SYTL4

Summary

SYTL4 (synaptotagmin like 4, HGNC:15588) is a protein-coding gene on chromosome Xq22.1, encoding Synaptotagmin-like protein 4 (Q96C24). Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary.

This gene encodes a member of the synaptotagmin like protein family. Members of this family are characterized by an N-terminal Rab27 binding domain and C-terminal tandem C2 domains. The encoded protein binds specific small Rab GTPases and is involved in intracellular membrane trafficking. This protein binds Rab27 and may be involved in inhibiting dense core vesicle exocytosis. Alternate splicing results in multiple transcript variants that encode the same protein.

Source: NCBI Gene 94121 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinal disorder (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 156 total
• MANE Select transcript: NM_001370165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15588
Approved symbol	SYTL4
Name	synaptotagmin like 4
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	Slp4
Ensembl gene	ENSG00000102362
Ensembl biotype	protein_coding
OMIM	300723
Entrez	94121

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 28 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263033, ENST00000276141, ENST00000372981, ENST00000372989, ENST00000491602, ENST00000685623, ENST00000877173, ENST00000877174, ENST00000877175, ENST00000877176, ENST00000877177, ENST00000877178, ENST00000877179, ENST00000877180, ENST00000877181, ENST00000877182, ENST00000877183, ENST00000877184, ENST00000877185, ENST00000877186, ENST00000877187, ENST00000942507, ENST00000942508, ENST00000942509, ENST00000942510, ENST00000942511, ENST00000942512, ENST00000942513, ENST00000942514

RefSeq mRNA: 13 — MANE Select: NM_001370165 NM_001129896, NM_001174068, NM_001370160, NM_001370161, NM_001370162, NM_001370163, NM_001370164, NM_001370165, NM_001370166, NM_001370167, NM_001370168, NM_001370169, NM_080737

CCDS: CCDS14472

Canonical transcript exons

ENST00000372989 — 20 exons

Exon	Start	End
ENSE00000673492	100678391	100678599
ENSE00000673528	100686679	100686781
ENSE00000673548	100687067	100687245
ENSE00000673560	100688351	100688443
ENSE00000673564	100689856	100689959
ENSE00000673572	100690075	100690165
ENSE00000673591	100690563	100690638
ENSE00001154529	100700897	100700999
ENSE00001154536	100701220	100701329
ENSE00001154545	100701458	100701673
ENSE00001217969	100679313	100679412
ENSE00001217979	100681227	100681335
ENSE00001218079	100685990	100686151
ENSE00001304452	100691108	100691209
ENSE00001382017	100701928	100702107
ENSE00001413788	100732004	100732121
ENSE00001459238	100674491	100676176
ENSE00001459251	100704811	100704886
ENSE00001459253	100731418	100731505
ENSE00001796780	100703093	100703185

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4568 / max 209.5142, expressed in 977 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199932	2.8609	953
199929	0.4044	139
199931	0.1218	55
199930	0.0697	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ovary	UBERON:0002119	97.49	gold quality
right ovary	UBERON:0002118	97.03	gold quality
body of uterus	UBERON:0009853	96.38	gold quality
endocervix	UBERON:0000458	94.33	gold quality
ovary	UBERON:0000992	94.21	gold quality
left uterine tube	UBERON:0001303	93.40	gold quality
pituitary gland	UBERON:0000007	92.41	gold quality
adenohypophysis	UBERON:0002196	92.31	gold quality
myometrium	UBERON:0001296	92.22	gold quality
uterine cervix	UBERON:0000002	90.53	gold quality
ectocervix	UBERON:0012249	90.30	gold quality
smooth muscle tissue	UBERON:0001135	89.84	gold quality
mucosa of stomach	UBERON:0001199	89.10	gold quality
tibial nerve	UBERON:0001323	89.02	gold quality
right lung	UBERON:0002167	88.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.24	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.09	gold quality
transverse colon	UBERON:0001157	87.96	gold quality
omental fat pad	UBERON:0010414	87.78	gold quality
peritoneum	UBERON:0002358	87.75	gold quality
mucosa of transverse colon	UBERON:0004991	87.74	gold quality
calcaneal tendon	UBERON:0003701	87.72	gold quality
prostate gland	UBERON:0002367	87.51	gold quality
sural nerve	UBERON:0015488	87.40	gold quality
metanephros cortex	UBERON:0010533	87.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	87.15	gold quality
uterus	UBERON:0000995	87.12	gold quality
vagina	UBERON:0000996	86.93	gold quality
secondary oocyte	CL:0000655	86.60	gold quality
decidua	UBERON:0002450	86.19	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.07
E-ENAD-17	no	1131.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA2, MAFA, ONECUT2, PPARGC1B, SREBF1

miRNA regulators (miRDB)

94 targeting SYTL4, 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-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769

Literature-anchored findings (GeneRIF, showing 12)

• Synaptotagmin-like protein 4 (Slp4)/granuphilin-a contains an N-terminal Slp homology domain (SHD) (PMID: 11327731). The SHD of Slp4 specifically and directly binds the GTP-bound form of Rab3A, Rab8, and Rab27A. (PMID:11773082)
• in insulin-producing cells adequate levels of mir-9 are mandatory for maintaining appropriate Granuphilin levels and optimal secretory capacity (PMID:16831872)
• Slp4 and Rab8 are expressed and interact in human platelets, and might be involved in dense granule release. (PMID:23140275)
• the mechanisms of granuphilin plasma membrane targeting and release (PMID:24184645)
• Recruitment of STXBP1 by the Rab27A effector SYTL4 promotes Weibel-Palade body exocytosis. (PMID:24700782)
• Phosphatidylinositol 4,5-bisphosphate binds to the concave surface of granuphilin-C2A domain. The key residues involved in the binding were validated by mutation analysis. (PMID:25595293)
• GLUT5 required an interaction cascade of Rab11, Myo5B, Slp4a, Munc18-2, and Vamp7 with Stx3. (PMID:26553929)
• Granuphilin makes granules immobile and fusion-reluctant beneath the plasma membrane. Those granuphilin-positive, docked granules release a portion of granuphilin upon fusion, and fuse at a frequency and time course similar to those of granuphilin-negative undocked granules. Granuphilin forms a 180-nm cluster at the site of each docked granule, along with granuphilin-interacting Rab27a and Munc18-1 clusters. (PMID:27032672)
• Determined the solution structure of human synaptotagmin-like protein 4 (Slp4). Through modification of cysteine residues, found Slp4 binding of two zinc atoms is required for correct folding. (PMID:28906046)
• LMP1 upregulates SDC2 and SYTL4. (PMID:31930596)
• SYTL4 downregulates microtubule stability and confers paclitaxel resistance in triple-negative breast cancer. (PMID:33042263)
• Multivalent lipid targeting by the calcium-independent C2A domain of synaptotagmin-like protein 4/granuphilin. (PMID:33277360)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sytl4	ENSDARG00000102433
mus_musculus	Sytl4	ENSMUSG00000031255
rattus_norvegicus	Sytl4	ENSRNOG00000003526

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT11 (ENSG00000132718), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), 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 4 — Q96C24 (reviewed: Q96C24)

Alternative names: Exophilin-2, Granuphilin

All UniProt accessions (1): Q96C24

UniProt curated annotations — full annotation on UniProt →

Function. Modulates exocytosis of dense-core granules and secretion of hormones in the pancreas and the pituitary. Interacts with vesicles containing negatively charged phospholipids in a Ca(2+)-independent manner.

Subunit / interactions. Part of a ternary complex containing STX1A and RAB27A. Can bind both dominant negative and dominant active mutants of RAB27A. Binds STXBP1, RAB3A, RAB8A and RAB27B. Interacts with MYO5A.

Subcellular location. Membrane. Cell membrane. Cytoplasmic vesicle. Secretory vesicle membrane.

Miscellaneous. May be due to an intron retention.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96C24-1	1	yes
Q96C24-2	2

RefSeq proteins (13): NP_001123368, NP_001167539, NP_001357089, NP_001357090, NP_001357091, NP_001357092, NP_001357093, NP_001357094, NP_001357095, NP_001357096, NP_001357097, NP_001357098, NP_542775 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001565	Synaptotagmin	Domain
IPR010911	Rab_BD	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037303	SLP-4/5_C2A	Domain
IPR041282	FYVE_2	Domain
IPR043567	SYTL1-5_C2B	Domain
IPR044134	FYVE_Slp4	Domain

Pfam: PF00168, PF02318

UniProt features (44 total): strand 14, modified residue 7, turn 6, sequence conflict 4, helix 4, domain 3, splice variant 2, chain 1, sequence variant 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3FDW	X-RAY DIFFRACTION	2.2
2CSZ	SOLUTION NMR
5X6T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96C24-F1	68.49	0.25

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 (7): 274, 289, 488, 201, 204, 217, 221

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 190 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_INSULIN_SECRETION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, AATGGAG_MIR136, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING

GO Biological Process (10): plasma membrane repair (GO:0001778), intracellular protein transport (GO:0006886), exocytosis (GO:0006887), insulin secretion (GO:0030073), lysosome localization (GO:0032418), positive regulation of exocytosis (GO:0045921), negative regulation of insulin secretion (GO:0046676), positive regulation of protein secretion (GO:0050714), multivesicular body sorting pathway (GO:0071985), regulation of plasma membrane repair (GO:1905684)

GO Molecular Function (6): phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), small GTPase binding (GO:0031267), neurexin family protein binding (GO:0042043), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): endosome (GO:0005768), plasma membrane (GO:0005886), transport vesicle membrane (GO:0030658), platelet alpha granule membrane (GO:0031092), exocytic vesicle (GO:0070382), membrane (GO:0016020), secretory granule (GO:0030141), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport	2
protein secretion	2
positive regulation of secretion by cell	2
endomembrane system	2
transport vesicle	2
secretory vesicle	2
plasma membrane organization	1
wound healing	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
peptide hormone secretion	1
vacuolar localization	1
exocytosis	1
regulation of exocytosis	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
plasma membrane repair	1
regulation of plasma membrane organization	1
lipid binding	1
transition metal ion binding	1
GTPase binding	1
signaling receptor binding	1
binding	1
cation binding	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
secretory granule membrane	1
platelet alpha granule	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYTL4	RAB27A	P51159	997
SYTL4	ONECUT2	O95948	930
SYTL4	STXBP1	P61764	925
SYTL4	INS	P01308	775
SYTL4	RAB27B	O00194	757
SYTL4	STX1A	Q16623	751
SYTL4	RAB3A	P20336	742
SYTL4	MYO5A	Q9Y4I1	735
SYTL4	STX3	Q13277	714
SYTL4	EXPH5	Q8NEV8	665
SYTL4	STXBP2	Q15833	650
SYTL4	RAB8A	P24407	631
SYTL4	VAMP8	Q9BV40	614
SYTL4	UNC13D	Q70J99	578
SYTL4	STX2	P32856	550

IntAct

105 interactions, top by confidence:

A	B	Type	Score
SYTL4	HMG20A	psi-mi:“MI:0915”(physical association)	0.780
HMG20A	SYTL4	psi-mi:“MI:0915”(physical association)	0.780
RAB27A	SYTL4	psi-mi:“MI:0915”(physical association)	0.740
FXR2	SYTL4	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SYTL4	CEP70	psi-mi:“MI:0915”(physical association)	0.670
CEP70	SYTL4	psi-mi:“MI:0915”(physical association)	0.670
RAB8A	WDR91	psi-mi:“MI:0914”(association)	0.600
SYTL4	ZBTB7B	psi-mi:“MI:0915”(physical association)	0.560
ZBTB7B	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
RAB3D	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
STXBP1	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
SPANXN2	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
DVL3	SYTL4	psi-mi:“MI:0915”(physical association)	0.560
SYTL4	ROPN1	psi-mi:“MI:0915”(physical association)	0.560
SYTL4	KIFC3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (130): STXBP1 (Reconstituted Complex), SYTL4 (Two-hybrid), SYTL4 (Two-hybrid), SYTL4 (Two-hybrid), SYTL4 (Two-hybrid), RAB8A (Affinity Capture-MS), RAB27A (Affinity Capture-MS), STXBP1 (Affinity Capture-MS), STX3 (Affinity Capture-MS), STX2 (Affinity Capture-MS), SYTL4 (Affinity Capture-Western), SYTL4 (Affinity Capture-MS), SYTL4 (Two-hybrid), SYTL4 (Affinity Capture-Western), SYTL4 (Affinity Capture-Western)

ESM2 similar proteins: A0AVI2, A0FGR9, A2AP18, A3KGK3, A6QQP7, F1LYQ8, F8VPU2, O00329, O08835, O14976, O15068, O35904, O75038, O75923, O94887, P19687, P40749, P50232, P58069, P97610, P97874, Q14644, Q15283, Q28013, Q5DTI8, Q5FWL4, Q5M7N9, Q5RAB8, Q5RJH2, Q60790, Q63406, Q63713, Q64096, Q6DN12, Q6P7F1, Q7L8C5, Q7ZWU7, Q8IV01, Q8VHQ7, Q91VS8

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
RAB geranylgeranylation	8	36.4×	1e-08
RAB GEFs exchange GTP for GDP on RABs	6	19.6×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
exocytosis	7	22.6×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3000 predictions. Top by Δscore:

Variant	Effect	Δscore
X:100681225:A:AC	donor_gain	1.0000
X:100681226:C:CC	donor_gain	1.0000
X:100681226:CT:C	donor_gain	1.0000
X:100686027:T:C	donor_gain	1.0000
X:100686147:TCATA:T	acceptor_gain	1.0000
X:100686148:CATA:C	acceptor_gain	1.0000
X:100686148:CATAC:C	acceptor_gain	1.0000
X:100686150:TA:T	acceptor_gain	1.0000
X:100686150:TAC:T	acceptor_loss	1.0000
X:100686151:AC:A	acceptor_loss	1.0000
X:100686152:C:CC	acceptor_gain	1.0000
X:100686153:T:A	acceptor_loss	1.0000
X:100686673:ACTT:A	donor_loss	1.0000
X:100686676:TA:T	donor_loss	1.0000
X:100686677:A:AC	donor_gain	1.0000
X:100686677:AC:A	donor_gain	1.0000
X:100686677:ACC:A	donor_gain	1.0000
X:100686677:ACCCT:A	donor_gain	1.0000
X:100686678:C:CT	donor_gain	1.0000
X:100686678:CC:C	donor_gain	1.0000
X:100686678:CCC:C	donor_gain	1.0000
X:100686678:CCCT:C	donor_gain	1.0000
X:100686678:CCCTC:C	donor_gain	1.0000
X:100686777:CATAT:C	acceptor_gain	1.0000
X:100686778:ATAT:A	acceptor_gain	1.0000
X:100686779:TAT:T	acceptor_gain	1.0000
X:100686780:AT:A	acceptor_gain	1.0000
X:100686782:C:CC	acceptor_gain	1.0000
X:100687065:A:AC	donor_gain	1.0000
X:100687066:C:CA	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015883 (X:100700780 T>C), RS1000161420 (X:100690370 G>T), RS1000294431 (X:100689985 A>G), RS1000339126 (X:100680752 T>G), RS1000387615 (X:100688566 T>C), RS1000432492 (X:100680223 C>T), RS1000514853 (X:100725992 GT>G), RS1000531852 (X:100710645 T>A), RS1000632049 (X:100691834 G>A), RS1000713770 (X:100725571 T>C,G), RS1000885570 (X:100728401 T>C), RS1000987642 (X:100711409 G>T), RS1001048380 (X:100718367 C>T), RS1001083071 (X:100682800 T>G), RS1001150663 (X:100717594 C>T)

Disease associations

OMIM: gene MIM:300723 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
retinal disorder	Limited	X-linked

Mondo (2): congenital portosystemic shunt (MONDO:0018811), retinal disorder (MONDO:0005283)

Orphanet (1): Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008153_67	Lean body mass	1.000000e-06
GCST90002395_642	Mean platelet volume	5.000000e-14
GCST90002401_291	Platelet distribution width	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004995	lean body mass
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D012164	Retinal Diseases	C11.768

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	8
trichostatin A	affects cotreatment, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	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, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT04311112	PHASE2/PHASE3	WITHDRAWN	Safety and Efficacy of Zuretinol Acetate in Subjects With Inherited Retinal Disease
NCT04008121	EARLY_PHASE1	RECRUITING	Feasibility and Safety of MB-102 in Ocular Angiography as Compared to Fluorescein Sodium
NCT00259701	Not specified	COMPLETED	Microvascular Reactivity.
NCT00331370	Not specified	UNKNOWN	Hypertension Related Damage to the Microcirculation in South Asian: Emergence, Predictive Power and Reversibility
NCT00618644	Not specified	WITHDRAWN	Ranibizumab for Neovascularization in Sickle Cell Retinopathy
NCT00735657	Not specified	COMPLETED	Anesthesia for Pars Plana Vitrectomy (PPV) With Insulin Needle
NCT00828425	Not specified	COMPLETED	Management of Diabetes Mellitus Patients With Retinopathy
NCT00969956	Not specified	TERMINATED	Time To Complications Occurs in Diabetes
NCT01412905	Not specified	COMPLETED	Telemedicine Retinal Screening Utilizing a Mobile Medical Unit
NCT01546766	Not specified	COMPLETED	Rapid, Non-invasive, Regional Functional Imaging of the Retina. (Diabetic Retinopathy Diagnosis Device)
NCT01552993	Not specified	TERMINATED	Registration and Treatment of Pain During Eye Examination of Prematurity
NCT01815567	Not specified	COMPLETED	DETECT and Retinal Outcomes in Hypertension
NCT02321904	Not specified	COMPLETED	Corneal Confocal Microscopy to Detect Diabetic Neuropathy in Children
NCT02466607	Not specified	COMPLETED	Study of Stimulus Parameters in Flicker Electroretinogram (ERG)
NCT02558478	Not specified	UNKNOWN	Identification of New Genes Implicated in Rare Neurosensory Diseases by Whole Exome Sequencing
NCT02702973	Not specified	UNKNOWN	Characteristic Analysis of Retinopathy Associated With High Doses of Interferon α-2b Therapy
NCT03011541	Not specified	RECRUITING	Stem Cell Ophthalmology Treatment Study II
NCT03542734	Not specified	RECRUITING	Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly
NCT03901898	Not specified	COMPLETED	Feasibility of an Intervention to Increase Diabetic Retinopathy Screening Attendance
NCT04819893	Not specified	RECRUITING	Study of the Involvement of Fatty Acids in Retinopathy of Prematurity: Relationship Between Retinopathy of Prematurity and the Rate of Expression of Transplacental Fatty Acid Receptors.
NCT05921981	Not specified	COMPLETED	Multisensory Stimulation Versus White Noise
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06355219	Not specified	COMPLETED	Macrovascular and Microvascular Morbidity and Mortality After Metabolic Surgery Versus Medicines
NCT06837181	Not specified	RECRUITING	Studying the Presence of CFRD Complications With Thoughtful Recruitment (SPeCTRuM)
NCT06041906	Not specified	ENROLLING_BY_INVITATION	International Registry of Congenital Portosystemic Shunt (IRCPSS)
NCT07314814	Not specified	NOT_YET_RECRUITING	Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension