ACTBL2

Summary

ACTBL2 (actin beta like 2, HGNC:17780) is a protein-coding gene on chromosome 5q11.2, encoding Beta-actin-like protein 2 (Q562R1). Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Predicted to enable protein kinase binding activity. Predicted to be a structural constituent of postsynaptic actin cytoskeleton. Predicted to be involved in axonogenesis and cell motility. Located in extracellular exosome and obsolete extracellular space.

Source: NCBI Gene 345651 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 77 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.62 (unconstrained)
• MANE Select transcript: NM_001017992
• Notable: 77 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17780
Approved symbol	ACTBL2
Name	actin beta like 2
Location	5q11.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686D0972
Ensembl gene	ENSG00000169067
Ensembl biotype	protein_coding
OMIM	614835
Entrez	345651

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000423391

ENST00000423391

RefSeq mRNA: 1 — MANE Select: NM_001017992 NM_001017992

CCDS: CCDS34163

Canonical transcript exons

ENST00000423391 — 1 exons

Exon	Start	End
ENSE00001649584	57480018	57482811

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 49.52.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3435 / max 18.5201, expressed in 139 samples.

Highest expression (Bgee): cortical plate, islet of Langerhans, olfactory segment of nasal mucosa, placenta, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACTBL2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.4e-09	-0.33	5:57442302:T:G
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-02	-0.16	5:58268066:G:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
61764	0.2800	113
61763	0.0635	32

