CALML6

Summary

CALML6 (calmodulin like 6, HGNC:24193) is a protein-coding gene on chromosome 1p36.33, encoding Calmodulin-like protein 6 (Q8TD86).

Predicted to enable calcium ion binding activity and enzyme regulator activity. Predicted to be involved in microtubule cytoskeleton organization. Predicted to be located in nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 163688 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total — 1 pathogenic, 3 likely-pathogenic
• MANE Select transcript: NM_138705

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24193
Approved symbol	CALML6
Name	calmodulin like 6
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Aliases	CAGLP
Ensembl gene	ENSG00000169885
Ensembl biotype	protein_coding
OMIM	610171
Entrez	163688

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000307786, ENST00000378604, ENST00000462293, ENST00000482402

RefSeq mRNA: 2 — MANE Select: NM_138705 NM_001330313, NM_138705

CCDS: CCDS30566, CCDS81255

Canonical transcript exons

ENST00000307786 — 6 exons

Exon	Start	End
ENSE00001127963	1916441	1916615
ENSE00001208002	1915260	1915307
ENSE00001478068	1915685	1915735
ENSE00003518147	1916974	1917074
ENSE00003651579	1916752	1916896
ENSE00003849672	1917147	1917296

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 94.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0598 / max 452.5956, expressed in 30 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155	0.7367	27
153	0.0660	11
201319	0.0627	14
151	0.0473	14
154	0.0467	12
149	0.0393	9
152	0.0321	9
150	0.0291	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	94.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.93	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.60	gold quality
biceps brachii	UBERON:0001507	86.76	gold quality
gastrocnemius	UBERON:0001388	85.96	gold quality
muscle of leg	UBERON:0001383	85.60	gold quality
skeletal muscle tissue	UBERON:0001134	85.53	gold quality
muscle tissue	UBERON:0002385	82.47	gold quality
body of tongue	UBERON:0011876	81.90	silver quality
quadriceps femoris	UBERON:0001377	77.84	gold quality
vastus lateralis	UBERON:0001379	76.94	silver quality
right lobe of liver	UBERON:0001114	72.51	gold quality
stromal cell of endometrium	CL:0002255	70.97	gold quality
lower esophagus mucosa	UBERON:0035834	69.83	gold quality
tongue	UBERON:0001723	69.11	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	68.04	gold quality
deltoid	UBERON:0001476	67.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.42	gold quality
cerebellar hemisphere	UBERON:0002245	66.41	gold quality
cerebellar cortex	UBERON:0002129	66.30	gold quality
body of pancreas	UBERON:0001150	66.28	gold quality
right frontal lobe	UBERON:0002810	64.60	gold quality
cerebellum	UBERON:0002037	64.49	gold quality
skin of leg	UBERON:0001511	64.41	gold quality
sural nerve	UBERON:0015488	64.14	gold quality
granulocyte	CL:0000094	64.09	gold quality
skin of abdomen	UBERON:0001416	64.00	gold quality
putamen	UBERON:0001874	63.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.39	gold quality
caudate nucleus	UBERON:0001873	62.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.54

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• a novel human gene, CAGLP (calglandulin-like protein) was predicted, and subsequently isolated from human skeleton muscle (PMID:15621662)
• The EF-hand protein calmodulin-like 6 (CALML6) directly bound to the phosphorylated serine-rich (SR) region of IRF3 and impaired its dimerization and nuclear translocation. (PMID:30699354)
• EP4-induced mitochondrial localization and cell migration mediated by CALML6 in human oral squamous cell carcinoma. (PMID:38745046)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	TpnC4	FBGN0033027
caenorhabditis_elegans		WBGENE00000285
caenorhabditis_elegans		WBGENE00000287
caenorhabditis_elegans	pat-10	WBGENE00003934
caenorhabditis_elegans		WBGENE00006583
caenorhabditis_elegans		WBGENE00008453
caenorhabditis_elegans	F35C12.3	WBGENE00009408
caenorhabditis_elegans		WBGENE00015264
caenorhabditis_elegans		WBGENE00019352

Paralogs (20): CABP7 (ENSG00000100314), CABP5 (ENSG00000105507), CALML4 (ENSG00000129007), CALM2 (ENSG00000143933), CETN2 (ENSG00000147400), CETN3 (ENSG00000153140), CABP1 (ENSG00000157782), CALM3 (ENSG00000160014), CABP2 (ENSG00000167791), EFCAB3 (ENSG00000172421), EFCAB12 (ENSG00000172771), CABP4 (ENSG00000175544), CETN1 (ENSG00000177143), CALML3 (ENSG00000178363), CALML5 (ENSG00000178372), CALN1 (ENSG00000183166), CALM1 (ENSG00000198668), EFCAB2 (ENSG00000203666), EFCAB7 (ENSG00000203965), EFCAB9 (ENSG00000214360)

Protein

Protein identifiers

Calmodulin-like protein 6 — Q8TD86 (reviewed: Q8TD86)

Alternative names: Calglandulin-like protein

All UniProt accessions (2): Q8TD86, B1AKR1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in prostate, thymus, heart, skeleton muscle, bone marrow and ovary.

Similarity. Belongs to the calmodulin family. Calglandulin subfamily.

RefSeq proteins (2): NP_001317242, NP_619650* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR050230	CALM/Myosin/TropC-like	Family

Pfam: PF13499

UniProt features (11 total): binding site 5, domain 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD86-F1	78.48	0.31

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 (5): 156; 158; 160; 162; 167

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): KEGG_OLFACTORY_TRANSDUCTION, KEGG_ALZHEIMERS_DISEASE, KEGG_NEUROTROPHIN_SIGNALING_PATHWAY, KEGG_OOCYTE_MEIOSIS, KEGG_INSULIN_SIGNALING_PATHWAY, KEGG_GLIOMA, GOMF_ENZYME_REGULATOR_ACTIVITY, chr1p36, ER_Q6_01, KEGG_GNRH_SIGNALING_PATHWAY, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, KEGG_CALCIUM_SIGNALING_PATHWAY, KEGG_LONG_TERM_POTENTIATION

GO Biological Process (1): microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (4): calcium ion binding (GO:0005509), enzyme regulator activity (GO:0030234), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoskeleton organization	1
microtubule-based process	1
metal ion binding	1
catalytic activity	1
molecular function regulator activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

6580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALML6	NOS3	P29474	996
CALML6	CALD1	Q05682	996
CALML6	NOS1	P29475	995
CALML6	MARCKS	P29966	995
CALML6	IQGAP1	P46940	993
CALML6	MYLK	Q15746	993
CALML6	RYR2	Q92736	993
CALML6	MYLK2	Q9H1R3	993
CALML6	CAMK2A	Q9UQM7	993
CALML6	NRGN	Q92686	992
CALML6	CACNA1C	Q13936	990
CALML6	TRPV1	Q8NER1	990
CALML6	RYR1	P21817	989
CALML6	MBP	P02686	987
CALML6	GAP43	P17677	987

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PCP4	CALML6	psi-mi:“MI:0915”(physical association)	0.560
CALML6	GRAMD1A	psi-mi:“MI:0915”(physical association)	0.400
PCP4	CALML6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): PCP4 (Two-hybrid), CALML6 (Affinity Capture-MS), CALML6 (Affinity Capture-Western), MAP3K7 (Affinity Capture-Western), MAP3K7 (Reconstituted Complex), CALML6 (Affinity Capture-Western), GRAMD1A (Affinity Capture-MS), CALML6 (Negative Genetic), CALML6 (Affinity Capture-MS), CALML6 (Affinity Capture-MS)

ESM2 similar proteins: A0T2M3, O64943, P02585, P04110, P06706, P06707, P06708, P20801, P21797, P29289, P29290, P29291, P35622, Q0IQB6, Q0IUU4, Q2R1Z5, Q3SB08, Q3SB09, Q3SB10, Q3SB11, Q3SB12, Q3SB13, Q3SB14, Q3SB15, Q6BWS8, Q84MN0, Q8AY75, Q8S1Y9, Q8TD86, Q94AZ4, Q9BLG0, Q9C8Y1, Q9C9U8, Q9FYK2, Q9JM83, Q9LE22, Q9LF55, Q9LNE7, Q9LPK5, Q9LQN4

Diamond homologs: A0A1B0GWK0, A0A7M4EAX1, D3GME4, P02597, P02614, P02615, P02616, P02617, P02618, P02619, P02620, P02621, P02622, P02623, P02624, P02625, P02628, P02629, P02631, P04464, P05419, P05939, P05940, P05941, P09227, P0CE72, P19753, P20472, P28582, P30187, P30563, P32848, P43305, P49101, P51879, P53683, P56503, P59747, P80026, P80050

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	3
Uncertain significance	33
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3247933	NC_000001.10:g.(?1718770)(2343941_?)del	Pathogenic
2640261	GRCh37/hg19 1p36.33(chr1:1569581-2005714)x1	Likely pathogenic
393731	GRCh37/hg19 1p36.33(chr1:1477184-2239438)x1	Likely pathogenic
980933	GRCh37/hg19 1p36.33(chr1:1717581-1910879)x1	Likely pathogenic

SpliceAI

1057 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1916575:GA:G	donor_gain	1.0000
1:1916600:G:GT	donor_gain	1.0000
1:1916612:GACA:G	donor_gain	1.0000
1:1916616:G:GG	donor_gain	1.0000
1:1916897:G:GG	donor_gain	1.0000
1:1916577:G:GG	donor_gain	0.9900
1:1916600:G:T	donor_gain	0.9900
1:1916614:CA:C	donor_gain	0.9900
1:1916871:GGC:G	donor_gain	0.9900
1:1917071:GAGG:G	donor_gain	0.9900
1:1917072:AGGGT:A	donor_loss	0.9900
1:1917073:GG:G	donor_gain	0.9900
1:1917074:GG:G	donor_gain	0.9900
1:1917074:GGTG:G	donor_loss	0.9900
1:1917076:TGAGT:T	donor_loss	0.9900
1:1917077:GAGTG:G	donor_loss	0.9900
1:1916611:AGACA:A	donor_gain	0.9800
1:1916612:GACAG:G	donor_gain	0.9800
1:1916750:A:AG	acceptor_gain	0.9800
1:1916751:G:GG	acceptor_gain	0.9800
1:1916832:C:G	donor_gain	0.9800
1:1916867:C:T	donor_gain	0.9800
1:1916885:G:GT	donor_gain	0.9800
1:1917075:G:GG	donor_gain	0.9800
1:1917145:A:AG	acceptor_gain	0.9800
1:1917146:G:GG	acceptor_gain	0.9800
1:1917146:GA:G	acceptor_gain	0.9800
1:1916440:GACA:G	acceptor_gain	0.9700
1:1916555:C:G	donor_gain	0.9700
1:1916614:CAGTG:C	donor_loss	0.9700

AlphaMissense

1222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1916844:T:C	F116L	0.977
1:1916846:C:A	F116L	0.977
1:1916846:C:G	F116L	0.977
1:1917149:T:C	F168L	0.976
1:1917151:T:A	F168L	0.976
1:1917151:T:G	F168L	0.976
1:1916853:T:C	F119L	0.970
1:1916855:T:A	F119L	0.970
1:1916855:T:G	F119L	0.970
1:1916486:T:C	F42L	0.965
1:1916488:T:A	F42L	0.965
1:1916488:T:G	F42L	0.965
1:1916778:T:C	F94L	0.958
1:1916780:C:A	F94L	0.958
1:1916780:C:G	F94L	0.958
1:1916779:T:C	F94S	0.954
1:1916495:T:C	F45L	0.945
1:1916497:C:A	F45L	0.945
1:1916497:C:G	F45L	0.945
1:1916845:T:C	F116S	0.931
1:1916982:T:C	L136P	0.928
1:1917017:G:C	A148P	0.927
1:1916893:T:C	L132P	0.922
1:1917038:G:C	A155P	0.918
1:1916841:G:C	A115P	0.911
1:1916833:T:C	L112P	0.907
1:1917150:T:C	F168S	0.899
1:1917150:T:G	F168C	0.896
1:1916893:T:A	L132H	0.895
1:1916788:T:C	L97P	0.894

dbSNP variants (sampled 300 via entrez): RS1000816459 (1:1915394 A>G), RS1001102779 (1:1914099 C>T), RS1001165328 (1:1917354 G>A,C,T), RS1001214542 (1:1917613 C>T), RS1001913530 (1:1913984 G>T), RS1002834430 (1:1913313 G>A,C,T), RS1002892798 (1:1916687 G>A,C,T), RS1003151755 (1:1917378 T>C), RS1003152724 (1:1915437 C>A,G,T), RS1004087285 (1:1914532 T>C,G), RS1004317254 (1:1913555 G>A), RS1005060542 (1:1917634 C>G,T), RS1005500309 (1:1913436 C>T), RS1005500629 (1:1916559 G>A,C), RS1006888131 (1:1914890 C>T)

Disease associations

OMIM: gene MIM:610171 | disease phenotypes: MIM:600669

GenCC curated gene-disease

Mondo (1): idiopathic generalized epilepsy (MONDO:0005579)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_34	Body mass index	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562694	Epilepsy, Idiopathic Generalized (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
sodium arsenite	increases expression	1
2-palmitoylglycerol	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03590197	PHASE4	COMPLETED	Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
NCT03940326	PHASE4	COMPLETED	Levetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT00150735	PHASE3	COMPLETED	Monotherapy With Levetiracetam in Newly Diagnosed Patients Suffering From Epilepsy
NCT00150748	PHASE3	COMPLETED	Long Term Follow up Treatment With Levetiracetam in Subjects of 4 Years and Older With Generalized Epilepsy
NCT03678753	PHASE3	COMPLETED	Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures
NCT05147571	PHASE3	ACTIVE_NOT_RECRUITING	RNS System NAUTILUS Study
NCT06908356	PHASE2	RECRUITING	An Open Label Trial to Evaluate the Efficacy and Safety of PRAX-628 in Adults With Focal Onset or Tonic-Clonic Seizures
NCT06425159	PHASE2/PHASE3	TERMINATED	A Study to Determine if BHV-7000 is Effective and Safe in Adults With Idiopathic Generalized Epilepsy With Generalized Tonic-clonic Seizures
NCT00001325	Not specified	COMPLETED	Metabolic Abnormalities in Children With Epilepsy
NCT00916903	Not specified	TERMINATED	Genetic Disease Gene Identification
NCT01311440	Not specified	COMPLETED	Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
NCT01432821	Not specified	COMPLETED	Blinking and Yawning in Epilepsy: The Role of Dopamine
NCT03368469	Not specified	WITHDRAWN	Transcranial Direct Current Stimulation (tDCS) in Children and Adolescents With Epilepsy and Depression
NCT03457961	Not specified	UNKNOWN	Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
NCT03955432	Not specified	TERMINATED	Long-term Cardiac Monitoring in Epilepsy
NCT04252846	Not specified	COMPLETED	A Study to Investigate Dosage, Effectiveness, and Safety of Perampanel When Used as First Add-on Therapy in Participants >=12 Years With Partial Onset Seizures With or Without Secondary Generalization or With Primary Generalized Tonic-Clonic Seizures Associated With Idiopathic Generalized Epilepsy
NCT04965571	Not specified	COMPLETED	Clinical Features and Outcome of Wilson’s Disease With Generalized Epilepsy in Chinese Patients
NCT05374928	Not specified	ACTIVE_NOT_RECRUITING	Human Epilepsy Project 3
NCT05530109	Not specified	TERMINATED	Study of Attentional Disorders in Patients Suffering From Idiopathic Generalized Epilepsy.
NCT06388174	Not specified	RECRUITING	Idiopathic Generalized Epilepsy Syndromes
NCT06797791	Not specified	COMPLETED	Assessment of Multifocal Continuous Theta Burst Transcranial Magnetic Stimulation (cTBS) Effects in Generalized Epilepsy Patients.