:TGTA:T	donor_loss	1.0000
20:1002083:TA:T	donor_loss	1.0000
20:1002085:CCTTG:C	donor_gain	1.0000
20:1002095:T:TA	donor_gain	1.0000
20:967172:AC:A	donor_gain	1.0000
20:967173:CC:C	donor_gain	1.0000
20:967183:C:CA	donor_gain	1.0000
20:967948:A:AC	donor_gain	1.0000
20:967949:C:CT	donor_gain	1.0000
20:967967:T:TA	donor_gain	1.0000
20:968144:C:T	acceptor_gain	1.0000
20:968152:C:CT	acceptor_gain	1.0000
20:1002084:A:AC	donor_gain	0.9900
20:1002085:C:CC	donor_gain	0.9900
20:1002092:T:TA	donor_gain	0.9900
20:960462:CCTCT:C	acceptor_gain	0.9900
20:960463:CTCT:C	acceptor_gain	0.9900
20:960463:CTCTC:C	acceptor_gain	0.9900
20:960464:TCTCT:T	acceptor_gain	0.9900
20:960465:CT:C	acceptor_gain	0.9900
20:960466:TC:T	acceptor_loss	0.9900
20:960467:C:CC	acceptor_gain	0.9900
20:960467:CTGCA:C	acceptor_loss	0.9900
20:960468:T:A	acceptor_loss	0.9900
20:967235:C:A	donor_gain	0.9900
20:967945:CGTAC:C	donor_loss	0.9900
20:967947:TAC:T	donor_loss	0.9900
20:967948:ACTT:A	donor_loss	0.9900
20:967949:CTT:C	donor_gain	0.9900

AlphaMissense

1516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:967274:G:C	F103L	0.999
20:967274:G:T	F103L	0.999
20:967275:A:C	F103C	0.999
20:967276:A:G	F103L	0.999
20:967287:A:C	F99C	0.999
20:968012:C:G	C69S	0.999
20:968013:A:T	C69S	0.999
20:968054:A:C	F55C	0.999
20:967263:C:G	C107S	0.998
20:967264:A:T	C107S	0.998
20:967286:G:C	F99L	0.998
20:967286:G:T	F99L	0.998
20:967288:A:G	F99L	0.998
20:967955:C:G	C88S	0.998
20:967956:A:T	C88S	0.998
20:968013:A:G	C69R	0.998
20:964089:C:A	W147C	0.997
20:964089:C:G	W147C	0.997
20:967230:C:G	C118S	0.997
20:967231:A:T	C118S	0.997
20:968011:G:C	C69W	0.997
20:968053:G:C	F55L	0.997
20:968053:G:T	F55L	0.997
20:968055:A:G	F55L	0.997
20:968078:C:G	C47S	0.997
20:968079:A:T	C47S	0.997
20:968082:C:A	G46C	0.997
20:967231:A:G	C118R	0.996
20:967271:G:C	C104W	0.996
20:967272:C:G	C104S	0.996

dbSNP variants (sampled 300 via entrez): RS1000008024 (20:979594 A>G), RS1000093856 (20:978148 A>C), RS1000231886 (20:981380 C>G), RS1000260768 (20:991004 C>G,T), RS1000287168 (20:969245 G>A), RS1000358782 (20:997061 G>A), RS1000418330 (20:996358 GT>G,GTT), RS1000685539 (20:960189 G>T), RS1000736087 (20:974032 T>G), RS1000770910 (20:996111 A>G), RS1000829388 (20:1003272 A>C), RS1000844899 (20:979608 G>C), RS1000862030 (20:992967 G>A), RS1000997026 (20:986638 G>A,T), RS1001142296 (20:994230 A>G)

Disease associations

OMIM: gene MIM:610573 | disease phenotypes: MIM:206800

GenCC curated gene-disease

Disease	Classification	Inheritance
nonsyndromic congenital nail disorder 4	Definitive	Autosomal recessive

Mondo (1): nonsyndromic congenital nail disorder 4 (MONDO:0008798)

Orphanet (2): Isolated congenital anonychia (Orphanet:79143), Anonychia congenita totalis (Orphanet:94150)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001507	Growth abnormality
HP:0001798	Anonychia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_237	Blood protein levels	9.000000e-14
GCST006994_4	Logical memory (immediate recall) in Alzheimer’s disease dementia	5.000000e-07
GCST008153_12	Lean body mass	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0004995	lean body mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536377	Anonychia congenita (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
GSK-J4	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Hydralazine	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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