FASTK

Summary

FASTK (Fas activated serine/threonine kinase, HGNC:24676) is a protein-coding gene on chromosome 7q36.1, encoding Fas-activated serine/threonine kinase (Q14296). Phosphorylates the splicing regulator TIA1, thereby promoting the inclusion of FAS exon 6, which leads to an mRNA encoding a pro-apoptotic form of the receptor.

The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase was shown to be activated rapidly during Fas-mediated apoptosis in Jurkat cells. In response to Fas receptor ligation, it phosphorylates TIA1, an apoptosis-promoting nuclear RNA-binding protein. The encoded protein is a strong inducer of lymphocyte apoptosis. Two transcript variants encoding different isoforms have been found for this gene. Other variants exist, but their full-length natures have not yet been determined.

Source: NCBI Gene 10922 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 81 total
• GTEx eGene: eQTL in 37 tissues, sQTL in 35 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.69 (unconstrained)
• MANE Select transcript: NM_006712
• Notable: 81 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24676
Approved symbol	FASTK
Name	Fas activated serine/threonine kinase
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	FASTKD0, FAST
Ensembl gene	ENSG00000164896
Ensembl biotype	protein_coding
OMIM	606965
Entrez	10922

Gene structure

Transcript identifiers

Ensembl transcripts: 131 — 85 nonsense_mediated_decay, 33 protein_coding, 9 retained_intron, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000297532

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 3, TSL 3: 2, TSL 5: 6

ENST00000297532, ENST00000353841, ENST00000459800, ENST00000460980, ENST00000461979, ENST00000465272, ENST00000466855, ENST00000467237, ENST00000469237, ENST00000478477, ENST00000478883, ENST00000482571, ENST00000482806, ENST00000483953, ENST00000489884, ENST00000496663, ENST00000899741, ENST00000899742, ENST00000899743, ENST00000899744, ENST00000899745, ENST00000899746, ENST00000899747, ENST00000899748, ENST00000899749, ENST00000899750, ENST00000899751, ENST00000914251, ENST00000959426, ENST00000959427, ENST00000959428, ENST00000959429, ENST00000959430, ENST00001006889, ENST00001006890, ENST00001006891, ENST00001006892, ENST00001006893, ENST00001006894, ENST00001006895, ENST00001006896, ENST00001006897, ENST00001006898, ENST00001006899, ENST00001006900, ENST00001006901, ENST00001006902, ENST00001006903, ENST00001006904, ENST00001006905, ENST00001006906, ENST00001006907, ENST00001006908, ENST00001006909, ENST00001034945, ENST00001034946, ENST00001034947, ENST00001034948, ENST00001034949, ENST00001034950, ENST00001034951, ENST00001034952, ENST00001034953, ENST00001034954, ENST00001034955, ENST00001034956, ENST00001034958, ENST00001034959, ENST00001034960, ENST00001034961, ENST00001034962, ENST00001034963, ENST00001034964, ENST00001034965, ENST00001034966, ENST00001034969, ENST00001034970, ENST00001034971, ENST00001034972, ENST00001034974, ENST00001034975, ENST00001034977, ENST00001034978, ENST00001034979, ENST00001034980, ENST00001034981, ENST00001034982, ENST00001066924, ENST00001066925, ENST00001066926, ENST00001066927, ENST00001066928, ENST00001066929, ENST00001066930, ENST00001066931, ENST00001066932, ENST00001066933, ENST00001066934, ENST00001066935, ENST00001066936, ENST00001066937, ENST00001092406, ENST00001092407, ENST00001092408, ENST00001110145, ENST00001110146, ENST00001114631, ENST00001114632, ENST00001114633, ENST00001120933, ENST00001120934, ENST00001120935, ENST00001120936, ENST00001120937, ENST00001120938, ENST00001120939, ENST00001120940, ENST00001120941, ENST00001120942, ENST00001120943, ENST00001120944, ENST00001120945, ENST00001120946, ENST00001123416, ENST00001123417, ENST00001123418, ENST00001123419, ENST00001123420, ENST00001123421, ENST00001123422, ENST00001139649

RefSeq mRNA: 3 — MANE Select: NM_006712 NM_001258461, NM_006712, NM_033015

CCDS: CCDS59088, CCDS5918, CCDS5919

Canonical transcript exons

ENST00000297532 — 10 exons

Exon	Start	End
ENSE00001831355	151080685	151080809
ENSE00003476596	151078562	151078701
ENSE00003485520	151077879	151078092
ENSE00003488016	151078842	151079021
ENSE00003497632	151077310	151077401
ENSE00003532150	151076913	151077027
ENSE00003610790	151077621	151077780
ENSE00003634419	151077101	151077236
ENSE00003727154	151079500	151079922
ENSE00003844475	151076624	151076832

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1617 / max 169.5902, expressed in 1818 samples.

Highest expression (Bgee): apex of heart, hindlimb stylopod muscle, hemisphere of cerebellum, mucosa of transverse colon, adenohypophysis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FASTK is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 72 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Muscle Skeletal	sqtl	4.2e-61	+1.77	7:151080283:T:A
Cells Cultured fibroblasts	sqtl	1.8e-56	+1.06	7:151080367:G:A
Esophagus Muscularis	eqtl	3.3e-34	+0.36	7:151080367:G:A
Artery Tibial	sqtl	9.7e-32	+0.70	7:151080367:G:A
Artery Tibial	eqtl	2.7e-31	+0.34	7:151076577:C:T
Cells Cultured fibroblasts	eqtl	5.1e-30	+0.46	7:151080367:G:A
Artery Aorta	eqtl	1.3e-29	+0.42	7:151080367:G:A
Esophagus Muscularis	sqtl	6.9e-28	+0.73	7:151080367:G:A
Heart Atrial Appendage	eqtl	3.3e-27	+0.49	7:151080367:G:A
Artery Aorta	sqtl	3.9e-27	+0.79	7:151080367:G:A
Esophagus Mucosa	sqtl	3.6e-24	+0.64	7:151080367:G:A
Colon Sigmoid	eqtl	6.6e-23	+0.39	7:151080367:G:A
Adipose Subcutaneous	sqtl	6.1e-22	+0.57	7:151080367:G:A
Nerve Tibial	sqtl	1.8e-21	+0.54	7:151080367:G:A
Esophagus Gastroesophageal Junction	sqtl	3.2e-20	+0.82	7:151080367:G:A
Skin Sun Exposed Lower leg	sqtl	3.9e-19	+0.52	7:151080367:G:A
Breast Mammary Tissue	sqtl	1.1e-18	+0.65	7:151080367:G:A
Esophagus Gastroesophageal Junction	eqtl	1.9e-18	+0.32	7:151080367:G:A
Thyroid	sqtl	6.3e-17	+0.47	7:151080367:G:A
Heart Atrial Appendage	sqtl	2.9e-16	+0.66	7:151080367:G:A

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
86860	25.7215	1814
86861	3.4465	1638
86862	0.8538	590
86859	0.1399	47

Top tissues by expression

showing 100 of 300 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.33	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.68	gold quality
mucosa of transverse colon	UBERON:0004991	97.56	gold quality
adenohypophysis	UBERON:0002196	97.55	gold quality
cerebellar hemisphere	UBERON:0002245	97.34	gold quality
cerebellar cortex	UBERON:0002129	97.17	gold quality
metanephros cortex	UBERON:0010533	97.16	gold quality
gastrocnemius	UBERON:0001388	97.07	gold quality
lower esophagus mucosa	UBERON:0035834	97.07	gold quality
right lobe of thyroid gland	UBERON:0001119	96.99	gold quality
right uterine tube	UBERON:0001302	96.83	gold quality
right lobe of liver	UBERON:0001114	96.57	gold quality
transverse colon	UBERON:0001157	96.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.46	gold quality
left lobe of thyroid gland	UBERON:0001120	96.45	gold quality
granulocyte	CL:0000094	96.42	gold quality
left ovary	UBERON:0002119	96.35	gold quality
pituitary gland	UBERON:0000007	96.34	gold quality
muscle of leg	UBERON:0001383	96.34	gold quality
right ovary	UBERON:0002118	96.33	gold quality
body of uterus	UBERON:0009853	96.15	gold quality
left uterine tube	UBERON:0001303	96.09	gold quality
endocervix	UBERON:0000458	96.08	gold quality
right atrium auricular region	UBERON:0006631	96.07	gold quality
right frontal lobe	UBERON:0002810	96.05	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.03	gold quality
body of stomach	UBERON:0001161	95.92	gold quality
right adrenal gland	UBERON:0001233	95.84	gold quality
ectocervix	UBERON:0012249	95.77	gold quality
right adrenal gland cortex	UBERON:0035827	95.68	gold quality
stromal cell of endometrium	CL:0002255	95.61	gold quality
left adrenal gland cortex	UBERON:0035825	95.56	gold quality
minor salivary gland	UBERON:0001830	95.49	gold quality
left adrenal gland	UBERON:0001234	95.45	gold quality
left coronary artery	UBERON:0001626	95.40	gold quality
cerebellum	UBERON:0002037	95.37	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.28	gold quality
heart left ventricle	UBERON:0002084	95.26	gold quality
lower esophagus	UBERON:0013473	95.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.25	gold quality
esophagus mucosa	UBERON:0002469	95.24	gold quality
skin of leg	UBERON:0001511	95.20	gold quality
spleen	UBERON:0002106	95.20	gold quality
skin of abdomen	UBERON:0001416	95.17	gold quality
thyroid gland	UBERON:0002046	95.13	gold quality
ascending aorta	UBERON:0001496	95.12	gold quality
thoracic aorta	UBERON:0001515	95.11	gold quality
esophagus	UBERON:0001043	94.99	gold quality
cardiac ventricle	UBERON:0002082	94.96	gold quality
peripheral nervous system	UBERON:0000010	94.89	gold quality
nerve	UBERON:0001021	94.89	gold quality
tibial nerve	UBERON:0001323	94.89	gold quality
coronary artery	UBERON:0001621	94.88	gold quality
triceps brachii	UBERON:0001509	94.82	gold quality
adrenal cortex	UBERON:0001235	94.77	gold quality
small intestine	UBERON:0002108	94.77	gold quality
body of pancreas	UBERON:0001150	94.75	gold quality
right coronary artery	UBERON:0001625	94.67	gold quality
muscle organ	UBERON:0001630	94.65	gold quality
skeletal muscle organ	UBERON:0014892	94.65	gold quality
cingulate cortex	UBERON:0003027	94.59	gold quality
descending thoracic aorta	UBERON:0002345	94.50	gold quality
anterior cingulate cortex	UBERON:0009835	94.49	gold quality
amygdala	UBERON:0001876	94.43	gold quality
nucleus accumbens	UBERON:0001882	94.43	gold quality
cardiac atrium	UBERON:0002081	94.41	gold quality
mucosa of stomach	UBERON:0001199	94.33	gold quality
aorta	UBERON:0000947	94.26	gold quality
caudate nucleus	UBERON:0001873	94.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.04	gold quality
upper lobe of left lung	UBERON:0008952	94.01	gold quality
putamen	UBERON:0001874	94.00	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.98	gold quality
omental fat pad	UBERON:0010414	93.92	gold quality
mouth mucosa	UBERON:0003729	93.87	gold quality
peritoneum	UBERON:0002358	93.86	gold quality
prefrontal cortex	UBERON:0000451	93.83	gold quality
heart	UBERON:0000948	93.80	gold quality
popliteal artery	UBERON:0002250	93.79	gold quality
tibial artery	UBERON:0007610	93.79	gold quality
stomach	UBERON:0000945	93.70	gold quality
fundus of stomach	UBERON:0001160	93.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.60	gold quality
saliva-secreting gland	UBERON:0001044	93.52	gold quality
adrenal gland	UBERON:0002369	93.51	gold quality
colon	UBERON:0001155	92.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.87	gold quality
right testis	UBERON:0004534	92.82	gold quality
intestine	UBERON:0000160	92.66	gold quality
right lung	UBERON:0002167	92.54	gold quality
sigmoid colon	UBERON:0001159	92.52	gold quality
zone of skin	UBERON:0000014	92.51	gold quality
left testis	UBERON:0004533	92.47	gold quality
large intestine	UBERON:0000059	92.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.23	gold quality
upper lobe of lung	UBERON:0008948	92.19	gold quality
endometrium epithelium	UBERON:0004811	92.11	gold quality
lymph node	UBERON:0000029	92.08	gold quality
vagina	UBERON:0000996	92.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.59

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	114.6	medium
Tongue	tissue	89.1
Frontal cortex	tissue	56.7
Caudate putamen	tissue	49.9
Pituitary gland	tissue	41.8
Heart muscle	tissue	40.9	medium
Parathyroid gland	tissue	29.0	medium
Salivary gland	tissue	26.0	medium
Cerebral cortex	tissue	25.4	medium
Motor cortex	tissue	25.4
Somatosensory cortex	tissue	25.0
Vagina	tissue	24.7	medium
Duodenum	tissue	24.6	medium
Prefrontal cortex	tissue	23.9
Occipital cortex	tissue	23.7
Pancreas	tissue	23.6	medium
Hippocampal formation	tissue	23.1
Entorhinal cortex	tissue	23.1
Insular cortex	tissue	23.0
Temporal cortex	tissue	22.5
Postcentral gyrus	tissue	22.4
Superior colliculi	tissue	22.1
Thalamus	tissue	21.7
Retrosplenial cortex	tissue	21.6
Retrosplenial and cingulate cortex	tissue	21.4
Hippocampus	tissue	21.3	low
Esophagus	tissue	20.7	medium
Basal ganglia	tissue	20.7	medium
Midbrain	tissue	20.7
Small intestine	tissue	20.6	medium
Putamen	tissue	20.5
Pons	tissue	20.3
Periaqueductal gray	tissue	20.1
Locus coeruleus	tissue	19.2
Amygdala	tissue	19.1
Ovary	tissue	19.0	not detected
Medulla oblongata	tissue	18.5
Hypothalamus	tissue	18.5
Substantia nigra	tissue	18.4
Spinal cord	tissue	18.3
Corpus callosum	tissue	18.1
Cervix	tissue	18.0	medium
Ventral forebrain	tissue	18.0
Nucleus accumbens	tissue	17.9
Colon	tissue	17.8	medium
Seminal vesicle	tissue	17.7	medium
Septum	tissue	17.6
Fallopian tube	tissue	17.4	low
Stomach 1	tissue	16.6	medium
Skin 1	tissue	16.3	medium
Urinary bladder	tissue	16.2	medium
Prostate	tissue	15.6	medium
Adipose tissue	tissue	15.5	not detected
Olfactory bulb	tissue	15.3
Liver	tissue	15.0	low
Adrenal gland	tissue	15.0	medium
Cerebellum	tissue	14.5	medium
Gallbladder	tissue	13.7	medium
Thymus	tissue	13.6
Lymph node	tissue	13.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Blood vessel (27.2), Medial dorsal thalamic nucleus (24.9), Ventral posterolateral thalamic nucleus (24.6), Central amygdala (24.3), Inferior parietal lobule (24.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, MEF2A, MYF5, MYOD1, NFATC1, NFATC3, PRDM1, SSRP1, TCF3

miRNA regulators (miRDB)

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

26 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-454-3P	99.91	74.01	1925
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-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
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-328-5P	99.08	64.65	1000
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-12120	98.05	68.44	1768

Functional genomics

gnomAD constraint: pLI 0.000607, LOEUF 0.693, missense Z 1.32 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000297532 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:151,076,728–151,079,761	471 / 605.9	0.78	no
7:151,079,762–151,080,766	124 / 107.9	1.15	no

Literature-anchored findings (GeneRIF, showing 8)

• FAST is a survival protein that senses mitochondrial stress and modulates TIA-1 regulated changes in protein expression. (PMID:15572676)
• FAST K synergizes with TIA-1/TIAR proteins to regulate Fas alternative splicing (PMID:17135269)
• Nuclear FAST can regulate the splicing of FGFR2 transcripts. (PMID:17592127)
• FAST expression on lung cells of hematopoietic origin is crucial in mediating lipopolysaccharide-induced neutrophil migration to the lung in transgenic FAST-deficient mice compared with wild type controls. (PMID:20363972)
• MIR-106a-5p functions as a tumor suppressor during the development of astrocytomas by targeting FASTK. (PMID:24013584)
• FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. (PMID:25704814)
• Systematic Analysis of FASTK Gene Family Alterations in Cancer. (PMID:34768773)
• Accuracy of FAST in detecting intraabdominal bleeding in major trauma with pelvic and/or acetabular fractures: a retrospective cohort study. (PMID:38253932)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fastk	ENSDARG00000077075
mus_musculus	Fastk	ENSMUSG00000028959
rattus_norvegicus	Fastk	ENSRNOG00000011667
caenorhabditis_elegans		WBGENE00007207

Paralogs (5): FASTKD2 (ENSG00000118246), FASTKD3 (ENSG00000124279), TBRG4 (ENSG00000136270), FASTKD1 (ENSG00000138399), FASTKD5 (ENSG00000215251)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913837) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased neutrophil cell number	1
hyperactivity	1
abnormal neutrophil physiology	1
increased heart weight	1
improved glucose tolerance	1
increased blood urea nitrogen level	1
decreased tumor necrosis factor secretion	1
decreased interleukin-23 secretion	1
decreased interleukin-6 secretion	1
abnormal chemokine secretion	1
decreased physiological sensitivity to xenobiotic	1

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
ABCB8	protein-coding	11194
SLC4A2	protein-coding	6522
ASIC3	protein-coding	9311
ASB10	protein-coding	136371
GBX1	protein-coding	2636
TMUB1	protein-coding	83590
AGAP3	protein-coding	116988
CDK5	protein-coding	1020

Protein

Protein identifiers

Fas-activated serine/threonine kinase — Q14296 (reviewed: Q14296)

All UniProt accessions (3): A0A090N8I0, A0A090N8Z7, Q14296

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates the splicing regulator TIA1, thereby promoting the inclusion of FAS exon 6, which leads to an mRNA encoding a pro-apoptotic form of the receptor. Required for the biogenesis of some mitochondrial-encoded mRNAs, specifically stabilizes ND6 (NADH dehydrogenase complex subunit 6) mRNA, and regulates its levels.

Subunit / interactions. Interacts with TIA1; the interactions leads to TIA1 phosphorylation. Interacts with TIAR.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Autophosphorylated on serine/threonine residues. Activated by dephosphorylation.

Domain organisation. The RAP domain is essential for RNA-binding.

Similarity. Belongs to the FAST protein kinase family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q14296-1	1	yes
Q14296-2	2
Q14296-3	3
Q14296-4	4

RefSeq proteins (3): NP_001245390, NP_006703, NP_148936 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010622	FAST_Leu-rich	Domain
IPR013579	FAST_2	Domain
IPR013584	RAP	Domain
IPR050870	FAST_kinase	Family

Pfam: PF06743, PF08368, PF08373

Enzyme classification (BRENDA)

• EC 2.7.11.8 — Fas-activated serine/threonine kinase (BRENDA: 2 organisms, 11 substrates, 3 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea)

• L-seryl-[Fas-activated protein] + ATP = O-phospho-L-seryl-[Fas-activated protein] + ADP + H(+) (RHEA:15881)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
• L-threonyl-[Fas-activated protein] + ATP = O-phospho-L-threonyl-[Fas-activated protein] + ADP + H(+) (RHEA:53920)

UniProt features (10 total): splice variant 4, sequence variant 2, chain 1, domain 1, region of interest 1, mutagenesis site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14296-F1	74.88	0.38

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Atypical kinases, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria; nuclear speckles

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.

Mutagenesis-validated functional residues (1)

Position	Phenotype
35	abolishes isoform 4 expression.

Function

Pathways and Gene Ontology

Reactome pathways

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

1 pathways:

ID	Pathway	Evidence
R-HSA-9837092	FASTK family proteins regulate processing and stability of mitochondrial RNAs	curated

MSigDB gene sets: 154 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, CHIBA_RESPONSE_TO_TSA_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, PATIL_LIVER_CANCER, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, YY1_02, GOBP_MITOCHONDRIAL_RNA_PROCESSING, ZIC1_01, GOBP_RNA_SPLICING, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS

GO Biological Process (6): mitochondrial RNA processing (GO:0000963), protein phosphorylation (GO:0006468), regulation of RNA splicing (GO:0043484), regulation of mitochondrial mRNA stability (GO:0044528), apoptotic signaling pathway (GO:0097190), apoptotic process (GO:0006915)

GO Molecular Function (9): RNA binding (GO:0003723), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), Fas-activated serine/threonine kinase activity (GO:0033867), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), ribonucleoprotein granule (GO:0035770)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Mitochondrial RNA degradation	1

GO top-level categories

31 GO namespaces:

Category	Terms
mitochondrion	2
protein kinase activity	2
mitochondrial RNA metabolic process	1
RNA processing	1
mitochondrial gene expression	1
phosphorylation	1
protein modification process	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
regulation of mRNA stability	1
apoptotic process	1
signal transduction	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein serine/threonine kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
intracellular membraneless organelle	1
supramolecular complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
protein phosphorylation	BP	direct assay
regulation of RNA splicing	BP	direct assay
mitochondrion	CC	direct assay
protein serine/threonine kinase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 718 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FASTK	FASTKD2	Q9NYY8	948
FASTK	FASTKD1	Q53R41	735
FASTK	TIA1	P31483	715
FASTK	TIAL1	Q01085	709
FASTK	FASTKD5	Q7L8L6	655
FASTK	GRSF1	Q12849	603
FASTK	SLIRP	Q9GZT3	569
FASTK	LRPPRC	P42704	545
FASTK	RPUSD4	Q96CM3	468
FASTK	RPUSD3	Q6P087	465
FASTK	MTPAP	Q9NVV4	450
FASTK	MT-ND6	P03923	439
FASTK	PNPT1	Q8TCS8	421
FASTK	FASTKD4	Q969Z0	415
FASTK	MRM1	Q6IN84	415

IntAct

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

12 partners by confidence:

Partner	Interaction type	MIscore	Records
ATN1	physical association	0.560	3
CHERP	physical association	0.560	3
ESRRG	physical association	0.560	3
KLK6	physical association	0.560	3
PRPF31	physical association	0.560	3
TOP3B	physical association	0.560	3
WIPF1	physical association	0.560	3
TNKS2	direct interaction	0.440	1
CRK	physical association	0.400	1
HSP90AB1	physical association	0.400	1
CALCOCO2	physical association	0.370	1
TGM1	association	0.350	1

BioGRID (29 interactions; top human partners by supporting records): HNRNPH2 (Affinity Capture-MS; 2 records), TIA1 (Reconstituted Complex; 2 records), AGL (Affinity Capture-MS), AGO2 (Affinity Capture-RNA), CALCOCO2 (Two-hybrid), CHERP (Two-hybrid), DSC3 (Affinity Capture-MS), ECM1 (Affinity Capture-MS), ESRRG (Two-hybrid), FKBP5 (Affinity Capture-MS), GDPD3 (Affinity Capture-MS), GSDMA (Affinity Capture-MS), HSP90AA1 (Affinity Capture-Luminescence), LARP4B (Affinity Capture-MS), MDFI (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for FASTK: 81 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	4
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 656):

Position(s)	Effect	Δscore	Sites
7:151076833–151076834	acceptor_loss	1.0000	5
7:151076911–151076912	donor_loss	1.0000	5
7:151077028	acceptor_gain	1.0000
7:151077028–151077029	acceptor_loss	1.0000	4
7:151077877–151077878	donor_loss	1.0000	4
7:151077999	donor_gain	1.0000
7:151078093	acceptor_loss	1.0000	2
7:151078560–151078561	donor_loss	1.0000	5
7:151078581	donor_gain	1.0000
7:151076833	acceptor_loss	0.9900

AlphaMissense

898 missense substitutions predicted likely pathogenic (of 3,450 scored), across 247 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
D431	8	0.972	0.993
F432	8	0.961	0.998
F337	8	0.957	0.986
N317	8	0.935	0.992
F284	8	0.926	0.978
F386	8	0.923	0.982
H504	8	0.911	0.985
F341	8	0.900	0.988
F153	8	0.874	0.961
D362	8	0.867	0.983
F296	8	0.862	0.979
D393	8	0.831	0.947
H486	8	0.813	0.944
W485	7	0.930	0.967
F264	7	0.925	0.985
M320	7	0.907	0.964
F487	7	0.897	0.977
E368	7	0.869	0.979
R501	7	0.868	0.974
W101	7	0.853	0.946

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:606965 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST003476_6	Eyebrow thickness	7e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6196088 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.82	IC50	150	nM	CHEMBL6165181
6.77	IC50	170	nM	CHEMBL6168517
6.50	IC50	320	nM	CHEMBL6159585

PubChem BioAssay actives

3 with measured affinity, of 3 total; 3 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
(E)-3-(3,4-dimethoxyphenyl)-1-[4-(5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-ylamino)phenyl]prop-2-en-1-one	2244190: Inhibition of full length human FASTK (355 to 444 residues) extracted from Escherichia coli BL21 (DE3) by Malachite Green dye based assay	ic50	0.1500	uM
(E)-3-(4-chlorophenyl)-1-[4-(5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-ylamino)phenyl]prop-2-en-1-one	2244190: Inhibition of full length human FASTK (355 to 444 residues) extracted from Escherichia coli BL21 (DE3) by Malachite Green dye based assay	ic50	0.1700	uM
(E)-3-phenyl-1-[4-(5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-ylamino)phenyl]prop-2-en-1-one	2244190: Inhibition of full length human FASTK (355 to 444 residues) extracted from Escherichia coli BL21 (DE3) by Malachite Green dye based assay	ic50	0.3200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Air Pollutants	increases abundance, increases expression, affects expression, affects cotreatment	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
tert-Butylhydroperoxide	decreases expression	2
aristolochic acid I	decreases expression	1
4-oxoretinoic acid	decreases expression	1
testosterone enanthate	affects expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
3,4-dihydroxyphenylethanol	increases expression	1
perfluorooctanoic acid	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Alitretinoin	decreases expression	1
Acrolein	increases expression, increases abundance, affects cotreatment	1
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	increases expression	1
Diazinon	increases methylation	1
Fluorouracil	decreases expression	1
Folic Acid	decreases expression	1
Formaldehyde	increases 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
CHEMBL6117360	Binding	Inhibition of full length human FASTK (355 to 444 residues) extracted from Escherichia coli BL21 (DE3) by Malachite Green dye based assay	Thienopyrimidine: A promising scaffold in the development of kinase inhibitors with anticancer activities. — *Bioorg Med Chem*

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1RZ	Abcam HeLa FASTK KO	Cancer cell line	Female
CVCL_SN18	HAP1 FASTK (-) 1	Cancer cell line	Male
CVCL_SN19	HAP1 FASTK (-) 2	Cancer cell line	Male
CVCL_SN20	HAP1 FASTK (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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