GIMAP6

Summary

GIMAP6 (GTPase, IMAP family member 6, HGNC:21918) is a protein-coding gene on chromosome 7q36.1, encoding GTPase IMAP family member 6 (Q6P9H5).

This gene encodes a member of the GTPases of immunity-associated proteins (GIMAP) family. GIMAP proteins contain GTP-binding and coiled-coil motifs, and may play roles in the regulation of cell survival. Decreased expression of this gene may play a role in non-small cell lung cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is found in a cluster with seven additional GIMAP genes on the long arm of chromosome 7.

Source: NCBI Gene 474344 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 70 total — 1 likely-pathogenic
• MANE Select transcript: NM_024711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21918
Approved symbol	GIMAP6
Name	GTPase, IMAP family member 6
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22690, IAN6
Ensembl gene	ENSG00000133561
Ensembl biotype	protein_coding
OMIM	616960
Entrez	474344

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000328902, ENST00000493969, ENST00000618759, ENST00000891915, ENST00000891916, ENST00000891917, ENST00000971114, ENST00000971115

RefSeq mRNA: 3 — MANE Select: NM_024711 NM_001244071, NM_001244072, NM_024711

CCDS: CCDS34778, CCDS59087, CCDS75676

Canonical transcript exons

ENST00000328902 — 3 exons

Exon	Start	End
ENSE00001367708	150625375	150628512
ENSE00001824602	150632169	150632385
ENSE00003757464	150630058	150630142

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 96.45.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9470 / max 251.0211, expressed in 551 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86802	6.1215	540
86803	0.6217	244
86800	0.5055	168
86801	0.4712	199
86799	0.1457	60
86804	0.0814	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.45	gold quality
lower lobe of lung	UBERON:0008949	95.59	gold quality
superficial temporal artery	UBERON:0001614	94.30	gold quality
leukocyte	CL:0000738	94.18	gold quality
parietal pleura	UBERON:0002400	93.97	gold quality
monocyte	CL:0000576	93.89	gold quality
mononuclear cell	CL:0000842	93.86	gold quality
lymph node	UBERON:0000029	93.47	gold quality
blood	UBERON:0000178	92.90	gold quality
pleura	UBERON:0000977	92.85	gold quality
heart right ventricle	UBERON:0002080	92.69	gold quality
spleen	UBERON:0002106	92.63	gold quality
visceral pleura	UBERON:0002401	92.51	gold quality
right lung	UBERON:0002167	92.09	gold quality
apex of heart	UBERON:0002098	92.03	gold quality
jejunal mucosa	UBERON:0000399	91.91	gold quality
vermiform appendix	UBERON:0001154	91.44	gold quality
adult organism	UBERON:0007023	91.30	gold quality
lung	UBERON:0002048	90.86	gold quality
skin of hip	UBERON:0001554	90.41	gold quality
caecum	UBERON:0001153	90.23	gold quality
myocardium	UBERON:0002349	90.21	gold quality
left ventricle myocardium	UBERON:0006566	89.96	gold quality
adipose tissue	UBERON:0001013	89.72	gold quality
decidua	UBERON:0002450	89.44	gold quality
urethra	UBERON:0000057	89.40	gold quality
placenta	UBERON:0001987	89.19	gold quality
upper lobe of lung	UBERON:0008948	89.13	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.12	gold quality
layer of synovial tissue	UBERON:0007616	89.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.98
E-MTAB-10137	no	261.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting GIMAP6, 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-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 5)

• These data,demonstrating the downregulation of the mRNA and protein expression levels of GIMAP5 and GIMAP6 in the tumor tissues and blood of patients with Hepatocellular carcinoma (HCC) , suggested the involvement of GIMAP5 and GIMAP6 in the pathogenesis of HCC, and indicate their possible use as diagnostic markers for HCC. (PMID:27667392)
• GIMAP6 plays a role in modulating immune function and that it does this by controlling cell death and the activation of T cells. (PMID:28381553)
• A human case of GIMAP6 deficiency: a novel primary immune deficiency. (PMID:33328581)
• GIMAP6 regulates autophagy, immune competence, and inflammation in mice and humans. (PMID:35551368)
• Investigation and verification of GIMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma. (PMID:37338641)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gimap6	ENSMUSG00000047867
rattus_norvegicus	Gimap6	ENSRNOG00000033338

Paralogs (7): GIMAP2 (ENSG00000106560), GIMAP4 (ENSG00000133574), GIMAP8 (ENSG00000171115), GIMAP7 (ENSG00000179144), GIMAP5 (ENSG00000196329), GIMAP1 (ENSG00000213203), GIMD1 (ENSG00000250298)

Protein

Protein identifiers

GTPase IMAP family member 6 — Q6P9H5 (reviewed: Q6P9H5)

Alternative names: Immunity-associated nucleotide 2 protein, Immunity-associated nucleotide 6 protein

All UniProt accessions (3): A0A090N7V4, B4DH95, Q6P9H5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in spleen, lymph nodes, lung and placenta. Expressed at moderate level in thymus, kidney, heart and digestive tract. Weakly expressed in other lymphoid tissues. Detected in T-cells.

Similarity. Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6P9H5-1	1	yes
Q6P9H5-2	2
Q6P9H5-3	3

RefSeq proteins (3): NP_001231000, NP_001231001, NP_078987* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006703	G_AIG1	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR045058	GIMA/IAN/Toc	Family

Pfam: PF04548

UniProt features (17 total): sequence variant 4, binding site 4, splice variant 3, sequence conflict 2, region of interest 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P9H5-F1	86.32	0.72

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 (4): 47–55; 68; 164–166; 201

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 177 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, GNF2_CASP8, VANHARANTA_UTERINE_FIBROID_DN, PARK_HSC_VS_MULTIPOTENT_PROGENITORS_UP, GNF2_CD97, CUI_TCF21_TARGETS_2_DN, GNF2_PTPRC, GNF2_SNRK, BOQUEST_STEM_CELL_DN, ALONSO_METASTASIS_DN, GAVIN_IL2_RESPONSIVE_FOXP3_TARGETS_DN, ZHENG_BOUND_BY_FOXP3, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, SCHUETZ_BREAST_CANCER_DUCTAL_INVASIVE_UP, GOMF_GTPASE_ACTIVITY

GO Biological Process (0):

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

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GIMAP6	GABARAPL2	P60520	644
GIMAP6	GIMAP8	Q8ND71	467
GIMAP6	CRACDL	Q6NV74	467
GIMAP6	GIMAP4	Q9NUV9	459
GIMAP6	ZNF775	Q96BV0	449
GIMAP6	GIMAP7	Q8NHV1	436
GIMAP6	GIMAP1	Q8WWP7	428
GIMAP6	SH2D3C	Q8N5H7	411
GIMAP6	TMEM176B	Q3YBM2	409
GIMAP6	AIG1	Q9NVV5	404
GIMAP6	BET1	O15155	362
GIMAP6	KLRK1	P26718	359
GIMAP6	CYYR1	Q96J86	348
GIMAP6	C7orf33	Q8WU49	348
GIMAP6	DRC11L	A6NCM1	329

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SOD1	GIMAP6	psi-mi:“MI:0915”(physical association)	0.400
GIMAP6	MICAL1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): GIMAP6 (Two-hybrid), GIMAP6 (Two-hybrid), GIMAP6 (Two-hybrid), DDIT3 (Two-hybrid), MICAL1 (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A2APT9, A5PJC7, A5PKB7, D7PDD4, O08672, O94761, O94989, P33076, P51617, P79621, Q16671, Q2LGB3, Q3T0Y9, Q496M5, Q49LS3, Q53GL7, Q5FVN6, Q5FWH6, Q5R866, Q5R8H1, Q5RA67, Q5VTJ3, Q60837, Q6P9H5, Q6UX68, Q75NR7, Q7Z6P3, Q86UT6, Q8BTN6, Q8BWA8, Q8BWF2, Q8CIE4, Q8IUD6, Q8IW93, Q8IYJ3, Q8K349, Q8K3L6, Q8K558, Q8NAG6, Q8R2S1

Diamond homologs: A5PKB7, F4HT21, G3X987, O23680, O81025, P54120, P70224, Q41009, Q4KLG2, Q5FVN6, Q6P9H5, Q75N62, Q8BWF2, Q8K349, Q8K3K9, Q8K3L6, Q8ND71, Q8NHV1, Q8WWP7, Q96F15, Q99JY3, Q99MI6, Q9C8U2, Q9C8V0, Q9C8V2, Q9NUV9, Q9T0F2, Q9T0F3, Q9T0F4, Q9UG22, E9PW74, Q9C8U5, Q9C8U6, Q9C8U7, Q9C8U8, Q9LVT3, O81283, C0HJV2, G3MZQ6, O81865

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	49
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929485	NM_024711.6(GIMAP6):c.257G>A (p.Trp86Ter)	Likely pathogenic

SpliceAI

439 predictions. Top by Δscore:

Variant	Effect	Δscore
7:150630053:TTTAC:T	donor_loss	1.0000
7:150630054:TTACC:T	donor_loss	1.0000
7:150630055:TACC:T	donor_loss	1.0000
7:150630056:ACCT:A	donor_gain	1.0000
7:150630057:CCTC:C	donor_gain	1.0000
7:150630059:T:TA	donor_gain	1.0000
7:150630139:CCAT:C	acceptor_gain	1.0000
7:150630140:CAT:C	acceptor_gain	1.0000
7:150630140:CATC:C	acceptor_gain	1.0000
7:150630141:ATCTA:A	acceptor_loss	1.0000
7:150630142:TCTAC:T	acceptor_loss	1.0000
7:150630143:C:CC	acceptor_gain	1.0000
7:150630143:C:CG	acceptor_loss	1.0000
7:150630144:T:A	acceptor_loss	1.0000
7:150632168:CCT:C	donor_gain	1.0000
7:150630138:TCCAT:T	acceptor_gain	0.9900
7:150630139:CCATC:C	acceptor_gain	0.9900
7:150630141:AT:A	acceptor_gain	0.9900
7:150630146:C:CT	acceptor_gain	0.9900
7:150630147:A:T	acceptor_gain	0.9900
7:150632165:TTACC:T	donor_loss	0.9900
7:150632166:TACC:T	donor_loss	0.9900
7:150632167:A:AC	donor_gain	0.9900
7:150632167:ACC:A	donor_loss	0.9900
7:150632168:C:CC	donor_gain	0.9900
7:150629644:CAA:C	donor_gain	0.9800
7:150631694:T:TA	donor_gain	0.9800
7:150631695:C:A	donor_gain	0.9800
7:150630057:CCT:C	donor_gain	0.9700
7:150632167:AC:A	donor_gain	0.9700

AlphaMissense

1891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:150628112:G:C	F162L	0.983
7:150628112:G:T	F162L	0.983
7:150628114:A:G	F162L	0.983
7:150628193:G:C	F135L	0.981
7:150628193:G:T	F135L	0.981
7:150628195:A:G	F135L	0.981
7:150628400:G:C	F66L	0.979
7:150628400:G:T	F66L	0.979
7:150628402:A:G	F66L	0.979
7:150628002:A:G	F199S	0.970
7:150628001:G:C	F199L	0.968
7:150628001:G:T	F199L	0.968
7:150628003:A:G	F199L	0.968
7:150628436:A:C	S54R	0.957
7:150628436:A:T	S54R	0.957
7:150628438:T:G	S54R	0.957
7:150628148:A:C	F150L	0.956
7:150628148:A:T	F150L	0.956
7:150628150:A:G	F150L	0.956
7:150628113:A:G	F162S	0.947
7:150628419:A:G	I60T	0.941
7:150628313:G:C	D95E	0.933
7:150628313:G:T	D95E	0.933
7:150628107:C:G	R164P	0.926
7:150628194:A:G	F135S	0.925
7:150628421:G:C	S59R	0.925
7:150628421:G:T	S59R	0.925
7:150628423:T:G	S59R	0.925
7:150628218:A:T	L127H	0.924
7:150628439:C:A	K53N	0.921

dbSNP variants (sampled 300 via entrez): RS1000105353 (7:150633515 T>C), RS1000377428 (7:150630245 T>C), RS1000832932 (7:150630548 T>C), RS1001607353 (7:150627071 A>T), RS1001659683 (7:150627292 TG>T), RS1001786369 (7:150632181 T>C), RS1001840303 (7:150631066 A>C,G,T), RS1001939150 (7:150625619 A>G), RS1001992016 (7:150626000 T>C), RS1002166301 (7:150633375 C>T), RS1002218620 (7:150633560 T>C), RS1002298287 (7:150629940 T>G), RS1002411269 (7:150628147 C>A), RS1002515249 (7:150630826 C>T), RS1002549200 (7:150632148 C>T)

Disease associations

OMIM: gene MIM:616960 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory syndrome	Strong	Autosomal recessive

Mondo (1): autoinflammatory syndrome (MONDO:0019751)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004121_33	Fibrinogen levels	2.000000e-09
GCST004122_25	Fibrinogen levels	2.000000e-10
GCST009597_163	Multiple sclerosis	1.000000e-06
GCST010242_154	HDL cholesterol levels	6.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs34940374	GIMAP6		0.00	0

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Air Pollutants, Occupational	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
cobaltous chloride	decreases expression	1
1-hydroxypyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Arsenic Trioxide	increases expression	1
Asbestos	affects expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Nickel	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION