TNNI2

Summary

TNNI2 (troponin I2, fast skeletal type, HGNC:11946) is a protein-coding gene on chromosome 11p15.5, encoding Troponin I, fast skeletal muscle (P48788). Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.

This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 7136 — RefSeq curated summary.

At a glance

• Gene–disease (curated): distal arthrogryposis type 2B1 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 112 total — 4 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• MANE Select transcript: NM_003282

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11946
Approved symbol	TNNI2
Name	troponin I2, fast skeletal type
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Aliases	FSSV, DA2B, fsTnI
Ensembl gene	ENSG00000130598
Ensembl biotype	protein_coding
OMIM	191043
Entrez	7136

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000252898, ENST00000381905, ENST00000381906, ENST00000381911, ENST00000468473

RefSeq mRNA: 3 — MANE Select: NM_003282 NM_001145829, NM_001145841, NM_003282

CCDS: CCDS31333, CCDS53594

Canonical transcript exons

ENST00000381911 — 8 exons

Exon	Start	End
ENSE00000689892	1841031	1841207
ENSE00000689896	1840819	1840908
ENSE00001490245	1841456	1841678
ENSE00001490325	1840528	1840656
ENSE00001490331	1840403	1840444
ENSE00001490337	1839675	1839704
ENSE00001490338	1838981	1839033
ENSE00001730868	1839849	1839855

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 117.8707 / max 32778.2804, expressed in 444 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
112498	112.6726	186
112504	1.9128	239
112501	1.5307	61
112502	0.2429	28
112505	0.2358	97
112503	0.2283	123
112509	0.1926	42
112508	0.1476	27
112506	0.1413	25
112512	0.1187	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.89	gold quality
skeletal muscle tissue	UBERON:0001134	99.84	gold quality
gastrocnemius	UBERON:0001388	99.81	gold quality
muscle organ	UBERON:0001630	98.04	gold quality
skeletal muscle organ	UBERON:0014892	98.04	gold quality
muscle of leg	UBERON:0001383	97.97	gold quality
skin of leg	UBERON:0001511	91.50	gold quality
zone of skin	UBERON:0000014	90.94	gold quality
skin of abdomen	UBERON:0001416	90.21	gold quality
blood	UBERON:0000178	90.07	gold quality
muscle tissue	UBERON:0002385	89.97	gold quality
minor salivary gland	UBERON:0001830	88.55	gold quality
lower esophagus mucosa	UBERON:0035834	88.03	gold quality
granulocyte	CL:0000094	88.00	gold quality
saliva-secreting gland	UBERON:0001044	87.74	gold quality
monocyte	CL:0000576	87.17	gold quality
leukocyte	CL:0000738	86.77	gold quality
esophagus mucosa	UBERON:0002469	85.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.41	gold quality
right lung	UBERON:0002167	83.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.84	silver quality
gall bladder	UBERON:0002110	82.47	gold quality
placenta	UBERON:0001987	80.57	gold quality
upper lobe of left lung	UBERON:0008952	80.22	gold quality
urinary bladder	UBERON:0001255	80.04	gold quality
spleen	UBERON:0002106	79.66	gold quality
bone marrow	UBERON:0002371	79.08	gold quality
body of pancreas	UBERON:0001150	78.96	gold quality
esophagus	UBERON:0001043	77.29	gold quality
thoracic mammary gland	UBERON:0005200	77.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.72
E-MTAB-9801	yes	6.90
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): YY1

miRNA regulators (miRDB)

3 targeting TNNI2, 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-6071	99.16	67.77	1780
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-4450	98.26	68.35	725

Literature-anchored findings (GeneRIF, showing 14)

