MYL4
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Also known as ALC1AMLCGT1PRO1957
Summary
MYL4 (myosin light chain 4, HGNC:7585) is a protein-coding gene on chromosome 17q21.32, encoding Myosin light chain 4 (P12829). Regulatory light chain of myosin.
Myosin is a hexameric ATPase cellular motor protein. It is composed of two myosin heavy chains, two nonphosphorylatable myosin alkali light chains, and two phosphorylatable myosin regulatory light chains. This gene encodes a myosin alkali light chain that is found in embryonic muscle and adult atria. Two alternatively spliced transcript variants encoding the same protein have been found for this gene.
Source: NCBI Gene 4635 — RefSeq curated summary.
At a glance
- Gene–disease (curated): atrial fibrillation, familial, 18 (Strong, GenCC) — +1 more curated relationship
- GWAS associations: 2
- Clinical variants (ClinVar): 297 total — 6 pathogenic, 10 likely-pathogenic
- Phenotypes (HPO): 18
- Druggable target: yes
- MANE Select transcript:
NM_002476
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:7585 |
| Approved symbol | MYL4 |
| Name | myosin light chain 4 |
| Location | 17q21.32 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | ALC1, AMLC, GT1, PRO1957 |
| Ensembl gene | ENSG00000198336 |
| Ensembl biotype | protein_coding |
| OMIM | 160770 |
| Entrez | 4635 |
Gene structure
Transcript identifiers
Ensembl transcripts: 30 — 27 protein_coding, 3 nonsense_mediated_decay
ENST00000354968, ENST00000393450, ENST00000536623, ENST00000570671, ENST00000570772, ENST00000571981, ENST00000572303, ENST00000572316, ENST00000573747, ENST00000576874, ENST00000869091, ENST00000954741, ENST00000954742, ENST00000954743, ENST00000954744, ENST00000954745, ENST00000954746, ENST00000954747, ENST00000954748, ENST00000954749, ENST00000954750, ENST00000954751, ENST00000954752, ENST00000954753, ENST00000954754, ENST00000954755, ENST00000954756, ENST00000954757, ENST00000954758, ENST00000954759
RefSeq mRNA: 2 — MANE Select: NM_002476
NM_001002841, NM_002476
CCDS: CCDS11510
Canonical transcript exons
ENST00000393450 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001110506 | 47213799 | 47213826 |
| ENSE00001515362 | 47223509 | 47223679 |
| ENSE00001515363 | 47209348 | 47209557 |
| ENSE00003499617 | 47219904 | 47220053 |
| ENSE00003632633 | 47222380 | 47222457 |
| ENSE00003644572 | 47221682 | 47221855 |
| ENSE00003647293 | 47223014 | 47223057 |
Expression profiles
Bgee: expression breadth ubiquitous, 186 present calls, max score 99.94.
FANTOM5 (CAGE): breadth broad, TPM avg 51.3839 / max 11702.8514, expressed in 420 samples.
FANTOM5 promoters (7 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 161338 | 38.3511 | 342 |
| 161335 | 5.4304 | 325 |
| 161339 | 5.2919 | 186 |
| 161340 | 2.0531 | 154 |
| 161336 | 0.1247 | 68 |
| 161337 | 0.1020 | 60 |
| 161334 | 0.0305 | 13 |
Top tissues by expression
285 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right atrium auricular region | UBERON:0006631 | 99.94 | gold quality |
| cardiac atrium | UBERON:0002081 | 99.93 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 99.92 | gold quality |
| apex of heart | UBERON:0002098 | 99.28 | gold quality |
| vena cava | UBERON:0004087 | 98.47 | gold quality |
| myocardium | UBERON:0002349 | 97.22 | gold quality |
| heart right ventricle | UBERON:0002080 | 96.35 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 96.22 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 96.04 | gold quality |
| heart left ventricle | UBERON:0002084 | 95.50 | gold quality |
| cardiac ventricle | UBERON:0002082 | 95.45 | gold quality |
| heart | UBERON:0000948 | 93.80 | gold quality |
| blood | UBERON:0000178 | 93.47 | gold quality |
| bone marrow | UBERON:0002371 | 92.01 | gold quality |
| tibialis anterior | UBERON:0001385 | 91.40 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 88.81 | silver quality |
| triceps brachii | UBERON:0001509 | 88.55 | silver quality |
| biceps brachii | UBERON:0001507 | 88.48 | silver quality |
| gluteal muscle | UBERON:0002000 | 87.96 | silver quality |
| left ventricle myocardium | UBERON:0006566 | 87.34 | gold quality |
| bone marrow cell | CL:0002092 | 86.76 | gold quality |
| right testis | UBERON:0004534 | 85.51 | gold quality |
| diaphragm | UBERON:0001103 | 85.04 | silver quality |
| monocyte | CL:0000576 | 84.47 | gold quality |
| mononuclear cell | CL:0000842 | 84.28 | gold quality |
| left testis | UBERON:0004533 | 83.70 | gold quality |
| deltoid | UBERON:0001476 | 83.17 | silver quality |
| leukocyte | CL:0000738 | 81.92 | gold quality |
| testis | UBERON:0000473 | 81.43 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 80.78 | silver quality |
Single-cell (SCXA)
Detected in 19 experiment(s), a significant marker in 16.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-GEOD-124472 | yes | 1601.07 |
| E-MTAB-9388 | yes | 959.65 |
| E-MTAB-7407 | yes | 907.90 |
| E-MTAB-10042 | yes | 802.50 |
| E-MTAB-8205 | yes | 581.18 |
| E-GEOD-130473 | yes | 421.76 |
| E-CURD-112 | yes | 370.39 |
| E-HCAD-4 | yes | 150.61 |
| E-MTAB-7316 | yes | 33.11 |
| E-CURD-122 | yes | 18.41 |
| E-MTAB-9221 | yes | 15.89 |
| E-MTAB-8271 | yes | 9.69 |
| E-MTAB-9067 | yes | 8.45 |
| E-HCAD-9 | yes | 7.39 |
| E-HCAD-10 | yes | 7.09 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): MITF, MYF5, MYOD1, MYOG, NR2F2, SRF
miRNA regulators (miRDB)
5 targeting MYL4, 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-486-3P | 99.51 | 66.82 | 1901 |
| HSA-MIR-6784-3P | 98.39 | 64.88 | 662 |
| HSA-MIR-6862-3P | 97.92 | 64.86 | 531 |
| HSA-MIR-4726-5P | 97.24 | 65.67 | 1299 |
| HSA-MIR-3189-3P | 96.80 | 66.34 | 896 |
Literature-anchored findings (GeneRIF, showing 9)
- NMR showed involvement of N-terminus and lysines 3 and 4 in interaction with actin. Mutations of these lysines (K3A,K4R,K4A,K4D) resulted in altered actin binding and actin activated MgATPase. Mutation of Ala-1 to val had no effect on binding or kinetics. (PMID:10373429)
- results demonstrate that the expression of hALC-1 could have a beneficial effect on the overloaded hypertrophied heart (PMID:16106982)
- A recessive frameshift mutation in MYL4 causes early-onset atrial fibrillation. (PMID:25807286)
- a novel, heterozygous p.Glu11Lys mutation in the atrial-specific myosin light chain gene MYL4, caused atrial fibrillation. (PMID:27066836)
- The authors describe in a population approach a loss of function mutation in the myosin gene MYL4 that, in the homozygous state, is completely penetrant for early-onset AF. The finding may provide novel mechanistic insight into the pathophysiology of this complex arrhythmia. (PMID:27742809)
- Metastable Atrial State Underlies the Primary Genetic Substrate for MYL4 Mutation-Associated Atrial Fibrillation. (PMID:31735076)
- Relationship between Serum miR-106 and MYL4 Levels and the Prevalence, Risk Stratification, and Prognosis of Atrial Fibrillation. (PMID:35874900)
- The (Ala-Pro) rich part of this protein acts as a “spacer arm” responsible for correct positioning of the N-terminal actin binding site. (PMID:9000508)
- The N-terminus of this protein is an actin binding site. (PMID:9738905)
Cross-species orthologs
8 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | myl4 | ENSDARG00000011519 |
| danio_rerio | cmlc1 | ENSDARG00000032976 |
| danio_rerio | zgc:163073 | ENSDARG00000099712 |
| mus_musculus | Myl4 | ENSMUSG00000061086 |
| rattus_norvegicus | Myl4 | ENSRNOG00000050675 |
| drosophila_melanogaster | Mlc-c | FBGN0004687 |
| caenorhabditis_elegans | WBGENE00010554 | |
| caenorhabditis_elegans | WBGENE00011734 |
Paralogs (4): MYL6 (ENSG00000092841), MYL3 (ENSG00000160808), MYL1 (ENSG00000168530), MYL6B (ENSG00000196465)
Protein
Protein identifiers
Myosin light chain 4 — P12829 (reviewed: P12829)
Alternative names: Myosin light chain 1, embryonic muscle/atrial isoform, Myosin light chain alkali GT-1 isoform
All UniProt accessions (7): A0A1C7CYY4, P12829, I3L1K6, I3L1R3, I3L3U1, I3L4B1, I3L532
UniProt curated annotations — full annotation on UniProt →
Function. Regulatory light chain of myosin. Does not bind calcium.
Subunit / interactions. Myosin is a hexamer of 2 heavy chains and 4 light chains.
Disease relevance. Atrial fibrillation, familial, 18 (ATFB18) [MIM:617280] A familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. The disease is caused by variants affecting the gene represented in this entry.
RefSeq proteins (2): NP_001002841, NP_002467* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR002048 | EF_hand_dom | Domain |
| IPR011992 | EF-hand-dom_pair | Homologous_superfamily |
| IPR050230 | CALM/Myosin/TropC-like | Family |
UniProt features (18 total): sequence conflict 7, compositionally biased region 3, sequence variant 2, domain 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P12829-F1 | 90.85 | 0.78 |
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 (1): 2
Function
Pathways and Gene Ontology
Reactome pathways
2 pathways
| ID | Pathway |
|---|---|
| R-HSA-390522 | Striated Muscle Contraction |
| R-HSA-397014 | Muscle contraction |
MSigDB gene sets: 245 (showing top):
GOBP_CIRCULATORY_SYSTEM_PROCESS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, MODULE_329, GOLDRATH_ANTIGEN_RESPONSE, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_DN, GOBP_MUSCLE_CONTRACTION, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_THE_FORCE_OF_HEART_CONTRACTION, TSENG_IRS1_TARGETS_DN, GOBP_REGULATION_OF_SYSTEM_PROCESS, GOMF_ACTIN_BINDING, GOBP_HEART_PROCESS, GOBP_MUSCLE_SYSTEM_PROCESS
GO Biological Process (3): regulation of the force of heart contraction (GO:0002026), muscle contraction (GO:0006936), cardiac muscle contraction (GO:0060048)
GO Molecular Function (4): actin monomer binding (GO:0003785), calcium ion binding (GO:0005509), myosin II heavy chain binding (GO:0032038), actin filament binding (GO:0051015)
GO Cellular Component (4): cytosol (GO:0005829), myosin II complex (GO:0016460), A band (GO:0031672), myosin complex (GO:0016459)
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 |
|---|---|
| actin binding | 2 |
| cellular anatomical structure | 2 |
| regulation of heart contraction | 1 |
| regulation of biological quality | 1 |
| muscle system process | 1 |
| striated muscle contraction | 1 |
| heart contraction | 1 |
| metal ion binding | 1 |
| myosin heavy chain binding | 1 |
| myosin II binding | 1 |
| protein-containing complex binding | 1 |
| cytoplasm | 1 |
| myosin complex | 1 |
| sarcomere | 1 |
| actin cytoskeleton | 1 |
| protein-containing complex | 1 |
Protein interactions and networks
STRING
0 interactions, top by confidence (×1000):
IntAct
21 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| S100A4 | OIP5 | psi-mi:“MI:0914”(association) | 0.530 |
| VCAM1 | PSMD11 | psi-mi:“MI:0914”(association) | 0.530 |
| PYROXD2 | MYL4 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ALB | CNOT1 | psi-mi:“MI:0914”(association) | 0.350 |
| rep | DDX3X | psi-mi:“MI:0914”(association) | 0.350 |
| ITM2B | ILVBL | psi-mi:“MI:0914”(association) | 0.350 |
| FILIP1 | DAPK3 | psi-mi:“MI:0914”(association) | 0.350 |
| MYL4 | MYL1 | psi-mi:“MI:0914”(association) | 0.350 |
| MYL3 | MYL4 | psi-mi:“MI:0914”(association) | 0.350 |
| IQGAP3 | CCDC85C | psi-mi:“MI:0914”(association) | 0.350 |
| MYL12B | MYL1 | psi-mi:“MI:0914”(association) | 0.350 |
| TTC4 | MYH7B | psi-mi:“MI:0914”(association) | 0.350 |
| VCAM1 | psi-mi:“MI:0914”(association) | 0.350 | |
| FN1 | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
| GPKOW | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.270 |
| LARP7 | SBNO1 | psi-mi:“MI:2364”(proximity) | 0.270 |
| SBDS | RPSA2 | psi-mi:“MI:2364”(proximity) | 0.270 |
| ZC3H11A | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.270 |
BioGRID (25): MYL4 (Affinity Capture-MS), MYL4 (Affinity Capture-MS), MYL4 (Affinity Capture-MS), MYL4 (Affinity Capture-MS), MYL1 (Affinity Capture-MS), MYO18A (Affinity Capture-MS), CAMKK2 (Affinity Capture-MS), MYL4 (Affinity Capture-MS), MYL4 (Affinity Capture-MS), OSBPL11 (Affinity Capture-MS), IQGAP1 (Affinity Capture-MS), OSBPL9 (Affinity Capture-MS), UBE3B (Affinity Capture-MS), CDC42 (Affinity Capture-MS), IQGAP3 (Affinity Capture-MS)
ESM2 similar proteins: A0A125YHX7, A0JNJ5, F1RRT2, J7HCX7, O15182, O35648, P02600, P02602, P02604, P02605, P02606, P05434, P05976, P05977, P06742, P08590, P09540, P09541, P09542, P12829, P14649, P16409, P17209, P41044, P41208, P41209, P53014, P53441, P54213, P54357, P82159, P82160, P85100, Q06827, Q09196, Q12798, Q24621, Q24654, Q24756, Q27177
Diamond homologs: A0JNJ5, A2Y609, A3E3H0, A3E4D8, A3E4F9, A4UHC0, A8CEP3, A8I1Q0, F1RRT2, J7HCX7, O14008, O60041, O82018, O94739, P02597, P02598, P02600, P02602, P02604, P02605, P02606, P02607, P04353, P04464, P05419, P05976, P05977, P06742, P06787, P07290, P07291, P07462, P07463, P08053, P08590, P09540, P09541, P09542, P0DH95, P0DH96
SIGNOR signaling
1 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| “MYOD1/SWI/SNF complex” | “up-regulates quantity by expression” | MYL4 | “transcriptional regulation” |
Disease & clinical
Clinical variants and AI predictions
ClinVar
297 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 6 |
| Likely pathogenic | 10 |
| Uncertain significance | 156 |
| Likely benign | 98 |
| Benign | 21 |
Top pathogenic / likely-pathogenic (16)
| Variant ID | HGVS | Classification |
|---|---|---|
| 2053340 | NM_002476.2(MYL4):c.532C>T (p.Gln178Ter) | Pathogenic |
| 2165639 | NM_002476.2(MYL4):c.361C>T (p.Gln121Ter) | Pathogenic |
| 224067 | NM_002476.2(MYL4):c.31G>A (p.Glu11Lys) | Pathogenic |
| 3243111 | NC_000017.10:g.(?45291145)(45291212_?)del | Pathogenic |
| 3656250 | NM_002476.2(MYL4):c.187_190del (p.Phe63fs) | Pathogenic |
| 3725515 | NM_002476.2(MYL4):c.455del (p.Gly152fs) | Pathogenic |
| 1474944 | NM_002476.2(MYL4):c.487+1G>A | Likely pathogenic |
| 2052621 | NM_002476.2(MYL4):c.314-1G>C | Likely pathogenic |
| 2090713 | NM_002476.2(MYL4):c.313+1G>T | Likely pathogenic |
| 2147045 | NM_002476.2(MYL4):c.135+1G>A | Likely pathogenic |
| 3020997 | NM_002476.2(MYL4):c.164-1G>C | Likely pathogenic |
| 3366361 | NM_002476.2(MYL4):c.234C>A (p.Cys78Ter) | Likely pathogenic |
| 3630172 | NM_002476.2(MYL4):c.163+1G>A | Likely pathogenic |
| 4728001 | NM_002476.2(MYL4):c.136-2A>C | Likely pathogenic |
| 476205 | NM_002476.2(MYL4):c.487+1G>C | Likely pathogenic |
| 648701 | NM_002476.2(MYL4):c.488-1G>A | Likely pathogenic |
SpliceAI
1349 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 17:47209558:G:GG | donor_gain | 1.0000 |
| 17:47219902:A:AG | acceptor_gain | 1.0000 |
| 17:47219903:G:GG | acceptor_gain | 1.0000 |
| 17:47219903:GA:G | acceptor_gain | 1.0000 |
| 17:47219933:C:A | acceptor_gain | 1.0000 |
| 17:47221665:A:AG | acceptor_gain | 1.0000 |
| 17:47221665:ACCCT:A | acceptor_gain | 1.0000 |
| 17:47221666:C:G | acceptor_gain | 1.0000 |
| 17:47221669:T:TA | acceptor_gain | 1.0000 |
| 17:47221673:T:A | acceptor_gain | 1.0000 |
| 17:47221673:T:TA | acceptor_loss | 1.0000 |
| 17:47221677:T:TA | acceptor_gain | 1.0000 |
| 17:47221677:TGAA:T | acceptor_loss | 1.0000 |
| 17:47221680:A:AG | acceptor_gain | 1.0000 |
| 17:47221680:AGAG:A | acceptor_loss | 1.0000 |
| 17:47221681:G:GG | acceptor_gain | 1.0000 |
| 17:47221681:GA:G | acceptor_gain | 1.0000 |
| 17:47221681:GAGA:G | acceptor_gain | 1.0000 |
| 17:47221681:GAGAT:G | acceptor_gain | 1.0000 |
| 17:47221801:G:GT | donor_gain | 1.0000 |
| 17:47221802:A:T | donor_gain | 1.0000 |
| 17:47221854:GG:G | donor_gain | 1.0000 |
| 17:47221855:GG:G | donor_gain | 1.0000 |
| 17:47221856:G:GC | donor_loss | 1.0000 |
| 17:47221857:T:A | donor_loss | 1.0000 |
| 17:47222378:A:AG | acceptor_gain | 1.0000 |
| 17:47222379:G:GG | acceptor_gain | 1.0000 |
| 17:47222455:AAG:A | donor_loss | 1.0000 |
| 17:47222457:GGTAT:G | donor_gain | 1.0000 |
| 17:47222458:G:T | donor_loss | 1.0000 |
AlphaMissense
1293 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 17:47219927:T:C | F63L | 1.000 |
| 17:47219929:T:A | F63L | 1.000 |
| 17:47219929:T:G | F63L | 1.000 |
| 17:47221784:T:C | L139P | 1.000 |
| 17:47221792:T:C | F142L | 1.000 |
| 17:47221794:T:A | F142L | 1.000 |
| 17:47221794:T:G | F142L | 1.000 |
| 17:47221817:T:A | V150D | 1.000 |
| 17:47221832:T:C | L155P | 1.000 |
| 17:47222380:G:A | G163E | 1.000 |
| 17:47219918:T:C | F60L | 0.999 |
| 17:47219920:T:A | F60L | 0.999 |
| 17:47219920:T:G | F60L | 0.999 |
| 17:47219972:T:C | C78R | 0.999 |
| 17:47219976:G:A | G79E | 0.999 |
| 17:47219988:G:C | R83P | 0.999 |
| 17:47221727:T:C | L120P | 0.999 |
| 17:47221780:G:C | G138R | 0.999 |
| 17:47221781:G:A | G138D | 0.999 |
| 17:47221787:G:C | R140P | 0.999 |
| 17:47221792:T:A | F142I | 0.999 |
| 17:47221792:T:G | F142V | 0.999 |
| 17:47221793:T:C | F142S | 0.999 |
| 17:47221793:T:G | F142C | 0.999 |
| 17:47221795:G:C | D143H | 0.999 |
| 17:47221796:A:C | D143A | 0.999 |
| 17:47221796:A:T | D143V | 0.999 |
| 17:47221800:G:C | K144N | 0.999 |
| 17:47221800:G:T | K144N | 0.999 |
| 17:47221811:G:T | G148V | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000046914 (17:47197130 G>A,T), RS1000151843 (17:47210063 T>G), RS1000171905 (17:47220462 A>C,G), RS1000280689 (17:47198766 G>A), RS1000356004 (17:47214730 A>C,G), RS1000561625 (17:47221552 A>G,T), RS1000580404 (17:47205703 C>G), RS1000677634 (17:47211744 G>A), RS1000690398 (17:47225855 C>A,T), RS1000742671 (17:47216108 T>C), RS1000769098 (17:47205309 T>A), RS1000848796 (17:47202806 A>G), RS1001057799 (17:47218194 A>G), RS1001078680 (17:47209823 A>G), RS1001084067 (17:47224227 C>T)
Disease associations
OMIM: gene MIM:160770 | disease phenotypes: MIM:617280, MIM:608583
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| atrial fibrillation, familial, 18 | Strong | Autosomal dominant |
| familial atrial fibrillation | Supportive | Autosomal dominant |
Mondo (2): atrial fibrillation, familial, 18 (MONDO:0015001), familial atrial fibrillation (MONDO:0018054)
Orphanet (1): Hereditary atrial fibrillation (Orphanet:334)
HPO phenotypes
18 total (18 of 18 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001279 | Syncope |
| HP:0001658 | Myocardial infarction |
| HP:0001662 | Bradycardia |
| HP:0001709 | Third degree atrioventricular block |
| HP:0001727 | Thromboembolic stroke |
| HP:0001907 | Thromboembolism |
| HP:0001962 | Palpitations |
| HP:0002094 | Dyspnea |
| HP:0002321 | Vertigo |
| HP:0003546 | Exercise intolerance |
| HP:0004754 | Permanent atrial fibrillation |
| HP:0004757 | Paroxysmal atrial fibrillation |
| HP:0005110 | Atrial fibrillation |
| HP:0011462 | Young adult onset |
| HP:0011705 | First degree atrioventricular block |
| HP:0012378 | Fatigue |
| HP:0100749 | Chest pain |
GWAS associations
2 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST002380_5 | Erythema nodosum in inflammatory bowel disease | 8.000000e-06 |
| GCST005951_16 | Body mass index | 4.000000e-08 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004340 | body mass index |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL3831286 (PROTEIN COMPLEX), CHEMBL6066959 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 7.44 | Kd | 36.39 | nM | CHEMBL5653589 |
| 6.93 | ED50 | 118.4 | nM | CHEMBL5653589 |
PubChem BioAssay actives
1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148808: Binding affinity to human MYL4 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0364 | uM |
CTD chemical–gene interactions
37 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Valproic Acid | affects expression, decreases expression | 3 |
| bisphenol A | increases expression | 2 |
| Doxorubicin | affects expression | 2 |
| ascorbate-2-phosphate | affects binding, affects cotreatment, increases expression | 1 |
| sodium arsenite | increases expression | 1 |
| 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid | affects cotreatment, decreases expression | 1 |
| diethyl malate | increases expression | 1 |
| azoxystrobin | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| deguelin | decreases expression | 1 |
| 4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide | decreases expression | 1 |
| Chir 99021 | affects binding, increases expression, affects cotreatment, decreases expression | 1 |
| clothianidin | decreases expression | 1 |
| thifluzamide | decreases expression | 1 |
| abrine | increases expression | 1 |
| pyrachlostrobin | decreases expression | 1 |
| XAV939 | affects binding, affects cotreatment, increases expression | 1 |
| incobotulinumtoxinA | decreases expression | 1 |
| picoxystrobin | decreases expression | 1 |
| 3-(4-pyridyl)-1H-indole | affects cotreatment, decreases expression | 1 |
| Sunitinib | decreases expression | 1 |
| Arsenic Trioxide | increases expression | 1 |
| Acetaminophen | decreases expression | 1 |
| Amiodarone | increases expression | 1 |
| Arsenic | affects methylation | 1 |
| Ascorbic Acid | affects binding, affects cotreatment, increases expression | 1 |
| Benzo(a)pyrene | affects methylation, increases methylation | 1 |
| Capsaicin | decreases expression | 1 |
| Carbamazepine | affects expression | 1 |
| Cytarabine | decreases expression | 1 |
ChEMBL screening assays
1 unique, capped per target: 1 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5651850 | Binding | Binding affinity to human MYL4 incubated for 45 mins by Kinobead based pull down assay | NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem |
Clinical trials (associated diseases)
2 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT04075994 | Not specified | COMPLETED | Atrial Fibrillation Health Literacy and Information Technology Trial |
| NCT04076020 | Not specified | COMPLETED | Atrial Fibrillation Health Literacy and Information Technology Trial in Rural Pennsylvania Counties |
Related Atlas pages
- Associated diseases: atrial fibrillation, familial, 18, familial atrial fibrillation
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): atrial fibrillation, familial, 18, familial atrial fibrillation