Top tissues by expression

showing 100 of 120 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	49.52	gold quality
islet of Langerhans	UBERON:0000006	45.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	43.81	gold quality
placenta	UBERON:0001987	41.47	gold quality
gastrocnemius	UBERON:0001388	41.45	silver quality
ganglionic eminence	UBERON:0004023	40.71	gold quality
muscle of leg	UBERON:0001383	40.58	silver quality
skeletal muscle tissue	UBERON:0001134	40.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.72	gold quality
muscle tissue	UBERON:0002385	38.40	gold quality
vermiform appendix	UBERON:0001154	38.00	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
minor salivary gland	UBERON:0001830	36.93	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
saliva-secreting gland	UBERON:0001044	36.23	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
granulocyte	CL:0000094	36.13	gold quality
apex of heart	UBERON:0002098	34.92	gold quality
pancreas	UBERON:0001264	34.05	gold quality
tonsil	UBERON:0002372	33.62	gold quality
smooth muscle tissue	UBERON:0001135	32.42	gold quality
descending thoracic aorta	UBERON:0002345	32.26	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
liver	UBERON:0002107	31.37	gold quality
left uterine tube	UBERON:0001303	31.03	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
gall bladder	UBERON:0002110	30.90	gold quality
tibial artery	UBERON:0007610	30.64	gold quality
popliteal artery	UBERON:0002250	30.62	gold quality
skin of abdomen	UBERON:0001416	30.48	gold quality
cortex of kidney	UBERON:0001225	30.39	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
kidney	UBERON:0002113	29.43	gold quality
prefrontal cortex	UBERON:0000451	29.37	gold quality
zone of skin	UBERON:0000014	29.14	gold quality
metanephros cortex	UBERON:0010533	28.78	silver quality
blood	UBERON:0000178	28.47	gold quality
stomach	UBERON:0000945	28.46	gold quality
adult mammalian kidney	UBERON:0000082	28.26	gold quality
body of stomach	UBERON:0001161	28.23	gold quality
skin of leg	UBERON:0001511	28.18	gold quality
duodenum	UBERON:0002114	28.14	gold quality
muscle layer of sigmoid colon	UBERON:0035805	28.06	gold quality
thoracic mammary gland	UBERON:0005200	27.83	gold quality
lymph node	UBERON:0000029	27.57	gold quality
thoracic aorta	UBERON:0001515	27.57	gold quality
leukocyte	CL:0000738	27.49	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	27.49	gold quality
ascending aorta	UBERON:0001496	27.41	gold quality
primary visual cortex	UBERON:0002436	27.35	gold quality
right lobe of liver	UBERON:0001114	27.29	gold quality
right lobe of thyroid gland	UBERON:0001119	27.16	gold quality
myometrium	UBERON:0001296	27.09	gold quality
lower esophagus muscularis layer	UBERON:0035833	26.97	gold quality
calcaneal tendon	UBERON:0003701	26.95	gold quality
lower esophagus	UBERON:0013473	26.95	gold quality
monocyte	CL:0000576	26.89	gold quality
right coronary artery	UBERON:0001625	26.57	gold quality
left lobe of thyroid gland	UBERON:0001120	26.55	silver quality
left coronary artery	UBERON:0001626	26.42	gold quality
multicellular organism	UBERON:0000468	26.30	gold quality
colon	UBERON:0001155	25.99	gold quality
left ovary	UBERON:0002119	25.95	gold quality
uterine cervix	UBERON:0000002	25.85	gold quality
ovary	UBERON:0000992	25.80	gold quality
endometrium	UBERON:0001295	25.39	gold quality
intestine	UBERON:0000160	25.21	gold quality
esophagus	UBERON:0001043	25.20	gold quality
body of uterus	UBERON:0009853	25.14	gold quality
prostate gland	UBERON:0002367	24.69	gold quality
frontal cortex	UBERON:0001870	24.58	gold quality
right lung	UBERON:0002167	24.21	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
fallopian tube	UBERON:0003889	24.08	silver quality
adipose tissue	UBERON:0001013	24.07	gold quality
endocervix	UBERON:0000458	23.27	gold quality
small intestine	UBERON:0002108	23.09	gold quality
esophagus mucosa	UBERON:0002469	23.04	gold quality
adrenal gland	UBERON:0002369	22.93	gold quality
left adrenal gland cortex	UBERON:0035825	22.82	gold quality
transverse colon	UBERON:0001157	22.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	22.49	gold quality
right ovary	UBERON:0002118	22.32	gold quality
rectum	UBERON:0001052	22.22	gold quality
ectocervix	UBERON:0012249	22.16	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
cerebral cortex	UBERON:0000956	21.83	gold quality
left testis	UBERON:0004533	21.64	gold quality
right adrenal gland cortex	UBERON:0035827	21.56	gold quality
left adrenal gland	UBERON:0001234	21.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	21.39	gold quality
right adrenal gland	UBERON:0001233	21.14	gold quality
fundus of stomach	UBERON:0001160	21.03	gold quality
adrenal tissue	UBERON:0018303	20.96	gold quality
tibial nerve	UBERON:0001323	20.88	gold quality
vagina	UBERON:0000996	20.65	gold quality
brain	UBERON:0000955	20.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	20.43	gold quality
hypothalamus	UBERON:0001898	20.18	gold quality
amygdala	UBERON:0001876	20.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.79

HPA expression

RNA tissue specificity: Not detected

15 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cervix	tissue	0.2	not detected
Basal ganglia	tissue	0.1	not detected
Spinal cord	tissue	0.1
Corpus callosum	tissue	0.1
Skin 1	tissue	0.0	medium
Lymph node	tissue	0.0	low
Rectum	tissue	0.0	high
Smooth muscle	tissue	0.0	low
Colon	tissue	0.0	high
Spleen	tissue	0.0	low
Small intestine	tissue	0.0	high
Duodenum	tissue	0.0	high
Bone marrow	tissue	0.0	low
Tonsil	tissue	0.0	low
Appendix	tissue	0.0	high

Brain sub-regions (HPA Brain Atlas): detected in 2; highest nTPM — Dorsal spinal cord (0.1), White matter (0.1).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KDM5B

miRNA regulators (miRDB)

Targeting ACTBL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 73 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-944	99.82	70.85	3042

Functional genomics

gnomAD constraint: pLI 1.98e-12, LOEUF 1.62, missense Z -0.114 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000423391 — one region, missense o/e 1.08.

Literature-anchored findings (GeneRIF, showing 5)

• -actin is downregulated in the corneal stroma of patients with KC, which may be related to reduced levels of a stabilizing factor (HuR) for beta-actin mRNA. (PMID:22562506)
• Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). (PMID:27378695)
• identified a novel protein, ACTBL2, which was demonstrated to be upregulated in colorectal cancer (PMID:27989943)
• The origin of the expressed retrotransposed gene ACTBL2 and its influence on human melanoma cells’ motility and focal adhesion formation. (PMID:33558623)
• Characterization and prognostic impact of ACTBL2-positive tumor-infiltrating leukocytes in epithelial ovarian cancer. (PMID:38114558)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Actbl2	ENSMUSG00000055194
rattus_norvegicus	Actbl2	ENSRNOG00000043292

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTRT1 (ENSG00000123165), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2444552) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	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
Caenorhabditis briggsae	Q61WW9	95.5%	Diamond
Caenorhabditis elegans	Q9N4I0	95.5%	Diamond
Acanthamoeba castellanii	P53490	75.6%	Diamond
Dictyostelium discoideum	Q54L54	57.9%	Diamond
Schizosaccharomyces pombe 972h-	Q9P7X7	50.0%	Diamond
Yarrowia lipolytica CLIB122	Q6C982	38.5%	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
RMEL3	ncRNA	102724122
GPBP1	protein-coding	65056
LNCBRM	ncRNA	100996645
LINC02225	ncRNA	101928539

Protein

Protein identifiers

Beta-actin-like protein 2 — Q562R1 (reviewed: Q562R1)

Alternative names: Kappa-actin

All UniProt accessions (1): Q562R1

UniProt curated annotations — full annotation on UniProt →

Function. Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.

Subunit / interactions. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with PFN1 and PFDN1.

Subcellular location. Cytoplasm. Cytoskeleton.

Post-translational modifications. Oxidation of Met-45 and Met-48 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization. Monomethylation at Lys-85 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.

Miscellaneous. In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.

Similarity. Belongs to the actin family.

RefSeq proteins (1): NP_001017992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR004001	Actin_CS	Conserved_site
IPR020902	Actin/actin-like_CS	Conserved_site
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

UniProt features (7 total): sequence conflict 4, modified residue 2, chain 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q562R1-F1	94.97	0.92

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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)

Type	Positions
Methionine (r)-sulfoxide	45, 48

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 63 (showing top): GOBP_NEUROGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, GOCC_H4_HISTONE_ACETYLTRANSFERASE_COMPLEX, GOCC_TRANSFERASE_COMPLEX, chr5q11, GOCC_SYNAPSE, MARSON_BOUND_BY_FOXP3_STIMULATED, GOCC_AXON, GOMF_KINASE_BINDING, GOMF_STRUCTURAL_CONSTITUENT_OF_CYTOSKELETON, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK

GO Biological Process (3): axonogenesis (GO:0007409), cell motility (GO:0048870), postsynaptic actin cytoskeleton organization (GO:0098974)

GO Molecular Function (5): ATP binding (GO:0005524), protein kinase binding (GO:0019901), structural constituent of postsynaptic actin cytoskeleton (GO:0098973), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): cytoplasm (GO:0005737), actin filament (GO:0005884), actin cytoskeleton (GO:0015629), membrane (GO:0016020), axon (GO:0030424), NuA4 histone acetyltransferase complex (GO:0035267), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), cytoskeleton (GO:0005856), synapse (GO:0045202)