• Atrial re-expression of ssTnI during paroxysmal atrial fibrillation in patients does not seem to be part of the process of AF-associated cardiomyocyte dedifferentiation but seems to result from transient cardiomyocyte stress at the onset of AF. (PMID:15289369)
• study found a novel TNNI2 mutation in a Chinese family with distal arthrogryposis type 2B (PMID:16802141)
• Implantation of stable human clone expressing fast-twitch skeletal muscle troponin I in female BALB/c nude mice inhibits primary tumor growth and suggests that grafts are self-inhibitory by halting angiogenesis. (PMID:17393089)
• These findings reveal a new function for TNNI2 as a co-activator of ERRalpha. (PMID:18331830)
• Data found that fTnI normally associated with fast twitch skeletal muscle were present at significant levels in the thoracic aorta, and that fTnI transcripts were expressed in the smooth muscle layer of mouse blood vessels of all sizes. (PMID:18548613)
• Gene expression revealed up-regulation of pro-angiogenic (PGF), anti-apoptotics (BAG-1, BCL-2), heart development (TNNT2, TNNC1) and extracellular matrix remodelling (MMP-2, MMP-7) genes in SM. (PMID:18805052)
• Molecular genetic investigations revealed pathogenic mutations in MYH3, TPM2, and TNNI2 in one sporadic and 19 familial cases of distal arthrogryposis. (PMID:22519952)
• report the first TNNI2 mutation in classical FSS and describe an atypical adult FSS case with only facial contractures resulting from somatic mosaicism (PMID:23850728)
• TNNI2 gene missense mutation is associated with distal arthrogryposis type 1. (PMID:26374086)
• Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3p.98trunc resulted in haploinsufficiency, increased Ca(2+) -sensitivity and reduced length-dependent activation. TNNT2p.K217del caused increased passive tension. (PMID:28436080)
• High TNNI2 expression is associated with Peritoneal Metastasis in Gastric Cancer. (PMID:29663169)
• Elevation of fast but not slow troponin I in the circulation of patients with Becker and Duchenne muscular dystrophy. (PMID:33683712)
• A TNNI2 variant c.525G>T causes distal arthrogryposis in a Chinese family. (PMID:36069346)
• Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism. (PMID:36631501)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnni2a.2	ENSDARG00000005841
danio_rerio	tnni2a.3	ENSDARG00000013752
danio_rerio	tnni2a.4	ENSDARG00000029069
danio_rerio	tnni2b.2	ENSDARG00000029995
danio_rerio	tnni2b.1	ENSDARG00000035958
danio_rerio	tnni2a.1	ENSDARG00000045592
mus_musculus	Tnni2	ENSMUSG00000031097
rattus_norvegicus	Tnni2	ENSRNOG00000020276
drosophila_melanogaster	wupA	FBGN0283471
caenorhabditis_elegans		WBGENE00006584
caenorhabditis_elegans		WBGENE00006585
caenorhabditis_elegans		WBGENE00006586
caenorhabditis_elegans		WBGENE00006764

Paralogs (2): TNNI3 (ENSG00000129991), TNNI1 (ENSG00000159173)

Protein

Protein identifiers

Troponin I, fast skeletal muscle — P48788 (reviewed: P48788)

Alternative names: Troponin I, fast-twitch isoform

All UniProt accessions (1): P48788

UniProt curated annotations — full annotation on UniProt →

Function. Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.

Subunit / interactions. Binds to actin and tropomyosin.

Disease relevance. Arthrogryposis, distal, 2B1 (DA2B1) [MIM:601680] A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2B is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. DA2B1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the troponin I family.

Isoforms (2)

UniProt ID	Names	Canonical?
P48788-1	1	yes
P48788-2	2

RefSeq proteins (3): NP_001139301, NP_001139313, NP_003273* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001978	Troponin	Family
IPR038077	Troponin_sf	Homologous_superfamily
IPR050875	Troponin_I	Family

Pfam: PF00992

UniProt features (12 total): modified residue 3, region of interest 2, initiator methionine 1, chain 1, helix 1, turn 1, splice variant 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2MKP	SOLUTION NMR
7KAA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48788-F1	80.65	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.

Post-translational modifications (3): 2, 12, 118

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-390522	Striated Muscle Contraction

MSigDB gene sets: 261 (showing top): GOBP_CIRCULATORY_SYSTEM_PROCESS, GCANCTGNY_MYOD_Q6, SP3_Q3, MAZ_Q6, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, GOBP_MULTICELLULAR_ORGANISMAL_MOVEMENT, MEF2_02, MODULE_329, GGGTGGRR_PAX4_03, LEE_LIVER_CANCER_CIPROFIBRATE_DN, GOBP_SKELETAL_MUSCLE_CONTRACTION, CAGCTG_AP4_Q5, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, SOX9_B1

GO Biological Process (3): skeletal muscle contraction (GO:0003009), positive regulation of DNA-templated transcription (GO:0045893), cardiac muscle contraction (GO:0060048)

GO Molecular Function (3): actin binding (GO:0003779), troponin T binding (GO:0031014), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), troponin complex (GO:0005861)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Muscle contraction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
striated muscle contraction	2
cytoskeletal protein binding	2
musculoskeletal movement	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
heart contraction	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
striated muscle thin filament	1
protein-containing complex	1

Protein interactions and networks

STRING

1178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNNI2	TNNT3	P45378	988
TNNI2	TPM2	P06468	964
TNNI2	TNNT1	P13805	949
TNNI2	MYH3	P11055	923
TNNI2	TNNT2	P45379	856
TNNI2	TNNC1	P02590	847
TNNI2	TNNC2	P02585	807
TNNI2	ACTA1	P02568	761
TNNI2	MYL3	P08590	701
TNNI2	TPM1	P09493	670
TNNI2	MYL2	P10916	661
TNNI2	MYL1	P05976	646
TNNI2	MYBPC1	Q00872	636
TNNI2	MYH4	Q9Y623	625
TNNI2	CHRNG	P07510	617

