STRADB

Summary

STRADB (STE20 related adaptor beta, HGNC:13205) is a protein-coding gene on chromosome 2q33.1, encoding STE20-related kinase adapter protein beta (Q9C0K7). Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1.

This gene encodes a protein that belongs to the serine/threonine protein kinase STE20 subfamily. One of the active site residues in the protein kinase domain of this protein is altered, and it is thus a pseudokinase. This protein is a component of a complex involved in the activation of serine/threonine kinase 11, a master kinase that regulates cell polarity and energy-generating metabolism. This complex regulates the relocation of this kinase from the nucleus to the cytoplasm, and it is essential for G1 cell cycle arrest mediated by this kinase. The protein encoded by this gene can also interact with the X chromosome-linked inhibitor of apoptosis protein, and this interaction enhances the anti-apoptotic activity of this protein via the JNK1 signal transduction pathway. Two pseudogenes, located on chromosomes 1 and 7, have been found for this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 55437 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 55 total — 1 pathogenic
• GTEx eGene: eQTL in 18 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.79 (unconstrained)
• MANE Select transcript: NM_018571
• Notable: 55 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13205
Approved symbol	STRADB
Name	STE20 related adaptor beta
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Aliases	STLK6, CALS-21, PAPK, ILPIPA, ILPIP
Ensembl gene	ENSG00000082146
Ensembl biotype	protein_coding
OMIM	607333
Entrez	55437

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 28 protein_coding, 12 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000194530

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 5, TSL 4: 1, TSL 5: 1

ENST00000194530, ENST00000392249, ENST00000415688, ENST00000447698, ENST00000458269, ENST00000466770, ENST00000468123, ENST00000484098, ENST00000488196, ENST00000498648, ENST00000861982, ENST00000861983, ENST00000861984, ENST00000861985, ENST00000861986, ENST00000861987, ENST00000861988, ENST00000861989, ENST00000861990, ENST00000974588, ENST00000974589, ENST00000974590, ENST00000974591, ENST00000974592, ENST00000974593, ENST00000974594, ENST00000974595, ENST00001038444, ENST00001038446, ENST00001038447, ENST00001038448, ENST00001089862, ENST00001101061, ENST00001119396, ENST00001119397, ENST00001119398, ENST00001119399, ENST00001119400, ENST00001119401, ENST00001126542, ENST00001126543, ENST00001126544, ENST00001126545, ENST00001131048, ENST00001143997

RefSeq mRNA: 2 — MANE Select: NM_018571 NM_001206864, NM_018571

CCDS: CCDS2348, CCDS56161

Canonical transcript exons

ENST00000194530 — 12 exons

Exon	Start	End
ENSE00000784664	201478357	201478601
ENSE00000784666	201479489	201479531
ENSE00000934611	201458784	201458864
ENSE00000934612	201469953	201470052
ENSE00001172825	201480032	201480846
ENSE00001200786	201451740	201451938
ENSE00003509333	201478087	201478191
ENSE00003522169	201472955	201473076
ENSE00003649504	201477619	201477790
ENSE00003667257	201454746	201454852
ENSE00003676503	201474647	201474755
ENSE00003690883	201475619	201475742

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 97.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5537 / max 924.9584, expressed in 1721 samples.

Highest expression (Bgee): adrenal tissue, adrenal gland cortex, adrenal gland, blood, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

STRADB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

18 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	eqtl	3.0e-08	+0.29	2:201482535:T:G
Artery Aorta	eqtl	3.2e-08	-0.27	2:201461274:T:G
Whole Blood	eqtl	1.2e-06	-0.08	2:201513640:T:C
Brain Spinal cord cervical c-1	eqtl	1.8e-06	-0.25	2:201431043:T:A
Esophagus Muscularis	eqtl	3.2e-06	-0.21	2:201469676:A:G
Colon Transverse	eqtl	3.3e-06	-0.13	2:201439317:C:T
Nerve Tibial	eqtl	1.2e-04	-0.19	2:201425728:A:AG
Heart Left Ventricle	eqtl	2.1e-04	-0.11	2:201465907:G:A
Artery Tibial	eqtl	1.4e-03	+0.24	2:201520600:A:G
Stomach	eqtl	2.9e-03	-0.22	2:201461274:T:G
Esophagus Gastroesophageal Junction	eqtl	3.0e-03	-0.20	2:201390479:A:G
Brain Nucleus accumbens basal ganglia	eqtl	7.9e-03	+0.40	2:201580886:C:G
Thyroid	eqtl	1.1e-02	+0.25	2:201268792:G:C
Adipose Visceral Omentum	eqtl	1.5e-02	-0.10	2:200842178:C:T
Brain Frontal Cortex BA9	eqtl	2.2e-02	-0.40	2:201386846:G:A
Brain Cerebellar Hemisphere	eqtl	3.0e-02	+0.15	2:200615386:A:G
Cells Cultured fibroblasts	eqtl	4.4e-02	-0.23	2:201848953:T:G
Skin Sun Exposed Lower leg	eqtl	4.7e-02	-0.34	2:201614323:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
24680	11.5537	1721

Top tissues by expression

showing 100 of 140 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	97.67	gold quality
right adrenal gland cortex	UBERON:0035827	97.01	gold quality
right adrenal gland	UBERON:0001233	96.75	gold quality
blood	UBERON:0000178	96.67	gold quality
left adrenal gland	UBERON:0001234	96.24	gold quality
gastrocnemius	UBERON:0001388	96.19	gold quality
muscle of leg	UBERON:0001383	96.03	gold quality
left adrenal gland cortex	UBERON:0035825	96.03	gold quality
skeletal muscle organ	UBERON:0014892	96.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.89	gold quality
right lobe of liver	UBERON:0001114	95.87	gold quality
adrenal gland	UBERON:0002369	95.80	gold quality
skeletal muscle tissue	UBERON:0001134	95.57	gold quality
liver	UBERON:0002107	95.45	gold quality
duodenum	UBERON:0002114	95.28	gold quality
rectum	UBERON:0001052	95.05	gold quality
adult mammalian kidney	UBERON:0000082	95.00	gold quality
mucosa of transverse colon	UBERON:0004991	94.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.55	gold quality
kidney	UBERON:0002113	93.94	gold quality
cortical plate	UBERON:0005343	93.81	gold quality
bone element	UBERON:0001474	93.80	gold quality
bone marrow	UBERON:0002371	93.80	gold quality
heart left ventricle	UBERON:0002084	93.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.50	gold quality
monocyte	CL:0000576	93.46	gold quality
endometrium	UBERON:0001295	93.28	gold quality
bone marrow cell	CL:0002092	93.20	gold quality
body of pancreas	UBERON:0001150	93.16	gold quality
metanephros cortex	UBERON:0010533	93.12	gold quality
transverse colon	UBERON:0001157	93.07	gold quality
substantia nigra	UBERON:0002038	92.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.95	gold quality
muscle tissue	UBERON:0002385	92.75	gold quality
leukocyte	CL:0000738	92.73	gold quality
apex of heart	UBERON:0002098	92.73	gold quality
small intestine	UBERON:0002108	92.68	gold quality
Ammon’s horn	UBERON:0001954	92.56	gold quality
cortex of kidney	UBERON:0001225	92.51	gold quality
right uterine tube	UBERON:0001302	91.99	gold quality
heart	UBERON:0000948	91.98	gold quality
amygdala	UBERON:0001876	91.93	gold quality
mucosa of stomach	UBERON:0001199	91.91	gold quality
temporal lobe	UBERON:0001871	91.80	gold quality
hypothalamus	UBERON:0001898	91.49	gold quality
pituitary gland	UBERON:0000007	91.48	gold quality
corpus callosum	UBERON:0002336	91.44	gold quality
intestine	UBERON:0000160	91.18	gold quality
anterior cingulate cortex	UBERON:0009835	91.13	gold quality
lower esophagus mucosa	UBERON:0035834	91.02	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.78	gold quality
caudate nucleus	UBERON:0001873	90.75	gold quality
right atrium auricular region	UBERON:0006631	90.67	gold quality
colon	UBERON:0001155	90.48	gold quality
putamen	UBERON:0001874	90.48	gold quality
right lobe of thyroid gland	UBERON:0001119	90.45	gold quality
right lung	UBERON:0002167	90.43	gold quality
adenohypophysis	UBERON:0002196	90.40	gold quality
nucleus accumbens	UBERON:0001882	90.38	gold quality
brain	UBERON:0000955	90.35	gold quality
thyroid gland	UBERON:0002046	90.31	gold quality
left lobe of thyroid gland	UBERON:0001120	90.28	gold quality
uterus	UBERON:0000995	90.26	gold quality
thoracic mammary gland	UBERON:0005200	90.19	gold quality
cerebral cortex	UBERON:0000956	90.15	gold quality
pancreas	UBERON:0001264	90.06	gold quality
adipose tissue	UBERON:0001013	89.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.79	gold quality
prefrontal cortex	UBERON:0000451	89.72	gold quality
colonic epithelium	UBERON:0000397	89.61	gold quality
cerebellar hemisphere	UBERON:0002245	89.59	gold quality
cerebellar cortex	UBERON:0002129	89.53	gold quality
anatomical system	UBERON:0000467	89.52	gold quality
material anatomical entity	UBERON:0000465	89.51	gold quality
multicellular organism	UBERON:0000468	89.51	gold quality
body of uterus	UBERON:0009853	89.50	gold quality
right frontal lobe	UBERON:0002810	89.44	gold quality
frontal cortex	UBERON:0001870	89.42	gold quality
cerebellum	UBERON:0002037	89.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.31	gold quality
tibial nerve	UBERON:0001323	89.08	gold quality
gall bladder	UBERON:0002110	88.99	gold quality
omental fat pad	UBERON:0010414	88.89	gold quality
smooth muscle tissue	UBERON:0001135	88.86	gold quality
esophagus mucosa	UBERON:0002469	88.48	gold quality
myometrium	UBERON:0001296	88.47	gold quality
stromal cell of endometrium	CL:0002255	88.46	gold quality
placenta	UBERON:0001987	88.30	gold quality
prostate gland	UBERON:0002367	88.17	gold quality
esophagus	UBERON:0001043	87.98	gold quality
endocervix	UBERON:0000458	87.97	gold quality
fallopian tube	UBERON:0003889	87.96	gold quality
right ovary	UBERON:0002118	87.93	gold quality
lymph node	UBERON:0000029	87.88	gold quality
descending thoracic aorta	UBERON:0002345	87.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.81	gold quality
left ovary	UBERON:0002119	87.65	gold quality
primary visual cortex	UBERON:0002436	87.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.57	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	146.94
E-CURD-112	yes	56.62
E-HCAD-6	yes	42.08
E-MTAB-10042	yes	41.13
E-MTAB-9221	yes	21.22
E-MTAB-7316	yes	20.83
E-HCAD-9	yes	8.87
E-MTAB-9388	yes	7.73
E-HCAD-10	yes	7.02
E-MTAB-9467	yes	6.55
E-MTAB-9067	no	4.33
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	102.2	low
Liver	tissue	97.9	medium
Bone marrow	tissue	76.2	not detected
Kidney	tissue	68.2	medium
Tongue	tissue	64.9
Putamen	tissue	47.4
Corpus callosum	tissue	41.3
Adrenal gland	tissue	41.0	medium
Small intestine	tissue	40.4	not detected
Ventral forebrain	tissue	39.3
Substantia nigra	tissue	38.7
Retina	tissue	37.5
Midbrain	tissue	36.6
Basal ganglia	tissue	36.4	not detected
Spinal cord	tissue	36.0
Duodenum	tissue	34.8	low
Thalamus	tissue	34.7
Septum	tissue	34.6
Medulla oblongata	tissue	34.2
Pons	tissue	34.0
Periaqueductal gray	tissue	32.4
Superior colliculi	tissue	31.4
Hypothalamus	tissue	31.2
Heart muscle	tissue	29.7	low
Hippocampal formation	tissue	29.1
Amygdala	tissue	29.0
Rectum	tissue	28.4	not detected
Cerebral cortex	tissue	28.2	low
Motor cortex	tissue	28.2
Adipose tissue	tissue	28.1	not detected
Retrosplenial cortex	tissue	27.8
Occipital cortex	tissue	27.7
Cerebellum	tissue	26.8	not detected
Somatosensory cortex	tissue	26.6
Temporal cortex	tissue	26.5
Entorhinal cortex	tissue	26.4
Insular cortex	tissue	26.0
Colon	tissue	25.9	low
Prefrontal cortex	tissue	25.7
Retrosplenial and cingulate cortex	tissue	25.3
Olfactory bulb	tissue	22.5
Hippocampus	tissue	20.5	not detected
Locus coeruleus	tissue	19.3
Placenta	tissue	18.5	not detected
Frontal cortex	tissue	17.3
Nucleus accumbens	tissue	17.1
Pituitary gland	tissue	16.9
Thyroid gland	tissue	16.7	low
Epididymis	tissue	16.4	low
Esophagus	tissue	15.9	not detected
Postcentral gyrus	tissue	15.9
Choroid plexus	tissue	15.4
Breast	tissue	15.0	not detected
Testis	tissue	14.8	low
Lymph node	tissue	13.6	not detected
Gallbladder	tissue	13.4	low
Salivary gland	tissue	13.1	not detected
Caudate putamen	tissue	12.8
Endometrium 1	tissue	12.3	not detected
Pancreas	tissue	11.2	low

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (41.3), Ventral spinal cord (36.0), Cerebellar white matter (30.9), Dorsal spinal cord (30.5), Corpus callosum, genu (white matter) (29.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting STRADB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 56 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4465	99.71	72.56	2096

Functional genomics

gnomAD constraint: pLI 3.16e-05, LOEUF 0.792, missense Z 2.3 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000194530 — one region, missense o/e 0.70.

Literature-anchored findings (GeneRIF, showing 1)

• a novel XIAP-interacting protein that acts as a co-factor enhancing XIAP-mediated activation of JNK1 and the caspase-independent protection of XIAP against apoptosis (PMID:12048196)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000088225
mus_musculus	Stradb	ENSMUSG00000026027
rattus_norvegicus	Stradb	ENSRNOG00000010728

Paralogs (35): MAP3K14 (ENSG00000006062), MAP4K3 (ENSG00000011566), MAP4K5 (ENSG00000012983), MAP2K3 (ENSG00000034152), SLK (ENSG00000065613), MAP4K4 (ENSG00000071054), STK10 (ENSG00000072786), PAK3 (ENSG00000077264), MAP3K1 (ENSG00000095015), STK4 (ENSG00000101109), PAK5 (ENSG00000101349), STK24 (ENSG00000102572), STK3 (ENSG00000104375), MAP4K1 (ENSG00000104814), MAP3K8 (ENSG00000107968), MAP2K6 (ENSG00000108984), NEK4 (ENSG00000114904), STK25 (ENSG00000115694), NRK (ENSG00000123572), PAK4 (ENSG00000130669), STK26 (ENSG00000134602), TAOK3 (ENSG00000135090), PAK6 (ENSG00000137843), MINK1 (ENSG00000141503), PAK1 (ENSG00000149269), TAOK2 (ENSG00000149930), TNIK (ENSG00000154310), TAOK1 (ENSG00000160551), MAP4K2 (ENSG00000168067), OXSR1 (ENSG00000172939), MAP3K19 (ENSG00000176601), PAK2 (ENSG00000180370), SBK2 (ENSG00000187550), STK39 (ENSG00000198648), STRADA (ENSG00000266173)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2144047) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased mean corpuscular volume	1
abnormal auditory brainstem response	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RBJ6	99.1%	Diamond
Macaca fascicularis	Q4R6X5	98.7%	Diamond
Bos taurus	Q5E9J9	95.4%	Diamond
Gallus gallus	Q5ZK47	86.0%	Diamond
Caenorhabditis elegans	G5ECN5	35.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FLACC1	protein-coding	130540
CATSPERT	protein-coding	151254
TRAK2	protein-coding	66008
CASP8	protein-coding	841
CASP10	protein-coding	843
MPP4	protein-coding	58538
TMEM237	protein-coding	65062

Protein

Protein identifiers

STE20-related kinase adapter protein beta — Q9C0K7 (reviewed: Q9C0K7)

Alternative names: Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein, CALS-21, ILP-interacting protein, Pseudokinase ALS2CR2

All UniProt accessions (4): C9JSU7, Q9C0K7, F8WCQ7, H7C3S5

UniProt curated annotations — full annotation on UniProt →

Function. Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation.

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. Interacts with BIRC4/XIAP. These two proteins are likely to coexist in a complex with TAK1, TRAF6, TAB1 and TAB2.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in heart, skeletal muscle, testis, liver and colon.

Domain organisation. The protein kinase domain is predicted to be catalytically inactive.

Similarity. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9C0K7-1	1, ILPIP-alpha	yes
Q9C0K7-2	2
Q9C0K7-3	3, ILPIP-beta

RefSeq proteins (2): NP_001193793, NP_061041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR047173	STRAD_A/B-like	Family

Pfam: PF00069

UniProt features (9 total): splice variant 3, binding site 2, sequence variant 2, chain 1, domain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C0K7-F1	74.39	0.52

Human Protein Atlas

Protein class: Enzymes, Kinases, STE Ser/Thr protein kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm; primary cilium; primary cilium tip

Antibody reliability (HPA): IH approved · IF supported

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 (2)

Position	Role
64–72	ATP
89	ATP

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

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

MSigDB gene sets: 223 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, AP1_01, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, RORA1_01, AREB6_03, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, TGACCTY_ERR1_Q2, GOBP_NUCLEAR_TRANSPORT, GOMF_KINASE_ACTIVATOR_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY

GO Biological Process (3): protein export from nucleus (GO:0006611), activation of protein kinase activity (GO:0032147), protein phosphorylation (GO:0006468)

GO Molecular Function (5): ATP binding (GO:0005524), protein serine/threonine kinase activator activity (GO:0043539), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

2 top-level categories:

Category	Pathways
MTOR signalling	1
Signal Transduction	1

GO top-level categories

22 GO namespaces:

Category	Terms
cellular anatomical structure	3
intracellular protein transport	1
nuclear export	1
positive regulation of protein kinase activity	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein serine/threonine kinase activity	1
protein kinase activator activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
protein kinase complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 13 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
activation of protein kinase activity	BP	direct assay
protein export from nucleus	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 706 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRADB	CAB39L	Q9H9S4	890
STRADB	TRAK2	O60296	863
STRADB	CAB39	Q9Y376	849
STRADB	STK11	Q15831	697
STRADB	ALS2	Q96Q42	591
STRADB	MAP3K7	O43318	548
STRADB	EPB42	P16452	531
STRADB	XIAP	P98170	508
STRADB	DCAF12	Q5T6F0	473
STRADB	NPRL3	Q12980	469
STRADB	UBXN6	Q9BZV1	467
STRADB	ANKS3	Q6ZW76	427
STRADB	DIABLO	Q9NR28	423
STRADB	COMMD1	Q8N668	421
STRADB	TRAF6	Q9Y4K3	388

IntAct

Human interaction partners of STRADB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
STK11	colocalization	0.920	4
CAB39	physical association	0.770	5
TCP1	association	0.530	1
CREB1	association	0.350	1
TIMM8A	association	0.350	1
GRB2	physical association	0.000	1
NEB	physical association	0.000	1
TNIK	physical association	0.000	1

BioGRID (52 interactions; top human partners by supporting records): STK11 (Affinity Capture-MS; 9 records), CAB39 (Affinity Capture-MS; 4 records), CCT2 (Affinity Capture-MS; 3 records), CCT6B (Affinity Capture-MS; 3 records), CCT3 (Affinity Capture-MS; 2 records), CCT7 (Affinity Capture-MS; 2 records), NBEA (Affinity Capture-MS; 2 records), PIP4K2A (Affinity Capture-MS; 2 records), TCP1 (Affinity Capture-MS; 2 records), XIAP (Reconstituted Complex; 2 records), CCT4 (Affinity Capture-MS), CCT5 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CCT8 (Affinity Capture-MS), CREB1 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for STRADB: 55 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1456057	NC_000002.11:g.(?201943606)(204824322_?)del	Pathogenic	criteria provided, single submitter	3

Per-variant reference — Sugi Variant

Explore STRADB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,083):

Position(s)	Effect	Δscore	Sites
2:201472954	acceptor_loss	1.0000
2:201473077–201473078	donor_loss	1.0000	5
2:201475743–201475744	donor_loss	1.0000	5
2:201476472	donor_gain	1.0000
2:201478085–201478086	acceptor_loss	1.0000	6
2:201478192–201478193	donor_loss	1.0000	4
2:201451967	donor_gain	0.9900
2:201472946	acceptor_gain	0.9900
2:201472952	acceptor_gain	0.9900
2:201472953–201472954	acceptor_loss	0.9900	2

AlphaMissense

781 missense substitutions predicted likely pathogenic (of 2,730 scored), across 204 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D250	8	0.996	0.999
H176	8	0.968	0.994
H182	8	0.963	0.992
S234	8	0.953	0.999
F126	8	0.928	0.992
H189	8	0.918	0.982
D241	8	0.904	0.961
F369	8	0.903	0.983
H116	8	0.896	0.983
S253	8	0.896	0.998
F342	8	0.832	0.980
M276	8	0.818	0.935
R357	7	0.994	0.999
E236	7	0.990	0.995
W232	7	0.988	0.999
F268	7	0.983	0.994
E260	7	0.963	0.992
C349	7	0.960	0.998
F152	7	0.947	0.991
R183	7	0.941	0.995

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Rectum Adenocarcinoma (validation)	unfavorable	0.000431
Thyroid Carcinoma (TCGA)	favorable	0.000437
Skin Cutaneous Melanoma (TCGA)	unfavorable	0.000807

Disease associations

OMIM: gene MIM:607333 | disease phenotypes: MIM:607271, MIM:607594, MIM:616100

GenCC curated gene-disease

Mondo (3): autoimmune lymphoproliferative syndrome type 2B (MONDO:0011804), immunodeficiency, common variable, 1 (MONDO:0011864), autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency (MONDO:0014493)

Orphanet (4): OBSOLETE: Common variable immunodeficiency (Orphanet:1572), Autoimmune lymphoproliferative syndrome-recurrent viral infections due to CASP8 deficiency (Orphanet:275517), Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency (Orphanet:436159), Late-onset combined immunodeficiency due to ICOS deficiency (Orphanet:695183)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105756 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — STLK subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression, increases expression	3
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Ozone	affects expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

20 unique, capped per target: 20 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4034498	Binding	Inhibition of STLK6 Lysine 1 labelling site (unknown origin) at 10 uM	Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3IH	Abcam HEK293T STRADB KO	Transformed cell line	Female
CVCL_TR00	HAP1 STRADB (-) 1	Cancer cell line	Male
CVCL_TR01	HAP1 STRADB (-) 2	Cancer cell line	Male
CVCL_TR02	HAP1 STRADB (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

3 trials:

NCT	Phase	Status	Title
NCT05235438	Phase 1	UNKNOWN	Safety and Toxicity Study of IMM27M in Patients With Advanced Solid Tumor
NCT04377867	Not specified	UNKNOWN	New Biomarkers for Diagnosis and Follow-up of Patients With LRBA or CTLA4 Deficiencies
NCT05040256	Not specified	COMPLETED	Neurologic and Immunologic Characteristics of CTLA-4 and LRBA Hereditary Deficiency