GIMAP4

Summary

GIMAP4 (GTPase, IMAP family member 4, HGNC:21872) is a protein-coding gene on chromosome 7q36.1, encoding GTPase IMAP family member 4 (Q9NUV9). During thymocyte development, may play a role in the regulation of apoptosis.

This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. The encoded protein of this gene may be negatively regulated by T-cell acute lymphocytic leukemia 1 (TAL1). In humans, the IAN subfamily genes are located in a cluster at 7q36.1.

Source: NCBI Gene 55303 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_018326

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21872
Approved symbol	GIMAP4
Name	GTPase, IMAP family member 4
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	HIMAP4, FLJ11110, IMAP4, IAN1
Ensembl gene	ENSG00000133574
Ensembl biotype	protein_coding
OMIM	608087
Entrez	55303

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000255945, ENST00000461940, ENST00000478135, ENST00000479232, ENST00000494750, ENST00000851189, ENST00000851190, ENST00000943245, ENST00000943246

RefSeq mRNA: 2 — MANE Select: NM_018326 NM_001363532, NM_018326

CCDS: CCDS5904, CCDS87564

Canonical transcript exons

ENST00000255945 — 3 exons

Exon	Start	End
ENSE00000872362	150569888	150569959
ENSE00001831826	150572129	150573953
ENSE00001887890	150567390	150567437

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 98.74.

FANTOM5 (CAGE): breadth broad, TPM avg 15.8899 / max 821.8797, expressed in 533 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81958	10.2456	506
81957	5.6443	484

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.74	gold quality
leukocyte	CL:0000738	98.72	gold quality
mononuclear cell	CL:0000842	98.68	gold quality
granulocyte	CL:0000094	98.59	gold quality
blood	UBERON:0000178	97.36	gold quality
right lung	UBERON:0002167	97.22	gold quality
lymph node	UBERON:0000029	96.97	gold quality
spleen	UBERON:0002106	96.09	gold quality
vermiform appendix	UBERON:0001154	95.75	gold quality
caecum	UBERON:0001153	95.20	gold quality
superficial temporal artery	UBERON:0001614	94.57	gold quality
pericardium	UBERON:0002407	94.41	gold quality
calcaneal tendon	UBERON:0003701	93.64	gold quality
lower lobe of lung	UBERON:0008949	93.53	gold quality
omental fat pad	UBERON:0010414	93.40	gold quality
peritoneum	UBERON:0002358	93.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.93	gold quality
upper lobe of left lung	UBERON:0008952	92.88	gold quality
upper lobe of lung	UBERON:0008948	92.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.62	gold quality
colonic epithelium	UBERON:0000397	92.59	gold quality
apex of heart	UBERON:0002098	92.40	gold quality
lung	UBERON:0002048	92.17	gold quality
gall bladder	UBERON:0002110	91.83	gold quality
vena cava	UBERON:0004087	91.66	silver quality
heart right ventricle	UBERON:0002080	91.57	gold quality
urethra	UBERON:0000057	91.04	gold quality
adipose tissue	UBERON:0001013	90.95	gold quality
layer of synovial tissue	UBERON:0007616	90.91	gold quality
right lobe of thyroid gland	UBERON:0001119	90.68	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	71.69
E-HCAD-8	yes	66.61
E-HCAD-1	yes	53.24
E-CURD-122	yes	49.43
E-CURD-88	yes	48.41
E-HCAD-11	yes	47.20
E-MTAB-8142	yes	40.65
E-HCAD-10	yes	30.54
E-CURD-112	yes	25.96
E-MTAB-8410	yes	25.00
E-GEOD-135922	yes	23.00
E-MTAB-8498	yes	11.14
E-MTAB-9801	yes	7.38
E-MTAB-9067	yes	3.75
E-MTAB-8207	no	468.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting GIMAP4, 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-6133	100.00	66.48	2064
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914

Literature-anchored findings (GeneRIF, showing 5)

• molecular and genetic properties; expression in resting T- and B-cells and decreased expression during lymphocyte activation (PMID:11964296)
• GIMAP1 and GIMAP4 genes are up-regulated by IL-12 and other Th1 differentiation-inducing cytokines in cells induced to differentiate toward Th1 lineage and down-regulated by IL-4 in cells induced to Th2. (PMID:18701445)
• Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet’s disease (PMID:23041938)
• GIMAP4 regulates secretion of cytokines in early differentiating human CD4(+) T helper lymphocytes and in particular the secretion of interferon-gamma also affecting its downstream targets. (PMID:25287446)
• Prognostic Value of GIMAP4 and Its Role in Promoting Immune Cell Infiltration into Tumor Microenvironment of Lung Adenocarcinoma. (PMID:36246963)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gimap4	ENSMUSG00000054435
rattus_norvegicus	Gimap4	ENSRNOG00000008369

Paralogs (7): GIMAP2 (ENSG00000106560), GIMAP6 (ENSG00000133561), GIMAP8 (ENSG00000171115), GIMAP7 (ENSG00000179144), GIMAP5 (ENSG00000196329), GIMAP1 (ENSG00000213203), GIMD1 (ENSG00000250298)

Protein

Protein identifiers

GTPase IMAP family member 4 — Q9NUV9 (reviewed: Q9NUV9)

Alternative names: Immunity-associated nucleotide 1 protein, Immunity-associated protein 4

All UniProt accessions (4): A0A090N7X0, C9IZQ3, Q9NUV9, G5E9W9

UniProt curated annotations — full annotation on UniProt →

Function. During thymocyte development, may play a role in the regulation of apoptosis. GTPase which exhibits a higher affinity for GDP than for GTP.

Subunit / interactions. May interact (via IQ domain) with calmodulin/CALM1 only in the absence of Ca(2+). Interacts with BAX, but not with other Bcl-2 family members.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Highly expressed in spleen and peripheral blood leukocytes that contain mostly T- and B-lymphocytes. Expressed specifically in resting T- and B-lymphocytes and expression significantly decreases during B- or T-lymphocyte activation. Expressed at lower levels in thymus, ovary, colon and small intestine.

Post-translational modifications. Phosphorylated at very low levels in resting splenocytes. Rapidly and transiently phosphorylated in response to splenocyte activation.

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

RefSeq proteins (2): NP_001350461, NP_060796* (*=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 (30 total): helix 7, strand 6, region of interest 6, binding site 4, domain 2, chain 1, compositionally biased region 1, sequence variant 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3LXX	X-RAY DIFFRACTION	2.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUV9-F1	85.98	0.68

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): 37–45; 58; 155–157; 191

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GNF2_CASP8, MORI_SMALL_PRE_BII_LYMPHOCYTE_DN, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_UP, LEE_EARLY_T_LYMPHOCYTE_DN, KIM_GERMINAL_CENTER_T_HELPER_UP, SANSOM_APC_TARGETS_DN, PU1_Q6, GREENBAUM_E2A_TARGETS_DN, FARMER_BREAST_CANCER_CLUSTER_1, CUI_TCF21_TARGETS_2_DN, RGAGGAARY_PU1_Q6, BOQUEST_STEM_CELL_DN, ZHENG_BOUND_BY_FOXP3, MARSON_BOUND_BY_FOXP3_UNSTIMULATED

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

1592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GIMAP4	TAL1	P17542	532
GIMAP4	GIMAP5	Q96F15	478
GIMAP4	GIMAP6	Q6P9H5	459
GIMAP4	AIG1	Q9NVV5	442
GIMAP4	ARHGAP30	Q7Z6I6	442
GIMAP4	BCL2L1	Q07817	423
GIMAP4	PANX1	Q96RD7	415
GIMAP4	KLRK1	P26718	411
GIMAP4	GIMAP8	Q8ND71	399
GIMAP4	ZNF775	Q96BV0	378
GIMAP4	OR13C5	Q8NGS8	372
GIMAP4	KLRC4	O43908	366
GIMAP4	FGF17	O60258	354
GIMAP4	FGF13	Q92913	354
GIMAP4	IL3	P08700	352

IntAct

5 interactions, top by confidence:

A	B	Type	Score
GIMAP4	GNA13	psi-mi:“MI:0915”(physical association)	0.400
CFTR	GIMAP4	psi-mi:“MI:0915”(physical association)	0.370
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
nhaD	GIMAP4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): GIMAP4 (Reconstituted Complex), GNA13 (Affinity Capture-MS), RBFOX2 (Two-hybrid), GIMAP4 (PCA), GIMAP4 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A1E2I4, A7VK00, B0BMZ3, E9PW74, F4HT21, G3MZQ6, G3X987, O81025, P09922, P0DJR0, P18588, P18589, P18590, P20591, P27473, P32455, P33237, P54120, P79135, Q28379, Q4ADG6, Q4ADG7, Q4ADG8, Q4KLG2, Q5D1D6, Q5R5G3, Q5RBE1, Q75N62, Q8BV66, Q8K3K9, Q8N8V2, Q8ND71, Q8NHV1, Q8TCB0, Q99JY3, Q9BDB7, Q9C8U2, Q9C8U5, Q9C8U6, Q9C8U7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

316 predictions. Top by Δscore:

Variant	Effect	Δscore
7:150569955:T:G	donor_gain	0.9900
7:150572118:T:TA	acceptor_gain	0.9900
7:150567433:TTCAG:T	donor_loss	0.9800
7:150567434:TCAG:T	donor_loss	0.9800
7:150567435:CAGGT:C	donor_loss	0.9800
7:150567436:AGGTA:A	donor_loss	0.9800
7:150567438:GTA:G	donor_loss	0.9800
7:150567439:T:G	donor_loss	0.9800
7:150569999:G:T	donor_gain	0.9800
7:150572127:A:AG	acceptor_gain	0.9800
7:150572127:AG:A	acceptor_gain	0.9800
7:150572128:G:GG	acceptor_gain	0.9800
7:150572128:GG:G	acceptor_gain	0.9800
7:150572128:GGGC:G	acceptor_gain	0.9800
7:150569887:GGA:G	acceptor_gain	0.9700
7:150572126:CAG:C	acceptor_loss	0.9700
7:150568211:G:GG	donor_gain	0.9600
7:150569967:GGCAT:G	donor_gain	0.9600
7:150572121:T:A	acceptor_gain	0.9600
7:150572121:T:G	acceptor_gain	0.9600
7:150572127:AGG:A	acceptor_gain	0.9600
7:150572128:GGG:G	acceptor_gain	0.9600
7:150572118:T:A	acceptor_loss	0.9500
7:150572128:GGGCC:G	acceptor_gain	0.9500
7:150569957:ATGGT:A	donor_loss	0.9400
7:150569958:TGG:T	donor_loss	0.9400
7:150569959:GGTGA:G	donor_loss	0.9400
7:150569960:GTGAG:G	donor_loss	0.9400
7:150569961:T:A	donor_loss	0.9400
7:150569962:GA:G	donor_loss	0.9400

AlphaMissense

2176 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:150572198:A:T	K43I	0.988
7:150572236:T:C	F56L	0.988
7:150572238:T:A	F56L	0.988
7:150572238:T:G	F56L	0.988
7:150572197:A:C	K43Q	0.985
7:150572198:A:C	K43T	0.979
7:150572325:C:A	D85E	0.977
7:150572325:C:G	D85E	0.977
7:150572512:T:C	F148L	0.975
7:150572514:C:A	F148L	0.975
7:150572514:C:G	F148L	0.975
7:150572199:A:C	K43N	0.974
7:150572199:A:T	K43N	0.974
7:150572491:T:C	F141L	0.972
7:150572493:T:A	F141L	0.972
7:150572493:T:G	F141L	0.972
7:150572534:G:C	R155P	0.970
7:150572197:A:G	K43E	0.969
7:150572323:G:C	D85H	0.968
7:150572200:A:C	S44R	0.967
7:150572202:T:A	S44R	0.967
7:150572202:T:G	S44R	0.967
7:150572684:T:C	L205S	0.965
7:150572180:G:T	G37V	0.962
7:150572614:T:C	F182L	0.962
7:150572616:C:A	F182L	0.962
7:150572616:C:G	F182L	0.962
7:150572338:T:C	F90L	0.961
7:150572340:C:A	F90L	0.961
7:150572340:C:G	F90L	0.961

dbSNP variants (sampled 300 via entrez): RS1000008363 (7:150566971 A>C), RS1000062778 (7:150567741 C>G), RS1000076770 (7:150568171 G>A), RS1000499613 (7:150571220 G>A), RS1000608830 (7:150565490 T>A,C), RS1000675234 (7:150566577 A>G), RS1001666257 (7:150573243 G>A), RS1001815538 (7:150566496 A>G), RS1001965946 (7:150571319 C>T), RS1001998565 (7:150571554 G>T), RS1002181964 (7:150569662 C>T), RS1003649916 (7:150569783 A>G,T), RS1003680938 (7:150570064 C>T), RS1005222137 (7:150573351 T>A), RS1005658330 (7:150567013 G>T)

Disease associations

OMIM: gene MIM:608087 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007446_20	vWF levels	3.000000e-08
GCST007446_27	vWF levels	2.000000e-08
GCST007446_3	vWF levels	6.000000e-08
GCST007446_62	vWF levels	7.000000e-09
GCST010244_266	Triglyceride levels	3.000000e-17
GCST90002382_166	Eosinophil percentage of white cells	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	increases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	increases reaction, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Pioglitazone	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases reaction, decreases expression, affects cotreatment	1
Nickel	decreases expression	1
Polystyrenes	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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