IntAct

42 interactions, top by confidence:

A	B	Type	Score
TNNC1	TNNI2	psi-mi:“MI:0407”(direct interaction)	0.590
TNNI2	TNNC1	psi-mi:“MI:0914”(association)	0.590
TNNT1	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
ESRRG	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
MNS1	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
DCAF11	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
PSMC5	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
ESRRA	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
CTNNA3	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
NME7	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
EFCAB2	TNNI2	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	ESRRG	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	MNS1	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	DCAF11	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	PSMC5	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	EFCAB2	psi-mi:“MI:0915”(physical association)	0.560
TNNI2	NME7	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (35): TNNI2 (Two-hybrid), TNNI2 (Two-hybrid), NUCB2 (Affinity Capture-MS), RFTN2 (Affinity Capture-MS), KLHL21 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), TLE1 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), TNNI2 (Two-hybrid), TNNI2 (Two-hybrid), TNNI2 (Two-hybrid), TNNI2 (Two-hybrid), MNS1 (Two-hybrid), NME7 (Two-hybrid), ESRRA (Two-hybrid)

ESM2 similar proteins: A0JN61, B5FZ63, O14737, O43242, O82197, P02643, P13412, P27768, P48788, P49205, P50502, P50503, P56812, Q06364, Q08AG7, Q15691, Q2HJH9, Q3ZBD9, Q3ZBJ0, Q4QQV8, Q5R7Z5, Q5RBR3, Q5RBT0, Q5RF31, Q5SRX1, Q5XGW6, Q5XGY9, Q5ZHP5, Q5ZLF0, Q61166, Q66HR2, Q6DD52, Q6GL11, Q6IQ73, Q6PBL0, Q6ZVM7, Q7ZVC4, Q8K396, Q8NFI4, Q99L47

Diamond homologs: O44572, P05547, P27768, P36188, P48788, Q20334, Q7M3Y3, Q969A1, Q9GYF1, Q9XUN9, P02643, P02645, P02646, P08057, P13412, P13413, P19237, P19429, P23693, P27672, P27673, P48787, P50754, P68246, P68247, Q5PYI0, Q863B6, Q8MKD5, Q9WUZ5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
“MYOD1/SWI/SNF complex”	“up-regulates quantity by expression”	TNNI2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	7
Uncertain significance	49
Likely benign	25
Benign	10

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
12435	NM_003282.4(TNNI2):c.521G>A (p.Arg174Gln)	Pathogenic
12436	NM_003282.4(TNNI2):c.466C>T (p.Arg156Ter)	Pathogenic
12439	NM_003282.4(TNNI2):c.496GAG[1] (p.Glu167del)	Pathogenic
694070	NM_003282.4(TNNI2):c.493A>T (p.Ile165Phe)	Pathogenic
1212076	NM_003282.4(TNNI2):c.316A>G (p.Lys106Glu)	Likely pathogenic
1333897	NM_003282.4(TNNI2):c.520C>T (p.Arg174Trp)	Likely pathogenic
2434182	NM_003282.4(TNNI2):c.503_505dup (p.Ser169Ter)	Likely pathogenic
2506365	NM_003282.4(TNNI2):c.496G>T (p.Glu166Ter)	Likely pathogenic
3064439	NM_003282.4(TNNI2):c.486G>T (p.Arg162Ser)	Likely pathogenic
374417	NM_003282.4(TNNI2):c.380_391del (p.Leu127_Lys130del)	Likely pathogenic
4293088	NM_003282.4(TNNI2):c.486G>C (p.Arg162Ser)	Likely pathogenic

SpliceAI

852 predictions. Top by Δscore:

Variant	Effect	Δscore
11:1839705:G:GG	donor_gain	1.0000
11:1839818:C:CA	acceptor_gain	1.0000
11:1840401:A:AG	acceptor_gain	1.0000
11:1840402:G:GG	acceptor_gain	1.0000
11:1840443:AGG:A	donor_loss	1.0000
11:1840445:G:GA	donor_loss	1.0000
11:1840523:C:CA	acceptor_gain	1.0000
11:1840523:CGCA:C	acceptor_loss	1.0000
11:1840524:GCA:G	acceptor_loss	1.0000
11:1840525:CA:C	acceptor_loss	1.0000
11:1840526:A:AG	acceptor_gain	1.0000
11:1840526:AGAGT:A	acceptor_gain	1.0000
11:1840527:G:GA	acceptor_gain	1.0000
11:1840527:GA:G	acceptor_gain	1.0000
11:1840527:GAGT:G	acceptor_gain	1.0000
11:1840527:GAGTG:G	acceptor_gain	1.0000
11:1840645:TCTG:T	donor_gain	1.0000
11:1840648:G:GT	donor_gain	1.0000
11:1840652:TGC:T	donor_gain	1.0000
11:1840654:CAG:C	donor_gain	1.0000
11:1840655:AGGTA:A	donor_loss	1.0000
11:1840657:G:GA	donor_loss	1.0000
11:1840658:T:G	donor_loss	1.0000
11:1840905:GGAG:G	donor_gain	1.0000
11:1840906:GAG:G	donor_gain	1.0000
11:1840906:GAGG:G	donor_gain	1.0000
11:1840907:AGG:A	donor_loss	1.0000
11:1840909:G:GG	donor_gain	1.0000
11:1840910:T:G	donor_loss	1.0000
11:1841028:CAGCT:C	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000147119 (11:1839738 C>A), RS1000366025 (11:1837915 G>A), RS1001285114 (11:1841904 C>T), RS1001406518 (11:1837553 C>T), RS1001466986 (11:1837666 G>A,C), RS1001708492 (11:1841635 G>A,C), RS1002165169 (11:1841791 C>T), RS1002266980 (11:1838513 A>G), RS1003253608 (11:1839397 C>T), RS1003410596 (11:1839582 C>A), RS1003648695 (11:1840834 C>A), RS1004419789 (11:1838307 G>A,T), RS1005368718 (11:1839366 G>A,T), RS1005820398 (11:1838608 C>T), RS1006158106 (11:1838329 C>T)

Disease associations

OMIM: gene MIM:191043 | disease phenotypes: MIM:601680, MIM:108120

GenCC curated gene-disease

Disease	Classification	Inheritance
distal arthrogryposis type 2B1	Strong	Autosomal dominant
digitotalar dysmorphism	Supportive	Autosomal dominant
Sheldon-hall syndrome	Supportive	Autosomal dominant

Mondo (4): distal arthrogryposis type 2B1 (MONDO:0020820), distal arthrogryposis (MONDO:0019942), digitotalar dysmorphism (MONDO:0015240), Sheldon-hall syndrome (MONDO:0011128)

Orphanet (2): Sheldon-Hall syndrome (Orphanet:1147), Distal arthrogryposis (Orphanet:97120)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000218	High palate
HP:0000275	Narrow face
HP:0000303	Mandibular prognathia
HP:0000325	Triangular face
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000598	Abnormality of the ear
HP:0001181	Adducted thumb
HP:0001193	Ulnar deviation of the hand or of fingers of the hand
HP:0001387	Joint stiffness
HP:0001762	Talipes equinovarus
HP:0001838	Rocker bottom foot
HP:0001840	Metatarsus adductus
HP:0001848	Calcaneovalgus deformity
HP:0001883	Talipes
HP:0002650	Scoliosis
HP:0002804	Arthrogryposis multiplex congenita
HP:0003049	Ulnar deviation of the wrist
HP:0003272	Abnormal hip bone morphology
HP:0003422	Vertebral segmentation defect
HP:0004322	Short stature
HP:0005272	Prominent nasolabial fold
HP:0005684	Distal arthrogryposis

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001725_8	Inflammatory bowel disease	3.000000e-10
GCST002112_1	Celiac disease	7.000000e-06
GCST006190_36	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-10
GCST006190_89	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-11
GCST006192_23	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-19
GCST006192_9	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-20
GCST006193_20	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	9.000000e-10
GCST006193_60	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-10
GCST006195_28	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-19
GCST006195_50	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	2.000000e-20
GCST007000_5	Logical memory (delayed recall) in mild cognitive impairment	2.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004874	memory performance

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565097	Digitotalar Dysmorphism (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831282 (PROTEIN COMPLEX)

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	affects expression, increases expression	4
bisphenol A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	increases expression	2
Cadmium Chloride	decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
notexin	increases secretion	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Allergens	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases expression, increases abundance	1
Cannabidiol	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Gasoline	increases abundance, increases expression, affects cotreatment	1
Hydrogen Peroxide	affects expression	1
Phenobarbital	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Quercetin	increases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01144741	Not specified	TERMINATED	Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome
NCT05419245	Not specified	UNKNOWN	Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome
NCT05137756	Not specified	COMPLETED	Mercuri Analysis Contribution on Handicap Evaluation in ArthrogypOsis, a Congenital Neuromuscular Disease