ARL9

Summary

ARL9 (ARF like GTPase 9, HGNC:23592) is a protein-coding gene on chromosome 4q12, encoding ADP-ribosylation factor-like protein 9 (Q6T311).

ARL9 is a member of the small GTPase protein family with a high degree of similarity to ARF (MIM 103180) proteins of the RAS superfamily.

Source: NCBI Gene 132946 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001363794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23592
Approved symbol	ARL9
Name	ARF like GTPase 9
Location	4q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196503
Ensembl biotype	protein_coding
OMIM	612405
Entrez	132946

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000360096, ENST00000640821, ENST00000645327, ENST00000915214, ENST00000948253

RefSeq mRNA: 6 — MANE Select: NM_001363794 NM_001363794, NM_001401357, NM_001401358, NM_001401359, NM_001401361, NM_206919

CCDS: CCDS59474, CCDS87224

Canonical transcript exons

ENST00000640821 — 4 exons

Exon	Start	End
ENSE00001399890	56518678	56518853
ENSE00003805982	56505791	56506141
ENSE00003809252	56511185	56511347
ENSE00003829566	56523697	56524453

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 81.06.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6309 / max 27.0525, expressed in 284 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47737	0.4084	201
47738	0.2225	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	81.06	gold quality
ganglionic eminence	UBERON:0004023	78.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.12	gold quality
sperm	CL:0000019	77.63	gold quality
left testis	UBERON:0004533	75.49	gold quality
right testis	UBERON:0004534	75.39	gold quality
testis	UBERON:0000473	74.07	gold quality
ventricular zone	UBERON:0003053	72.82	gold quality
smooth muscle tissue	UBERON:0001135	68.97	gold quality
buccal mucosa cell	CL:0002336	66.78	silver quality
prefrontal cortex	UBERON:0000451	65.89	gold quality
right frontal lobe	UBERON:0002810	65.32	gold quality
nucleus accumbens	UBERON:0001882	65.08	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.75	gold quality
anterior cingulate cortex	UBERON:0009835	64.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	63.98	gold quality
hypothalamus	UBERON:0001898	63.63	gold quality
neocortex	UBERON:0001950	63.54	gold quality
gall bladder	UBERON:0002110	63.51	gold quality
primary visual cortex	UBERON:0002436	63.20	gold quality
frontal cortex	UBERON:0001870	62.77	gold quality
caudate nucleus	UBERON:0001873	62.41	gold quality
amygdala	UBERON:0001876	62.18	gold quality
putamen	UBERON:0001874	62.00	gold quality
skin of leg	UBERON:0001511	61.68	gold quality
gingival epithelium	UBERON:0001949	61.62	gold quality
islet of Langerhans	UBERON:0000006	61.59	gold quality
cerebral cortex	UBERON:0000956	61.57	gold quality
ectocervix	UBERON:0012249	61.51	gold quality
right adrenal gland cortex	UBERON:0035827	61.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.98

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• Prognostic significance of ARL9 and its methylation in low-grade glioma. (PMID:32882327)
• ARL9 is upregulated and serves as a biomarker for a poor prognosis in colon adenocarcinoma. (PMID:36823542)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	arl9	ENSDARG00000071881
mus_musculus	Arl9	ENSMUSG00000063820
rattus_norvegicus	Arl9	ENSRNOG00000029628

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

ADP-ribosylation factor-like protein 9 — Q6T311 (reviewed: Q6T311)

All UniProt accessions (3): A0A1W2PS79, A0A2R8YGM7, Q6T311

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the small GTPase superfamily. Arf family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6T311-1	1	yes
Q6T311-2	2

RefSeq proteins (6): NP_001350723, NP_001388286, NP_001388287, NP_001388288, NP_001388290, NP_996802 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006689	Small_GTPase_ARF/SAR	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR053254	Arf-like_GTPase	Family

Pfam: PF00025

Enzyme classification (BRENDA):

• EC 3.6.5.2 — small monomeric GTPase (BRENDA: 49 organisms, 138 substrates, 55 inhibitors, 5 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	—	0

UniProt features (5 total): binding site 3, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6T311-F1	88.66	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 25–32; 69–73; 126–129

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 14 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOMF_GTPASE_ACTIVITY, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, chr4q12, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_BALBC_MOUSE_UP, HAY_BONE_MARROW_ERYTHROBLAST, GSE9946_IMMATURE_VS_MATURE_STIMULATORY_DC_DN, GSE17974_CTRL_VS_ACT_IL4_AND_ANTI_IL12_0.5H_CD4_TCELL_DN, GOMF_GUANYL_NUCLEOTIDE_BINDING, GOMF_PURINE_NUCLEOTIDE_BINDING, BENPORATH_EED_TARGETS, BENPORATH_PRC2_TARGETS, GSE43863_NAIVE_VS_MEMORY_TH1_CD4_TCELL_D150_LCMV_UP, BENPORATH_SUZ12_TARGETS

GO Biological Process (1): nervous system development (GO:0007399)

GO Molecular Function (3): GTPase activity (GO:0003924), GTP binding (GO:0005525), nucleotide binding (GO:0000166)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1205 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARL9	RASL11A	Q6T310	916
ARL9	RASL11B	Q9BPW5	851
ARL9	ARL16	Q0P5N6	707
ARL9	RAP2A	P10114	549
ARL9	SRP72	O76094	474
ARL9	TASOR2	Q5VWN6	447
ARL9	PDCL2	Q8N4E4	435
ARL9	CDKN2A	P42771	398
ARL9	ANKRD50	Q9ULJ7	381
ARL9	SIAH3	Q8IW03	380
ARL9	ARL17B	I3L3L1	380
ARL9	CRACD	Q6ZU35	375
ARL9	ARL17A	Q8IVW1	374
ARL9	TMEM165	Q9HC07	373
ARL9	ADAD1	Q96M93	364

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ARL9	CKAP2L	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): CKAP2L (Affinity Capture-MS)

ESM2 similar proteins: A2VE14, A9CQL8, D3ZVR7, P22234, P51583, Q0VCJ8, Q0VD27, Q29RZ1, Q4R5H6, Q58CY6, Q5EA19, Q5F415, Q5H8A4, Q5NVN7, Q5R7S9, Q5RB59, Q5REA8, Q5RES2, Q5RFN0, Q5RKN4, Q5TM64, Q5VYX0, Q5XIC4, Q5ZIL9, Q5ZJB7, Q5ZMH6, Q67FW5, Q6AXQ0, Q6T311, Q86XW9, Q8BGB7, Q8BGR6, Q8BUH1, Q8BZI6, Q8MJJ1, Q8TBF2, Q8WWQ2, Q96MZ0, Q96NT3, Q9BRA2

Diamond homologs: A3LTA2, A5DR82, A5E5G3, A8INQ0, O45379, P26990, P34212, P36406, P36407, P36536, P40617, P40946, P49703, P51645, P61209, P61210, P61213, P61214, P62330, P62331, P62332, Q007T5, Q01475, Q02804, Q0IIM2, Q0VC18, Q18510, Q3SXC5, Q3SXY8, Q3T0D7, Q3T0M9, Q3T0T7, Q4P0I7, Q52NJ3, Q54HK2, Q54JJ3, Q54V41, Q559R0, Q59S78, Q5BK71

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

665 predictions. Top by Δscore:

Variant	Effect	Δscore
4:56511343:GGAGA:G	donor_gain	1.0000
4:56511344:GAGA:G	donor_gain	1.0000
4:56511344:GAGAG:G	donor_gain	1.0000
4:56511345:A:T	donor_gain	1.0000
4:56511346:GA:G	donor_gain	1.0000
4:56511348:G:GG	donor_gain	1.0000
4:56523684:A:AG	acceptor_gain	1.0000
4:56505690:CGAGG:C	donor_loss	0.9900
4:56505694:GTAAG:G	donor_loss	0.9900
4:56505695:T:G	donor_loss	0.9900
4:56511179:TCACA:T	acceptor_loss	0.9900
4:56511180:CACAG:C	acceptor_loss	0.9900
4:56511182:CAGGA:C	acceptor_loss	0.9900
4:56511183:A:AG	acceptor_gain	0.9900
4:56511183:A:C	acceptor_loss	0.9900
4:56511184:G:GG	acceptor_gain	0.9900
4:56511184:G:T	acceptor_loss	0.9900
4:56511184:GGA:G	acceptor_gain	0.9900
4:56511184:GGAGA:G	acceptor_gain	0.9900
4:56511345:AGA:A	donor_gain	0.9900
4:56511346:GAG:G	donor_gain	0.9900
4:56511347:AGTA:A	donor_loss	0.9900
4:56511348:GT:G	donor_loss	0.9900
4:56511349:TAA:T	donor_loss	0.9900
4:56518676:A:AG	acceptor_gain	0.9900
4:56518676:AGTT:A	acceptor_gain	0.9900
4:56518677:G:GA	acceptor_gain	0.9900
4:56518677:GTTG:G	acceptor_gain	0.9900
4:56518803:C:G	donor_gain	0.9900
4:56520804:AAC:A	donor_gain	0.9900

AlphaMissense

1751 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000146355 (4:56518944 A>C,G,T), RS10002045 (4:56504400 C>T), RS1000333576 (4:56508906 G>A), RS1000388816 (4:56505676 A>G), RS10004163 (4:56512233 G>A), RS1000692363 (4:56506623 C>A,T), RS1000966458 (4:56522802 C>A,T), RS1001019646 (4:56515578 C>A), RS1001072215 (4:56515909 G>C), RS1001489845 (4:56512353 A>G), RS1001632364 (4:56519566 C>T), RS1001657662 (4:56506165 C>T), RS1001676284 (4:56519926 A>T), RS1001681847 (4:56511986 T>C), RS1001734325 (4:56512307 C>T)

Disease associations

OMIM: gene MIM:612405 | 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
GCST005174_12	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	7.000000e-06
GCST005175_11	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Cisplatin	affects expression	1
Triclosan	decreases expression	1
Levonorgestrel	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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