ABRA

Summary

ABRA (actin binding Rho activating protein, HGNC:30655) is a protein-coding gene on chromosome 8q23.1, encoding Actin-binding Rho-activating protein (Q8N0Z2). Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling.

Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization; positive regulation of Rho protein signal transduction; and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of DNA-templated transcription and protein import into nucleus. Located in plasma membrane.

Source: NCBI Gene 137735 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 84 total — 3 pathogenic
• MANE Select transcript: NM_139166

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30655
Approved symbol	ABRA
Name	actin binding Rho activating protein
Location	8q23.1
Locus type	gene with protein product
Status	Approved
Aliases	STARS
Ensembl gene	ENSG00000174429
Ensembl biotype	protein_coding
OMIM	609747
Entrez	137735

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000311955, ENST00000910664

RefSeq mRNA: 1 — MANE Select: NM_139166 NM_139166

CCDS: CCDS6305

Canonical transcript exons

ENST00000311955 — 2 exons

Exon	Start	End
ENSE00001207130	106769523	106770244
ENSE00001217002	106759483	106761514

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 99.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.4948 / max 281.2727, expressed in 91 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94361	1.4138	87
94360	0.0810	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.56	gold quality
biceps brachii	UBERON:0001507	98.55	gold quality
quadriceps femoris	UBERON:0001377	98.54	gold quality
vastus lateralis	UBERON:0001379	98.52	gold quality
deltoid	UBERON:0001476	98.38	gold quality
skeletal muscle tissue	UBERON:0001134	98.19	gold quality
heart right ventricle	UBERON:0002080	97.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.04	gold quality
gastrocnemius	UBERON:0001388	95.79	gold quality
skeletal muscle organ	UBERON:0014892	94.88	gold quality
muscle of leg	UBERON:0001383	94.15	gold quality
myocardium	UBERON:0002349	93.73	gold quality
muscle tissue	UBERON:0002385	92.66	gold quality
body of tongue	UBERON:0011876	91.12	gold quality
cardiac atrium	UBERON:0002081	87.18	gold quality
right atrium auricular region	UBERON:0006631	87.15	gold quality
vena cava	UBERON:0004087	87.11	gold quality
cardiac ventricle	UBERON:0002082	86.20	gold quality
heart left ventricle	UBERON:0002084	86.02	gold quality
tongue	UBERON:0001723	84.02	gold quality
heart	UBERON:0000948	83.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.51	gold quality
apex of heart	UBERON:0002098	77.43	gold quality
superior surface of tongue	UBERON:0007371	71.67	gold quality
saphenous vein	UBERON:0007318	70.29	gold quality
mucosa of stomach	UBERON:0001199	67.55	gold quality
popliteal artery	UBERON:0002250	67.35	gold quality
tibial artery	UBERON:0007610	67.25	gold quality
sperm	CL:0000019	66.52	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.24

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2, MEF2A

miRNA regulators (miRDB)

83 targeting ABRA, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-202-3P	99.84	71.41	1290

Literature-anchored findings (GeneRIF, showing 9)

• STARS activates serum response factor by inducing the nuclear translocation of myocardin-related transcription factors . (PMID:15798203)
• Modulates the responsiveness of the heart to stress signaling by functioning as a cytoskeletal intermediary between human and transgenic myocyte enhancer factor-2 and serum response factor. (PMID:17415416)
• STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy (PMID:19255118)
• STARS signalling pathway is upregulated in response to acute endurance exercise and suggest suggest a novel role co-ordination of PGC-1alpha-induced upregulation of the fat oxidative gene, CPT-1beta. (PMID:21486805)
• These results show that resistance exercise provides an acute stimulation of the STARS pathway that is contraction mode dependent. (PMID:23753523)
• These results suggest a connection between Ca(2+)-signaling via excitation-contraction coupling and the regulation of STARS-mediated gene expression in muscles. (PMID:27132186)
• we established that miR-628-5p, a miRNA regulated by age and exercise, binds to the STARS 3’UTR to directly downregulate its transcription (PMID:27739650)
• STARS expression is acutely upregulated following exercise, but there is no cumulative effect to long-term training. (PMID:29504288)
• Isogenic human pluripotent stem cell disease models reveal ABRA deficiency underlies cTnT mutation-induced familial dilated cardiomyopathy. (PMID:33884582)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	abrab	ENSDARG00000033854
mus_musculus	Abra	ENSMUSG00000042895
rattus_norvegicus	Abra	ENSRNOG00000007999
drosophila_melanogaster	CG3630	FBGN0023540
drosophila_melanogaster	CG2113	FBGN0035384
caenorhabditis_elegans		WBGENE00007897
caenorhabditis_elegans		WBGENE00008659
caenorhabditis_elegans		WBGENE00008660
caenorhabditis_elegans	F36F2.1	WBGENE00009475
caenorhabditis_elegans		WBGENE00015193
caenorhabditis_elegans		WBGENE00018548
caenorhabditis_elegans		WBGENE00018575
caenorhabditis_elegans		WBGENE00019950
caenorhabditis_elegans		WBGENE00021288
caenorhabditis_elegans		WBGENE00021579

Protein

Protein identifiers

Actin-binding Rho-activating protein — Q8N0Z2 (reviewed: Q8N0Z2)

Alternative names: Striated muscle activator of Rho-dependent signaling

All UniProt accessions (1): Q8N0Z2

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an activator of serum response factor (SRF)-dependent transcription possibly by inducing nuclear translocation of MKL1 or MKL2 and through a mechanism requiring Rho-actin signaling.

Subunit / interactions. Binds F-actin and ABLIM1, ABLIM2 and ABLIM3. Interaction with ABLIM2 and ABLIM3 enhances activity.

Subcellular location. Cytoplasm. Myofibril. Sarcomere. Cytoskeleton.

Domain organisation. The actin-binding domain 1 (ABD1) is intrinsically disordered, and binds to F-actin with higher affinity than ABD2.

RefSeq proteins (1): NP_631905* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026111	Abra	Family
IPR027817	Costars_dom	Domain
IPR038095	Costars_sf	Homologous_superfamily

Pfam: PF14705

UniProt features (12 total): region of interest 6, compositionally biased region 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N0Z2-F1	67.14	0.25

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): 156, 188

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 71 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, RORA1_01, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, TGACCTY_ERR1_Q2, MEF2_02, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_NUCLEAR_TRANSPORT, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_ACTIN_BINDING, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (7): transcription by RNA polymerase II (GO:0006366), protein import into nucleus (GO:0006606), actin cytoskeleton organization (GO:0030036), positive regulation of Rho protein signal transduction (GO:0035025), positive regulation of transcription by RNA polymerase II (GO:0045944), protein transport (GO:0015031), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (2): actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), sarcomere (GO:0030017), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), myofibril (GO:0030016)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
cellular anatomical structure	2
intracellular protein transport	1
protein localization to nucleus	1
import into nucleus	1
establishment of protein localization to organelle	1
cytoskeleton organization	1
actin filament-based process	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cytoskeletal protein binding	1
binding	1
membrane	1
cell periphery	1
cytoskeleton	1
myofibril	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
contractile muscle fiber	1

Protein interactions and networks

STRING

608 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABRA	ABLIM3	O94929	942
ABRA	ABLIM2	Q6H8Q1	941
ABRA	ABLIM1	O14639	853
ABRA	SRF	P11831	666
ABRA	PRDX3	P30048	553
ABRA	MRTFB	Q9ULH7	533
ABRA	ZNG1F	Q4V339	413
ABRA	MRTFA	Q969V6	387
ABRA	TXNRD1	Q16881	382
ABRA	ABRACL	Q9P1F3	372
ABRA	GOSR1	O95249	357
ABRA	PRDX2	P31945	356
ABRA	FOXO3	O43524	356
ABRA	ITGB1BP2	Q9UKP3	350
ABRA	C6orf163	Q5TEZ5	348

IntAct

8 interactions, top by confidence:

A	B	Type	Score
PPP1R18	ABRA	psi-mi:“MI:0915”(physical association)	0.560
MYC		psi-mi:“MI:0914”(association)	0.350
ABRA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ABRA	SPTBN2	psi-mi:“MI:0914”(association)	0.350
PPP1R18	ABRA	psi-mi:“MI:0915”(physical association)	0.000
TRAPPC2	ABRA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): ABRA (Two-hybrid), ABRA (Two-hybrid), FLII (Affinity Capture-MS), TMOD1 (Affinity Capture-MS), ADD2 (Affinity Capture-MS), BTRC (Affinity Capture-MS), FBXO34 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), CAPZB (Affinity Capture-MS), TMOD2 (Affinity Capture-MS), ACTR10 (Affinity Capture-MS), ACTB (Affinity Capture-MS), MYO1B (Affinity Capture-MS), SVIL (Affinity Capture-MS), DCTN4 (Affinity Capture-MS)

ESM2 similar proteins: A0A097I2D0, A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PPW3, A0A1W2PQ09, A0A1W2PR64, A0A1W2PRV1, A6NLC8, F4HR03, O54825, O75461, P0C1H6, P0CV38, P0DMV1, P0DMV2, P0DW11, P0DW12, P0DW13, P0DW14, P40914, P49585, P49906, P81195, Q0MTC0, Q13895, Q15544, Q2N2K6, Q3SZB8, Q5DJT8, Q5RA91, Q5U1X0, Q6CER9, Q6RG77, Q6XL73, Q75DE4, Q7XHR2, Q7Z2G1, Q80WL2

Diamond homologs: A2XKU9, A4IHJ3, A7RHL5, A9NK39, B4YYA9, B5SNZ6, B5X8A5, Q3ZBN0, Q498C5, Q4KML4, Q558Y7, Q6AVK1, Q6TGV7, Q6V289, Q8BUZ1, Q8K4K7, Q8LBN7, Q8N0Z2, Q9P1F3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	76
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
144641	GRCh38/hg38 8q22.3-23.1(chr8:101884819-107356143)x1	Pathogenic
149076	GRCh38/hg38 8q22.3-23.1(chr8:101171263-109127664)x1	Pathogenic
57335	GRCh38/hg38 8q22.3-23.1(chr8:105053530-107803535)x1	Pathogenic

SpliceAI

370 predictions. Top by Δscore:

Variant	Effect	Δscore
8:106761513:CC:C	acceptor_gain	1.0000
8:106761514:CC:C	acceptor_gain	1.0000
8:106769521:A:AC	donor_gain	1.0000
8:106769522:C:CC	donor_gain	1.0000
8:106761512:ACCC:A	acceptor_loss	0.9900
8:106761515:C:CG	acceptor_loss	0.9900
8:106761515:C:T	acceptor_gain	0.9900
8:106769522:CT:C	donor_gain	0.9900
8:106769522:CTG:C	donor_gain	0.9900
8:106769522:CTGG:C	donor_gain	0.9900
8:106761510:TTACC:T	acceptor_gain	0.9800
8:106761511:TACC:T	acceptor_gain	0.9800
8:106761512:ACC:A	acceptor_gain	0.9800
8:106761513:CCC:C	acceptor_gain	0.9800
8:106761515:C:CC	acceptor_gain	0.9800
8:106769518:CTT:C	donor_loss	0.9800
8:106769519:T:TC	donor_loss	0.9800
8:106769520:TACTG:T	donor_loss	0.9800
8:106769521:ACT:A	donor_loss	0.9800
8:106769522:CTGGG:C	donor_gain	0.9800
8:106769549:G:T	donor_gain	0.9800
8:106769515:TCAC:T	donor_loss	0.9700
8:106769518:CTTA:C	donor_gain	0.9600
8:106769571:T:TA	donor_gain	0.9600
8:106761520:G:C	acceptor_gain	0.9500
8:106761520:G:GC	acceptor_gain	0.9500
8:106765294:T:TA	donor_gain	0.9500
8:106763765:C:G	acceptor_gain	0.9400
8:106769557:C:CT	donor_gain	0.9300
8:106769558:C:CT	donor_gain	0.9300

AlphaMissense

2515 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:106761376:A:C	F269L	0.997
8:106761376:A:T	F269L	0.997
8:106761378:A:G	F269L	0.997
8:106761097:A:C	F362L	0.996
8:106761097:A:T	F362L	0.996
8:106761099:A:G	F362L	0.996
8:106761172:A:C	F337L	0.996
8:106761172:A:T	F337L	0.996
8:106761174:A:G	F337L	0.996
8:106761184:A:C	F333L	0.996
8:106761184:A:T	F333L	0.996
8:106761186:A:G	F333L	0.996
8:106761388:G:C	F265L	0.996
8:106761388:G:T	F265L	0.996
8:106761390:A:G	F265L	0.996
8:106761146:T:A	K346I	0.994
8:106761081:A:G	W368R	0.993
8:106761081:A:T	W368R	0.993
8:106761118:C:A	R355S	0.993
8:106761118:C:G	R355S	0.993
8:106761119:C:G	R355T	0.993
8:106761122:G:T	A354D	0.993
8:106761131:A:T	L351H	0.993
8:106761079:C:A	W368C	0.992
8:106761079:C:G	W368C	0.992
8:106761053:A:C	I377S	0.991
8:106761119:C:A	R355M	0.991
8:106761176:A:G	L336P	0.991
8:106761053:A:T	I377N	0.990
8:106761098:A:G	F362S	0.990

dbSNP variants (sampled 300 via entrez): RS1000096862 (8:106771002 A>G), RS1000521681 (8:106760757 A>C), RS1000727099 (8:106772109 T>C), RS1000851991 (8:106765053 C>A), RS1001212417 (8:106771895 G>T), RS1001281990 (8:106771545 C>T), RS1001282944 (8:106764700 G>T), RS1001388905 (8:106765676 T>C), RS1002434500 (8:106770696 T>C), RS1002738990 (8:106769604 T>C), RS1002761820 (8:106769279 G>A), RS1002836921 (8:106762170 C>T), RS1003241995 (8:106760295 T>C), RS1003321134 (8:106761830 G>A), RS1003647154 (8:106762644 C>A,T)

Disease associations

OMIM: gene MIM:609747 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001786_8	Dental caries	4.000000e-06
GCST002949_25	Epilepsy and lamotrigine-induced maculopapular eruptions	5.000000e-07
GCST006394_18	Intraocular pressure	4.000000e-08
GCST006394_71	Intraocular pressure	1.000000e-16
GCST009391_1673	Metabolite levels	9.000000e-06
GCST009725_22	Intraocular pressure	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:1001253	maculopapular eruption
EFO:0004695	intraocular pressure measurement
EFO:0010470	carnosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression, increases expression, affects expression	4
aristolochic acid I	increases expression	1
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases expression	1
Etoposide	increases expression	1
Folic Acid	decreases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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