ACTRT1

Summary

ACTRT1 (actin related protein T1, HGNC:24027) is a protein-coding gene on chromosome Xq25, encoding Actin-related protein T1 (Q8TDG2). Negatively regulates the Hedgehog (SHH) signaling.

This gene encodes a protein related to the cytoskeletal protein beta-actin. This protein is a major component of the calyx in the perinuclear theca of mammalian sperm heads, and it therefore likely functions in spermatid formation. This gene is intronless and is similar to a related gene located on chromosome 1. A related pseudogene has also been identified approximately 75 kb downstream of this gene on chromosome X.

Source: NCBI Gene 139741 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 87 total — 11 pathogenic
• MANE Select transcript: NM_138289

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24027
Approved symbol	ACTRT1
Name	actin related protein T1
Location	Xq25
Locus type	gene with protein product
Status	Approved
Aliases	AIP1, KIAA0705, ARIP1, Arp-T1
Ensembl gene	ENSG00000123165
Ensembl biotype	protein_coding
OMIM	300487
Entrez	139741

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000371124

RefSeq mRNA: 1 — MANE Select: NM_138289 NM_138289

CCDS: CCDS14611

Canonical transcript exons

ENST00000371124 — 1 exons

Exon	Start	End
ENSE00001454396	128050962	128052403

Expression profiles

Bgee: expression breadth tissue_specific, 5 present calls, max score 91.30.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.30	gold quality
right testis	UBERON:0004534	61.80	gold quality
testis	UBERON:0000473	61.57	gold quality
left testis	UBERON:0004533	61.32	gold quality
granulocyte	CL:0000094	38.78	gold quality
bone marrow cell	CL:0002092	38.12	gold quality
sural nerve	UBERON:0015488	37.54	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
primary visual cortex	UBERON:0002436	30.55	gold quality
prefrontal cortex	UBERON:0000451	30.26	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.59	gold quality
gall bladder	UBERON:0002110	28.68	gold quality
tonsil	UBERON:0002372	28.64	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	28.00	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.35	gold quality
islet of Langerhans	UBERON:0000006	27.29	gold quality
frontal cortex	UBERON:0001870	27.27	gold quality
urinary bladder	UBERON:0001255	26.79	gold quality
blood	UBERON:0000178	26.46	gold quality
fundus of stomach	UBERON:0001160	26.44	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.32

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
GLI1	Repression

miRNA regulators (miRDB)

3 targeting ACTRT1, 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-5197-5P	99.64	69.08	1494
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-6730-3P	97.03	67.54	889

Literature-anchored findings (GeneRIF, showing 4)

• Describes the discovery of two actin-related proteins as major components in a cytoskeletal, nonmotile structure of bull spermatozoa, suggesting that certain members of this family of proteins may serve functions other than nucleation of actin filaments. (PMID:12243744)
• Study identified mutations in the ACTRT1 gene, which encodes actin-related protein T1 (ARP-T1), in two of the six families with Bazex-Dupre-Christol syndrome (BDCS) that were examined in this study. ARP-T1 was found to directly bind to the GLI1 promoter, thus inhibiting GLI1 expression, and loss of ARP-T1 led to activation of the Hedgehog pathway in individuals with BDCS. (PMID:28869610)
• ARP-T1-associated Bazex-Dupre-Christol syndrome is an inherited basal cell cancer with ciliary defects characteristic of ciliopathies. (PMID:33972689)
• Deletion of ACTRT1 is associated with male infertility as sperm acrosomal ultrastructural defects and fertilization failure in human. (PMID:38414365)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Actrt1	ENSMUSG00000046615
rattus_norvegicus	Actrt1	ENSRNOG00000003456

Paralogs (26): ACTR6 (ENSG00000075089), ACTB (ENSG00000075624), ACTL6B (ENSG00000077080), ACTR5 (ENSG00000101442), ACTR3C (ENSG00000106526), ACTA2 (ENSG00000107796), ACTR8 (ENSG00000113812), ACTR1B (ENSG00000115073), ACTR3 (ENSG00000115091), ACTL8 (ENSG00000117148), ACTR10 (ENSG00000131966), ACTR3B (ENSG00000133627), ACTL6A (ENSG00000136518), ACTR2 (ENSG00000138071), ACTR1A (ENSG00000138107), ACTA1 (ENSG00000143632), ACTL7B (ENSG00000148156), ACTC1 (ENSG00000159251), ACTG2 (ENSG00000163017), ACTBL2 (ENSG00000169067), ACTRT2 (ENSG00000169717), ACTL9 (ENSG00000181786), ACTG1 (ENSG00000184009), ACTRT3 (ENSG00000184378), ACTL7A (ENSG00000187003), ACTL10 (ENSG00000288649)

Protein

Protein identifiers

Actin-related protein T1 — Q8TDG2 (reviewed: Q8TDG2)

All UniProt accessions (1): Q8TDG2

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates the Hedgehog (SHH) signaling. Binds to the promoter of the SHH signaling mediator, GLI1, and inhibits its expression.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. In skin, expressed in the basal, spinous and granular layers of the epidermis. Also expressed in hair follicles, sebaceaous glands, eccrine sweat glands and semen.

Disease relevance. Mutations and insertions in the coding sequence or in regulatory non-coding elements of this gene may be associated with Bazex syndrome; a cancer-prone genodermatosis with an X-linked dominant inheritance pattern.

Similarity. Belongs to the actin family.

RefSeq proteins (1): NP_612146* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004000	Actin	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00022

UniProt features (6 total): sequence conflict 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDG2-F1	92.94	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): GNF2_RTN1, GCM_MAP4K4, GCM_PTPRD, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_SMOOTHENED_SIGNALING_PATHWAY, RFX1_02, GCM_CALM1, GCM_MAPK10, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, GCM_PTK2, GOMF_CHROMATIN_BINDING, GOCC_SECRETORY_VESICLE, GOCC_ACROSOMAL_VESICLE, GOMF_STRUCTURAL_CONSTITUENT_OF_CYTOSKELETON

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), regulation of smoothened signaling pathway (GO:0008589), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (1): chromatin binding (GO:0003682)

GO Cellular Component (6): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), cytoplasm (GO:0005737), actin cytoskeleton (GO:0015629), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
smoothened signaling pathway	1
regulation of signal transduction	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
binding	1
secretory granule	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoskeleton	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1919 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACTRT1	TCP11X2	Q5H9J9	620
ACTRT1	PRR32	B1ATL7	523
ACTRT1	CTTN	Q14247	488
ACTRT1	HCLS1	P14317	485
ACTRT1	CCIN	Q13939	482
ACTRT1	ACTRT2	Q8TDY3	449
ACTRT1	SPATA46	Q5T0L3	432
ACTRT1	SPANXN4	Q5MJ08	397
ACTRT1	H2AB3	P0C5Z0	355
ACTRT1	GMCL2	Q8NEA9	353
ACTRT1	HUS1B	Q8NHY5	353
ACTRT1	PDCL2	Q8N4E4	343
ACTRT1	DCAF12L1	Q5VU92	324
ACTRT1	SPACA5B	Q96QH8	320
ACTRT1	ASB17	Q8WXJ9	315

IntAct

9 interactions, top by confidence:

A	B	Type	Score
Calml3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PDLIM7	TPM1	psi-mi:“MI:0914”(association)	0.350
PPP1CB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
GAK	PARP10	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ACTRT1	CCT6A	psi-mi:“MI:0914”(association)	0.350
ACTRT1	TCP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (17): ACTRT1 (Affinity Capture-MS), ACTRT1 (Affinity Capture-MS), ACTRT1 (Affinity Capture-MS), ACTRT1 (Affinity Capture-MS), ACTRT1 (Affinity Capture-MS), PDCL3 (Affinity Capture-MS), USP8 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), SERPINB9 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT6A (Affinity Capture-MS), TCP1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNU3, A2AKE7, A6H603, A6QQ74, D3ZBP4, F1MH07, O43542, Q149M9, Q2T9W4, Q2TA43, Q2V057, Q32KZ2, Q32L91, Q3ZBE0, Q49HH9, Q49KI5, Q4QR76, Q4R317, Q4R6Q3, Q4R821, Q5JWF8, Q5REQ1, Q5XIK1, Q641W9, Q643R3, Q68FW7, Q6AY16, Q6NVG1, Q76HM9, Q86U10, Q8CG27, Q8K4F6, Q8TC94, Q8TDG2, Q8TDY3, Q8TDZ2, Q8VCZ9, Q8VDP3, Q8VEI3, Q95JK8

Diamond homologs: A2WKK5, A2XLF2, A2XNS1, A2ZP58, A3C6D7, D0LWX4, O16808, O18499, O65314, O65315, O65316, O81221, P02576, P04751, P07828, P07830, P07836, P07837, P08023, P0C539, P0C540, P0C542, P0CJ46, P0CJ47, P10981, P12716, P12717, P17126, P17304, P18601, P23343, P24902, P30162, P30164, P30165, P30167, P30168, P30169, P30171, P30172

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	0
Uncertain significance	63
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
145170	GRCh38/hg38 Xq25(chrX:123859097-128717147)x3	Pathogenic
149087	GRCh38/hg38 Xq23-27.1(chrX:117260292-140201321)x3	Pathogenic
149544	GRCh38/hg38 Xq22.3-28(chrX:106465610-156003242)x1	Pathogenic
1526848	GRCh37/hg19 Xq25-26.2(chrX:126307810-131646710)	Pathogenic
208017	NC_000023.11:g.(?126549383)(129592556_?)del	Pathogenic
4076045	GRCh37/hg19 Xq24-26.2(chrX:118228490-133002510)x3	Pathogenic
564888	GRCh37/hg19 Xq24-27.1(chrX:117998704-140159954)x3	Pathogenic
564891	GRCh37/hg19 Xq24-27.1(chrX:120777368-139345946)x1	Pathogenic
564898	GRCh37/hg19 Xq25-26.3(chrX:126759247-135790885)x1	Pathogenic
816382	GRCh37/hg19 Xq24-26.1(chrX:117119895-129850963)x2	Pathogenic
980319	GRCh37/hg19 Xq24-26.1(chrX:117120780-129850994)x3	Pathogenic

SpliceAI

83 predictions. Top by Δscore:

Variant	Effect	Δscore
X:128052156:ACC:A	acceptor_gain	0.5700
X:128052158:CAT:C	acceptor_gain	0.5500
X:128052157:C:A	acceptor_gain	0.5100
X:128052153:T:TA	acceptor_gain	0.4300
X:128051590:A:AC	acceptor_gain	0.4200
X:128052154:G:GT	acceptor_gain	0.4200
X:128052236:C:CT	acceptor_gain	0.4200
X:128052155:A:AA	acceptor_gain	0.4000
X:128052237:A:T	acceptor_gain	0.3700
X:128051228:GAGTA:G	donor_loss	0.3600
X:128051229:AGTAC:A	donor_loss	0.3600
X:128051230:GTA:G	donor_loss	0.3600
X:128051231:TA:T	donor_loss	0.3600
X:128051232:A:AT	donor_loss	0.3600
X:128051233:C:CT	donor_loss	0.3600
X:128051405:G:C	donor_gain	0.3600
X:128051581:T:C	acceptor_gain	0.3600
X:128051234:C:G	donor_loss	0.3500
X:128051580:CT:C	acceptor_gain	0.3500
X:128051581:TT:T	acceptor_gain	0.3500
X:128052175:G:GT	acceptor_gain	0.3500
X:128052257:CGTCA:C	donor_gain	0.3500
X:128051186:A:C	acceptor_gain	0.3400
X:128051257:T:TA	donor_gain	0.3400
X:128052184:TC:T	acceptor_gain	0.3400
X:128052236:C:T	acceptor_gain	0.3400
X:128052257:CGT:C	donor_gain	0.3400
X:128051741:C:CT	donor_gain	0.3300
X:128051181:A:T	acceptor_gain	0.3100
X:128051184:CCA:C	acceptor_gain	0.3100

AlphaMissense

2473 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:128051186:A:G	W341R	0.977
X:128051186:A:T	W341R	0.977
X:128051559:T:A	K216N	0.976
X:128051559:T:G	K216N	0.976
X:128051733:A:C	S158R	0.976
X:128051733:A:T	S158R	0.976
X:128051735:T:G	S158R	0.976
X:128052141:T:A	K22N	0.975
X:128052141:T:G	K22N	0.975
X:128051361:G:C	S282R	0.970
X:128051361:G:T	S282R	0.970
X:128051363:T:G	S282R	0.970
X:128051138:A:G	W357R	0.963
X:128051138:A:T	W357R	0.963
X:128051148:G:C	F353L	0.962
X:128051148:G:T	F353L	0.962
X:128051150:A:G	F353L	0.962
X:128051826:A:C	F127L	0.962
X:128051826:A:T	F127L	0.962
X:128051828:A:G	F127L	0.962
X:128051179:C:T	G343D	0.958
X:128051942:A:G	W89R	0.953
X:128051942:A:T	W89R	0.953
X:128051632:A:G	L192P	0.949
X:128051079:A:C	F376L	0.946
X:128051079:A:T	F376L	0.946
X:128051081:A:G	F376L	0.946
X:128051707:G:T	P167H	0.945
X:128051266:A:G	L314P	0.944
X:128051749:C:T	G153D	0.944

dbSNP variants (sampled 300 via entrez): RS1000763724 (X:128050538 A>G), RS1000974791 (X:128050972 A>G), RS1002844271 (X:128052385 T>G), RS1003105812 (X:128054344 G>A), RS1006593521 (X:128053422 G>C), RS1006950887 (X:128053885 C>A), RS1009383485 (X:128051024 C>A,T), RS1009435775 (X:128050583 C>T), RS1010008434 (X:128054342 T>A), RS1011060006 (X:128053097 T>C), RS1013836072 (X:128052877 T>C), RS1013908376 (X:128052443 G>A), RS1016188894 (X:128052135 G>A,C), RS1016568477 (X:128053904 G>A,T), RS1017264649 (X:128053477 C>G,T)

Disease associations

OMIM: gene MIM:300487 | disease phenotypes: MIM:309000

GenCC curated gene-disease

Mondo (1): oculocerebrorenal syndrome (MONDO:0010645)

Orphanet (2): Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Oculocerebrorenal syndrome of Lowe (Orphanet:534)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST007095_120	Systolic blood pressure	2.000000e-08
GCST007095_121	Systolic blood pressure	8.000000e-08
GCST007097_157	Pulse pressure	7.000000e-08
GCST007097_158	Pulse pressure	2.000000e-07
GCST012310_26	Schizophrenia x sex interaction	7.000000e-06
GCST012310_27	Schizophrenia x sex interaction	9.000000e-06
GCST012311_5	Schizophrenia x sex interaction	7.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009800	Oculocerebrorenal Syndrome	C10.228.140.163.100.640; C12.050.351.968.419.815.720; C12.200.777.419.815.720; C12.950.419.815.720; C16.131.077.662; C16.320.322.750; C16.320.565.151.600; C16.320.565.189.640; C16.320.709; C16.320.831.750; C18.452.132.100.640; C18.452.648.151.600; C18.452.648.189.640

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07410455	PHASE2	NOT_YET_RECRUITING	An Open-label, Phase 2 Pilot Study on the Efficacy and Safety of Piclidenoson in Patients With Lowe Syndrome
NCT00359515	Not specified	COMPLETED	Genetic Analysis of Oculocerebrorenal Syndrome of Lowe
NCT01314560	Not specified	COMPLETED	Study of the Pathophysiological Mechanisms Involved in Bleeding Events
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases