GARIN4

Summary

GARIN4 (golgi associated RAB2 interactor family member 4, HGNC:26541) is a protein-coding gene on chromosome 1q32.3, encoding Golgi-associated RAB2 interactor protein 4 (Q8IYT1). RAB2B effector protein required for the compacted Golgi morphology, probably through interaction with small GTPase RAB2B.

This gene encodes a protein that interacts with the Rab2B small GTPase and may be important for integrity of the Golgi body. A knockdown of this gene induces fragmentation of the Golgi, similar to the effect seen with a knockdown of the Rab2B small GTPase. The encoded protein has an N-terminal Rab-binding domain specific for Rab2B.

Source: NCBI Gene 149647 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 126 total
• MANE Select transcript: NM_153606

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26541
Approved symbol	GARIN4
Name	golgi associated RAB2 interactor family member 4
Location	1q32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32796, GARI-L4
Ensembl gene	ENSG00000162771
Ensembl biotype	protein_coding
OMIM	619852
Entrez	149647

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000294829

RefSeq mRNA: 1 — MANE Select: NM_153606 NM_153606

CCDS: CCDS1507

Canonical transcript exons

ENST00000294829 — 1 exons

Exon	Start	End
ENSE00001068444	212624474	212626775

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1302 / max 129.9125, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8481	0.1219	3
8482	0.0083	3

Top tissues by expression

185 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	94.67	gold quality
sperm	CL:0000019	92.66	gold quality
left testis	UBERON:0004533	92.64	gold quality
right testis	UBERON:0004534	92.36	gold quality
testis	UBERON:0000473	90.50	gold quality
vena cava	UBERON:0004087	88.35	silver quality
parotid gland	UBERON:0001831	87.99	silver quality
tendon of biceps brachii	UBERON:0008188	86.24	gold quality
gingival epithelium	UBERON:0001949	86.11	silver quality
buccal mucosa cell	CL:0002336	86.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.47	gold quality
myocardium	UBERON:0002349	84.60	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.04	silver quality
body of tongue	UBERON:0011876	83.65	silver quality
cerebellar vermis	UBERON:0004720	82.94	silver quality
pharyngeal mucosa	UBERON:0000355	82.81	silver quality
adult organism	UBERON:0007023	82.76	gold quality
pons	UBERON:0000988	82.23	gold quality
pericardium	UBERON:0002407	82.18	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.96	silver quality
cardia of stomach	UBERON:0001162	81.84	gold quality
superficial temporal artery	UBERON:0001614	81.84	silver quality
subthalamic nucleus	UBERON:0001906	81.51	silver quality
tongue	UBERON:0001723	81.34	silver quality
lateral globus pallidus	UBERON:0002476	81.25	silver quality
pylorus	UBERON:0001166	81.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	81.14	gold quality
biceps brachii	UBERON:0001507	80.64	silver quality
dorsal plus ventral thalamus	UBERON:0001897	80.07	silver quality
ventral tegmental area	UBERON:0002691	80.04	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	827.96
E-ANND-3	no	0.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting GARIN4, 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-4267	99.96	66.53	2368
HSA-MIR-3942-3P	99.57	69.03	2854

Literature-anchored findings (GeneRIF, showing 1)

• Data identified Golgi-associated Rab2B interactor-like 4 (GARI-L4) as a novel Golgi-resident Rab2B-specific binding protein whose knockdown induced fragmentation of the Golgi (PMID:26209634)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Garin4	ENSMUSG00000091017
rattus_norvegicus	Garin4	ENSRNOG00000029371

Paralogs (7): GARIN1B (ENSG00000135248), GARIN5A (ENSG00000142530), GARIN3 (ENSG00000170613), GARIN2 (ENSG00000172717), GARIN5B (ENSG00000180043), GARIN6 (ENSG00000180219), GARIN1A (ENSG00000205085)

Protein

Protein identifiers

Golgi-associated RAB2 interactor protein 4 — Q8IYT1 (reviewed: Q8IYT1)

Alternative names: Golgi-associated Rab2B interactor-like 4

All UniProt accessions (1): Q8IYT1

UniProt curated annotations — full annotation on UniProt →

Function. RAB2B effector protein required for the compacted Golgi morphology, probably through interaction with small GTPase RAB2B.

Subunit / interactions. Interacts (via N-terminus) with RAB2B (in GTP-bound form).

Subcellular location. Golgi apparatus.

Similarity. Belongs to the GARIN family.

RefSeq proteins (1): NP_705834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022168	GARIL-like_Rab2B-bd	Domain

Pfam: PF12480

UniProt features (12 total): sequence variant 5, compositionally biased region 5, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYT1-F1	53.14	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_MALE_GAMETE_GENERATION, GGGTGGRR_PAX4_03, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION, GOBP_GOLGI_ORGANIZATION, SREBP1_Q6, GOBP_PENETRATION_OF_ZONA_PELLUCIDA, GOCC_SPERM_HEAD, SREBP_Q3, GOBP_CELL_MORPHOGENESIS, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_UP

GO Biological Process (4): cell morphogenesis (GO:0000902), Golgi organization (GO:0007030), spermatid development (GO:0007286), penetration of zona pellucida (GO:0007341)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), Golgi apparatus (GO:0005794), sperm head (GO:0061827)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
anatomical structure morphogenesis	1
organelle organization	1
endomembrane system organization	1
germ cell development	1
spermatid differentiation	1
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
binding	1
cytoplasm	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GARIN4	MORN5	Q5VZ52	509
GARIN4	RAB2B	Q8WUD1	474
GARIN4	SMIM31	A0A1B0GVY4	471
GARIN4	IFTAP	Q86VG3	358
GARIN4	TMEM91	Q6ZNR0	353
GARIN4	INTS6L	Q5JSJ4	348
GARIN4	PEBP4	Q96S96	346
GARIN4	CCNYL1	Q8N7R7	329
GARIN4	CIMIP4	O43247	323
GARIN4	CCER1	Q8TC90	323
GARIN4	NPIPA5	E9PKD4	317
GARIN4	ALKAL2	Q6UX46	305
GARIN4	EFR3A	Q14156	304
GARIN4	SAMD12	Q8N8I0	298
GARIN4	PCNX1	Q96RV3	298

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RAB2A	GARIN4	psi-mi:“MI:0915”(physical association)	0.560
GARIN4	RAB2B	psi-mi:“MI:0915”(physical association)	0.560
RAB2B	GARIN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): FAM71A (Two-hybrid), FAM71A (Two-hybrid)

ESM2 similar proteins: A0A8I5ZN27, A4FU49, B9EKR1, E1AZ71, O54963, O60721, O88422, P15304, P23471, P24054, P70663, Q05469, Q13127, Q14028, Q14515, Q28139, Q28181, Q28858, Q4R729, Q4V8E9, Q5R7U0, Q5SRN2, Q5STT6, Q5TCY1, Q66H38, Q6MG22, Q6PCN3, Q7TSG5, Q7Z7G0, Q8BUY8, Q8C102, Q8IWC1, Q8IYT1, Q8N9W8, Q8R1W8, Q8TC56, Q8VIG1, Q91WD8, Q921B4, Q923B3

Diamond homologs: A1L3C1, B2RXB0, D3YV92, Q2KIP3, Q2YDE8, Q32L49, Q3UZD7, Q4R323, Q5STT6, Q66H38, Q68FV5, Q6IPT2, Q6NXP2, Q8IYT1, Q8N5Q1, Q8N9W8, Q8NEG0, Q8TC56, Q95K21, Q95K27, Q96KD3, Q5RJN7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	107
Likely benign	17
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

10 predictions. Top by Δscore:

Variant	Effect	Δscore
1:212625513:A:T	donor_gain	0.5500
1:212625534:C:A	donor_gain	0.5400
1:212625658:A:AG	acceptor_gain	0.4100
1:212625568:T:A	donor_gain	0.4000
1:212625537:C:T	donor_gain	0.3000
1:212625475:G:GT	donor_gain	0.2400
1:212625512:G:GT	donor_gain	0.2400
1:212625567:G:A	donor_gain	0.2400
1:212625659:A:G	acceptor_gain	0.2400
1:212625046:G:T	donor_gain	0.2000

AlphaMissense

3916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:212625025:T:C	F50L	0.991
1:212625027:T:A	F50L	0.991
1:212625027:T:G	F50L	0.991
1:212625019:A:C	S48R	0.986
1:212625021:C:A	S48R	0.986
1:212625021:C:G	S48R	0.986
1:212625367:T:C	F164L	0.986
1:212625369:T:A	F164L	0.986
1:212625369:T:G	F164L	0.986
1:212625378:G:C	W167C	0.983
1:212625378:G:T	W167C	0.983
1:212625376:T:A	W167R	0.981
1:212625376:T:C	W167R	0.981
1:212625026:T:C	F50S	0.980
1:212624996:T:C	F40S	0.979
1:212625263:T:C	I129T	0.973
1:212625368:T:G	F164C	0.969
1:212625293:T:C	L139P	0.968
1:212625304:T:C	F143L	0.968
1:212625306:C:A	F143L	0.968
1:212625306:C:G	F143L	0.968
1:212624938:T:C	F21L	0.967
1:212624940:C:A	F21L	0.967
1:212624940:C:G	F21L	0.967
1:212624995:T:C	F40L	0.967
1:212624997:C:A	F40L	0.967
1:212624997:C:G	F40L	0.967
1:212625013:T:C	F46L	0.965
1:212625015:T:A	F46L	0.965
1:212625015:T:G	F46L	0.965

dbSNP variants (sampled 300 via entrez): RS1001758553 (1:212624022 A>G), RS1002202600 (1:212625938 A>T), RS1002505237 (1:212626908 A>G), RS1004666707 (1:212627219 G>T), RS1004990015 (1:212626933 C>G), RS1005108945 (1:212623043 C>T), RS1005126125 (1:212626569 C>T), RS1005721211 (1:212626259 G>A), RS1007411588 (1:212624760 C>T), RS1009065838 (1:212624090 T>C), RS1009073735 (1:212623696 G>A), RS1009171166 (1:212626848 G>C), RS1010117225 (1:212623243 G>GGT), RS1010475046 (1:212622593 C>T), RS1011252260 (1:212624386 C>T)

Disease associations

OMIM: gene MIM:619852 | disease phenotypes: MIM:157900

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (2): Mobius syndrome (MONDO:0008006), Tourette syndrome (MONDO:0007661)

Orphanet (1): Moebius syndrome (Orphanet:570)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006202_1	Thiopurine-induced leukopenia in inflammatory bowel disease (conditioned on rs116855232)	1.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome