FASTKD1

Summary

FASTKD1 (FAST kinase domains 1, HGNC:26150) is a protein-coding gene on chromosome 2q31.1, encoding FAST kinase domain-containing protein 1, mitochondrial (Q53R41). Involved in the down-regulation of mitochondrial MT-ND3 mRNA levels which leads to decreased respiratory complex I abundance and activity.

Enables RNA binding activity. Involved in mitochondrial RNA metabolic process and regulation of mitochondrial mRNA stability. Located in mitochondrion and nucleoplasm.

Source: NCBI Gene 79675 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 146 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_024622

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26150
Approved symbol	FASTKD1
Name	FAST kinase domains 1
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21901
Ensembl gene	ENSG00000138399
Ensembl biotype	protein_coding
OMIM	617529
Entrez	79675

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 28 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000417376, ENST00000438035, ENST00000445210, ENST00000453153, ENST00000453929, ENST00000487293, ENST00000488516, ENST00000488951, ENST00000490590, ENST00000495505, ENST00000879632, ENST00000879633, ENST00000879634, ENST00000879635, ENST00000879636, ENST00000879637, ENST00000879638, ENST00000879639, ENST00000879640, ENST00000879641, ENST00000879642, ENST00000879643, ENST00000913270, ENST00000913271, ENST00000913272, ENST00000913273, ENST00000913274, ENST00000913275, ENST00000913276, ENST00000913277, ENST00000913278, ENST00000913279, ENST00000964947

RefSeq mRNA: 5 — MANE Select: NM_024622 NM_001281476, NM_001322046, NM_001322048, NM_001322049, NM_024622

CCDS: CCDS33318, CCDS63051

Canonical transcript exons

ENST00000453153 — 15 exons

Exon	Start	End
ENSE00001391362	169571653	169572171
ENSE00001652687	169573669	169573865
ENSE00001658753	169537227	169537340
ENSE00001664964	169528508	169529926
ENSE00001703416	169557187	169557297
ENSE00001724790	169540051	169540179
ENSE00001729020	169555124	169555255
ENSE00001745563	169546218	169546704
ENSE00001775667	169544721	169544835
ENSE00002174691	169560387	169560785
ENSE00003471815	169538013	169538141
ENSE00003553632	169569184	169569252
ENSE00003564053	169563225	169563350
ENSE00003656107	169531352	169531490
ENSE00003658578	169530587	169530701

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1229 / max 169.1686, expressed in 1704 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31733	6.4776	1500
31735	1.5362	940
31734	1.1091	689

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.27	gold quality
heart right ventricle	UBERON:0002080	97.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.81	gold quality
left ventricle myocardium	UBERON:0006566	96.66	gold quality
colonic mucosa	UBERON:0000317	96.64	gold quality
tongue squamous epithelium	UBERON:0006919	96.33	gold quality
oocyte	CL:0000023	96.27	gold quality
mucosa of transverse colon	UBERON:0004991	96.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.71	gold quality
apex of heart	UBERON:0002098	94.48	gold quality
cardiac ventricle	UBERON:0002082	93.99	gold quality
heart left ventricle	UBERON:0002084	93.89	gold quality
visceral pleura	UBERON:0002401	93.87	gold quality
lower esophagus mucosa	UBERON:0035834	93.58	gold quality
tibia	UBERON:0000979	93.57	gold quality
rectum	UBERON:0001052	93.42	gold quality
jejunum	UBERON:0002115	93.39	gold quality
jejunal mucosa	UBERON:0000399	93.34	gold quality
choroid plexus epithelium	UBERON:0003911	93.24	gold quality
esophagus squamous epithelium	UBERON:0006920	93.21	gold quality
parietal pleura	UBERON:0002400	93.18	gold quality
pleura	UBERON:0000977	92.90	gold quality
primary visual cortex	UBERON:0002436	92.89	gold quality
squamous epithelium	UBERON:0006914	92.73	gold quality
duodenum	UBERON:0002114	92.56	gold quality
hair follicle	UBERON:0002073	92.48	gold quality
diaphragm	UBERON:0001103	92.45	gold quality
body of tongue	UBERON:0011876	92.38	gold quality
cortical plate	UBERON:0005343	92.37	gold quality
middle temporal gyrus	UBERON:0002771	92.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting FASTKD1, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-1227-5P	98.65	65.32	1549

Literature-anchored findings (GeneRIF, showing 2)

• Disruption of FASTKD1 increases ND3 mRNA level. Disrupting FASTKD1 and FASTKD4 decreases ND3 mRNA like depleting FASTKD4 alone. Each RAP domain of FASTK proteins contains a nuclease fold with a conserved aspartate residue at the putative active site. The RAP domain is essential for the function of the FASTK proteins, while the region upstream determines RNA targeting and protein localization. (PMID:28335001)
• Despite the fact that proteins of the FASTK family FASTKD1-5 share the same domains, they exhibit various-sometimes opposing-functions in almost all steps of mitochondrial RNA metabolism. (PMID:29036396)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fastkd1	ENSDARG00000056128
mus_musculus	Fastkd1	ENSMUSG00000027086
rattus_norvegicus	Fastkd1	ENSRNOG00000024335
drosophila_melanogaster	CG31643	FBGN0051643

Paralogs (5): FASTKD2 (ENSG00000118246), FASTKD3 (ENSG00000124279), TBRG4 (ENSG00000136270), FASTK (ENSG00000164896), FASTKD5 (ENSG00000215251)

Protein

Protein identifiers

FAST kinase domain-containing protein 1, mitochondrial — Q53R41 (reviewed: Q53R41)

All UniProt accessions (4): C9JMM4, C9JTP4, E7EW60, Q53R41

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the down-regulation of mitochondrial MT-ND3 mRNA levels which leads to decreased respiratory complex I abundance and activity.

Subcellular location. Mitochondrion.

Tissue specificity. Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in heart.

Domain organisation. The RAP domain is essential to regulate MT-ND3 mRNA levels.

Similarity. Belongs to the FAST kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53R41-1	1	yes
Q53R41-2	2

RefSeq proteins (5): NP_001268405, NP_001308975, NP_001308977, NP_001308978, NP_078898* (*=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

UniProt features (13 total): sequence conflict 5, sequence variant 3, transit peptide 1, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53R41-F1	85.17	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 360

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, ONKEN_UVEAL_MELANOMA_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_MITOCHONDRIAL_RNA_PROCESSING, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP, MODULE_48, MODULE_95, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR

GO Biological Process (3): mitochondrial RNA metabolic process (GO:0000959), mitochondrial RNA processing (GO:0000963), regulation of mitochondrial mRNA stability (GO:0044528)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), ribonucleoprotein granule (GO:0035770)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
RNA metabolic process	1
mitochondrial RNA metabolic process	1
RNA processing	1
mitochondrial gene expression	1
regulation of mRNA stability	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
intracellular membraneless organelle	1
supramolecular complex	1

Protein interactions and networks

STRING

614 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FASTKD1	FASTK	Q14296	749
FASTKD1	TWNK	Q96RR1	586
FASTKD1	FASTKD2	Q9NYY8	554
FASTKD1	TRUB2	O95900	542
FASTKD1	RPUSD3	Q6P087	540
FASTKD1	RPUSD4	Q96CM3	514
FASTKD1	MT-ND6	P03923	506
FASTKD1	PTCD1	O75127	501
FASTKD1	FOXH1	O75593	493
FASTKD1	LRPPRC	P42704	486
FASTKD1	TACO1	Q9BSH4	474
FASTKD1	MTPAP	Q9NVV4	458
FASTKD1	GRSF1	Q12849	448
FASTKD1	CHCHD1	Q96BP2	447
FASTKD1	PRAMEF20	Q5VT98	440

IntAct

163 interactions, top by confidence:

A	B	Type	Score
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
FASTKD1	EIF2S3	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	GFAP	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	GRN	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	HSPA2	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	NEFL	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	P4HB	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	ST13	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
FASTKD1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
HTT	FASTKD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (119): FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P5, A1L2L5, A1Z9A8, B5DF07, O15091, P42704, Q07DV3, Q08CK1, Q0IHP3, Q14C51, Q14CX7, Q14CZ7, Q28C74, Q28DE0, Q2KI62, Q32LU7, Q32N55, Q32PI8, Q3SZ55, Q4R366, Q4R6I5, Q53R41, Q566X6, Q58CX2, Q5R503, Q5R8W8, Q5RFI6, Q5SGE0, Q5XIR8, Q5ZKK3, Q5ZLS8, Q68FN9, Q6AYP3, Q6DI86, Q6GQ66, Q6PB66, Q6QI44, Q7L8L6, Q7TMV3, Q7Z3E5

Diamond homologs: Q28DE0, Q53R41, Q6DI86, Q6GQ66, Q5RFI6, Q7L8L6, Q95KD0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 166 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	10	7.7×	3e-04
G alpha (s) signalling events	9	5.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	7	15.6×	2e-04
cell surface receptor signaling pathway	13	5.5×	3e-04
G protein-coupled receptor signaling pathway	21	5.0×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	112
Likely benign	9
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
548952	NM_024622.6(FASTKD1):c.2230T>A (p.Tyr744Asn)	Pathogenic

SpliceAI

2506 predictions. Top by Δscore:

Variant	Effect	Δscore
2:169530584:TAC:T	donor_loss	1.0000
2:169530585:A:C	donor_loss	1.0000
2:169530586:C:CA	donor_loss	1.0000
2:169530697:CAATC:C	acceptor_gain	1.0000
2:169530700:TC:T	acceptor_gain	1.0000
2:169530700:TCCT:T	acceptor_loss	1.0000
2:169530701:CC:C	acceptor_gain	1.0000
2:169530702:C:CC	acceptor_gain	1.0000
2:169530706:A:C	acceptor_gain	1.0000
2:169531492:T:C	acceptor_gain	1.0000
2:169540049:A:AC	donor_gain	1.0000
2:169540050:C:CC	donor_gain	1.0000
2:169540136:C:CT	acceptor_gain	1.0000
2:169544716:CCTA:C	donor_loss	1.0000
2:169544718:TACCT:T	donor_loss	1.0000
2:169544720:C:G	donor_loss	1.0000
2:169544831:TGGAT:T	acceptor_gain	1.0000
2:169544835:TCTG:T	acceptor_loss	1.0000
2:169544836:C:CA	acceptor_loss	1.0000
2:169544836:C:CC	acceptor_gain	1.0000
2:169544837:T:C	acceptor_loss	1.0000
2:169546333:T:TA	donor_gain	1.0000
2:169546392:T:TA	donor_gain	1.0000
2:169546415:T:TA	donor_gain	1.0000
2:169555118:TCTTA:T	donor_loss	1.0000
2:169555119:CTTA:C	donor_loss	1.0000
2:169555120:TTACC:T	donor_loss	1.0000
2:169555121:TACC:T	donor_loss	1.0000
2:169555122:A:C	donor_loss	1.0000
2:169555161:T:TA	donor_gain	1.0000

AlphaMissense

5613 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:169530621:C:G	R803P	0.982
2:169538049:A:G	W680R	0.977
2:169538049:A:T	W680R	0.977
2:169540079:G:C	F639L	0.975
2:169540079:G:T	F639L	0.975
2:169540081:A:G	F639L	0.975
2:169538044:A:C	F681L	0.974
2:169538044:A:T	F681L	0.974
2:169538046:A:G	F681L	0.974
2:169538089:A:C	N666K	0.973
2:169538089:A:T	N666K	0.973
2:169563287:A:C	S170R	0.973
2:169563287:A:T	S170R	0.973
2:169563289:T:G	S170R	0.973
2:169529911:A:G	W820R	0.972
2:169529911:A:T	W820R	0.972
2:169540091:A:C	F635L	0.970
2:169540091:A:T	F635L	0.970
2:169540093:A:G	F635L	0.970
2:169560647:A:C	F237L	0.967
2:169560647:A:T	F237L	0.967
2:169560649:A:G	F237L	0.967
2:169538093:A:G	L665S	0.963
2:169544797:G:C	F580L	0.963
2:169544797:G:T	F580L	0.963
2:169544799:A:G	F580L	0.963
2:169538081:A:T	V669D	0.960
2:169538047:C:A	W680C	0.959
2:169538047:C:G	W680C	0.959
2:169540135:C:G	A621P	0.954

dbSNP variants (sampled 300 via entrez): RS1000060754 (2:169533896 C>T), RS1000072155 (2:169575676 C>T), RS1000077641 (2:169569708 G>T), RS1000096391 (2:169556552 G>A), RS1000129351 (2:169569960 C>T), RS1000284907 (2:169564525 T>A,C), RS1000348146 (2:169533601 A>G), RS1000423476 (2:169575413 G>A), RS1000440700 (2:169557575 A>T), RS1000466092 (2:169571467 G>A), RS1000471833 (2:169557862 T>C), RS1000480350 (2:169559224 T>C), RS1000493683 (2:169553068 A>G), RS1000688282 (2:169564040 G>T), RS1000722868 (2:169546469 C>T)

Disease associations

OMIM: gene MIM:617529 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066386 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.77	Kd	169.7	nM	CHEMBL5653589
6.77	ED50	169.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148374: Binding affinity to human FASTKD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1696	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	affects expression	1
Hydrogen Peroxide	affects expression	1
Nickel	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Valproic Acid	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651416	Binding	Binding affinity to human FASTKD1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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