GIT2

Summary

GIT2 (GIT ArfGAP 2, HGNC:4273) is a protein-coding gene on chromosome 12q24.11, encoding ARF GTPase-activating protein GIT2 (Q14161). GTPase-activating protein for ADP ribosylation factor family members, including ARF1.

This gene encodes a member of the GIT protein family, which interact with G protein-coupled receptor kinases and possess ADP-ribosylation factor (ARF) GTPase-activating protein (GAP) activity. GIT proteins traffic between cytoplasmic complexes, focal adhesions, and the cell periphery, and interact with Pak interacting exchange factor beta (PIX) to form large oligomeric complexes that transiently recruit other proteins. GIT proteins regulate cytoskeletal dynamics and participate in receptor internalization and membrane trafficking. This gene has been shown to repress lamellipodial extension and focal adhesion turnover, and is thought to regulate cell motility. This gene undergoes extensive alternative splicing to generate multiple isoforms, but the full-length nature of some of these variants has not been determined. The various isoforms have functional differences, with respect to ARF GAP activity and to G protein-coupled receptor kinase 2 binding.

Source: NCBI Gene 9815 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 117 total
• MANE Select transcript: NM_057169

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4273
Approved symbol	GIT2
Name	GIT ArfGAP 2
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0148, PKL
Ensembl gene	ENSG00000139436
Ensembl biotype	protein_coding
OMIM	608564
Entrez	9815

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 28 protein_coding, 8 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000320063, ENST00000355312, ENST00000361006, ENST00000457474, ENST00000546613, ENST00000547267, ENST00000547694, ENST00000547815, ENST00000548000, ENST00000548643, ENST00000548655, ENST00000549999, ENST00000550186, ENST00000550480, ENST00000551209, ENST00000551455, ENST00000551721, ENST00000552978, ENST00000553118, ENST00000876494, ENST00000876495, ENST00000876496, ENST00000876497, ENST00000876498, ENST00000876499, ENST00000876500, ENST00000876501, ENST00000876502, ENST00000876503, ENST00000876504, ENST00000876505, ENST00000876506, ENST00000876507, ENST00000876508, ENST00000876509, ENST00000876510, ENST00000935696, ENST00000935697, ENST00000956023

RefSeq mRNA: 8 — MANE Select: NM_057169 NM_001135213, NM_001135214, NM_001330153, NM_001330154, NM_014776, NM_057169, NM_057170, NM_139201

CCDS: CCDS44968, CCDS44969, CCDS55884, CCDS81736, CCDS81737, CCDS9138, CCDS9139

Canonical transcript exons

ENST00000355312 — 20 exons

Exon	Start	End
ENSE00000938140	109945260	109945349
ENSE00002335873	109929804	109933190
ENSE00003305995	109947256	109947504
ENSE00003462211	109988963	109989068
ENSE00003480426	109951167	109951316
ENSE00003514875	109953092	109953234
ENSE00003516849	109934022	109934085
ENSE00003533288	109983373	109983503
ENSE00003537722	109983608	109983694
ENSE00003543003	109991627	109991760
ENSE00003548064	109939165	109939247
ENSE00003556117	109961613	109961685
ENSE00003578795	109965526	109965577
ENSE00003589341	109938380	109938568
ENSE00003592898	109961278	109961375
ENSE00003639479	109967458	109967503
ENSE00003657286	109980952	109981046
ENSE00003657338	109959847	109959958
ENSE00003757057	109989690	109989802
ENSE00003851122	109996173	109996368

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 95.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6390 / max 452.1721, expressed in 1817 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133212	12.2281	1800
133210	6.8418	1674
133208	0.8467	275
133209	0.7763	295
133213	0.7199	427
133211	0.7055	382
133207	0.4766	174
133206	0.0443	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.74	gold quality
mononuclear cell	CL:0000842	95.37	gold quality
leukocyte	CL:0000738	95.36	gold quality
middle temporal gyrus	UBERON:0002771	95.28	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.01	gold quality
granulocyte	CL:0000094	94.54	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.52	gold quality
blood	UBERON:0000178	94.26	gold quality
cerebellar hemisphere	UBERON:0002245	94.09	gold quality
cerebellar cortex	UBERON:0002129	93.99	gold quality
body of pancreas	UBERON:0001150	92.66	gold quality
visceral pleura	UBERON:0002401	92.63	gold quality
cerebellum	UBERON:0002037	92.49	gold quality
spleen	UBERON:0002106	92.43	gold quality
bone marrow	UBERON:0002371	92.32	gold quality
secondary oocyte	CL:0000655	92.26	gold quality
bone marrow cell	CL:0002092	92.15	gold quality
primary visual cortex	UBERON:0002436	92.13	gold quality
lymph node	UBERON:0000029	92.12	gold quality
heart right ventricle	UBERON:0002080	91.94	gold quality
parietal pleura	UBERON:0002400	91.92	gold quality
right ovary	UBERON:0002118	91.11	gold quality
colonic epithelium	UBERON:0000397	91.08	gold quality
adrenal tissue	UBERON:0018303	90.86	gold quality
left ovary	UBERON:0002119	90.73	gold quality
tonsil	UBERON:0002372	90.72	gold quality
left adrenal gland	UBERON:0001234	90.71	gold quality
tibia	UBERON:0000979	90.61	gold quality
right lobe of thyroid gland	UBERON:0001119	90.59	gold quality
sural nerve	UBERON:0015488	90.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting GIT2, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3910	99.95	71.13	2227
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-141-3P	99.94	72.79	2421

Literature-anchored findings (GeneRIF, showing 14)

• Git2-short, weakly interacting with paxillin, functions in the regulation of Golgi organization, actin cytoskeletal organization, and subcellular localization of paxillin, important in integrin-mediated cell adhesion and intracellular signaling. (PMID:11251077)
• GIT2 protein is tightly associated with PIX family Rac1/Cdc42 guanine nucleotide exchange factors as a multimeric nexus capable of linking together important signaling molecules. (PMID:15212761)
• The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients. (PMID:16501306)
• GTI proteins regulate cytoskeletal dynamics by feedback inhibition of Rac1, they participate in receptor internalization by regulating membrane trafficking between (PMID:16598076)
• These results suggest that inactivation of GIT2 function is a required step for induction of cell motility and that GIT2 may be a target of oncogenic signaling pathways that regulate cell migration. (PMID:16628223)
• Zeb1 is regulated by the Arf GTPase-activating protein (GAP) Git2. (PMID:23591815)
• ADMA and L-arginine are substrates of human CAT2A, CAT2B, OCT2 and MATE1. Transport kinetics of CAT2A, CAT2B, and OCT2 indicate a low affinity, high capacity transport, which may be relevant for renal and hepatic elimination of ADMA or L-arginine (PMID:23864433)
• GIT2 plays an important role in MRE11/ATM/H2AX-mediated DNA damage responses. (PMID:25605334)
• we discuss recent findings in key physiological systems that exemplify current understanding of the function of this important regulatory complex. Further, we draw attention to gaps in crucial information that remain to be filled to allow a better understanding of the many roles of the GIT-PIX complex in health and disease (PMID:27182061)
• Short-term EGF stimulation if of lung tumor cells can increase the interaction between RUSC2 and GIT2, prolonged stimulation leads to a decrease of their interaction through activating Rab35. (PMID:27238570)
• our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases. (PMID:27669437)
• GIT2 deficiency attenuates inflammation-induced expression of pro-labor mediators in human amnion and myometrial cellsdagger. (PMID:30915469)
• Long non-coding RNA MALAT1 promotes odontogenic differentiation of human dental pulp stem cells by impairing microRNA-140-5p-dependent downregulation of GIT2. (PMID:32743695)
• Genetic architecture of the inflammatory bowel diseases across East Asian and European ancestries. (PMID:37156999)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	git2b	ENSDARG00000042791
danio_rerio	git2a	ENSDARG00000061915
mus_musculus	Git2	ENSMUSG00000041890
rattus_norvegicus	Git2	ENSRNOG00000001190

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), AGFG1 (ENSG00000173744), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

ARF GTPase-activating protein GIT2 — Q14161 (reviewed: Q14161)

Alternative names: Cool-interacting tyrosine-phosphorylated protein 2, G protein-coupled receptor kinase-interactor 2, GRK-interacting protein 2

All UniProt accessions (5): Q14161, F8VXI9, F8W822, Q6FI58, R4GNG3

UniProt curated annotations — full annotation on UniProt →

Function. GTPase-activating protein for ADP ribosylation factor family members, including ARF1.

Subunit / interactions. May form heterooligomers with GIT1. Directly interacts with protein Piccolo/PCLO. Interacts with PPFIA1 and PPFIA2. Interacts with ARHGEF7. Identified in a complex with ARHGEF6 and BIN2. Interacts with PAK3. Interacts with PXN/paxillin. Interacts with TGFB1I1. Forms a complex with EFNB1 and GRB4/NCK2.

