TMOD1

Summary

TMOD1 (tropomodulin 1, HGNC:11871) is a protein-coding gene on chromosome 9q22.33, encoding Tropomodulin-1 (P28289). Blocks the elongation and depolymerization of the actin filaments at the pointed end.

This gene encodes a member of the tropomodulin family. The encoded protein is an actin-capping protein that regulates tropomyosin by binding to its N-terminus, inhibiting depolymerization and elongation of the pointed end of actin filaments and thereby influencing the structure of the erythrocyte membrane skeleton. Multiple transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 7111 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Limited, ClinGen)
• GWAS associations: 7
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_003275

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11871
Approved symbol	TMOD1
Name	tropomodulin 1
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	ETMOD
Ensembl gene	ENSG00000136842
Ensembl biotype	protein_coding
OMIM	190930
Entrez	7111

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000259365, ENST00000375175, ENST00000395211, ENST00000900211, ENST00000900212, ENST00000900213, ENST00000900214, ENST00000900215, ENST00000900216, ENST00000900217, ENST00000900218, ENST00000937335, ENST00000950652, ENST00000950653, ENST00000950654, ENST00000950655, ENST00000950656, ENST00000950657, ENST00000950658, ENST00000950659, ENST00000950660, ENST00000950661

RefSeq mRNA: 2 — MANE Select: NM_003275 NM_001166116, NM_003275

CCDS: CCDS6726

Canonical transcript exons

ENST00000259365 — 10 exons

Exon	Start	End
ENSE00000926468	97524141	97524308
ENSE00000926469	97546185	97546341
ENSE00000926470	97553281	97553400
ENSE00000926471	97562732	97562821
ENSE00000926472	97564038	97564168
ENSE00000926473	97565848	97565955
ENSE00000926474	97568894	97569037
ENSE00000926475	97591291	97591435
ENSE00001420434	97501666	97501803
ENSE00003705677	97599634	97601743

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.13.

FANTOM5 (CAGE): breadth broad, TPM avg 13.2254 / max 527.7752, expressed in 835 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97552	12.2863	814
97553	0.3179	156
97555	0.2555	127
97556	0.1184	63
97554	0.0981	52
97559	0.0728	16
97557	0.0453	24
97558	0.0312	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.14	gold quality
islet of Langerhans	UBERON:0000006	98.01	gold quality
gastrocnemius	UBERON:0001388	97.88	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.86	gold quality
muscle of leg	UBERON:0001383	97.70	gold quality
mucosa of stomach	UBERON:0001199	97.59	gold quality
cardiac atrium	UBERON:0002081	97.57	gold quality
muscle organ	UBERON:0001630	97.54	gold quality
skeletal muscle organ	UBERON:0014892	97.54	gold quality
right atrium auricular region	UBERON:0006631	97.53	gold quality
dorsal root ganglion	UBERON:0000044	97.42	gold quality
heart left ventricle	UBERON:0002084	97.32	gold quality
cardiac ventricle	UBERON:0002082	97.27	gold quality
skeletal muscle tissue	UBERON:0001134	97.23	gold quality
body of tongue	UBERON:0011876	97.21	gold quality
left ventricle myocardium	UBERON:0006566	97.18	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.16	gold quality
quadriceps femoris	UBERON:0001377	97.12	gold quality
vastus lateralis	UBERON:0001379	97.04	gold quality
deltoid	UBERON:0001476	97.04	gold quality
myocardium	UBERON:0002349	97.03	gold quality
apex of heart	UBERON:0002098	96.92	gold quality
heart	UBERON:0000948	96.76	gold quality
gluteal muscle	UBERON:0002000	96.72	gold quality
trigeminal ganglion	UBERON:0001675	96.66	gold quality
diaphragm	UBERON:0001103	96.62	gold quality
tibialis anterior	UBERON:0001385	96.62	gold quality
triceps brachii	UBERON:0001509	96.59	gold quality
biceps brachii	UBERON:0001507	96.48	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	922.09
E-MTAB-5061	yes	14.07
E-GEOD-83139	yes	7.95
E-MTAB-9388	yes	7.53
E-CURD-10	no	287.65
E-MTAB-9467	no	0.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

93 targeting TMOD1, 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-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4677-5P	99.70	70.09	1940

Literature-anchored findings (GeneRIF, showing 15)

• Tropomyosin requires an intact N-terminal coiled coil to interact with this protein (PMID:11964245)
• levels of TM1, TM2 and TM3 are reduced in human transitional cell carcinoma cells, but significantly upregulated by inhibition of the mitogen-activated protein kinase-signaling pathway (PMID:15095301)
• The N-terminal “KRK ring” may participate in balancing electrostatic force with hydrophobic interaction in dimerization of TM and its binding to E-Tmod. (PMID:16297372)
• study identifies several amino acid residues on Tmod-1 that are important for its interaction with TM5 (a nonmuscle TM isoform) (PMID:16434395)
• Tmod1 and Tmod3 showed somewhat different tropomyosin-binding site utilization. (PMID:24922351)
• The structures and biochemical analysis of structure-inspired mutants showed that one Tmod molecule interacts with three actin subunits at the pointed end, while also contacting two tropomyosin molecules on each side of the filament. (PMID:25061212)
• Study highlighted a novel TMOD1-mediated link between NF-kappaB activation and MMP13 induction, which accounts in part for the NF-kappaB-dependent malignant phenotype of TNBC. (PMID:25398440)
• The mutation reduced binding affinity for both Lmod2 and Tmod1. The effect of the K15N mutation on Tpm1.1 binding to Lmod2 and Tmod1 provides a molecular rationale for the development of familial dilated cardiomyopathies . (PMID:26873245)
• Tmod1 function in mouse and human erythroblasts, was investigated. (PMID:28729432)
• Targeted regulation of miR-17-5p on TMOD1 promotes the development of cardia cancer. (PMID:31364131)
• Tropomodulins Control the Balance between Protrusive and Contractile Structures by Stabilizing Actin-Tropomyosin Filaments. (PMID:32037094)
• MicroRNA-885 regulates the growth and epithelial mesenchymal transition of human liver cancer cells by suppressing tropomodulin 1 expression. (PMID:32937160)
• Suggestive evidence of the genetic association of TMOD1 and PTCSC2 polymorphisms with thyroid carcinoma in the Chinese Han population. (PMID:36316666)
• Recessive TMOD1 mutation causes childhood cardiomyopathy. (PMID:38168645)
• Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis. (PMID:39276234)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmod1	ENSDARG00000078318
mus_musculus	Tmod1	ENSMUSG00000028328
rattus_norvegicus	Tmod1	ENSRNOG00000009761
drosophila_melanogaster	tmod	FBGN0082582
caenorhabditis_elegans	unc-94	WBGENE00006823

Paralogs (6): TMOD2 (ENSG00000128872), TMOD3 (ENSG00000138594), TMOD4 (ENSG00000163157), LMOD3 (ENSG00000163380), LMOD1 (ENSG00000163431), LMOD2 (ENSG00000170807)

Protein

Protein identifiers

Tropomodulin-1 — P28289 (reviewed: P28289)

Alternative names: Erythrocyte tropomodulin

All UniProt accessions (1): P28289

UniProt curated annotations — full annotation on UniProt →

Function. Blocks the elongation and depolymerization of the actin filaments at the pointed end. The Tmod/TM complex contributes to the formation of the short actin protofilament, which in turn defines the geometry of the membrane skeleton. May play an important role in regulating the organization of actin filaments by preferentially binding to a specific tropomyosin isoform at its N-terminus.

Subunit / interactions. Binds to the N-terminus of tropomyosin and to actin. Interacts with FLII.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Highly expressed in the erythrocyte, heart and skeletal muscle.

Similarity. Belongs to the tropomodulin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P28289-1	1	yes
P28289-2	2

RefSeq proteins (2): NP_001159588, NP_003266* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004934	TMOD	Family
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF03250

UniProt features (23 total): helix 8, strand 5, sequence conflict 3, region of interest 2, splice variant 2, chain 1, turn 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4PKG	X-RAY DIFFRACTION	1.8
4Z8G	X-RAY DIFFRACTION	2.1
4PKH	X-RAY DIFFRACTION	2.15
4PKI	X-RAY DIFFRACTION	2.3
4Z94	X-RAY DIFFRACTION	2.4
8F8T	ELECTRON MICROSCOPY	3.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28289-F1	84.83	0.48

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-390522	Striated Muscle Contraction

MSigDB gene sets: 222 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_BEHAVIOR, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ADULT_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_POLYMERIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_ADULT_LOCOMOTORY_BEHAVIOR

GO Biological Process (6): muscle contraction (GO:0006936), actin filament organization (GO:0007015), adult locomotory behavior (GO:0008344), myofibril assembly (GO:0030239), pointed-end actin filament capping (GO:0051694), lens fiber cell development (GO:0070307)

GO Molecular Function (2): actin binding (GO:0003779), tropomyosin binding (GO:0005523)

GO Cellular Component (10): cytosol (GO:0005829), cytoskeleton (GO:0005856), striated muscle thin filament (GO:0005865), actin filament (GO:0005884), membrane (GO:0016020), myofibril (GO:0030016), sarcomere (GO:0030017), cortical cytoskeleton (GO:0030863), cytoplasm (GO:0005737), COP9 signalosome (GO:0008180)

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
cellular anatomical structure	4
supramolecular fiber organization	2
cytoskeletal protein binding	2
actin cytoskeleton	2
muscle system process	1
actin cytoskeleton organization	1
locomotory behavior	1
adult behavior	1
cellular component assembly involved in morphogenesis	1
actomyosin structure organization	1
striated muscle cell development	1
membraneless organelle assembly	1
actin filament capping	1
epithelial cell development	1
lens fiber cell differentiation	1
cytoplasm	1
intracellular membraneless organelle	1
sarcomere	1
myofilament	1
polymeric cytoskeletal fiber	1
contractile muscle fiber	1
myofibril	1
cytoskeleton	1
cell cortex	1
intracellular anatomical structure	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TMOD1	ADD1	P35611	956
TMOD1	ADD2	P35612	947
TMOD1	ADD3	Q9UEY8	939
TMOD1	NEB	P20929	920
TMOD1	DMTN	Q08495	905
TMOD1	CARMIL2	Q6F5E8	845
TMOD1	EPB41	P11171	828
TMOD1	ALDOB	P05062	824
TMOD1	CAPZA2	P47755	815
TMOD1	CAPZA1	P52907	814
TMOD1	BAAT	Q14032	814
TMOD1	TTN	Q8WZ42	801
TMOD1	MYPN	Q86TC9	799
TMOD1	ANK1	P16157	745
TMOD1	ANK2	Q01484	716

IntAct

112 interactions, top by confidence:

A	B	Type	Score
NDUFA13	NDUFS8	psi-mi:“MI:0914”(association)	0.640
FLII	TMOD1	psi-mi:“MI:0914”(association)	0.640
PLEKHG6	CST4	psi-mi:“MI:0914”(association)	0.530
KLHL10	PXDNL	psi-mi:“MI:0914”(association)	0.530
CACNB3	CACNB4	psi-mi:“MI:0914”(association)	0.530
MYO1C	TMOD1	psi-mi:“MI:0914”(association)	0.530
TMOD1	GSN	psi-mi:“MI:0914”(association)	0.530
TMOD1	APC	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	BUB1	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	CDH1	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	CDKN2A	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	DCC	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	DLC1	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	TMOD1	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	MLH3	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	ODC1	psi-mi:“MI:0915”(physical association)	0.370
TMOD1	PIK3CA	psi-mi:“MI:0915”(physical association)	0.370
TLR2	TMOD1	psi-mi:“MI:0915”(physical association)	0.370
Ppp1cb	MYO1C	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ANLN	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Flot2	ACTG1	psi-mi:“MI:0914”(association)	0.350
MYO18A	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO1C	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
FLNA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
Flnb	RPL22	psi-mi:“MI:0914”(association)	0.350
Lima1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (207): GSN (Affinity Capture-MS), MYO5C (Affinity Capture-MS), MYO5B (Affinity Capture-MS), FLII (Affinity Capture-MS), LRRFIP1 (Affinity Capture-MS), LRRFIP2 (Affinity Capture-MS), TBC1D4 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), SCIN (Affinity Capture-MS), AGTPBP1 (Affinity Capture-MS), NIN (Affinity Capture-MS), TMOD1 (Co-fractionation), WARS (Co-fractionation), TMOD1 (Affinity Capture-MS), TMOD1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNC0, A1A5Q0, A2VE39, A4IHS2, D2HRF1, E1BTG2, O08808, O14730, O35226, O60870, O95801, P28289, P42898, P49813, P70566, P70567, Q0VC48, Q13576, Q1JQD4, Q1RMT7, Q2M146, Q3UQ44, Q58DA0, Q5BLF0, Q5EA11, Q5I598, Q5R981, Q5U2Z5, Q60HE5, Q6GNS3, Q6P2Z6, Q6P5Q4, Q6TH47, Q7T0W1, Q7ZXX9, Q803R5, Q8K339, Q8N1G2, Q8R3H9, Q8R424

Diamond homologs: A0A0G2K0D3, A0JNC0, A1A5Q0, E1BTG2, E7F7X0, E9QA62, O01479, P28289, P29536, P49813, P70566, P70567, Q0VAK6, Q0VC48, Q3UHZ5, Q6P5Q4, Q8BVA4, Q9JHJ0, Q9JKK7, Q9JLH8, Q9NYL9, Q9NZQ9, Q9NZR1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TMOD1	“down-regulates activity”	TPM3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
Sensory processing of sound	6	19.5×	3e-04
RHO GTPases activate IQGAPs	5	18.2×	9e-04
MITF-M-dependent gene expression	6	11.4×	1e-03
Sensory processing of sound by outer hair cells of the cochlea	5	10.7×	4e-03
Sensory processing of sound by inner hair cells of the cochlea	6	10.3×	2e-03
FCGR3A-mediated phagocytosis	5	9.8×	6e-03
Regulation of actin dynamics for phagocytic cup formation	5	9.7×	6e-03
VEGFA-VEGFR2 Pathway	6	8.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
barbed-end actin filament capping	5	33.2×	4e-04
platelet aggregation	5	13.9×	7e-03
actin filament organization	9	8.8×	5e-04
actin cytoskeleton organization	10	6.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1929 predictions. Top by Δscore:

Variant	Effect	Δscore
9:97524306:GAT:G	donor_gain	1.0000
9:97524309:GTGA:G	donor_gain	1.0000
9:97524311:GA:G	donor_gain	1.0000
9:97524313:G:GG	donor_gain	1.0000
9:97546169:A:AG	acceptor_gain	1.0000
9:97546170:C:G	acceptor_gain	1.0000
9:97546171:A:AG	acceptor_gain	1.0000
9:97546172:A:G	acceptor_gain	1.0000
9:97546339:GAGG:G	donor_loss	1.0000
9:97546340:AGG:A	donor_loss	1.0000
9:97546341:GGTAC:G	donor_loss	1.0000
9:97546342:G:A	donor_loss	1.0000
9:97546343:T:G	donor_loss	1.0000
9:97553399:AG:A	donor_loss	1.0000
9:97553400:GG:G	donor_loss	1.0000
9:97553401:G:GA	donor_loss	1.0000
9:97553402:T:A	donor_loss	1.0000
9:97562729:CAGCG:C	acceptor_loss	1.0000
9:97562730:A:AG	acceptor_gain	1.0000
9:97562730:AGC:A	acceptor_gain	1.0000
9:97562731:G:GG	acceptor_gain	1.0000
9:97562731:GC:G	acceptor_gain	1.0000
9:97562731:GCG:G	acceptor_gain	1.0000
9:97562819:ACA:A	donor_gain	1.0000
9:97562819:ACAGT:A	donor_loss	1.0000
9:97562820:CA:C	donor_gain	1.0000
9:97562820:CAGTG:C	donor_loss	1.0000
9:97562821:AG:A	donor_loss	1.0000
9:97562822:GTGA:G	donor_gain	1.0000
9:97562823:TGA:T	donor_loss	1.0000

AlphaMissense

2364 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:97568953:C:A	N262K	1.000
9:97568953:C:G	N262K	1.000
9:97553362:T:C	L120S	0.999
9:97564155:T:C	L202P	0.999
9:97565935:A:C	S236R	0.999
9:97565937:T:A	S236R	0.999
9:97565937:T:G	S236R	0.999
9:97553350:T:C	L116P	0.998
9:97553358:G:C	A119P	0.998
9:97553397:G:C	A132P	0.998
9:97564159:T:A	N203K	0.998
9:97564159:T:G	N203K	0.998
9:97565867:T:C	L213P	0.998
9:97568937:T:C	L257P	0.998
9:97568948:T:C	S261P	0.998
9:97546211:G:C	R49S	0.997
9:97546211:G:T	R49S	0.997
9:97553371:C:A	A123D	0.997
9:97553386:T:C	L128P	0.997
9:97553398:C:A	A132E	0.997
9:97553400:G:C	A133P	0.997
9:97562738:T:C	L135P	0.997
9:97565951:C:A	A241E	0.997
9:97568910:T:C	L248P	0.997
9:97568952:A:T	N262I	0.997
9:97599638:G:C	R340S	0.997
9:97599638:G:T	R340S	0.997
9:97546210:G:C	R49T	0.996
9:97546264:T:C	L67P	0.996
9:97564149:T:A	V200D	0.996

dbSNP variants (sampled 300 via entrez): RS1000018993 (9:97589586 A>C), RS1000050005 (9:97589429 G>A,C), RS1000097778 (9:97499904 G>A), RS1000106248 (9:97518866 T>A), RS1000107243 (9:97533442 G>A), RS1000137449 (9:97552130 C>T), RS1000156816 (9:97549387 T>A,C), RS1000190844 (9:97509234 A>G), RS1000211480 (9:97601814 G>C), RS1000242650 (9:97601707 T>C), RS1000246911 (9:97583061 G>T), RS1000251995 (9:97515913 T>C), RS1000260907 (9:97558866 G>A), RS1000315493 (9:97594214 A>C), RS1000319340 (9:97503151 G>C)

Disease associations

OMIM: gene MIM:190930 | disease phenotypes:

GenCC curated gene-disease

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AR

Mondo (1): idiopathic cardiomyopathy (MONDO:0005110)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000640_1	Thyroid cancer (Papillary, radiation-related)	5.000000e-12
GCST001762_926	Obesity-related traits	5.000000e-06
GCST002934_6	Zinc levels	1.000000e-06
GCST003074_13	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	1.000000e-07
GCST003738_4	Barrett’s esophagus	4.000000e-09
GCST003740_11	Barrett’s esophagus or Esophageal adenocarcinoma	2.000000e-08
GCST007354_5	Intracranial aneurysm	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0007707	cerebral amyloid deposition measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
sodium arsenite	affects methylation, decreases expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, affects expression	2
Tamoxifen	affects cotreatment, increases expression, decreases expression, affects expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, increases expression, decreases expression	2
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sulforaphane	decreases expression	1
cobaltous chloride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
benzo(e)pyrene	decreases methylation	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Troglitazone	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722748	Not specified	ACTIVE_NOT_RECRUITING	Genomic Investigation of Cardiovascular Diseases
NCT06920030	Not specified	RECRUITING	Performance of the Cardiac Microcurrent (C-MIC) System With a Less Invasively Placed Left Ventricular Lead
NCT07336394	Not specified	RECRUITING	Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques