AKIRIN1

Summary

AKIRIN1 (akirin 1, HGNC:25744) is a protein-coding gene on chromosome 1p34.3, encoding Akirin-1 (Q9H9L7). Molecular adapter that acts as a bridge between proteins, and which is involved skeletal muscle development. It is a selective cancer dependency (DepMap: 21.9% of cell lines).

Predicted to enable transcription coregulator activity. Predicted to be involved in several processes, including myoblast migration involved in skeletal muscle regeneration; negative regulation of satellite cell differentiation; and positive regulation of lamellipodium assembly. Located in nuclear membrane and nucleoplasm.

Source: NCBI Gene 79647 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 37 total — 1 pathogenic, 1 likely-pathogenic
• Cancer dependency (DepMap): dependent in 21.9% of screened cell lines
• MANE Select transcript: NM_024595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25744
Approved symbol	AKIRIN1
Name	akirin 1
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12666
Ensembl gene	ENSG00000174574
Ensembl biotype	protein_coding
OMIM	615164
Entrez	79647

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000372984, ENST00000432648, ENST00000446189, ENST00000531822, ENST00000876891, ENST00000962555

RefSeq mRNA: 2 — MANE Select: NM_024595 NM_001136275, NM_024595

CCDS: CCDS433, CCDS44113

Canonical transcript exons

ENST00000432648 — 5 exons

Exon	Start	End
ENSE00001198662	39003347	39003418
ENSE00001940036	39004045	39006059
ENSE00002145185	38991276	38991600
ENSE00003264788	38998171	38998311
ENSE00003348344	39000972	39001106

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 98.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.7704 / max 782.4449, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2255	77.7704	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.36	gold quality
male germ cell	CL:0000015	97.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.68	gold quality
right testis	UBERON:0004534	96.62	gold quality
left testis	UBERON:0004533	96.57	gold quality
adult organism	UBERON:0007023	95.42	gold quality
testis	UBERON:0000473	95.40	gold quality
secondary oocyte	CL:0000655	95.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.70	gold quality
monocyte	CL:0000576	94.68	gold quality
mononuclear cell	CL:0000842	94.62	gold quality
leukocyte	CL:0000738	94.58	gold quality
endothelial cell	CL:0000115	94.56	gold quality
spinal cord	UBERON:0002240	94.45	gold quality
islet of Langerhans	UBERON:0000006	94.21	gold quality
ventricular zone	UBERON:0003053	93.82	gold quality
adenohypophysis	UBERON:0002196	93.77	gold quality
smooth muscle tissue	UBERON:0001135	93.44	gold quality
adrenal tissue	UBERON:0018303	93.40	gold quality
rectum	UBERON:0001052	93.36	gold quality
gall bladder	UBERON:0002110	93.26	gold quality
subthalamic nucleus	UBERON:0001906	93.22	gold quality
prefrontal cortex	UBERON:0000451	93.18	gold quality
inferior vagus X ganglion	UBERON:0005363	93.16	gold quality
ganglionic eminence	UBERON:0004023	92.98	gold quality
corpus epididymis	UBERON:0004359	92.95	gold quality
lymph node	UBERON:0000029	92.82	gold quality
pituitary gland	UBERON:0000007	92.79	gold quality
buccal mucosa cell	CL:0002336	92.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	9.74
E-MTAB-6819	no	593.43
E-ENAD-17	no	290.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting AKIRIN1, 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-5193	100.00	67.26	1744
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
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-150-5P	99.99	66.69	1976
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Inspection of external neutrophil transcriptome datasets further support unchanged AKIRIN1 expression in human systemic inflammation. (PMID:31075840)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	akirin1	ENSDARG00000039969
mus_musculus	Akirin1	ENSMUSG00000023075
rattus_norvegicus	Akirin1	ENSRNOG00000026610
drosophila_melanogaster	akirin	FBGN0082598
caenorhabditis_elegans	akir-1	WBGENE00017088

Paralogs (1): AKIRIN2 (ENSG00000135334)

Protein

Protein identifiers

Akirin-1 — Q9H9L7 (reviewed: Q9H9L7)

All UniProt accessions (3): Q9H9L7, B4DQP0, H0YEQ5

UniProt curated annotations — full annotation on UniProt →

Function. Molecular adapter that acts as a bridge between proteins, and which is involved skeletal muscle development. Functions as a signal transducer for MSTN during skeletal muscle regeneration and myogenesis. May regulate chemotaxis of both macrophages and myoblasts by reorganising actin cytoskeleton, leading to more efficient lamellipodia formation via a PI3 kinase dependent pathway. In contrast to AKIRIN2, not involved in nuclear import of proteasomes.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed with the highest expression in heart, liver, placenta and peripheral blood leukocytes.

Miscellaneous. ‘Akiraka ni suru’ means ‘making things clear’ in Japanese. The name is given based on the presence of the clear nuclear localization signal.

Similarity. Belongs to the akirin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H9L7-1	1	yes
Q9H9L7-2	2

RefSeq proteins (2): NP_001129747, NP_078871* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024132	Akirin	Family

UniProt features (12 total): compositionally biased region 3, region of interest 2, short sequence motif 2, modified residue 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9L7-F1	70.03	0.32

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 (2): 22, 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 299 (showing top): ATF_B, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_SKELETAL_MUSCLE_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_REGENERATION, CREBP1_Q2, CAGGTCC_MIR492, GOBP_MUSCLE_CELL_PROLIFERATION, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION

GO Biological Process (7): positive regulation of lamellipodium assembly (GO:0010592), positive regulation of macrophage chemotaxis (GO:0010759), myoblast migration involved in skeletal muscle regeneration (GO:0014839), positive regulation of myoblast differentiation (GO:0045663), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of skeletal muscle satellite cell proliferation (GO:1902723), negative regulation of satellite cell differentiation (GO:1902725)

GO Molecular Function (2): transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear membrane (GO:0031965)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
positive regulation of leukocyte chemotaxis	1
regulation of macrophage chemotaxis	1
macrophage chemotaxis	1
regulation of granulocyte chemotaxis	1
positive regulation of macrophage migration	1
skeletal muscle tissue regeneration	1
myoblast migration	1
myoblast differentiation	1
positive regulation of cell differentiation	1
regulation of myoblast differentiation	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
skeletal muscle satellite cell proliferation	1
regulation of skeletal muscle satellite cell proliferation	1
negative regulation of skeletal muscle cell proliferation	1
skeletal muscle satellite cell differentiation	1
negative regulation of skeletal muscle cell differentiation	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKIRIN1	UHMK1	Q8TAS1	537
AKIRIN1	PRPF40A	O75400	533
AKIRIN1	TMEM239	Q8WW34	485
AKIRIN1	SNRNP200	O75643	464
AKIRIN1	HNRNPA3	P51991	454
AKIRIN1	RBM8A	Q9Y5S9	432
AKIRIN1	DDX17	Q92841	429
AKIRIN1	KHDRBS1	Q07666	425
AKIRIN1	ACIN1	Q9UKV3	418
AKIRIN1	PPIG	Q13427	397
AKIRIN1	GEMIN7	Q9H840	392
AKIRIN1	MSTN	O14793	376
AKIRIN1	PDCD4	Q53EL6	371
AKIRIN1	YIPF4	Q9BSR8	363
AKIRIN1	LMTK3	Q96Q04	344

IntAct

17 interactions, top by confidence:

A	B	Type	Score
PSMA5	PSMA7	psi-mi:“MI:0914”(association)	0.800
PSMB3	PSMD11	psi-mi:“MI:0914”(association)	0.640
AKIRIN1	GOPC	psi-mi:“MI:0915”(physical association)	0.560
GOPC	AKIRIN1	psi-mi:“MI:0915”(physical association)	0.560
RAN	NEMP2	psi-mi:“MI:0914”(association)	0.530
AKIRIN2	RGPD3	psi-mi:“MI:0914”(association)	0.530
PSMB9	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSMA2	PSMD11	psi-mi:“MI:0914”(association)	0.530
AKIRIN2	RGPD8	psi-mi:“MI:0914”(association)	0.530
USP7	AKIRIN1	psi-mi:“MI:0407”(direct interaction)	0.440
PSMA6	PSMD1	psi-mi:“MI:0914”(association)	0.350
PSMB7	PSMD1	psi-mi:“MI:0914”(association)	0.350
RNF181	CHEK1	psi-mi:“MI:0914”(association)	0.350
AKIRIN2	HSPG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): AKIRIN1 (Two-hybrid), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-RNA), AKIRIN1 (Affinity Capture-RNA), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), AKIRIN1 (Affinity Capture-MS), HNRNPF (Affinity Capture-MS)

ESM2 similar proteins: A0A287BDC1, A8YXY8, B1AXD8, B3F209, B3KU38, B5DF41, O00287, O14503, O15079, O35185, O54972, P03966, P04198, P12755, P18444, P26014, Q0D2I5, Q25C79, Q2KJ58, Q3MHV6, Q3UR85, Q50H33, Q53H80, Q5BL57, Q5EA15, Q5FWN7, Q5RAI7, Q60591, Q60698, Q61976, Q63379, Q68FF7, Q6GQB5, Q6ZWB6, Q7ZY70, Q8BXL9, Q8CEG5, Q8CI08, Q8N228, Q8ND83

Diamond homologs: A0A287BDC1, A8YXY8, B1AXD8, Q25C79, Q53H80, Q5BL57, Q5FWN7, Q6GQB5, Q7ZY70, Q99LF1, Q9H9L7, Q9VS59, Q966L3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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
Antigen processing: Ub, ATP-independent proteasomal degradation	7	266.5×	2e-15
Cross-presentation of soluble exogenous antigens (endosomes)	9	152.3×	6e-17
Regulation of activated PAK-2p34 by proteasome mediated degradation	8	148.6×	2e-15
Regulation of ornithine decarboxylase (ODC)	8	145.0×	2e-15
Vpu mediated degradation of CD4	8	141.6×	2e-15
Autodegradation of the E3 ubiquitin ligase COP1	8	141.6×	2e-15
Ubiquitin-dependent degradation of Cyclin D	8	141.6×	2e-15
Vif-mediated degradation of APOBEC3G	8	135.3×	2e-15

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	9	26.1×	2e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	27
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
59934	GRCh38/hg38 1p34.3-34.2(chr1:38108665-42327551)x1	Pathogenic
1526937	GRCh37/hg19 1p34.3-34.2(chr1:38679545-42556292)	Likely pathogenic

SpliceAI

614 predictions. Top by Δscore:

Variant	Effect	Δscore
1:38991629:G:GT	donor_gain	1.0000
1:38998169:A:AG	acceptor_gain	1.0000
1:38998170:G:GG	acceptor_gain	1.0000
1:38998170:GA:G	acceptor_gain	1.0000
1:38998170:GAGCA:G	acceptor_gain	1.0000
1:39001102:AGCAG:A	donor_loss	1.0000
1:39001104:CAGG:C	donor_loss	1.0000
1:39001105:AGG:A	donor_loss	1.0000
1:39001106:GGTA:G	donor_loss	1.0000
1:39001108:T:A	donor_loss	1.0000
1:39003345:A:AG	acceptor_gain	1.0000
1:39003346:G:GG	acceptor_gain	1.0000
1:39003346:GAACA:G	acceptor_gain	1.0000
1:39004044:GAT:G	acceptor_gain	1.0000
1:38991598:CGGG:C	donor_loss	0.9900
1:38991599:GG:G	donor_gain	0.9900
1:38991600:GG:G	donor_gain	0.9900
1:38991600:GGTA:G	donor_loss	0.9900
1:38991602:T:G	donor_loss	0.9900
1:38998167:TTAGA:T	acceptor_gain	0.9900
1:38998168:TAGA:T	acceptor_gain	0.9900
1:38998169:AGAG:A	acceptor_gain	0.9900
1:38998170:GAGC:G	acceptor_gain	0.9900
1:39000968:CCA:C	acceptor_loss	0.9900
1:39000969:CAGGT:C	acceptor_loss	0.9900
1:39000970:A:AG	acceptor_gain	0.9900
1:39000970:AGGTT:A	acceptor_loss	0.9900
1:39000971:G:GG	acceptor_gain	0.9900
1:39000971:G:GT	acceptor_loss	0.9900
1:39001103:GCAG:G	donor_gain	0.9900

AlphaMissense

1237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:39001005:T:C	F132S	1.000
1:39001089:T:C	L160P	1.000
1:39001101:T:C	L164P	1.000
1:39003350:A:C	Q167P	1.000
1:39003361:T:C	F171L	1.000
1:39003363:T:A	F171L	1.000
1:39003363:T:G	F171L	1.000
1:39003370:T:C	F174L	1.000
1:39003371:T:C	F174S	1.000
1:39003371:T:G	F174C	1.000
1:39003372:C:A	F174L	1.000
1:39003372:C:G	F174L	1.000
1:39003383:A:C	Q178P	1.000
1:38991387:T:C	C3R	0.999
1:38991388:G:A	C3Y	0.999
1:38991391:G:A	G4E	0.999
1:38991400:T:A	L7Q	0.999
1:38991400:T:C	L7P	0.999
1:38991404:G:C	K8N	0.999
1:38991404:G:T	K8N	0.999
1:38991417:T:C	F13L	0.999
1:38991419:C:A	F13L	0.999
1:38991419:C:G	F13L	0.999
1:39001031:T:C	C141R	0.999
1:39001032:G:A	C141Y	0.999
1:39001041:T:C	L144P	0.999
1:39001068:G:C	R153P	0.999
1:39001076:T:C	Y156H	0.999
1:39001076:T:G	Y156D	0.999
1:39001089:T:A	L160H	0.999

dbSNP variants (sampled 300 via entrez): RS1000015835 (1:38997032 G>T), RS1000620110 (1:38990093 CA>C), RS1000827724 (1:38994453 T>A,C,G), RS1001049762 (1:38989826 G>A,T), RS1001262162 (1:39002025 A>C,G), RS1001646764 (1:39005787 A>G), RS1001712763 (1:38991890 T>A,C), RS1001945306 (1:38994189 C>G), RS1002015925 (1:38991709 C>T), RS1002466098 (1:38993046 A>G,T), RS1002549839 (1:39004959 C>T), RS1002654594 (1:39004426 G>A), RS1002893452 (1:38989520 C>T), RS1003030967 (1:38998795 A>G), RS1003824167 (1:39000610 A>G)

Disease associations

OMIM: gene MIM:615164 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003475_2	Beard thickness	8.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
uranyl acetate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
torcetrapib	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Uranium	increases expression	1
Zinc	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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