Isoforms (11)

UniProt ID	Names	Canonical?
Q14161-1	1	yes
Q14161-2	2, GIT2-short
Q14161-3	3, C-
Q14161-4	4, BC-
Q14161-5	5, E-
Q14161-6	6, CD-
Q14161-7	7, DE-
Q14161-8	8, BE-
Q14161-9	9, AE-
Q14161-10	10
Q14161-11	11

RefSeq proteins (8): NP_001128685, NP_001128686, NP_001317082, NP_001317083, NP_055591, NP_476510, NP_476511, NP_631940 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR013724	GIT_SHD	Domain
IPR022018	GIT1_C	Domain
IPR032352	GIT1/2_CC	Domain
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR047161	GIT-like	Family

Pfam: PF01412, PF08518, PF12205, PF12796, PF16559

UniProt features (40 total): modified residue 12, splice variant 9, compositionally biased region 5, repeat 3, sequence variant 3, region of interest 3, chain 1, domain 1, sequence conflict 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14161-F1	75.44	0.54

Functional residue map

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

Post-translational modifications (12): 394, 397, 401, 415, 418, 421, 484, 559, 562, 570, 587, 614

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013406	RHOQ GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9013424	RHOV GTPase cycle

MSigDB gene sets: 310 (showing top): MODULE_45, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GNF2_LYN, GOMF_GTPASE_BINDING, YY1_Q6, GOBP_SYNAPTIC_VESICLE_RECYCLING, AMIT_EGF_RESPONSE_480_MCF10A, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, MODULE_289, MARTINEZ_RB1_TARGETS_DN, GNF2_ICAM3, FISCHER_G2_M_CELL_CYCLE, TGANTCA_AP1_C, CCCNNNNNNAAGWT_UNKNOWN

GO Biological Process (4): brain development (GO:0007420), regulation of G protein-coupled receptor signaling pathway (GO:0008277), regulation of ARF protein signal transduction (GO:0032012), synaptic vesicle recycling (GO:0036465)

GO Molecular Function (6): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), protein binding (GO:0005515), kinase activity (GO:0016301), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), focal adhesion (GO:0005925), synapse (GO:0045202), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RHO GTPase cycle	8

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
central nervous system development	1
animal organ development	1
head development	1
G protein-coupled receptor signaling pathway	1
regulation of signal transduction	1
ARF protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
transport	1
establishment of localization in cell	1
synaptic vesicle cycle	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
GTPase binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
cation binding	1
nuclear lumen	1
cell-substrate junction	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GIT2	PXN	P49023	996
GIT2	ARHGEF6	Q15052	991
GIT2	ARHGEF7	Q14155	981
GIT2	GRK4	P32298	961
GIT2	GRK6	P43250	943
GIT2	GRK5	P34947	934
GIT2	RASA1	P20936	766
GIT2	VCL	P18206	726
GIT2	NCK1	P16333	710
GIT2	PAK3	O75914	700
GIT2	ARF6	P26438	694
GIT2	CDKN2A	P42771	673
GIT2	PAK1	Q13153	650
GIT2	PARVA	Q9NVD7	650
GIT2	ARF1	P10947	643

IntAct

175 interactions, top by confidence:

A	B	Type	Score
ARHGEF7	PAK1	psi-mi:“MI:0914”(association)	0.950
PAK1	NCK2	psi-mi:“MI:0914”(association)	0.940
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
PAK2	NCK2	psi-mi:“MI:0914”(association)	0.840
ARHGEF6	PAK1	psi-mi:“MI:0914”(association)	0.800
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
FBXO28	TRAF5	psi-mi:“MI:0914”(association)	0.740
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
GIT2	PXN	psi-mi:“MI:0915”(physical association)	0.690
ARHGEF7	GIT2	psi-mi:“MI:0915”(physical association)	0.670
GIT2	PAK1	psi-mi:“MI:0915”(physical association)	0.670
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
ARHGEF7	NCK2	psi-mi:“MI:0914”(association)	0.640
PFDN1	PFDN6	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
IKBKG	GIT2	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (194): GIT2 (Affinity Capture-RNA), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Proximity Label-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), ARHGEF6 (Affinity Capture-MS), ARHGEF7 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS), GIT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PTPN12	down-regulates	GIT2	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 150 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	31.4×	4e-05
Ephrin signaling	5	26.7×	7e-05
RHOV GTPase cycle	7	18.7×	1e-05
RHOU GTPase cycle	7	18.2×	1e-05
RHO GTPases activate PKNs	6	17.8×	7e-05
RHOQ GTPase cycle	7	11.9×	1e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	11.5×	4e-05
RHOJ GTPase cycle	6	11.2×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	12.4×	8e-03
mitotic spindle organization	6	11.7×	4e-03
endocytic recycling	6	11.6×	4e-03
cell migration	11	4.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3465 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109933189:TT:T	acceptor_gain	1.0000
12:109938375:CTTA:C	donor_loss	1.0000
12:109938376:TTA:T	donor_loss	1.0000
12:109938377:TAC:T	donor_loss	1.0000
12:109938378:ACC:A	donor_loss	1.0000
12:109938379:C:CG	donor_loss	1.0000
12:109938379:CCTGT:C	donor_gain	1.0000
12:109938568:CCT:C	acceptor_loss	1.0000
12:109938569:C:CC	acceptor_gain	1.0000
12:109938570:T:A	acceptor_loss	1.0000
12:109939037:TTAAG:T	donor_gain	1.0000
12:109939137:C:A	donor_gain	1.0000
12:109939151:T:TA	donor_gain	1.0000
12:109939246:GCC:G	acceptor_loss	1.0000
12:109939247:CCT:C	acceptor_loss	1.0000
12:109939248:C:CC	acceptor_gain	1.0000
12:109939248:CT:C	acceptor_loss	1.0000
12:109939249:T:C	acceptor_loss	1.0000
12:109945257:AAC:A	donor_gain	1.0000
12:109945257:AACC:A	donor_gain	1.0000
12:109945258:A:C	donor_gain	1.0000
12:109953086:TCTCA:T	donor_loss	1.0000
12:109953087:CTCA:C	donor_loss	1.0000
12:109953088:TCA:T	donor_loss	1.0000
12:109953089:CACCT:C	donor_loss	1.0000
12:109953091:C:CG	donor_loss	1.0000
12:109953091:CCTT:C	donor_gain	1.0000
12:109953230:ATTGT:A	acceptor_gain	1.0000
12:109953231:TTGT:T	acceptor_gain	1.0000
12:109953232:TGT:T	acceptor_gain	1.0000

