SLITRK4

Summary

SLITRK4 (SLIT and NTRK like family member 4, HGNC:23502) is a protein-coding gene on chromosome Xq27.3, encoding SLIT and NTRK-like protein 4 (Q8IW52). It is involved in synaptogenesis and promotes synapse differentiation.

This gene encodes a transmembrane protein belonging to the the SLITRK family. These family members include two N-terminal leucine-rich repeat domains similar to those found in the axonal growth-controlling protein SLIT, as well as C-terminal regions similar to neurotrophin receptors. Studies of an homologous protein in mouse suggest that this family member functions to suppress neurite outgrowth. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 139065 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001184749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23502
Approved symbol	SLITRK4
Name	SLIT and NTRK like family member 4
Location	Xq27.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547M2010
Ensembl gene	ENSG00000179542
Ensembl biotype	protein_coding
OMIM	300562
Entrez	139065

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000338017, ENST00000356928, ENST00000596188, ENST00000851621, ENST00000851622, ENST00000964901, ENST00000964902, ENST00000964903, ENST00000964904, ENST00000964905

RefSeq mRNA: 3 — MANE Select: NM_001184749 NM_001184749, NM_001184750, NM_173078

CCDS: CCDS14679

Canonical transcript exons

ENST00000356928 — 2 exons

Exon	Start	End
ENSE00001406390	143635735	143636101
ENSE00002983329	143622790	143631158

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 94.91.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6880 / max 918.6313, expressed in 594 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
209849	2.5173	299
200754	0.8157	370
200755	0.4971	174
200753	0.4340	222
200756	0.4238	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 23	UBERON:0013554	94.91	gold quality
stromal cell of endometrium	CL:0002255	94.45	gold quality
middle temporal gyrus	UBERON:0002771	93.96	gold quality
endothelial cell	CL:0000115	90.66	gold quality
cartilage tissue	UBERON:0002418	90.52	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.98	gold quality
cerebellar vermis	UBERON:0004720	88.67	gold quality
postcentral gyrus	UBERON:0002581	88.05	gold quality
superior frontal gyrus	UBERON:0002661	88.04	gold quality
primary visual cortex	UBERON:0002436	87.09	gold quality
parietal lobe	UBERON:0001872	86.55	gold quality
entorhinal cortex	UBERON:0002728	85.74	gold quality
occipital lobe	UBERON:0002021	85.37	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.87	gold quality
left adrenal gland	UBERON:0001234	82.35	gold quality
left adrenal gland cortex	UBERON:0035825	82.32	gold quality
buccal mucosa cell	CL:0002336	82.10	gold quality
adrenal cortex	UBERON:0001235	81.55	gold quality
cortical plate	UBERON:0005343	81.51	gold quality
right adrenal gland	UBERON:0001233	80.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.77	gold quality
adrenal gland	UBERON:0002369	79.88	gold quality
right adrenal gland cortex	UBERON:0035827	79.80	gold quality
cerebellum	UBERON:0002037	79.79	gold quality
cerebral cortex	UBERON:0000956	79.73	gold quality
frontal cortex	UBERON:0001870	79.55	gold quality
monocyte	CL:0000576	79.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.48	gold quality
neocortex	UBERON:0001950	79.25	gold quality
cerebellar cortex	UBERON:0002129	79.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

291 targeting SLITRK4, 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-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 1)

• Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription. (PMID:35292404)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slitrk4	ENSDARG00000079781
mus_musculus	Slitrk4	ENSMUSG00000046699
rattus_norvegicus	Slitrk4	ENSRNOG00000062783

Paralogs (25): SLITRK3 (ENSG00000121871), LRFN3 (ENSG00000126243), LRFN1 (ENSG00000128011), SLIT2 (ENSG00000145147), LRFN2 (ENSG00000156564), LRRC38 (ENSG00000162494), SLITRK5 (ENSG00000165300), LRFN5 (ENSG00000165379), LRTM2 (ENSG00000166159), LINGO1 (ENSG00000169783), LRRN2 (ENSG00000170382), LRRN3 (ENSG00000173114), LRFN4 (ENSG00000173621), LINGO2 (ENSG00000174482), LRRN1 (ENSG00000175928), SLITRK1 (ENSG00000178235), GP5 (ENSG00000178732), LRRC55 (ENSG00000183908), SLIT3 (ENSG00000184347), SLITRK6 (ENSG00000184564), SLITRK2 (ENSG00000185985), LRRC70 (ENSG00000186105), SLIT1 (ENSG00000187122), TLR9 (ENSG00000239732), TPBGL (ENSG00000261594)

Protein

Protein identifiers

SLIT and NTRK-like protein 4 — Q8IW52 (reviewed: Q8IW52)

All UniProt accessions (1): Q8IW52

UniProt curated annotations — full annotation on UniProt →

Function. It is involved in synaptogenesis and promotes synapse differentiation. Suppresses neurite outgrowth.

Subunit / interactions. Interacts (via LRR 1 and 2 repeats) with PTPRD (via extracellular domain).

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Expressed in the cerebral cortex of the brain and at higher levels in some astrocytic brain tumors such as astrocytomas, glioblastomas and primitive neuroectodermal tumors.

Similarity. Belongs to the SLITRK family.

RefSeq proteins (3): NP_001171678, NP_001171679, NP_775101 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (24 total): repeat 12, domain 3, topological domain 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IW52-F1	68.55	0.33

Functional residue map

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

Glycosylation sites (2): 81, 325

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-388844	Receptor-type tyrosine-protein phosphatases
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 220 (showing top): GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, AREB6_01, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_MULTICELLULAR_ORGANISMAL_RESPONSE_TO_STRESS, GOBP_CELL_CELL_SIGNALING, GTGCCTT_MIR506

GO Biological Process (8): behavioral fear response (GO:0001662), smoothened signaling pathway (GO:0007224), axonogenesis (GO:0007409), memory (GO:0007613), cell population proliferation (GO:0008283), regulation of synapse organization (GO:0050807), positive regulation of synapse assembly (GO:0051965), long-term synaptic potentiation (GO:0060291)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
behavioral defense response	1
fear response	1
cell surface receptor signaling pathway	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
learning or memory	1
cellular process	1
regulation of synapse structure or activity	1
synapse organization	1
regulation of cellular component organization	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
regulation of synaptic plasticity	1
positive regulation of synaptic transmission	1
binding	1
membrane	1
cell periphery	1
synapse	1
cellular anatomical structure	1

Protein interactions and networks

STRING

920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLITRK4	NTRK1	P04629	544
SLITRK4	PTS	Q03393	460
SLITRK4	LRR1	Q96L50	416
SLITRK4	SEMA4F	O95754	397
SLITRK4	EOLA2	Q96DE9	395
SLITRK4	ZDHHC15	Q96MV8	393
SLITRK4	CXorf51A	A0A1B0GTR3	392
SLITRK4	SVOPL	Q8N434	383
SLITRK4	EPHA6	Q9UF33	379
SLITRK4	MPV17	P39210	359
SLITRK4	HTR1F	P30939	353
SLITRK4	DRD3	P35462	353
SLITRK4	GBE1	Q04446	353
SLITRK4	FAM47B	Q8NA70	349
SLITRK4	SLIT1	O75093	338

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SLITRK4	CNPY3	psi-mi:“MI:0915”(physical association)	0.590
OLR1	SLITRK4	psi-mi:“MI:0407”(direct interaction)	0.560
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): CNPY3 (Affinity Capture-MS), SLITRK4 (Proximity Label-MS), CNPY3 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS), SLITRK4 (Affinity Capture-MS)

ESM2 similar proteins: A0N0X6, B1H134, B1H234, D3ZAL8, D3ZTV3, F1NUK7, O43155, O94769, O94991, P28653, P58874, P70186, P79119, Q32Q07, Q3MHH9, Q3SXY7, Q504C1, Q5FW85, Q5R482, Q5R6T0, Q5R7M3, Q5RAC4, Q61809, Q6RKD8, Q6UXK5, Q70AK3, Q7TNJ4, Q80ZD9, Q810B7, Q810B8, Q810C0, Q810C1, Q86SJ2, Q86VH5, Q8BGT1, Q8BLU0, Q8BZ81, Q8C110, Q8CBC6, Q8IW52

Diamond homologs: A6H793, A6NJW4, G5EG78, O35367, O75093, O88186, O88279, O93233, P14770, P22792, P35858, P59034, P59035, Q5R6T0, Q6NUI6, Q6RKD8, Q6WRH9, Q6WRI0, Q7M6Z0, Q80TR4, Q810B8, Q8C110, Q8IW52, Q8N967, Q9BY71, Q9DBB9, Q9H5Y7, Q9JJM7, Q9NZU0, Q9NZU1, Q9R1B9, Q9WVB4, Q9WVC1, O15335, O55226, O70210, O94933, O94991, Q27972, Q5RAC4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

896 predictions. Top by Δscore:

Variant	Effect	Δscore
X:143631155:TAAT:T	acceptor_gain	0.9900
X:143631159:C:CC	acceptor_gain	0.9900
X:143632345:T:C	donor_gain	0.9900
X:143624503:A:T	acceptor_gain	0.9800
X:143624654:TTTTT:T	acceptor_gain	0.9800
X:143631158:TC:T	acceptor_loss	0.9800
X:143631159:C:CG	acceptor_loss	0.9800
X:143631160:T:A	acceptor_loss	0.9800
X:143632332:G:C	donor_gain	0.9800
X:143634327:CCGG:C	donor_gain	0.9800
X:143634335:T:TA	donor_gain	0.9800
X:143624656:TTT:T	acceptor_gain	0.9700
X:143624659:C:CC	acceptor_gain	0.9700
X:143631154:ATAAT:A	acceptor_gain	0.9700
X:143631156:AAT:A	acceptor_gain	0.9700
X:143631157:AT:A	acceptor_gain	0.9700
X:143634263:AGGCC:A	donor_gain	0.9700
X:143634319:G:C	donor_gain	0.9700
X:143633470:AGAG:A	donor_gain	0.9600
X:143626020:ACCTT:A	acceptor_gain	0.9500
X:143633456:CCAG:C	donor_gain	0.9500
X:143626022:C:A	acceptor_gain	0.9400
X:143624655:TTTT:T	acceptor_gain	0.9300
X:143624657:TT:T	acceptor_gain	0.9100
X:143633857:C:A	donor_gain	0.9100
X:143634257:A:C	donor_gain	0.9100
X:143634319:GTTAC:G	donor_loss	0.9100
X:143634320:TTAC:T	donor_loss	0.9100
X:143634321:TAC:T	donor_loss	0.9100
X:143634322:ACCC:A	donor_loss	0.9100

AlphaMissense

5518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:143629510:C:A	W533C	1.000
X:143629510:C:G	W533C	1.000
X:143629512:A:G	W533R	1.000
X:143629512:A:T	W533R	1.000
X:143629676:A:G	L478P	1.000
X:143629732:A:C	N459K	1.000
X:143629732:A:T	N459K	1.000
X:143629748:A:G	L454P	1.000
X:143629804:A:C	N435K	1.000
X:143629804:A:T	N435K	1.000
X:143629814:A:G	L432P	1.000
X:143629820:A:G	L430P	1.000
X:143629892:A:G	L406P	1.000
X:143629964:A:G	L382P	1.000
X:143630026:G:C	C361W	1.000
X:143630027:C:G	C361S	1.000
X:143630028:A:G	C361R	1.000
X:143630028:A:T	C361S	1.000
X:143630073:A:G	C346R	1.000
X:143630383:A:C	C242W	1.000
X:143630384:C:A	C242F	1.000
X:143630384:C:G	C242S	1.000
X:143630384:C:T	C242Y	1.000
X:143630385:A:G	C242R	1.000
X:143630385:A:T	C242S	1.000
X:143630428:C:A	W227C	1.000
X:143630428:C:G	W227C	1.000
X:143630430:A:G	W227R	1.000
X:143630430:A:T	W227R	1.000
X:143630458:A:C	C217W	1.000

dbSNP variants (sampled 300 via entrez): RS1000113808 (X:143625200 A>G), RS1000555977 (X:143625749 C>A,T), RS1000885522 (X:143633887 C>G,T), RS1000978305 (X:143633672 G>T), RS1001129919 (X:143623182 A>C,G), RS1001403830 (X:143634460 C>G), RS1001433332 (X:143634736 T>C), RS1001518947 (X:143622589 T>C,G), RS1002408385 (X:143632701 G>A,C,T), RS1002440977 (X:143633123 G>A,C,T), RS1002628948 (X:143622528 T>C), RS1004930177 (X:143629243 T>C), RS1005350 (X:143634794 C>A,G,T), RS1005752528 (X:143636649 T>A,C), RS1005783618 (X:143637038 C>T)

Disease associations

OMIM: gene MIM:300562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003123_34	Severe influenza A (H1N1) infection	2.000000e-16
GCST006014_32	Creatine kinase levels	7.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0004534	creatine kinase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
Estradiol	affects cotreatment, decreases expression, affects binding, increases expression	4
trichostatin A	increases expression	3
sodium arsenite	affects splicing, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
Am 580	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, increases expression, affects cotreatment	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Rosiglitazone	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	increases expression	1
Aldehydes	increases expression	1
Allergens	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Doxorubicin	increases expression	1
Lead	affects expression	1
Progesterone	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Testosterone	decreases expression	1
Zearalenone	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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