SYTL2

Summary

SYTL2 (synaptotagmin like 2, HGNC:15585) is a protein-coding gene on chromosome 11q14.1, encoding Synaptotagmin-like protein 2 (Q9HCH5). Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes.

The protein encoded by this gene is a synaptotagmin-like protein (SLP) that belongs to a C2 domain-containing protein family. The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTP-bound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27A-dependent vesicle trafficking and controls melanosome distribution in the cell periphery. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 54843 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 310 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_206927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15585
Approved symbol	SYTL2
Name	synaptotagmin like 2
Location	11q14.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20163, FLJ21219, KIAA1597, exophilin-4, CHR11SYT, SLP2, SGA72M, MGC102768, PPP1R151
Ensembl gene	ENSG00000137501
Ensembl biotype	protein_coding
OMIM	612880
Entrez	54843

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 26 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000316356, ENST00000359152, ENST00000389958, ENST00000389959, ENST00000389960, ENST00000438197, ENST00000524452, ENST00000524830, ENST00000524911, ENST00000525423, ENST00000525692, ENST00000525702, ENST00000526999, ENST00000527523, ENST00000527794, ENST00000528231, ENST00000528566, ENST00000529534, ENST00000529581, ENST00000529662, ENST00000530351, ENST00000531496, ENST00000532221, ENST00000532995, ENST00000533057, ENST00000533577, ENST00000533892, ENST00000534554, ENST00000634661, ENST00000897958, ENST00000897959, ENST00000897960, ENST00000897961, ENST00000897962, ENST00000897963, ENST00000966560

RefSeq mRNA: 47 — MANE Select: NM_206927 NM_001162951, NM_001162952, NM_001162953, NM_001289608, NM_001289609, NM_001289610, NM_001365826, NM_001365827, NM_001365828, NM_001365829, NM_001365830, NM_001365831, NM_001365832, NM_001365833, NM_001365834, NM_001365835, NM_001394447, NM_001394448, NM_001394449, NM_001394450, NM_001394451, NM_001394452, NM_001394453, NM_001394454, NM_001394455, NM_001394456, NM_001394457, NM_001394458, NM_001394459, NM_001394460, NM_001394461, NM_001394462, NM_001394464, NM_001394465, NM_001394466, NM_001394467, NM_001394468, NM_001394469, NM_001394470, NM_001394471, NM_001394472, NM_001394473, NM_032943, NM_206927, NM_206928, NM_206929, NM_206930

CCDS: CCDS31649, CCDS31652, CCDS41698, CCDS53687, CCDS53688, CCDS53689, CCDS76461, CCDS91568, CCDS91569

Canonical transcript exons

ENST00000359152 — 20 exons

Exon	Start	End
ENSE00001749316	85733939	85734742
ENSE00002151716	85757625	85758114
ENSE00002170653	85736501	85736615
ENSE00002183634	85810954	85811141
ENSE00003489405	85700515	85700593
ENSE00003491736	85714413	85714507
ENSE00003518602	85696183	85696388
ENSE00003568907	85717483	85717530
ENSE00003572467	85737575	85737656
ENSE00003612672	85718790	85718843
ENSE00003616696	85697979	85698078
ENSE00003646842	85707429	85707531
ENSE00003683946	85711113	85711232
ENSE00003686170	85745637	85745772
ENSE00003690664	85748272	85748423
ENSE00003693765	85709331	85709500
ENSE00003737442	85720858	85720959
ENSE00003788238	85704858	85705028
ENSE00003789365	85724032	85727967
ENSE00003928799	85694229	85695340

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6514 / max 450.2867, expressed in 1292 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121707	13.8642	962
121698	3.2171	723
206405	1.9146	320
121699	1.1517	388
121697	0.9597	383
121708	0.8417	382
121700	0.6924	305
121703	0.3022	108
121692	0.1530	58
121696	0.0928	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	98.68	gold quality
rectum	UBERON:0001052	98.45	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.50	gold quality
bronchial epithelial cell	CL:0002328	97.45	gold quality
endothelial cell	CL:0000115	97.30	gold quality
colonic mucosa	UBERON:0000317	97.22	gold quality
urethra	UBERON:0000057	96.81	gold quality
vena cava	UBERON:0004087	96.76	gold quality
right coronary artery	UBERON:0001625	96.71	gold quality
tibial artery	UBERON:0007610	96.63	gold quality
popliteal artery	UBERON:0002250	96.61	gold quality
mucosa of transverse colon	UBERON:0004991	96.58	gold quality
pylorus	UBERON:0001166	96.39	gold quality
calcaneal tendon	UBERON:0003701	96.18	gold quality
right frontal lobe	UBERON:0002810	96.17	gold quality
anterior cingulate cortex	UBERON:0009835	96.11	gold quality
metanephros cortex	UBERON:0010533	96.07	gold quality
cingulate cortex	UBERON:0003027	95.92	gold quality
superficial temporal artery	UBERON:0001614	95.84	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.76	gold quality
adrenal tissue	UBERON:0018303	95.70	gold quality
gall bladder	UBERON:0002110	95.16	gold quality
prefrontal cortex	UBERON:0000451	95.10	gold quality
colonic epithelium	UBERON:0000397	94.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.41	gold quality
transverse colon	UBERON:0001157	94.32	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.28	gold quality
frontal cortex	UBERON:0001870	94.08	gold quality
superior frontal gyrus	UBERON:0002661	94.01	gold quality
body of stomach	UBERON:0001161	93.78	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	4772.81
E-MTAB-6678	yes	2066.05
E-MTAB-10855	yes	918.21
E-CURD-7	yes	609.55
E-ENAD-21	yes	609.55
E-MTAB-8142	yes	90.39
E-GEOD-137537	yes	20.08
E-MTAB-8410	yes	9.36
E-MTAB-9801	yes	5.91
E-HCAD-5	no	2909.33
E-MTAB-7316	no	1381.38
E-CURD-89	no	910.44
E-MTAB-6379	no	121.16
E-GEOD-81608	no	81.18
E-HCAD-1	no	20.17

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2

Literature-anchored findings (GeneRIF, showing 13)

• Synaptotagmin-like protein 2-a (Slp2-a) contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slp2-a specifically and directly binds the GTP-bound form of Rab27A. (PMID:11773082)
• Exophilin4/Slp2-a is specifically expressed in pancreatic alpha cells. (PMID:17182843)
• occurrence of an unusual TG 3’ splice site in intron 9 (PMID:17672918)
• These results suggest that both Slp1 and Slp2-a may form part of a docking complex, capturing secretory lysosomes at the immunological synapse. (PMID:18266782)
• Rab27a recruits Slp2a-hem on vesicular structures in peripheral CTLs and following CTL-target cell conjugate formation, the Slp2a-hem/Rab27a complex colocalizes with perforin-containing granules at the immunologic synapse (PMID:18812475)
• Rab27A/Slp2a expression in limb girdle muscular dystrophy 2B muscle provides a compensatory vesicular trafficking pathway that is able to repair membrane damage in the absence of dysferlin. (PMID:18832576)
• A high expression level of SLP-2 may be associating with the development of invasion and metastasis in laryngeal squamous cell carcinoma and breast cancer. (PMID:20654157)
• Calmodulin suppresses synaptotagmin-2 transcription in cortical neurons (PMID:20729199)
• SLP2 may play an important role in tumorigenesis of esophageal squamous cell carcinoma. (PMID:21223688)
• Overexpression of SYTL2 promoted metastatic potential. (PMID:27220283)
• Synaptotagmin-Like Protein 2a Regulates Angiogenic Lumen Formation via Weibel-Palade Body Apical Secretion of Angiopoietin-2. (PMID:33853352)
• SYTL2 promotes metastasis of prostate cancer cells by enhancing FSCN1-mediated pseudopodia formation and invasion. (PMID:37147713)
• Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm. (PMID:37640670)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sytl2a	ENSDARG00000061956
mus_musculus	Sytl2	ENSMUSG00000030616
rattus_norvegicus	Sytl2	ENSRNOG00000030776

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-like protein 2 — Q9HCH5 (reviewed: Q9HCH5)

Alternative names: Breast cancer-associated antigen SGA-72M, Exophilin-4

All UniProt accessions (13): A0A0U1RQH1, A0A0U1RR07, A0A0U1RRJ3, A0A1Y8EH08, A0A8J9FM55, E9PIB5, E9PK22, E9PPL3, E9PQL8, E9PRW5, E9PS29, E9PS39, Q9HCH5

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 1 acts as a RAB27A effector protein and plays a role in cytotoxic granule exocytosis in lymphocytes. It is required for cytotoxic granule docking at the immunologic synapse. Isoform 4 binds phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PIP2) and promotes the recruitment of glucagon-containing granules to the cell membrane in pancreatic alpha cells. Binding to PS is inhibited by Ca(2+) while binding to PIP2 is Ca(2+) insensitive.

Subunit / interactions. Monomer. Binds NRXN1. Interacts with RAB27B. Binds RAB27A that has been activated by GTP-binding.

Subcellular location. Cytoplasm. Cell membrane Cell membrane.

Tissue specificity. Isoform 1 is expressed in hematopoietic lineages with a strong expression in CD4 and CD8 T-lymphocytes. It is also widely expressed in nonhematopoietic tissues. Isoform 5 is expressed only in nonhematopoietic tissues. Isoform 4 is expressed in pancreatic alpha cells.

Post-translational modifications. Isoform 1 is highly susceptible to proteolytic degradation and is stabilized by the interaction with RAB27A.

Domain organisation. The RabBD domain mediates interaction with RAB27A and recruitment on to vesicular structures in cytotoxic T-lymphocytes (CTL). The C2 1 domain mediates binding to phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2) and localization to the cell membrane.

Isoforms (12)

UniProt ID	Names	Canonical?
Q9HCH5-1	1, Hematopoietic form of Slp2a, Slp2a-hem	yes
Q9HCH5-2	2
Q9HCH5-4	3
Q9HCH5-6	4
Q9HCH5-7	5
Q9HCH5-8	6
Q9HCH5-9	7
Q9HCH5-11	8
Q9HCH5-12	9
Q9HCH5-13	10
Q9HCH5-14	11
Q9HCH5-15	12

RefSeq proteins (47): NP_001156423, NP_001156424, NP_001156425, NP_001276537, NP_001276538, NP_001276539, NP_001352755, NP_001352756, NP_001352757, NP_001352758, NP_001352759, NP_001352760, NP_001352761, NP_001352762, NP_001352763, NP_001352764, NP_001381376, NP_001381377, NP_001381378, NP_001381379, NP_001381380, NP_001381381, NP_001381382, NP_001381383, NP_001381384, NP_001381385, NP_001381386, NP_001381387, NP_001381388, NP_001381389, NP_001381390, NP_001381391, NP_001381393, NP_001381394, NP_001381395, NP_001381396, NP_001381397, NP_001381398, NP_001381399, NP_001381400, NP_001381401, NP_001381402, NP_116561, NP_996810, NP_996811, NP_996812, NP_996813 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR010911	Rab_BD	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR041282	FYVE_2	Domain
IPR043567	SYTL1-5_C2B	Domain

Pfam: PF00168, PF02318

UniProt features (42 total): compositionally biased region 12, splice variant 10, sequence conflict 5, helix 4, domain 3, mutagenesis site 2, region of interest 2, sequence variant 2, chain 1, strand 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3BC1	X-RAY DIFFRACTION	1.8
8P3I	X-RAY DIFFRACTION	2
8P3G	X-RAY DIFFRACTION	2.13
8P3J	X-RAY DIFFRACTION	2.16
7OPQ	X-RAY DIFFRACTION	2.23
7OPP	X-RAY DIFFRACTION	2.32
7OPR	X-RAY DIFFRACTION	2.32
8P3K	X-RAY DIFFRACTION	2.58
8P3H	X-RAY DIFFRACTION	2.76

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCH5-F1	58.62	0.23

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
11	abolishes interaction with rab27a.
32	abolishes interaction with rab27a.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation
R-HSA-1266738	Developmental Biology
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 295 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, AP4_Q6, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, CAGCTG_AP4_Q5, FOXD3_01, GOBP_MEMBRANE_DOCKING, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, CTAGGAA_MIR384, TCF4_Q5

GO Biological Process (4): intracellular protein transport (GO:0006886), exocytosis (GO:0006887), obsolete vesicle docking involved in exocytosis (GO:0006904), vesicle-mediated transport (GO:0016192)

GO Molecular Function (6): phosphatidylserine binding (GO:0001786), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatase binding (GO:0019902), small GTPase binding (GO:0031267), neurexin family protein binding (GO:0042043), protein binding (GO:0005515)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), melanosome (GO:0042470), exocytic vesicle (GO:0070382), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
MITF-M-dependent gene expression	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
intracellular protein localization	1
protein transport	1
intracellular transport	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
transport	1
cellular process	1
phospholipid binding	1
anion binding	1
modified amino acid binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
enzyme binding	1
GTPase binding	1
signaling receptor binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
pigment granule	1
transport vesicle	1
secretory vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

750 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYTL2	RAB27A	P51159	991
SYTL2	MLPH	Q9BV36	941
SYTL2	MYO5A	Q9Y4I1	784
SYTL2	RAB27B	O00194	720
SYTL2	ARF3	P16587	675
SYTL2	RAP2B	P17964	669
SYTL2	MYRIP	Q8NFW9	662
SYTL2	RAB3A	P20336	658
SYTL2	STXBP2	Q15833	649
SYTL2	CHML	P26374	645
SYTL2	STX3	Q13277	640
SYTL2	VAMP8	Q9BV40	628
SYTL2	UNC13D	Q70J99	588
SYTL2	HMGN2	P05204	580
SYTL2	CD8A	P01732	546

IntAct

17 interactions, top by confidence:

A	B	Type	Score
Rab27a	SYTL2	psi-mi:“MI:0407”(direct interaction)	0.620
SYTL2	PPP1CA	psi-mi:“MI:0407”(direct interaction)	0.590
PPP1CA	SYTL2	psi-mi:“MI:0915”(physical association)	0.590
RAB27B	GBA1	psi-mi:“MI:0914”(association)	0.530
SYTL2	Rab27b	psi-mi:“MI:0407”(direct interaction)	0.440
SYTL2	ANXA2	psi-mi:“MI:0915”(physical association)	0.400
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
RAB27A	GTPBP1	psi-mi:“MI:0914”(association)	0.350
RAB27A	ATE1	psi-mi:“MI:0914”(association)	0.350
RAB27B	MYH7B	psi-mi:“MI:0914”(association)	0.350
MTERF1	SYTL2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): SYTL2 (Affinity Capture-MS), SYTL2 (Synthetic Lethality), SYTL2 (Affinity Capture-MS), SYTL2 (Affinity Capture-Western), SYTL2 (Two-hybrid), MORN4 (Two-hybrid), YIF1A (Two-hybrid), SYTL2 (Proximity Label-MS), SYTL2 (Two-hybrid), SYTL2 (Two-hybrid), RAB27A (Affinity Capture-Western), SYTL2 (Affinity Capture-Western), SYTL2 (Reconstituted Complex), SYTL2 (Affinity Capture-MS), SYTL2 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1L8H8C0, A0A1L8HFX9, A0A2R6X6S3, A0JM08, A2ARZ3, A2RUV4, A5WUN7, A6QP06, D4AEC2, E9Q309, O76039, P51960, Q03898, Q05935, Q06190, Q08AD1, Q08D57, Q0WPH8, Q3KQW7, Q3UTQ8, Q498L0, Q5RAU1, Q5SW79, Q5T0W9, Q5T5U3, Q5VT06, Q62770, Q66J90, Q69Z38, Q6A065, Q6DFG0, Q6DFV3, Q6IRN6, Q71M21, Q80TN7, Q8AV28, Q8C1B1, Q8IVL0, Q8IZ21

Diamond homologs: A0A075F932, A0FGR8, A0FGR9, A4IJ05, A6QP06, O00443, O00445, O00750, O08625, O08835, O35681, P04409, P05128, P05129, P10829, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232, P59926, P63318, P63319, P70169, P70610, P70611

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	256
Likely benign	25
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3607 predictions. Top by Δscore:

Variant	Effect	Δscore
11:85695338:TACC:T	acceptor_loss	1.0000
11:85695340:CCT:C	acceptor_loss	1.0000
11:85695341:C:A	acceptor_loss	1.0000
11:85696178:AGTAC:A	donor_loss	1.0000
11:85696179:GTA:G	donor_loss	1.0000
11:85696180:TA:T	donor_loss	1.0000
11:85696181:ACCT:A	donor_loss	1.0000
11:85696182:C:CA	donor_loss	1.0000
11:85696384:TGGTA:T	acceptor_gain	1.0000
11:85696389:C:CC	acceptor_gain	1.0000
11:85698005:T:TA	donor_gain	1.0000
11:85698007:C:A	donor_gain	1.0000
11:85698013:G:C	donor_gain	1.0000
11:85705029:C:CC	acceptor_gain	1.0000
11:85707319:T:TA	donor_gain	1.0000
11:85707527:CATAT:C	acceptor_gain	1.0000
11:85709329:A:AC	donor_gain	1.0000
11:85709330:C:CC	donor_gain	1.0000
11:85709496:CTCAC:C	acceptor_gain	1.0000
11:85709499:ACC:A	acceptor_loss	1.0000
11:85709500:CCTGA:C	acceptor_loss	1.0000
11:85709501:C:CA	acceptor_loss	1.0000
11:85709502:T:C	acceptor_loss	1.0000
11:85720856:A:AC	donor_gain	1.0000
11:85720857:C:CC	donor_gain	1.0000
11:85736500:CCCT:C	donor_gain	1.0000
11:85736613:CTG:C	acceptor_gain	1.0000
11:85745631:CCTTA:C	donor_loss	1.0000
11:85745632:CTTA:C	donor_loss	1.0000
11:85745633:TTA:T	donor_loss	1.0000

AlphaMissense

14778 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:85695281:A:G	W907R	0.999
11:85695281:A:T	W907R	0.999
11:85695314:A:G	W896R	0.999
11:85695314:A:T	W896R	0.999
11:85696251:A:G	L864P	0.999
11:85697985:A:T	V816D	0.999
11:85700541:A:G	L776P	0.999
11:85700545:C:G	A775P	0.999
11:85695251:A:G	W917R	0.998
11:85695251:A:T	W917R	0.998
11:85695279:C:A	W907C	0.998
11:85695279:C:G	W907C	0.998
11:85696200:C:G	R881P	0.998
11:85696203:A:G	L880P	0.998
11:85696245:A:T	V866D	0.998
11:85696287:A:G	F852S	0.998
11:85696380:A:G	L821P	0.998
11:85697980:A:G	C818R	0.998
11:85700547:A:G	L774P	0.998
11:85704940:C:T	G731E	0.998
11:85704941:C:A	G731W	0.998
11:85704941:C:G	G731R	0.998
11:85704941:C:T	G731R	0.998
11:85695280:C:G	W907S	0.997
11:85696272:A:G	L857P	0.997
11:85696308:T:G	H845P	0.997
11:85696314:A:G	F843S	0.997
11:85696377:G:T	P822Q	0.997
11:85698043:A:G	W797R	0.997
11:85698043:A:T	W797R	0.997

dbSNP variants (sampled 300 via entrez): RS1000002268 (11:85850215 C>A,T), RS1000026097 (11:85717591 G>T), RS1000045909 (11:85766665 T>C), RS1000051038 (11:85808710 T>C), RS1000058070 (11:85722868 G>A), RS1000064276 (11:85791099 G>A), RS1000071510 (11:85799748 C>T), RS1000113845 (11:85749918 G>A), RS1000186082 (11:85751361 G>A), RS1000191677 (11:85732206 C>T), RS1000193267 (11:85815685 T>C), RS1000198257 (11:85773060 T>A), RS1000205648 (11:85855093 T>G), RS1000206418 (11:85781315 C>T), RS1000213754 (11:85823451 C>A)

Disease associations

OMIM: gene MIM:612880 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): angioedema (MONDO:0010481)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100665	Angioedema

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009261_8	Pallidum volume	7.000000e-06
GCST010002_244	Refractive error	2.000000e-53

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D000799	Angioedema	C14.907.079; C17.800.862.945.066; C20.543.480.904.066

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
methylmercuric chloride	decreases expression, affects cotreatment	4
sodium arsenite	decreases expression, increases abundance, increases expression	4
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	3
perfluorooctane sulfonic acid	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases methylation, decreases expression	2
Arsenic	decreases expression, increases abundance	2
Estradiol	decreases expression, decreases reaction, affects cotreatment	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	affects expression	1
dorsomorphin	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02966314	PHASE4	COMPLETED	Treatment of Idiopathic Angioedema With Xolair as Add-on Therapy
NCT06818474	PHASE4	RECRUITING	Lanadelumab in Long-term Prophylaxis of Acquired Angioedema
NCT00097695	PHASE3	COMPLETED	Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema
NCT00125151	PHASE3	COMPLETED	C1-Esteraseremmer-N for the Treatment of Hereditary (and Acquired) Angioedema
NCT00262301	PHASE3	COMPLETED	Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
NCT01723072	PHASE3	COMPLETED	Impact of Omalizumab on Quality of Life Measures and Angioedema Occurrence in Patients With CSU Refractory to Therapy
NCT04206605	PHASE3	COMPLETED	A Study of Lanadelumab in Teenagers and Adults to Prevent Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH)
NCT04444895	PHASE3	COMPLETED	A Study of Long-Term Safety and Efficacy of Lanadelumab for Prevention of Acute Attacks of Non-histaminergic Angioedema With Normal C1-Inhibitor
NCT00119431	PHASE2	COMPLETED	Kinetics, Efficacy and Safety of C1-Esteraseremmer-N
NCT00890162	PHASE2	COMPLETED	A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis
NCT01036659	PHASE2	UNKNOWN	Evaluation of Ecallantide for the Acute Treatment of Angiotensin Converting Enzyme Inhibitor Induced Angioedema
NCT01154361	PHASE2	COMPLETED	AMelioration of Angiotensin Converting Enzyme Inhibitor Induced Angioedema Study
NCT03749135	PHASE2	COMPLETED	Dupilumab in Chronic Spontaneous Urticaria
NCT04128371	PHASE2	TERMINATED	Mepolizumab in Episodic Angioedema With Eosinophilia
NCT05936567	PHASE2	COMPLETED	Study Evaluating the Efficacy and Safety of Povorcitinib in Adults With Chronic Spontaneous Urticaria
NCT00517582	PHASE1	TERMINATED	Bradykinin Receptor Blocker in ACE Inhibitor-associated Angioedema
NCT00125541	PHASE2/PHASE3	COMPLETED	C1-Esteraseremmer-N for the Treatment of Hereditary (and Acquired) Angioedema
NCT00225147	PHASE2/PHASE3	COMPLETED	Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
NCT07046806	PHASE1/PHASE2	RECRUITING	Oral Deucrictibant for Prophylactic and Acute Treatment in Hereditary Angioedema Patients
NCT00004694	Not specified	COMPLETED	Study of Heparin Prophylaxis of Hereditary Angioedema Exacerbations
NCT00163839	Not specified	UNKNOWN	The Efficacy of a Pseudoallergen-Free Diet in the Treatment of Chronic Idiopathic Urticaria and/or Angioedema
NCT00385372	Not specified	COMPLETED	Significance of an Elimination and Provocation Diet in Patients With Chronic Urticaria
NCT00876369	Not specified	COMPLETED	Vitamin D Levels in Subjects With Chronic Urticaria and Angioedema
NCT01371877	Not specified	COMPLETED	The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment
NCT02833675	Not specified	COMPLETED	Determination of Specific Biomarkers of Angioneurotic Crisis
NCT03240991	Not specified	COMPLETED	Study of Clinical, Biological Characteristics and Quality of Life of Patients With Hereditary or Acquired Non Drug-induced Bradykinin-mediated Angioedema, Monitored in Besançon’s Partner Site Reference Center for Studies of Kinin-mediated Angioedema (CREAK)
NCT03845946	Not specified	RECRUITING	CLOUD-R HAE REGISTRY
NCT04334031	Not specified	RECRUITING	Deployment o the Multidisciplinary Prospective Cohort Imminent
NCT04583007	Not specified	NO_LONGER_AVAILABLE	Expanded Access for the Prevention of Acute Attacks of 1) Hereditary Angioedema (HAE) in Children and 2) Non-histaminergic Angioedema With Normal C1-Inhibitor (C1-INH) in Teenagers and Adults
NCT04597944	Not specified	UNKNOWN	Lanadelumab in Bradykinin Angioedema
NCT05578417	Not specified	COMPLETED	A Study to Review the Treatment and Outcomes of Teenagers and Adults With Non-histaminergic Angioedema With Normal C1 Inhibitor in Canada
NCT06096077	Not specified	COMPLETED	Evaluation of Tranexamic Acid for Angiotensin-converting Enzyme Inhibitor-induced Angioedema in the Emergency Department
NCT06210698	Not specified	UNKNOWN	Angioedema Biomarker Research Study
NCT07001280	Not specified	RECRUITING	A Study Investigating the Effectiveness and Safety of Garadacimab for Treating Patients With Hereditary Angioedema (HAE)
NCT07611032	Not specified	COMPLETED	A Single-Arm Exploratory Study of NatureU Histra Disslove on Chronic Urticaria Symptoms