GGT5

Summary

GGT5 (gamma-glutamyltransferase 5, HGNC:4260) is a protein-coding gene on chromosome 22q11.23, encoding Glutathione hydrolase 5 proenzyme (P36269). Cleaves the gamma-glutamyl bond of extracellular glutathione tripeptide (gamma-Glu-Cys-Gly) and certain glutathione conjugates.

This gene is a member of the gamma-glutamyl transpeptidase gene family, and some reports indicate that it is capable of cleaving the gamma-glutamyl moiety of glutathione. The protein encoded by this gene is synthesized as a single, catalytically-inactive polypeptide, that is processed post-transcriptionally to form a heavy and light subunit, with the catalytic activity contained within the small subunit. The encoded enzyme is able to convert leukotriene C4 to leukotriene D4, but appears to have distinct substrate specificity compared to gamma-glutamyl transpeptidase. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 2687 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 133 total — 1 pathogenic
• MANE Select transcript: NM_004121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4260
Approved symbol	GGT5
Name	gamma-glutamyltransferase 5
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	GGT-REL
Ensembl gene	ENSG00000099998
Ensembl biotype	protein_coding
OMIM	137168
Entrez	2687

Gene structure

Transcript identifiers

Ensembl transcripts: 52 — 51 protein_coding, 1 retained_intron

ENST00000263112, ENST00000327365, ENST00000398292, ENST00000424217, ENST00000425408, ENST00000623756, ENST00000907654, ENST00000907655, ENST00000907656, ENST00000907657, ENST00000907658, ENST00000907659, ENST00000907660, ENST00000907661, ENST00000907662, ENST00000907663, ENST00000907664, ENST00000907665, ENST00000907666, ENST00000907667, ENST00000907668, ENST00000907669, ENST00000907670, ENST00000907671, ENST00000907672, ENST00000907673, ENST00000907674, ENST00000907675, ENST00000907676, ENST00000907677, ENST00000907678, ENST00000907679, ENST00000907680, ENST00000907681, ENST00000907682, ENST00000907683, ENST00000941026, ENST00000941027, ENST00000941028, ENST00000941029, ENST00000941030, ENST00000941031, ENST00000941032, ENST00000941033, ENST00000941034, ENST00000941035, ENST00000941036, ENST00000941037, ENST00000941038, ENST00000941039, ENST00000941040, ENST00000941041

RefSeq mRNA: 5 — MANE Select: NM_004121 NM_001099781, NM_001099782, NM_001302464, NM_001302465, NM_004121

CCDS: CCDS13825, CCDS42989, CCDS42990

Canonical transcript exons

ENST00000327365 — 12 exons

Exon	Start	End
ENSE00000879531	24232051	24232208
ENSE00000910938	24233498	24233593
ENSE00000910941	24233874	24234004
ENSE00001615911	24226076	24226266
ENSE00001633537	24225245	24225411
ENSE00001714442	24226631	24226767
ENSE00001734797	24244553	24245082
ENSE00001742378	24224996	24225106
ENSE00001750189	24219660	24220116
ENSE00001756157	24231384	24231530
ENSE00001765405	24225546	24225652
ENSE00003644772	24232823	24233018

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 97.72.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.72	gold quality
right coronary artery	UBERON:0001625	97.62	gold quality
left lobe of thyroid gland	UBERON:0001120	97.27	gold quality
left coronary artery	UBERON:0001626	97.15	gold quality
coronary artery	UBERON:0001621	96.51	gold quality
left uterine tube	UBERON:0001303	96.43	gold quality
metanephros cortex	UBERON:0010533	96.43	gold quality
endocervix	UBERON:0000458	95.94	gold quality
omental fat pad	UBERON:0010414	95.90	gold quality
peritoneum	UBERON:0002358	95.83	gold quality
right atrium auricular region	UBERON:0006631	95.62	gold quality
thyroid gland	UBERON:0002046	95.45	gold quality
mucosa of stomach	UBERON:0001199	94.91	gold quality
nerve	UBERON:0001021	94.82	gold quality
tibial nerve	UBERON:0001323	94.82	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.50	gold quality
popliteal artery	UBERON:0002250	94.37	gold quality
tibial artery	UBERON:0007610	94.36	gold quality
apex of heart	UBERON:0002098	94.33	gold quality
ascending aorta	UBERON:0001496	94.14	gold quality
aorta	UBERON:0000947	94.13	gold quality
thoracic aorta	UBERON:0001515	94.11	gold quality
ectocervix	UBERON:0012249	94.09	gold quality
right adrenal gland	UBERON:0001233	93.88	gold quality
left adrenal gland	UBERON:0001234	93.86	gold quality
left adrenal gland cortex	UBERON:0035825	93.81	gold quality
gall bladder	UBERON:0002110	93.41	gold quality
cardiac atrium	UBERON:0002081	93.35	gold quality
right adrenal gland cortex	UBERON:0035827	93.27	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	53.98
E-CURD-46	yes	19.95
E-HCAD-4	yes	19.78
E-MTAB-8410	yes	18.59
E-ANND-3	yes	16.84
E-GEOD-84465	yes	8.97
E-GEOD-81547	yes	8.25
E-HCAD-35	yes	6.59
E-GEOD-137537	yes	6.50
E-MTAB-10553	yes	5.73
E-HCAD-9	yes	5.70
E-HCAD-25	yes	4.28
E-HCAD-30	no	123.93
E-MTAB-10137	no	5.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting GGT5, 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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-204-3P	97.80	66.84	1656
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-4646-5P	97.70	66.84	1692
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-4515	95.70	65.73	716
HSA-MIR-6732-5P	93.97	64.65	422
HSA-MIR-1269A	92.75	64.61	542
HSA-MIR-1269B	92.75	64.73	538

Literature-anchored findings (GeneRIF, showing 7)

• There is a significant association of GGT with individual metabolic syndrome components, except HDL and inflammatory parameters (hs-CRP, ferritin). (PMID:24847614)
• Report different pattern of expression of GGT1 and GGT5 in normal human tissues. (PMID:25377544)
• Formation of LTD4 was rapid when catalyzed by gamma-glutamyl transpeptidase (GGT)1 in the A549 epithelial lung cancer cell line, but considerably slower when catalyzed by GGT5 in primary bronchial epithelial cells. When A549 cells were cultured in the presence of IL-1beta, GGT1 expression increased about 2-fold. Also exosomes from A549 cells contained GGT1 and augmented LTD4 formation. (PMID:27436590)
• Cancer-associated fibroblasts-derived gamma-glutamyltransferase 5 promotes tumor growth and drug resistance in lung adenocarcinoma. (PMID:32640421)
• Abcc1 and Ggt5 support lymphocyte guidance through export and catabolism of S-geranylgeranyl-l-glutathione. (PMID:34088745)
• GGT5 facilitates migration and invasion through the induction of epithelial-mesenchymal transformation in gastric cancer. (PMID:38581025)
• GGT5: a potential immunotherapy response inhibitor in gastric cancer by modulating GSH metabolism and sustaining memory CD8+ T cell infiltration. (PMID:38748299)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ggt5a	ENSDARG00000052045
danio_rerio		ENSDARG00000078258
mus_musculus	Ggt5	ENSMUSG00000006344
rattus_norvegicus	AABR07044631.2	ENSRNOG00000062276
drosophila_melanogaster	CG17636	FBGN0025837
drosophila_melanogaster	CG1492	FBGN0030361
drosophila_melanogaster	CG4829	FBGN0030796
drosophila_melanogaster	Ggt-1	FBGN0030932
caenorhabditis_elegans		WBGENE00012416
caenorhabditis_elegans	C53D5.5	WBGENE00016906

Paralogs (6): GGT1 (ENSG00000100031), GGTLC2 (ENSG00000100121), GGT7 (ENSG00000131067), GGTLC1 (ENSG00000149435), GGT6 (ENSG00000167741), GGTLC3 (ENSG00000274252)

Protein

Protein identifiers

Glutathione hydrolase 5 proenzyme — P36269 (reviewed: P36269)

Alternative names: Gamma-glutamyl transpeptidase-related enzyme, Gamma-glutamyltransferase 5, Gamma-glutamyltransferase-like activity 1, Gamma-glutamyltranspeptidase 5, Leukotriene-C4 hydrolase

All UniProt accessions (3): P36269, C9JU68, H7C1X2

UniProt curated annotations — full annotation on UniProt →

Function. Cleaves the gamma-glutamyl bond of extracellular glutathione tripeptide (gamma-Glu-Cys-Gly) and certain glutathione conjugates. Hydrolyzes glutathione releasing L-Glu and Cys-Gly dipeptide which is further metabolized to maintain extracellular cysteine levels but also to provide cysteine necessary for intracellular glutathione synthesis. Among glutathione-S-conjugates metabolizes leukotriene C4 (LTC4) and S-geranylgeranyl-glutathione (GGG), but is inactive toward gamma-glutamyl leucine. Converts extracellular LTC4 to LTD4 during acute inflammatory response. Acts as a negative regulator of GGG bioactivity. GGT5 (via GGG catabolism) and ABCC1 (via extracellular transport) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to bone marrow parenchyma. The transpeptidation reaction, i.e. the transfer of gamma-glutamyl moiety to an acceptor molecule to yield a new gamma-glutamyl compound requires high concentration of dipeptide acceptor and is considered nonphysiological.

Subunit / interactions. Heterodimer composed of the light and heavy chains. The active site is located in the light chain.

Subcellular location. Membrane.

Tissue specificity. Expressed in follicular dendritic cells in lymphoid follicles (at protein level).

Post-translational modifications. Cleaved by autocatalysis into a large and a small subunit. Glycosylated.

Activity regulation. Inhibited by serine-borate.

Pathway. Sulfur metabolism; glutathione metabolism. Lipid metabolism; leukotriene D4 biosynthesis.

Miscellaneous. A previous study reported that GSH and oxidized glutathione (GSSG) are not substrates for murine GGT5. However, this result contrasts with two studies reported that GSH is indeed a substrate for GGT5.

Similarity. Belongs to the gamma-glutamyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P36269-1	1	yes
P36269-2	2
P36269-3	3

RefSeq proteins (5): NP_001093251, NP_001093252, NP_001289393, NP_001289394, NP_004112* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000101	GGT_peptidase	Family
IPR029055	Ntn_hydrolases_N	Homologous_superfamily
IPR043137	GGT_ssub_C	Homologous_superfamily
IPR043138	GGT_lsub	Homologous_superfamily
IPR055262	GGT_CS	Conserved_site

Pfam: PF01019

Enzyme classification (BRENDA):

• EC 2.3.2.2 — gamma-glutamyltransferase (BRENDA: 55 organisms, 489 substrates, 299 inhibitors, 203 Km, 46 kcat entries)
• EC 3.4.19.13 — glutathione gamma-glutamate hydrolase (BRENDA: 24 organisms, 31 substrates, 20 inhibitors, 29 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

54 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
5-L-GLUTAMYL-4-NITROANILIDE	0.0109–15.3	33
L-GLU-4-NITROANILIDE	0.0068–4	27
L-GAMMA-GLUTAMYL-4-NITROANILIDE	0.021–10.6	21
GLYCYLGLYCINE	0.007–590	17
GLUTATHIONE	0.0057–18	9
L-GLUTAMIC ACID-(4-NITROANILIDE)	0.0125–1.06	8
GSH	0.0105–0.66	6
GSSG	0.008–0.44	6
GAMMA-L-GLUTAMYL-4-NITROANILIDE	0.0143–0.1	5
5-L-GLUTAMYL-7-AMIDO-4-METHYLCOUMARIN	0.03–0.49	4
GAMMA-GLU-CYS	0.038–2.4	4
GS-BIMANE	0.21–0.47	4
L-GLUTAMINE	0.0013–0.52	4
(GAMMA-L-GLUTAMYL)-4-NITROANILIDE	0.046–0.054	3
GLUTAMYL-(3-CARBOXYL)-4-NITROANILIDE	16.7–26.9	3

Catalyzed reactions (Rhea), 5 shown:

• an N-terminal (5-L-glutamyl)-[peptide] + an alpha-amino acid = 5-L-glutamyl amino acid + an N-terminal L-alpha-aminoacyl-[peptide] (RHEA:23904)
• glutathione + H2O = L-cysteinylglycine + L-glutamate (RHEA:28807)
• leukotriene C4 + H2O = leukotriene D4 + L-glutamate (RHEA:31563)
• an S-substituted glutathione + H2O = an S-substituted L-cysteinylglycine + L-glutamate (RHEA:59468)
• S-[(2E,6E,10E)-geranylgeranyl]-L-glutathione + H2O = S-[(2E,6E,10E)-geranylgeranyl]-L-cysteinylglycine + L-glutamate (RHEA:65120)

UniProt features (24 total): glycosylation site 6, sequence variant 4, binding site 4, chain 2, splice variant 2, topological domain 2, sequence conflict 2, transmembrane region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36269-F1	92.40	0.82

Functional residue map

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

Catalytic / active sites (1): 388 (nucleophile)

Ligand- & substrate-binding residues (4): 110; 406; 427; 469–470

Glycosylation sites (6): 98, 204, 303, 347, 535, 550

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-174403	Glutathione synthesis and recycling
R-HSA-2142691	Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-5423646	Aflatoxin activation and detoxification
R-HSA-9664535	LTC4-CYSLTR mediated IL4 production
R-HSA-9753281	Paracetamol ADME

MSigDB gene sets: 189 (showing top): MORF_RAGE, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_INFLAMMATORY_RESPONSE, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GOBP_LEUKOTRIENE_BIOSYNTHETIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_PEPTIDE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_LEUKOCYTE_MIGRATION, GOBP_SULFUR_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_SULFUR_COMPOUND_CATABOLIC_PROCESS, KEGG_TAURINE_AND_HYPOTAURINE_METABOLISM, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_NONRIBOSOMAL_PEPTIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (10): proteolysis (GO:0006508), amino acid metabolic process (GO:0006520), fatty acid metabolic process (GO:0006631), glutathione biosynthetic process (GO:0006750), glutathione catabolic process (GO:0006751), inflammatory response (GO:0006954), lymphocyte migration (GO:0072676), leukotriene D4 biosynthetic process (GO:1901750), glutathione metabolic process (GO:0006749), leukotriene biosynthetic process (GO:0019370)

GO Molecular Function (8): peptidyltransferase activity (GO:0000048), leukotriene-C(4) hydrolase activity (GO:0002951), glutathione gamma-glutamate hydrolase (GO:0036374), obsolete leukotriene C4 gamma-glutamyl transferase activity (GO:0103068), peptidase activity (GO:0008233), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Glutathione conjugation	1
Arachidonate metabolism	1
Biological oxidations	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Drug ADME	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glutathione metabolic process	2
sulfur compound biosynthetic process	2
catalytic activity, acting on a protein	2
omega peptidase activity	2
catalytic activity	2
protein metabolic process	1
primary metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
nonribosomal peptide biosynthetic process	1
modified amino acid biosynthetic process	1
modified amino acid catabolic process	1
sulfur compound catabolic process	1
defense response	1
mononuclear cell migration	1
leukotriene biosynthetic process	1
fatty acid derivative biosynthetic process	1
modified amino acid metabolic process	1
sulfur compound metabolic process	1
leukotriene metabolic process	1
icosanoid biosynthetic process	1
aminoacyltransferase activity	1
catalytic activity, acting on a tRNA	1
threonine-type peptidase activity	1
hydrolase activity	1
transferase activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1064 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGT5	GNB5	O14775	967
GGT5	RGS6	P49758	916
GGT5	RGS7	P49802	862
GGT5	RGS11	O94810	859
GGT5	RGS9BP	Q6ZS82	814
GGT5	SUCLG2	Q96I99	811
GGT5	RGS9	O75916	712
GGT5	ALPG	P10696	698
GGT5	PLEK2	Q9NYT0	665
GGT5	RGS7BP	Q6MZT1	664
GGT5	GOT1L1	Q8NHS2	650
GGT5	PLEK	P08567	632
GGT5	GOT1	P17174	593
GGT5	ALPI	P09923	591
GGT5	ALPP	P05187	588

IntAct

6 interactions, top by confidence:

A	B	Type	Score
GGT5	POTEI	psi-mi:“MI:0914”(association)	0.530
	TK2	psi-mi:“MI:0915”(physical association)	0.400
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): MVK (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), POTEI (Affinity Capture-MS), SLC1A4 (Affinity Capture-MS), GGT5 (Affinity Capture-MS), POTEI (Affinity Capture-MS), MVK (Affinity Capture-MS), SLC20A2 (Affinity Capture-MS), GGT5 (Negative Genetic), GGTLC1 (Negative Genetic)

ESM2 similar proteins: A6NGU5, B5MD39, B6EWW8, D4B387, F8S0Z7, O35409, O77564, P07314, P07686, P0DPU3, P0DPU6, P15693, P17439, P19111, P19440, P20735, P21588, P24822, P24823, P36268, P36269, P49614, P58242, P70627, Q04609, Q05927, Q0V8L2, Q14390, Q29548, Q2KHZ8, Q501L1, Q5RFI5, Q5RFU0, Q5TYS5, Q5XIG6, Q60928, Q680I5, Q68FH4, Q6DH69, Q6GMR7

Diamond homologs: A6NGU5, B5MD39, B8NM71, D4B387, O14194, P07314, P0DPU3, P0DPU6, P18956, P19440, P20735, P36267, P36268, P36269, P54422, P63186, Q05902, Q0V8L2, Q14390, Q60928, Q680I5, Q8VYW6, Q99JP7, Q99MZ4, Q9BX51, Q9CAR5, Q9I406, Q9M0G0, Q9QWE9, Q9UJ14, Q9US04, Q9Z2A9, A6T9C8, P15557, Q05053, Q6IE08, A7YWM1, Q51693, P74181

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	104
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
684928	GRCh37/hg19 22q11.23(chr22:23650871-25066472)x3	Pathogenic

SpliceAI

2425 predictions. Top by Δscore:

Variant	Effect	Δscore
22:24224991:CTCA:C	donor_loss	1.0000
22:24224992:TCA:T	donor_loss	1.0000
22:24224994:ACC:A	donor_loss	1.0000
22:24224995:C:A	donor_loss	1.0000
22:24224995:CCTGG:C	donor_gain	1.0000
22:24225102:ATGGC:A	acceptor_gain	1.0000
22:24225103:TGGC:T	acceptor_gain	1.0000
22:24225104:GGC:G	acceptor_gain	1.0000
22:24225105:GC:G	acceptor_gain	1.0000
22:24225105:GCCTG:G	acceptor_loss	1.0000
22:24225106:CC:C	acceptor_gain	1.0000
22:24225107:C:CA	acceptor_loss	1.0000
22:24225107:C:CC	acceptor_gain	1.0000
22:24225108:T:C	acceptor_loss	1.0000
22:24225542:TCACC:T	donor_loss	1.0000
22:24225543:CACCA:C	donor_loss	1.0000
22:24225544:ACCA:A	donor_loss	1.0000
22:24225660:CG:C	acceptor_gain	1.0000
22:24225661:G:C	acceptor_gain	1.0000
22:24226267:C:CC	acceptor_gain	1.0000
22:24226625:CCTCA:C	donor_loss	1.0000
22:24226626:CTCA:C	donor_loss	1.0000
22:24226628:CACCT:C	donor_loss	1.0000
22:24226629:ACCTG:A	donor_loss	1.0000
22:24226766:CC:C	acceptor_gain	1.0000
22:24226767:CC:C	acceptor_gain	1.0000
22:24226767:CCTG:C	acceptor_loss	1.0000
22:24226768:C:CA	acceptor_loss	1.0000
22:24226768:C:CC	acceptor_gain	1.0000
22:24231383:CCT:C	donor_gain	1.0000

AlphaMissense

3745 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:24233947:G:C	C77W	0.995
22:24226090:G:C	S405R	0.994
22:24226090:G:T	S405R	0.994
22:24226092:T:G	S405R	0.994
22:24233949:A:G	C77R	0.992
22:24244567:G:C	C53W	0.992
22:24233948:C:T	C77Y	0.991
22:24220044:C:G	A563P	0.990
22:24225608:T:A	N425I	0.990
22:24232942:C:A	W159C	0.990
22:24232942:C:G	W159C	0.990
22:24233948:C:G	C77S	0.990
22:24233949:A:T	C77S	0.990
22:24244568:C:T	C53Y	0.990
22:24225647:C:T	G412E	0.986
22:24226088:G:A	T406I	0.986
22:24233973:C:G	D69H	0.986
22:24244568:C:G	C53S	0.986
22:24244569:A:G	C53R	0.986
22:24244569:A:T	C53S	0.986
22:24244589:A:T	V46D	0.986
22:24244565:G:C	S54W	0.985
22:24244581:C:G	D49H	0.984
22:24244584:C:G	A48P	0.983
22:24220004:T:A	D576V	0.982
22:24225283:C:A	G489W	0.982
22:24226097:G:T	A403D	0.982
22:24219997:C:A	R578S	0.981
22:24219997:C:G	R578S	0.981
22:24219998:C:A	R578M	0.981

dbSNP variants (sampled 300 via entrez): RS1000213324 (22:24226219 G>A), RS1000229856 (22:24221544 G>A,T), RS1000438926 (22:24245510 C>A), RS1000470174 (22:24245370 G>A,C), RS1000482412 (22:24235381 T>C,G), RS1000493290 (22:24231979 C>G,T), RS1000539564 (22:24221887 C>T), RS1000597090 (22:24241429 G>A), RS1000762737 (22:24232298 C>G), RS1000872425 (22:24224536 A>G), RS1001028544 (22:24241173 A>C,G), RS1001120975 (22:24229855 A>G), RS1001126440 (22:24222844 A>C,G), RS1001270585 (22:24243576 A>G), RS1001271560 (22:24227776 C>A,T)

Disease associations

OMIM: gene MIM:137168 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001981_2	Amyotrophic lateral sclerosis	2.000000e-09
GCST002481_6	Acne (severe)	6.000000e-07
GCST004606_97	Eosinophil count	2.000000e-09
GCST004608_119	Granulocyte percentage of myeloid white cells	7.000000e-12
GCST004609_168	Monocyte percentage of white cells	3.000000e-14
GCST004624_29	Sum eosinophil basophil counts	8.000000e-11
GCST004625_195	Monocyte count	4.000000e-25
GCST008159_8	Waist-to-hip ratio adjusted for BMI	9.000000e-06
GCST011947_22	White matter hyperintensity volume	2.000000e-06
GCST011950_26	White matter hyperintensity volume (adjusted for hypertension)	6.000000e-06
GCST90002381_440	Eosinophil count	2.000000e-28
GCST90002382_501	Eosinophil percentage of white cells	4.000000e-17
GCST90002390_312	Mean corpuscular hemoglobin	2.000000e-09
GCST90002392_130	Mean corpuscular volume	1.000000e-11
GCST90002393_587	Monocyte count	5.000000e-37
GCST90002394_207	Monocyte percentage of white cells	1.000000e-14
GCST90002407_193	White blood cell count	9.000000e-18

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005665	white matter hyperintensity measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
Acrolein	increases expression, increases abundance, affects cotreatment	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	increases activity, affects binding, decreases expression	1
lead acetate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
maleic acid	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases expression	1
Fluticasone	increases activity, increases metabolic processing, increases expression	1
Troglitazone	decreases expression	1
Allergens	increases expression	1
Beclomethasone	increases activity, increases metabolic processing, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Progesterone	increases expression	1
Thiram	decreases expression	1

Clinical trials (associated diseases)

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