AlphaMissense

5012 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109933009:A:T	V750D	1.000
12:109933012:A:G	L749P	1.000
12:109933017:C:A	K747N	1.000
12:109933017:C:G	K747N	1.000
12:109933019:T:C	K747E	1.000
12:109933021:G:T	A746D	1.000
12:109933022:C:G	A746P	1.000
12:109933025:C:G	A745P	1.000
12:109933030:G:T	A743D	1.000
12:109933031:C:G	A743P	1.000
12:109933033:A:T	I742N	1.000
12:109933040:A:C	Y740D	1.000
12:109933040:A:G	Y740H	1.000
12:109933042:G:T	A739E	1.000
12:109933051:A:T	I736N	1.000
12:109933129:A:G	L710P	1.000
12:109933138:G:T	A707D	1.000
12:109933150:A:G	L703P	1.000
12:109934041:A:C	M683R	1.000
12:109934041:A:T	M683K	1.000
12:109934050:A:T	V680D	1.000
12:109934062:A:C	I676R	1.000
12:109934062:A:T	I676K	1.000
12:109938401:G:T	A661D	1.000
12:109938410:A:G	L658S	1.000
12:109938413:A:G	L657P	1.000
12:109938422:A:C	I654R	1.000
12:109938422:A:T	I654K	1.000
12:109938434:A:C	I650S	1.000
12:109938455:A:T	V643D	1.000

dbSNP variants (sampled 300 via entrez): RS1000001728 (12:109955823 C>T), RS1000129338 (12:109963235 A>C,G), RS1000154710 (12:109995029 T>C), RS1000156171 (12:109963193 A>C), RS1000182247 (12:109963691 G>A), RS1000212854 (12:109956377 A>C), RS1000280322 (12:109995395 A>G), RS1000393697 (12:109970078 T>C), RS1000400103 (12:109949851 G>A,C), RS1000413870 (12:109942322 G>A), RS1000443099 (12:109962988 G>A), RS1000458172 (12:109956329 G>A), RS1000552033 (12:109958000 A>G), RS1000602985 (12:109954058 C>T), RS1000612918 (12:109996617 A>G,T)

Disease associations

OMIM: gene MIM:608564 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000753_10	Metabolic syndrome	7.000000e-06
GCST001822_15	Metabolite levels (MHPG)	4.000000e-07
GCST004953_2	Disturbances of the gamma-frequency band of electroencephalography measures in schizophrenia	4.000000e-06
GCST008103_145	Bipolar disorder	3.000000e-06
GCST009391_789	Metabolite levels	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0000195	metabolic syndrome
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0005133	MHPG measurement
EFO:0008388	gamma wave measurement
EFO:0010395	sphingomyelin 22:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment, decreases expression, affects expression	9
bisphenol A	decreases expression, affects cotreatment, decreases methylation	2
Formaldehyde	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression, decreases reaction, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
sodium arsenate	increases expression	1
trichostatin A	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	decreases expression	1
Decitabine	decreases expression, decreases reaction	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	affects expression	1

Clinical trials (associated diseases)

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