CAB39L

Summary

CAB39L (calcium binding protein 39 like, HGNC:20290) is a protein-coding gene on chromosome 13q14.2, encoding Calcium-binding protein 39-like (Q9H9S4). Component of a complex that binds and activates STK11/LKB1.

Predicted to enable protein serine/threonine kinase activator activity. Predicted to be involved in intracellular signal transduction. Predicted to be located in cytoplasm. Predicted to be part of serine/threonine protein kinase complex.

Source: NCBI Gene 81617 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_001079670

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20290
Approved symbol	CAB39L
Name	calcium binding protein 39 like
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Aliases	bA103J18.3, FLJ12577, MO2L, MLAA-34
Ensembl gene	ENSG00000102547
Ensembl biotype	protein_coding
OMIM	612175
Entrez	81617

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 26 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000347776, ENST00000355854, ENST00000409082, ENST00000409130, ENST00000409308, ENST00000410043, ENST00000413278, ENST00000425242, ENST00000457041, ENST00000470410, ENST00000476943, ENST00000610540, ENST00000856912, ENST00000856913, ENST00000856914, ENST00000856915, ENST00000856916, ENST00000856917, ENST00000856918, ENST00000856919, ENST00000856920, ENST00000856921, ENST00000856922, ENST00000856923, ENST00000856924, ENST00000856925, ENST00000965681, ENST00000965682

RefSeq mRNA: 5 — MANE Select: NM_001079670 NM_001079670, NM_001287337, NM_001287338, NM_001287339, NM_030925

CCDS: CCDS9416

Canonical transcript exons

ENST00000409308 — 11 exons

Exon	Start	End
ENSE00000836848	49359714	49359832
ENSE00000836850	49344179	49344238
ENSE00000836851	49339677	49339742
ENSE00001586489	49433318	49433393
ENSE00001682104	49376967	49377131
ENSE00001802910	49331947	49332090
ENSE00001802992	49382800	49382941
ENSE00001882214	49308650	49310993
ENSE00001925108	49443986	49444064
ENSE00003510388	49434086	49434223
ENSE00003598414	49350744	49350912

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3578 / max 358.8404, expressed in 1759 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137315	8.1650	1717
137316	1.6595	939
137313	1.3746	315
137309	0.9442	249
137312	0.6620	273
137311	0.1957	105
137310	0.1944	105
137306	0.1046	52
137308	0.0241	11
137307	0.0210	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	97.67	gold quality
calcaneal tendon	UBERON:0003701	96.18	gold quality
sural nerve	UBERON:0015488	95.55	gold quality
tibial nerve	UBERON:0001323	93.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.50	gold quality
endothelial cell	CL:0000115	92.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.71	gold quality
tendon	UBERON:0000043	91.64	gold quality
sperm	CL:0000019	90.93	gold quality
lower esophagus mucosa	UBERON:0035834	90.93	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.83	gold quality
lower esophagus	UBERON:0013473	90.82	gold quality
popliteal artery	UBERON:0002250	90.78	gold quality
tibial artery	UBERON:0007610	90.78	gold quality
male germ cell	CL:0000015	90.17	gold quality
prefrontal cortex	UBERON:0000451	90.11	gold quality
right adrenal gland cortex	UBERON:0035827	90.05	gold quality
left coronary artery	UBERON:0001626	89.93	gold quality
right lung	UBERON:0002167	89.90	gold quality
middle temporal gyrus	UBERON:0002771	89.88	gold quality
colonic epithelium	UBERON:0000397	89.63	gold quality
amniotic fluid	UBERON:0000173	89.37	gold quality
aorta	UBERON:0000947	89.30	gold quality
palpebral conjunctiva	UBERON:0001812	89.25	gold quality
coronary artery	UBERON:0001621	89.19	gold quality
right coronary artery	UBERON:0001625	89.07	gold quality
anterior cingulate cortex	UBERON:0009835	89.02	gold quality
cingulate cortex	UBERON:0003027	89.01	gold quality
cortical plate	UBERON:0005343	88.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.64	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.40
E-CURD-46	yes	10.01
E-MTAB-6058	no	238.97
E-MTAB-7249	no	58.71

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting CAB39L, 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-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
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-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-1912-3P	99.32	67.40	936

Literature-anchored findings (GeneRIF, showing 10)

• It was proposed that a splice variant MLAA-34 of CAB39L associated with acute monocytic leukemia. MLAA-34 was identified and characterized. Identification and functional characterization of the novel acute monocytic leukemia associated antigen MLAA-34 (PMID:18592235)
• our data indicate that MLAA-34 may be used as a prognostic marker for treatment decision-making in acute monocytic leukemia (PMID:21240483)
• In conclusion, our current results provide new evidence that MLAA-34 may be a novel anti-apoptotic factor in vitro, and the data presented here show a strong correlation between anti-apoptosis with the upregulation of MLAA-34. (PMID:23135622)
• Frameshift Mutations of CAB39L are associated with Gastric and Colorectal Cancers. (PMID:26306467)
• Our data demonstrate that CAB39L is a novel tumor suppressor in gastric cancer (PMID:30054562)
• minimal active region of MLAA-34 located between 402 bp and 200 bp (PMID:31204911)
• Targeted silencing of genes related to acute monocytic leukaemia by CpG(B)-MLAA-34 siRNA conjugates. (PMID:31718329)
• Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia. (PMID:33596023)
• Bioinformatics Prediction and Experimental Verification Identify CAB39L as a Diagnostic and Prognostic Biomarker of Kidney Renal Clear Cell Carcinoma. (PMID:37109674)
• Loss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis. (PMID:38676926)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cab39l	ENSDARG00000036658
mus_musculus	Cab39l	ENSMUSG00000021981
rattus_norvegicus	Cab39l	ENSRNOG00000011603
drosophila_melanogaster	Mo25	FBGN0017572
caenorhabditis_elegans		WBGENE00013140
caenorhabditis_elegans		WBGENE00019827

Paralogs (1): CAB39 (ENSG00000135932)

Protein

Protein identifiers

Calcium-binding protein 39-like — Q9H9S4 (reviewed: Q9H9S4)

Alternative names: Antigen MLAA-34, MO25beta, Mo25-like protein

All UniProt accessions (6): Q9H9S4, B7ZBJ4, B7ZBJ5, B7ZBJ6, B7ZBJ7, Q5TAW7

UniProt curated annotations — full annotation on UniProt →

Function. Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.

Subunit / interactions. Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.

Miscellaneous. Found in serum of 50% of patients with acute monocytic leukemia.

Similarity. Belongs to the Mo25 family.

RefSeq proteins (5): NP_001073138, NP_001274266, NP_001274267, NP_001274268, NP_112187 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011989	ARM-like	Homologous_superfamily
IPR013878	Mo25	Family
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF08569

UniProt features (29 total): helix 24, sequence conflict 2, turn 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3ZHP	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9S4-F1	93.88	0.90

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-380972	Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-162582	Signal Transduction
R-HSA-165159	MTOR signalling

MSigDB gene sets: 164 (showing top): GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, CHANDRAN_METASTASIS_DN, GOMF_KINASE_ACTIVATOR_ACTIVITY, MARTINEZ_RB1_TARGETS_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, KMCATNNWGGA_UNKNOWN, HFH3_01, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, MARTINEZ_RB1_AND_TP53_TARGETS_UP, chr13q14, TGGAAA_NFAT_Q4_01, GOCC_TRANSFERASE_COMPLEX_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, GCCATNTTG_YY1_Q6

GO Biological Process (1): intracellular signal transduction (GO:0035556)

GO Molecular Function (2): protein serine/threonine kinase activator activity (GO:0043539), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
MTOR signalling	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular anatomical structure	2
cellular anatomical structure	2
signal transduction	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
binding	1
cytoplasm	1
protein kinase complex	1

Protein interactions and networks

STRING

804 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAB39L	STRADB	Q9C0K7	974
CAB39L	STK11	Q15831	963
CAB39L	STRADA	Q7RTN6	928
CAB39L	MLNR	O43193	649
CAB39L	CDADC1	Q9BWV3	646
CAB39L	STK39	Q9UEW8	641
CAB39L	FNDC3A	Q9Y2H6	627
CAB39L	OXSR1	O95747	583
CAB39L	SETDB2	Q96T68	535
CAB39L	STK24	Q9Y6E0	507
CAB39L	PHF11	Q9UIL8	506
CAB39L	LPAR6	P43657	495
CAB39L	CIB2	O75838	426
CAB39L	RCBTB2	O95199	425
CAB39L	ITM2B	Q9Y287	425

IntAct

18 interactions, top by confidence:

A	B	Type	Score
STK11	FKBP5	psi-mi:“MI:0914”(association)	0.910
CAB39L	MX1	psi-mi:“MI:0915”(physical association)	0.560
MX1	CAB39L	psi-mi:“MI:0915”(physical association)	0.560
CAB39L	SCML2	psi-mi:“MI:0915”(physical association)	0.560
CAB39L	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
SRPK1	CAB39L	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
MLH1	CAB39L	psi-mi:“MI:0915”(physical association)	0.370
CFTR	CAB39L	psi-mi:“MI:0915”(physical association)	0.370
PAF1	PGRMC1	psi-mi:“MI:0914”(association)	0.350
CAB39L	ACOT7	psi-mi:“MI:0914”(association)	0.350
CAB39L	METTL15	psi-mi:“MI:0914”(association)	0.350
BCKDK	CAB39L	psi-mi:“MI:0915”(physical association)	0.000
CAB39L	SCML2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): CAB39L (Two-hybrid), STRADA (Affinity Capture-MS), CAB39 (Affinity Capture-MS), ACOT7 (Affinity Capture-MS), STK11 (Affinity Capture-MS), CAB39L (Co-fractionation), CAB39 (Affinity Capture-MS), STRADA (Affinity Capture-MS), STK11 (Affinity Capture-MS), ACOT7 (Affinity Capture-MS), CAB39L (Affinity Capture-RNA), CAB39L (Affinity Capture-MS), CAB39L (Two-hybrid), PAF1 (Affinity Capture-MS), CAB39 (Affinity Capture-MS)

ESM2 similar proteins: A5D785, A5WW24, B8ARW2, B9FDR3, F4IZR5, O15397, O18388, O95373, P14068, P30822, P45437, P55060, P91891, P91926, Q26626, Q29G21, Q29N38, Q2HJG5, Q54EV7, Q569Z2, Q5R9G4, Q5R9J2, Q5SPJ8, Q5ZLT0, Q6GMY9, Q704U0, Q7SZC2, Q7TMY7, Q8AY73, Q8GUL2, Q8H0U4, Q8K2V6, Q8W207, Q92368, Q96QK1, Q9CRT8, Q9DB16, Q9EPK7, Q9EPL8, Q9EQH3

Diamond homologs: O18211, O60032, P32464, P91891, Q06138, Q29RI6, Q9DB16, Q9FGK3, Q9H9S4, Q9M0M4, Q9P7Q8, Q9XFY6, Q9Y376, Q9ZQ77

SIGNOR signaling

0 interactions.

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	41
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2076 predictions. Top by Δscore:

Variant	Effect	Δscore
13:49310989:AACAC:A	acceptor_gain	1.0000
13:49310990:ACAC:A	acceptor_gain	1.0000
13:49310991:CAC:C	acceptor_gain	1.0000
13:49310991:CACC:C	acceptor_gain	1.0000
13:49310992:AC:A	acceptor_gain	1.0000
13:49310993:CC:C	acceptor_gain	1.0000
13:49310994:C:CA	acceptor_loss	1.0000
13:49310994:C:CC	acceptor_gain	1.0000
13:49331943:TTA:T	donor_loss	1.0000
13:49331945:ACCTT:A	donor_loss	1.0000
13:49332087:GCAG:G	acceptor_gain	1.0000
13:49332088:CAG:C	acceptor_gain	1.0000
13:49332088:CAGC:C	acceptor_gain	1.0000
13:49332091:C:CC	acceptor_gain	1.0000
13:49343999:T:TA	donor_gain	1.0000
13:49359712:A:AC	donor_gain	1.0000
13:49359712:AC:A	donor_gain	1.0000
13:49359713:C:CC	donor_gain	1.0000
13:49359713:CC:C	donor_gain	1.0000
13:49359760:C:CA	donor_gain	1.0000
13:49359829:TTCCC:T	acceptor_loss	1.0000
13:49359830:TCCC:T	acceptor_loss	1.0000
13:49359833:C:CC	acceptor_gain	1.0000
13:49359833:CT:C	acceptor_loss	1.0000
13:49359834:T:G	acceptor_loss	1.0000
13:49376961:GCTTA:G	donor_loss	1.0000
13:49376962:CTTAC:C	donor_loss	1.0000
13:49376963:TTACC:T	donor_loss	1.0000
13:49376964:TACCT:T	donor_loss	1.0000
13:49376965:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000039244 (13:49394904 G>A), RS1000085002 (13:49407529 C>T), RS1000095124 (13:49324306 G>A), RS1000117272 (13:49339063 G>A), RS1000137740 (13:49412166 T>C), RS1000167518 (13:49391315 T>C), RS1000195449 (13:49365370 T>C), RS1000197397 (13:49342979 C>A), RS1000200937 (13:49359603 T>C,G), RS1000205249 (13:49357770 C>A,T), RS1000242470 (13:49349953 T>A,G), RS1000357978 (13:49317422 C>T), RS1000394777 (13:49317471 G>A), RS1000408587 (13:49338693 C>T), RS1000435971 (13:49357006 G>A)

Disease associations

OMIM: gene MIM:612175 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008476_1	Emphysema annual change measurement in smokers (percent low attenuation area)	2.000000e-07
GCST009325_13	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-08
GCST010321_147	PR interval	8.000000e-15
GCST012489_67	Heel bone mineral density x serum urate levels interaction	2.000000e-09
GCST90000025_1043	Appendicular lean mass	8.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:0004462	PR interval
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, affects cotreatment, increases expression	5
sodium arsenite	decreases expression, increases expression	3
Estradiol	decreases expression, increases reaction	3
Cadmium Chloride	decreases expression, increases expression	3
mercuric bromide	affects cotreatment, increases expression	2
(+)-JQ1 compound	decreases expression	2
Arsenic Trioxide	decreases expression, increases expression, decreases reaction, decreases response to substance	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
kojic acid	increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sulforaphane	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
phenethyl isothiocyanate	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
jinfukang	decreases expression, affects cotreatment	1
MT19c compound	increases expression	1
Sunitinib	decreases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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