GARIN2

Summary

GARIN2 (golgi associated RAB2 interactor family member 2, HGNC:20101) is a protein-coding gene on chromosome 14q23.3, encoding Golgi-associated RAB2 interactor protein 2 (Q8N9W8). Seems to play a role in sperm motility.

Predicted to be involved in flagellated sperm motility. Predicted to act upstream of or within cell morphogenesis; penetration of zona pellucida; and spermatid development. Predicted to be located in sperm midpiece. Predicted to be active in sperm head.

Source: NCBI Gene 161142 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_001395907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20101
Approved symbol	GARIN2
Name	golgi associated RAB2 interactor family member 2
Location	14q23.3
Locus type	gene with protein product
Status	Approved
Aliases	GARI-L2
Ensembl gene	ENSG00000172717
Ensembl biotype	protein_coding
OMIM	619898
Entrez	161142

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000524532, ENST00000524914, ENST00000530728, ENST00000531566, ENST00000534174, ENST00000554500, ENST00000556046, ENST00000556117, ENST00000557671, ENST00000612183, ENST00000696955, ENST00000696956, ENST00000696957, ENST00000696958, ENST00000696959, ENST00000696960, ENST00000696961

RefSeq mRNA: 2 — MANE Select: NM_001395907 NM_001395907, NM_173526

CCDS: CCDS91889, CCDS9778

Canonical transcript exons

ENST00000696955 — 8 exons

Exon	Start	End
ENSE00002178507	67189440	67189569
ENSE00002604070	67197271	67197357
ENSE00003493988	67208202	67208449
ENSE00003513958	67203094	67203293
ENSE00003556500	67204537	67205089
ENSE00003639000	67198136	67198320
ENSE00003665501	67221779	67221807
ENSE00003969038	67223753	67223940

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 89.15.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0896 / max 71.2714, expressed in 8 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140201	0.0759	3
140200	0.0137	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	89.15	gold quality
right testis	UBERON:0004534	89.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.03	gold quality
sperm	CL:0000019	85.89	gold quality
testis	UBERON:0000473	85.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.59	silver quality
mucosa of paranasal sinus	UBERON:0005030	67.65	gold quality
lower lobe of lung	UBERON:0008949	65.95	silver quality
epithelium of nasopharynx	UBERON:0001951	65.87	gold quality
superficial temporal artery	UBERON:0001614	63.67	gold quality
buccal mucosa cell	CL:0002336	62.06	silver quality
apex of heart	UBERON:0002098	60.74	gold quality
right lobe of liver	UBERON:0001114	59.20	gold quality
calcaneal tendon	UBERON:0003701	57.18	gold quality
right lobe of thyroid gland	UBERON:0001119	57.01	gold quality
skin of leg	UBERON:0001511	55.74	gold quality
cerebellar hemisphere	UBERON:0002245	55.19	gold quality
cerebellar cortex	UBERON:0002129	55.15	gold quality
lower esophagus mucosa	UBERON:0035834	54.80	gold quality
sural nerve	UBERON:0015488	54.25	silver quality
skin of abdomen	UBERON:0001416	54.24	gold quality
cerebellum	UBERON:0002037	54.16	gold quality
thyroid gland	UBERON:0002046	53.49	gold quality
left lobe of thyroid gland	UBERON:0001120	53.42	gold quality
zone of skin	UBERON:0000014	53.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	53.32	gold quality
body of pancreas	UBERON:0001150	53.24	gold quality
mucosa of stomach	UBERON:0001199	53.19	gold quality
adult organism	UBERON:0007023	52.66	gold quality
upper leg skin	UBERON:0004262	52.65	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting GARIN2, 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-5696	99.98	72.36	4487
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-4769-3P	97.95	68.17	1002
HSA-MIR-6817-5P	97.95	67.86	1026

Literature-anchored findings (GeneRIF, showing 4)

• The unique in-frame MPP5-FAM71D fusion product is important for proliferation of PC346C cells. (PMID:24488012)
• Our results showed that FAM71D was exclusively expressed in the testis in an age-dependent manner. FAM71D expression exhibited dynamic change in the cytoplasm of spermatids during spermiogenesis and was finally retained in sperm flagella. FAM71D could interact with calmodulin. (PMID:29025071)
• FAM71D is dispensable for spermatogenesis and male fertility in mice. (PMID:37992210)
• Deleterious variant in FAM71D cause male infertility with asthenoteratospermia. (PMID:38489045)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Garin2	ENSMUSG00000056987
rattus_norvegicus	Garin2	ENSRNOG00000028351

Paralogs (7): GARIN1B (ENSG00000135248), GARIN5A (ENSG00000142530), GARIN4 (ENSG00000162771), GARIN3 (ENSG00000170613), GARIN5B (ENSG00000180043), GARIN6 (ENSG00000180219), GARIN1A (ENSG00000205085)

Protein

Protein identifiers

Golgi-associated RAB2 interactor protein 2 — Q8N9W8 (reviewed: Q8N9W8)

All UniProt accessions (13): Q8N9W8, A0A8V8TKH0, A0A8V8TKJ2, A0A8V8TKV5, A0A8V8TLQ8, A0A8V8TLY4, A0A8V8TLY9, E9PM27, E9PPX0, G3V4K8, H0YJ27, H0YJQ5, H3BMS9

UniProt curated annotations — full annotation on UniProt →

Function. Seems to play a role in sperm motility.

Subunit / interactions. Interacts with CALM1.

Subcellular location. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in spermatozoa (at protein level).

Similarity. Belongs to the GARIN family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N9W8-1	1	yes
Q8N9W8-2	2

RefSeq proteins (2): NP_001382836, NP_775797 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022168	GARIL-like_Rab2B-bd	Domain

Pfam: PF12480

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9W8-F1	55.89	0.14

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 45 (showing top): KMCATNNWGGA_UNKNOWN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, AACTTT_UNKNOWN, chr14q23, GOCC_MOTILE_CILIUM, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOCC_SPERM_MIDPIECE, GOCC_CILIUM, GOCC_9PLUS2_MOTILE_CILIUM, MIR5696, MIR4516, MIR511_5P, MIR4319, MIR125B_5P

GO Biological Process (4): flagellated sperm motility (GO:0030317), cell morphogenesis (GO:0000902), spermatid development (GO:0007286), penetration of zona pellucida (GO:0007341)

GO Molecular Function (0):

GO Cellular Component (6): sperm midpiece (GO:0097225), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995), sperm head (GO:0061827)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
anatomical structure morphogenesis	1
germ cell development	1
spermatid differentiation	1
single fertilization	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
sperm flagellum	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GARIN2	WBP2NL	Q6ICG8	575
GARIN2	TULP2	O00295	565
GARIN2	MS4A5	Q9H3V2	549
GARIN2	OR51I2	Q9H344	545
GARIN2	ROPN1L	Q96C74	543
GARIN2	RNF17	Q9BXT8	532
GARIN2	SLC9B1	Q4ZJI4	531
GARIN2	SPATA16	Q9BXB7	531
GARIN2	SOX30	O94993	528
GARIN2	SYCE3	A1L190	528
GARIN2	DMRT1	Q9Y5R6	511
GARIN2	PLCZ1	Q86YW0	507
GARIN2	FAM209A	Q5JX71	507
GARIN2	OR2H1	Q9GZK4	488
GARIN2	SPATA31G1	Q5VYM1	480

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GARIN2	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
GARIN2	PGK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): FAM71D (Two-hybrid), PGK2 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), FAM71D (Synthetic Lethality), PGK2 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A2AFS9, A2AVR2, A2CI98, A2CJ06, A2RUW0, A4FU69, O70167, O70173, P0C2Y1, P15304, P59729, Q08EC4, Q3U1D0, Q4R744, Q4R9E9, Q5T4T6, Q5TGP6, Q5VWK0, Q68CQ1, Q6AYJ3, Q6IFT4, Q6IRU7, Q6REY9, Q6ZUA9, Q7Z572, Q80TQ5, Q80VH0, Q86WZ0, Q86XG9, Q8C0X8, Q8CCC3, Q8N9W8, Q8ND61, Q8NDZ2, Q90WN7, Q91YE5, Q96M43, Q96QP1, Q9CX83

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1608 predictions. Top by Δscore:

Variant	Effect	Δscore
14:67189566:GTTG:G	donor_gain	1.0000
14:67189570:G:A	donor_loss	1.0000
14:67189570:G:GG	donor_gain	1.0000
14:67189571:T:A	donor_loss	1.0000
14:67197266:A:AG	acceptor_gain	1.0000
14:67198134:A:AG	acceptor_gain	1.0000
14:67198135:G:GG	acceptor_gain	1.0000
14:67198269:A:T	donor_gain	1.0000
14:67189567:TTG:T	donor_gain	0.9900
14:67197267:A:G	acceptor_gain	0.9900
14:67198135:GT:G	acceptor_gain	0.9900
14:67198135:GTTT:G	acceptor_gain	0.9900
14:67198135:GTTTT:G	acceptor_gain	0.9900
14:67204532:TGCA:T	acceptor_loss	0.9900
14:67204533:GCA:G	acceptor_loss	0.9900
14:67204534:CAG:C	acceptor_loss	0.9900
14:67205087:AAGGT:A	donor_loss	0.9900
14:67205088:AGG:A	donor_loss	0.9900
14:67205089:GGTA:G	donor_loss	0.9900
14:67205090:GTAT:G	donor_loss	0.9900
14:67205091:T:G	donor_loss	0.9900
14:67189565:TGTTG:T	donor_gain	0.9800
14:67189566:GTTGG:G	donor_gain	0.9800
14:67189567:TTGGT:T	donor_gain	0.9800
14:67189568:TG:T	donor_gain	0.9800
14:67189569:GG:G	donor_gain	0.9800
14:67189572:AAGT:A	donor_loss	0.9800
14:67197265:C:G	acceptor_gain	0.9800
14:67197622:C:G	donor_gain	0.9800
14:67198132:TCA:T	acceptor_loss	0.9800

AlphaMissense

2760 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:67204676:T:A	W167R	0.984
14:67204676:T:C	W167R	0.984
14:67198312:T:C	F51L	0.978
14:67198314:T:A	F51L	0.978
14:67198314:T:G	F51L	0.978
14:67204678:G:C	W167C	0.968
14:67204678:G:T	W167C	0.968
14:67204667:T:C	F164L	0.962
14:67204669:T:A	F164L	0.962
14:67204669:T:G	F164L	0.962
14:67204629:T:C	L151S	0.953
14:67198306:A:C	S49R	0.944
14:67198308:C:A	S49R	0.944
14:67198308:C:G	S49R	0.944
14:67204610:A:C	S145R	0.940
14:67204612:T:A	S145R	0.940
14:67204612:T:G	S145R	0.940
14:67198313:T:C	F51S	0.936
14:67204538:T:C	F121L	0.931
14:67204540:T:A	F121L	0.931
14:67204540:T:G	F121L	0.931
14:67204677:G:C	W167S	0.920
14:67198282:T:C	F41L	0.914
14:67198284:T:A	F41L	0.914
14:67198284:T:G	F41L	0.914
14:67203203:C:A	A90D	0.913
14:67203197:T:C	L88P	0.911
14:67203194:T:C	M87T	0.909
14:67204565:T:C	S130P	0.909
14:67204686:T:C	L170P	0.905

dbSNP variants (sampled 300 via entrez): RS1000152798 (14:67224715 T>C), RS1000245495 (14:67211997 C>A), RS1000267006 (14:67200952 T>G), RS1000308030 (14:67209853 T>A,C,G), RS1000310251 (14:67207780 CA>C,CAA), RS1000314937 (14:67217696 C>T), RS1000350013 (14:67192536 G>A,C), RS1000438733 (14:67214380 A>C,G), RS1000516771 (14:67194736 G>T), RS1000532033 (14:67219534 G>T), RS1000599296 (14:67199819 C>T), RS1000639169 (14:67211646 C>A,T), RS1000745257 (14:67207657 A>G), RS1000774825 (14:67213140 AT>A,ATT), RS1000902024 (14:67198744 A>T)

Disease associations

OMIM: gene MIM:619898 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002387_145	Immature fraction of reticulocytes	1.000000e-10

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
bisphenol F	decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	decreases expression, decreases reaction	1
Formaldehyde	increases expression	1
Malathion	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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