GAS2L1

Summary

GAS2L1 (growth arrest specific 2 like 1, HGNC:16955) is a protein-coding gene on chromosome 22q12.2, encoding GAS2-like protein 1 (Q99501). Involved in the cross-linking of microtubules and microfilaments.

This gene encodes a member of the growth arrest-specific 2 protein family. This protein binds components of the cytoskeleton and may be involved in mediating interactions between microtubules and microfilaments. This protein localizes to the proximal end of mature centrioles and links centrosomes to both microtubules and actin. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 9.

Source: NCBI Gene 10634 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001362985

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16955
Approved symbol	GAS2L1
Name	growth arrest specific 2 like 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	GAR22
Ensembl gene	ENSG00000185340
Ensembl biotype	protein_coding
OMIM	602128
Entrez	10634

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 retained_intron

ENST00000406549, ENST00000416823, ENST00000428622, ENST00000487341, ENST00000491016, ENST00000610653, ENST00000611648, ENST00000616432, ENST00000618518, ENST00000621062, ENST00000882335, ENST00000882336, ENST00000882337, ENST00000882338, ENST00000882339, ENST00000882340, ENST00000882341, ENST00000911504, ENST00000911505, ENST00000911506, ENST00000911507, ENST00000911508, ENST00000911509, ENST00000952246

RefSeq mRNA: 6 — MANE Select: NM_001362985 NM_001278730, NM_001362985, NM_001395196, NM_001395197, NM_006478, NM_152236

CCDS: CCDS63438, CCDS74840

Canonical transcript exons

ENST00000616432 — 6 exons

Exon	Start	End
ENSE00001294416	29310439	29310546
ENSE00001299975	29308087	29308738
ENSE00001387553	29310827	29310998
ENSE00003607387	29310638	29310734
ENSE00003978193	29311462	29312787
ENSE00003978194	29306650	29307153

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 95.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4594 / max 107.6414, expressed in 1662 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191603	8.7507	1644
191601	0.6808	367
191602	0.0279	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	95.98	gold quality
gingival epithelium	UBERON:0001949	95.73	gold quality
tendon of biceps brachii	UBERON:0008188	95.73	gold quality
seminal vesicle	UBERON:0000998	95.16	gold quality
endothelial cell	CL:0000115	95.14	gold quality
CA1 field of hippocampus	UBERON:0003881	95.12	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.95	gold quality
gingiva	UBERON:0001828	94.88	gold quality
olfactory bulb	UBERON:0002264	94.27	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.98	gold quality
primary visual cortex	UBERON:0002436	93.53	gold quality
parotid gland	UBERON:0001831	93.51	gold quality
skin of hip	UBERON:0001554	93.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.17	gold quality
lateral globus pallidus	UBERON:0002476	93.04	gold quality
cingulate cortex	UBERON:0003027	92.99	gold quality
right frontal lobe	UBERON:0002810	92.98	gold quality
anterior cingulate cortex	UBERON:0009835	92.94	gold quality
right testis	UBERON:0004534	92.90	gold quality
mammalian vulva	UBERON:0000997	92.81	gold quality
occipital lobe	UBERON:0002021	92.75	gold quality
apex of heart	UBERON:0002098	92.74	gold quality
male germ cell	CL:0000015	92.70	gold quality
upper leg skin	UBERON:0004262	92.48	gold quality
nipple	UBERON:0002030	92.40	gold quality
sperm	CL:0000019	92.21	gold quality
left testis	UBERON:0004533	92.18	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.06	gold quality
putamen	UBERON:0001874	92.05	gold quality
entorhinal cortex	UBERON:0002728	92.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	186.57
E-ANND-3	yes	6.18

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
GATA2	Repression
KIT	Repression

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

9 targeting GAS2L1, 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-7152-3P	99.97	67.47	849
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-4717-5P	98.19	67.97	894

Literature-anchored findings (GeneRIF, showing 6)

• The beta isoforms of hGAR17 and hGAR22 appear to be able to crosslink microtubules and microfilaments (PMID:12584248)
• T3-induced genes identified basic transcription element binding protein 1/Kruppel-like factor 9 (BTEB1/KLF9) and GAR22 as TR target genes (PMID:19375645)
• There was no significant difference in the frequency six marker haplotype in the GAS2L1 gene between the cases of schizophreina and controls. (PMID:20537721)
• GAS2L1 and GAS2L2 are differentially involved in mediating the crosstalk between F-actin and microtubules. (PMID:24706950)
• This work reveals a GAS2L1-mediated centriole-tethering mechanism of microtubules and actin, which provide the forces required for centrosome dynamics and separation. (PMID:28017616)
• Nek2-mediated GAS2L1 phosphorylation and centrosome-linker disassembly induce centrosome disjunction. (PMID:32289147)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gas2l1	ENSDARG00000078803
mus_musculus	Gas2l1	ENSMUSG00000034201
rattus_norvegicus	Gas2l1	ENSRNOG00000009040
drosophila_melanogaster	pigs	FBGN0029881

Paralogs (7): ASPM (ENSG00000066279), MICALL1 (ENSG00000100139), EHBP1 (ENSG00000115504), GAS2 (ENSG00000148935), MICALL2 (ENSG00000164877), EHBP1L1 (ENSG00000173442), SMTNL1 (ENSG00000214872)

Protein

Protein identifiers

GAS2-like protein 1 — Q99501 (reviewed: Q99501)

Alternative names: GAS2-related protein on chromosome 22, Growth arrest-specific protein 2-like 1

All UniProt accessions (5): A0A384P5D0, A0A5E8, C9JFI0, C9JRR6, Q99501

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the cross-linking of microtubules and microfilaments. Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers.

Subunit / interactions. Interacts with MAPRE1.

Subcellular location. Cytoplasm. Cytoskeleton. Stress fiber.

Similarity. Belongs to the GAS2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99501-1	1, Beta	yes
Q99501-2	2, Alpha
Q99501-3	3
Q99501-4	4

RefSeq proteins (6): NP_001265659, NP_001349914, NP_001382125, NP_001382126, NP_006469, NP_689422 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR003108	GAR_dom	Domain
IPR036534	GAR_dom_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily

Pfam: PF00307, PF02187

UniProt features (47 total): modified residue 20, compositionally biased region 11, splice variant 4, region of interest 3, sequence conflict 3, domain 2, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99501-F1	60.82	0.22

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 (20): 2, 193, 306, 316, 334, 352, 355, 391, 394, 436, 438, 479, 486, 487, 490, 492, 498, 504, 633, 657

Mutagenesis-validated functional residues (1):

Position	Phenotype
647–648	loss of microtubule-end localization and microtubule plus-end tracking. decreases mapre1 binding.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): GGGACCA_MIR133A_MIR133B, ELVIDGE_HYPOXIA_DN, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, BILD_SRC_ONCOGENIC_SIGNATURE, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_MICROTUBULE_DEPOLYMERIZATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ACTIN_FILAMENT_ORGANIZATION, ACATTCC_MIR1_MIR206, GOBP_MICROTUBULE_BUNDLE_FORMATION, NRF2_Q4, MAGRANGEAS_MULTIPLE_MYELOMA_IGLL_VS_IGLK_DN

GO Biological Process (6): microtubule bundle formation (GO:0001578), negative regulation of microtubule depolymerization (GO:0007026), cellular response to starvation (GO:0009267), regulation of microtubule polymerization or depolymerization (GO:0031110), actin crosslink formation (GO:0051764), protein localization to microtubule plus-end (GO:1904825)

GO Molecular Function (4): microtubule binding (GO:0008017), cytoskeletal adaptor activity (GO:0008093), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (6): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874), actin filament (GO:0005884), microtubule plus-end (GO:0035371)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
polymeric cytoskeletal fiber	2
microtubule cytoskeleton organization	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
microtubule polymerization or depolymerization	1
regulation of microtubule cytoskeleton organization	1
actin filament organization	1
protein localization to microtubule end	1
tubulin binding	1
cytoskeletal protein binding	1
protein-macromolecule adaptor activity	1
actin binding	1
protein-containing complex binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1
microtubule cytoskeleton	1
actin cytoskeleton	1
microtubule end	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GAS2L1	RASL10A	Q92737	922
GAS2L1	AP1B1	P78436	852
GAS2L1	LIPI	Q6XZB0	761
GAS2L1	SPA17	Q15506	695
GAS2L1	EWSR1	Q01844	684
GAS2L1	LRRC45	Q96CN5	606
GAS2L1	ASCC2	Q9H1I8	601
GAS2L1	PLEC	Q15149	590
GAS2L1	CROCC	Q5TZA2	581
GAS2L1	PTK2B	Q14289	497
GAS2L1	KLHDC1	Q8N7A1	496
GAS2L1	CNTLN	Q9NXG0	491
GAS2L1	CTDSPL2	Q05D32	477
GAS2L1	CDK5RAP2	Q96SN8	471
GAS2L1	MRPS5	P82675	446

IntAct

23 interactions, top by confidence:

A	B	Type	Score
PRMT8	SYNCRIP	psi-mi:“MI:0914”(association)	0.830
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
GPSM2	GAS2L1	psi-mi:“MI:0915”(physical association)	0.560
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
POT1	GAS2L1	psi-mi:“MI:0915”(physical association)	0.370
Racgap1	DDX3X	psi-mi:“MI:0914”(association)	0.350
Smad3		psi-mi:“MI:0914”(association)	0.350
MYO19	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Actb		psi-mi:“MI:0914”(association)	0.350
RTEL1-TNFRSF6B	FAM13A	psi-mi:“MI:0914”(association)	0.350
MAPRE1	CTNNB1	psi-mi:“MI:0914”(association)	0.350
Myh9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Mapre1	TPM1	psi-mi:“MI:0914”(association)	0.350
CAPZA2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
IQGAP1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PPP1CB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GAS2L1	GSN	psi-mi:“MI:0914”(association)	0.350
GAS2L1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
SH3KBP1	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
GAS2L1	GPSM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (89): MAPRE1 (Affinity Capture-MS), MAPRE3 (Affinity Capture-MS), NXN (Affinity Capture-MS), SNX5 (Affinity Capture-MS), EPN1 (Affinity Capture-MS), SH3KBP1 (Affinity Capture-MS), DIS3 (Affinity Capture-MS), USP7 (Affinity Capture-MS), CCNB1 (Affinity Capture-MS), GSN (Affinity Capture-MS), WDR45B (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), RBM12 (Affinity Capture-MS), NAGK (Affinity Capture-MS), PLCG1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA5, A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A0JNN8, A2ARS0, A2VDX9, A5PJP1, A6NGB7, A8MVW0, C9JTQ0, O14511, O14559, O35392, O35569, O43541, O60548, O70220, P0DPE3, Q08102, Q14V87, Q19A40, Q29RK8, Q2HJ59, Q3TYP4, Q5BLP8, Q5T442, Q63244, Q6F5E0, Q6QNY0, Q6VUP9, Q80WY3, Q80XF7, Q8BQU6, Q8K025, Q8K071, Q8TD94, Q8WY41, Q8WZ71

Diamond homologs: A0A1L8H8C0, A0A1L8HFX9, D3ZHV2, D3ZUE1, O43903, O94854, P11862, Q03001, Q3UWW6, Q5SSG4, Q69ZZ9, Q86XJ1, Q8JZP9, Q8NHY3, Q91ZU6, Q99501, Q9QXZ0, Q9UPN3, Q9W3Y4

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NEK2	“up-regulates activity”	GAS2L1	phosphorylation
GAS2L1	up-regulates	F-actin_assembly

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1118 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29308735:GCTG:G	donor_gain	1.0000
22:29310430:T:TA	acceptor_gain	1.0000
22:29310732:CTGG:C	donor_loss	1.0000
22:29310733:TGGT:T	donor_loss	1.0000
22:29310735:G:GG	donor_gain	1.0000
22:29310824:CA:C	acceptor_loss	1.0000
22:29310825:A:AG	acceptor_gain	1.0000
22:29310826:G:GT	acceptor_gain	1.0000
22:29310826:GCT:G	acceptor_gain	1.0000
22:29310826:GCTC:G	acceptor_gain	1.0000
22:29308737:TGG:T	donor_loss	0.9900
22:29308738:GGTGA:G	donor_loss	0.9900
22:29308739:G:GG	donor_gain	0.9900
22:29308739:GT:G	donor_loss	0.9900
22:29308740:TGAGT:T	donor_loss	0.9900
22:29308741:GA:G	donor_loss	0.9900
22:29310431:G:A	acceptor_gain	0.9900
22:29310434:CTCAG:C	acceptor_loss	0.9900
22:29310435:TCA:T	acceptor_loss	0.9900
22:29310436:CAG:C	acceptor_loss	0.9900
22:29310438:GGTGA:G	acceptor_gain	0.9900
22:29310504:G:GT	donor_gain	0.9900
22:29310504:G:T	donor_gain	0.9900
22:29310543:GCGG:G	donor_gain	0.9900
22:29310544:CGGGT:C	donor_loss	0.9900
22:29310545:GG:G	donor_gain	0.9900
22:29310545:GGGT:G	donor_loss	0.9900
22:29310546:GG:G	donor_gain	0.9900
22:29310546:GGTAA:G	donor_loss	0.9900
22:29310547:G:GG	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000414742 (22:29306977 C>T), RS1000858612 (22:29305810 G>A,C,T), RS1001024675 (22:29305774 G>A), RS1001076924 (22:29306074 C>A,T), RS1001423787 (22:29310892 C>A), RS1001554088 (22:29307927 C>A,T), RS1001630912 (22:29306792 A>T), RS1001910549 (22:29305302 C>T), RS1001977037 (22:29306663 G>A), RS1002362999 (22:29305655 C>G,T), RS1002370543 (22:29310253 A>C,G,T), RS1002764846 (22:29309320 G>A,T), RS1003634868 (22:29309256 G>A), RS1003760124 (22:29309562 A>C,G), RS1004644698 (22:29310258 T>A,G)

Disease associations

OMIM: gene MIM:602128 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002553_2	Pancreatic cancer	1.000000e-08
GCST009391_1429	Metabolite levels	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010408	triacylglycerol 50:1 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	4
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Cyclosporine	decreases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
arsenite	decreases methylation	1
cupric chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
jinfukang	increases reaction, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects cotreatment, affects expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, affects expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	increases reaction, increases expression	1
Copper	affects binding, decreases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Hydrogen Peroxide	affects expression	1

Clinical trials (associated diseases)

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