GO top-level categories

28 GO namespaces:

Category	Terms
cellular anatomical structure	2
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
cellular process	1
actin cytoskeleton organization	1
postsynaptic cytoskeleton organization	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
kinase binding	1
structural constituent of cytoskeleton	1
postsynaptic actin cytoskeleton	1
postsynaptic actin cytoskeleton organization	1
structural constituent of postsynapse	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
neuron projection	1
H4/H2A histone acetyltransferase complex	1
extracellular vesicle	1
synapse	1
intracellular membraneless organelle	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 19 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,682 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTBL2	PFDN2	Q9UHV9	796
ACTBL2	PFDN1	O60925	772
ACTBL2	PFN1	P07737	572
ACTBL2	DYNC1H1	Q14204	386
ACTBL2	OR13C3	Q8NGS6	358
ACTBL2	COL6A6	A6NMZ7	357
ACTBL2	FAM78B	Q5VT40	356
ACTBL2	MARCKSL1	P49006	327
ACTBL2	PHB2	Q99623	314
ACTBL2	MYH9	P35579	312
ACTBL2	TUFM	P49411	304
ACTBL2	GSN	P06396	302
ACTBL2	DDX39A	O00148	299
ACTBL2	WFDC9	Q8NEX5	283
ACTBL2	POTED	Q86YR6	280

IntAct

Human interaction partners of ACTBL2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

17 partners by confidence:

Partner	Interaction type	MIscore	Records
CEP97	physical association	0.610	2
SRD5A1	physical association	0.590	2
POTEF	association	0.530	3
HIPK2	physical association	0.400	2
LIMA1	physical association	0.400	1
OPN1LW	physical association	0.400	1
PPP1R1B	physical association	0.400	1
SLC13A1	physical association	0.400	1
SOX4	physical association	0.400	1
ZNF185	physical association	0.400	1
CLDN18	association	0.350	2
SLC30A6	association	0.350	2
BTN1A1	association	0.350	1
CCDC34	association	0.350	1
CCDC90B	association	0.350	1
DCTN3	association	0.350	1
NOX4	association	0.350	1

BioGRID (478 interactions; top human partners by supporting records): ACTB (Proximity Label-MS; 7 records), ACTA2 (Affinity Capture-MS; 6 records), ACTA1 (Cross-Linking-MS (XL-MS); 5 records), ACTG1 (Cross-Linking-MS (XL-MS); 5 records), ACTC1 (Affinity Capture-MS; 4 records), PARK2 (Affinity Capture-MS; 4 records), CAP1 (Affinity Capture-MS; 3 records), CCT3 (Affinity Capture-MS; 3 records), CFL1 (Affinity Capture-MS; 3 records), DBN1 (Affinity Capture-MS; 3 records), LRRC20 (Affinity Capture-MS; 3 records), MTSS1 (Affinity Capture-Western; 3 records), PNMA1 (Affinity Capture-MS; 3 records), RC3H2 (Affinity Capture-MS; 3 records), SLC25A11 (Affinity Capture-MS; 3 records)

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
Spliceosome, E complex	129	RBM17, DDX39A, GEMIN2, NCBP2, PRPF31, SART3, SF3A2, SNRPA, SRSF7, DDX39B, DHX15, GEMIN5, SCAF4, SMARCB1, SNRPD3, SYNCRIP, U2AF2, HNRNPC, SF3B2, SMARCC2, SFSWAP, USP39, GEMIN6, HNRNPK, RBM42, SF3B1, SF3B4, SNRPG, SRSF6, BCAS2, SMN1, CPSF7, SMARCE1, SRSF8, ARID1A, LSM4, SNRPC, CHD8, FUS, SNRNP70, SRSF11, NUDT21, PBRM1, SNRPB2, SNRPD1, YBX1, SF1, SNRPD2, SRSF2, SRSF5, PPIH, SRSF3, DDX20, SART1, SRSF1, SRSF4, PRPF19, RBM39, RBMXL2, SREK1, PRPF3, SMARCA2, U2AF1, SF3B6, SMARCA1, CPSF1, DDX23, DHX9, RUVBL1, SNRPF, SRRM2, ALYREF, HNRNPA0, HNRNPH1, PCBP2, RBM10, SF3B3, STRAP, HNRNPR, RBM25, ACTBL2, CHERP, SNRPA1, ACTL6A, DDX46, HNRNPL, RBM7, CPSF6, ARID2, DNAJC8, EFTUD2, KHSRP, RUVBL2, SMARCA4, PCBP1, SNRNP40, SNRPE, PRPF4, PRPF8, SF3A1, SF3A3, SNRNP200, ZCCHC8, DDX5, LUC7L3, SMARCC1, HNRNPA2B1, HNRNPD, HTATSF1, LUC7L2, PHF5A, PRPF6, SMARCD1, SNRPB, GEMIN8, U2SURP, NCBP1, GEMIN4, HNRNPU, MTREX, ARID1B, CHD4, HNRNPM, PRPF40A, HNRNPF, SRRT, DDX17, HNRNPA1, PUF60
★ TIP60-C complex	23	TRRAP, DMAP1, H2AZ2, H2BC18, MORF4L2, RUVBL2, EP400, EPC1, H2AC20, KAT5, TUBB, YEATS4, ACTL6A, BRD8, MEAF6, MORF4L1, MRGBP, RUVBL1, VPS72, ACTBL2, CREB3L2, ING3, MBTD1

Disease & clinical

Genetic variants

Variant evidence for ACTBL2: 77 ClinVar records (4 pathogenic / likely pathogenic); 11 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	70
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
57149	GRCh38/hg38 5q11.1-12.1(chr5:50288355-63149770)x1	Pathogenic	criteria provided, single submitter	1
3062842	GRCh37/hg19 5q11.1-11.2(chr5:49430268-57925870)x1	Likely pathogenic	criteria provided, single submitter	1
144590	GRCh38/hg38 5q11.2-12.1(chr5:56947850-61725401)x3	Pathogenic	no assertion criteria provided	1
148227	GRCh38/hg38 5p13.2-q12.1(chr5:35201559-61903141)x3	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACTBL2’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 1 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 1 predictions of 1):

Position(s)	Effect	Δscore	Sites
5:57481700	donor_gain	0.3200

AlphaMissense

1,275 missense substitutions predicted likely pathogenic (of 2,477 scored), across 311 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
D12	8	0.986	0.995
D155	8	0.964	0.989
F353	8	0.961	0.998
F125	8	0.944	0.992
F263	8	0.924	0.977
D289	8	0.921	0.966
F32	8	0.904	0.989
D287	8	0.868	0.939
D245	8	0.837	0.939
D158	8	0.754	0.889
D26	8	0.716	0.897
W341	7	0.994	0.999
W80	7	0.987	0.998
R313	7	0.964	0.994
F128	7	0.954	0.985
W87	7	0.947	0.998
C375	7	0.910	0.989
F256	7	0.897	0.982
E260	7	0.897	0.963
E108	7	0.879	0.973

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:614835 | disease phenotypes:

GWAS associations

11 associations:

Study	Trait	p-value
GCST008362_178	Birth weight	9e-16
GCST006630_89	Diastolic blood pressure	9e-13
GCST011211_7	Hypertrophic cardiomyopathy	2e-10
GCST011205_12	Hypertrophic cardiomyopathy (MTAG)	4e-9
GCST007094_48	Diastolic blood pressure	3e-8
GCST006530_2	Esophageal adenocarcinoma x smoking interaction	7e-7
GCST002209_3	Orthostatic hypotension	2e-6
GCST008363_41	Offspring birth weight	2e-6
GCST003542_6	Night sleep phenotypes	3e-6
GCST004800_1	Forced expiratory volume in 1 second (environmental tobacco smoke interaction)	4e-6
GCST003542_139	Night sleep phenotypes	5e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0008361	environmental tobacco smoke exposure measurement
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression, affects cotreatment, affects expression, increases abundance	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, decreases methylation	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
2,4,6-tribromophenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment, increases expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tetrabromobisphenol A	decreases expression	1
epigallocatechin gallate	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Benztropine	increases expression	1
Caffeine	increases expression	1
Clozapine	increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Dopamine	decreases expression	1
Furaldehyde	affects cotreatment, increases expression, affects localization, decreases expression	1
Ivermectin	decreases expression	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1

Clinical trials (associated diseases)

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