SLC35E4

Summary

SLC35E4 (solute carrier family 35 member E4, HGNC:17058) is a protein-coding gene on chromosome 22q12.2, encoding Solute carrier family 35 member E4 (Q6ICL7). Putative transporter.

Predicted to enable antiporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in membrane. Predicted to be active in Golgi apparatus.

Source: NCBI Gene 339665 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_001001479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17058
Approved symbol	SLC35E4
Name	solute carrier family 35 member E4
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100036
Ensembl biotype	protein_coding
Entrez	339665

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000343605, ENST00000406566, ENST00000451479

RefSeq mRNA: 3 — MANE Select: NM_001001479 NM_001001479, NM_001318370, NM_001318371

CCDS: CCDS13882, CCDS82708

Canonical transcript exons

ENST00000343605 — 2 exons

Exon	Start	End
ENSE00001391765	30646598	30647893
ENSE00001911787	30635781	30637069

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 84.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1487 / max 213.3632, expressed in 1696 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191708	6.9492	1653
191709	0.5513	294
191710	0.3929	183
191712	0.2314	62
191711	0.0240	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.94	gold quality
left testis	UBERON:0004533	83.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.67	gold quality
sperm	CL:0000019	82.22	silver quality
right testis	UBERON:0004534	80.94	gold quality
testis	UBERON:0000473	80.63	gold quality
gastrocnemius	UBERON:0001388	78.50	gold quality
muscle of leg	UBERON:0001383	78.13	gold quality
mucosa of transverse colon	UBERON:0004991	76.94	gold quality
stromal cell of endometrium	CL:0002255	76.90	gold quality
cartilage tissue	UBERON:0002418	76.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.63	gold quality
prefrontal cortex	UBERON:0000451	73.34	gold quality
apex of heart	UBERON:0002098	72.53	gold quality
skin of abdomen	UBERON:0001416	72.19	gold quality
right frontal lobe	UBERON:0002810	72.06	gold quality
skin of leg	UBERON:0001511	72.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	71.37	gold quality
lower esophagus	UBERON:0013473	71.34	gold quality
right coronary artery	UBERON:0001625	71.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.80	gold quality
thoracic aorta	UBERON:0001515	70.56	gold quality
transverse colon	UBERON:0001157	70.48	gold quality
ascending aorta	UBERON:0001496	70.47	gold quality
body of stomach	UBERON:0001161	70.37	gold quality
zone of skin	UBERON:0000014	70.33	gold quality
anterior cingulate cortex	UBERON:0009835	70.29	gold quality
descending thoracic aorta	UBERON:0002345	70.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting SLC35E4, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-6840-3P	98.68	65.95	1923
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-7114-3P	98.42	66.53	569
HSA-MIR-1180-5P	98.16	65.32	460
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-4642	97.52	67.60	916
HSA-MIR-711	96.60	65.75	528
HSA-MIR-4701-5P	96.45	68.41	1121

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc35e4	ENSDARG00000009459
mus_musculus	Slc35e4	ENSMUSG00000048807
rattus_norvegicus	Slc35e4	ENSRNOG00000004168
drosophila_melanogaster	frc	FBGN0042641
caenorhabditis_elegans		WBGENE00005025

Paralogs (9): SLC35C2 (ENSG00000080189), SLC35D1 (ENSG00000116704), SLC35E1 (ENSG00000127526), SLC35D2 (ENSG00000130958), TMEM241 (ENSG00000134490), SLC35E3 (ENSG00000175782), SLC35C1 (ENSG00000181830), SLC35D3 (ENSG00000182747), SLC35E2B (ENSG00000189339)

Protein

Protein identifiers

Solute carrier family 35 member E4 — Q6ICL7 (reviewed: Q6ICL7)

All UniProt accessions (2): Q6ICL7, H7C3S2

UniProt curated annotations — full annotation on UniProt →

Function. Putative transporter.

Subcellular location. Membrane.

Similarity. Belongs to the TPT transporter family. SLC35E subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ICL7-1	1	yes
Q6ICL7-2	2

RefSeq proteins (3): NP_001001479, NP_001305299, NP_001305300 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004853	Sugar_P_trans_dom	Domain
IPR037185	EmrE-like	Homologous_superfamily
IPR050186	TPT_transporter	Family

Pfam: PF03151

UniProt features (14 total): transmembrane region 8, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ICL7-F1	80.99	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): AP1_01, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, CCANNAGRKGGC_UNKNOWN, TGANTCA_AP1_C, PEREZ_TP53_AND_TP63_TARGETS, BERENJENO_TRANSFORMED_BY_RHOA_UP, GOBP_TRANSMEMBRANE_TRANSPORT, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_DN, AP1FJ_Q2, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK

GO Biological Process (1): transmembrane transport (GO:0055085)

GO Molecular Function (2): antiporter activity (GO:0015297), protein binding (GO:0005515)

GO Cellular Component (2): Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
secondary active transmembrane transporter activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

308 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35E4	TMEM121B	Q9BXQ6	560
SLC35E4	RIMBP3B	A6NNM3	507
SLC35E4	FAM227A	F5H4B4	507
SLC35E4	ATP5MGL	Q7Z4Y8	507
SLC35E4	ACTL10	Q5JWF8	476
SLC35E4	ZNF358	Q9NW07	455
SLC35E4	PIP4P2	Q8N4L2	452
SLC35E4	RIMBP3C	A6NJZ7	433
SLC35E4	SLC10A5	Q5PT55	421
SLC35E4	TMEM255A	Q5JRV8	417
SLC35E4	NOL9	Q5SY16	415
SLC35E4	SLC7A4	O43246	400
SLC35E4	KLHL11	Q9NVR0	398
SLC35E4	POTEH	Q6S545	397
SLC35E4	DDTL	A6NHG4	396

IntAct

50 interactions, top by confidence:

A	B	Type	Score
SLC35E4	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	MUC1	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	MMGT1	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	GPR101	psi-mi:“MI:0915”(physical association)	0.560
GPR42	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
VMA21	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
CNR2	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	UNC93A	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
MUC1	SLC35E4	psi-mi:“MI:0915”(physical association)	0.560
SLC35E4	XPO1	psi-mi:“MI:0914”(association)	0.350
SLC35E4	SLC13A4	psi-mi:“MI:0915”(physical association)	0.000
SLC35E4	TMEM237	psi-mi:“MI:0915”(physical association)	0.000
SLC35E4		psi-mi:“MI:0915”(physical association)	0.000
SLC35E4	TIMMDC1	psi-mi:“MI:0915”(physical association)	0.000
SLC35E4	GPR101	psi-mi:“MI:0915”(physical association)	0.000
SLC35E4	GPR42	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (58): SLC35E4 (Two-hybrid), SLC10A1 (Two-hybrid), UNC93A (Two-hybrid), TIMMDC1 (Two-hybrid), GPR42 (Two-hybrid), TMEM14B (Two-hybrid), TMEM237 (Two-hybrid), VMA21 (Two-hybrid), SLC13A4 (Two-hybrid), GPR101 (Two-hybrid), SCN3B (Two-hybrid), MMGT1 (Two-hybrid), HSD17B13 (Two-hybrid), TMEM31 (Two-hybrid), MUC1 (Two-hybrid)

ESM2 similar proteins: A2XGM7, A7YW81, O08520, O16658, P31421, P49133, P55019, P78381, P78382, P87041, Q02334, Q05B73, Q0D2K0, Q10LI8, Q10LN5, Q14416, Q14BI2, Q19VE6, Q2QR07, Q58DA6, Q5RA79, Q5RFT1, Q5RKH7, Q5RKL7, Q5VQL3, Q61420, Q69VR7, Q6ICL7, Q6YZF3, Q755H7, Q7RTP0, Q84QU8, Q8AWB6, Q8BHK1, Q8BZF2, Q8K3D6, Q8MXJ9, Q8N357, Q8VE96, Q8WMS0

Diamond homologs: Q5RKL7, Q6ICL7, Q8K3D6, Q3E6T0, Q5VQL3, Q5XF09, Q6DBP3, Q9C521, Q9FYE5, Q9LDH3, Q9LFN3, Q9LNH5, Q9LRP2, Q9SFE9, Q9SKJ7, Q9SS40, Q9SUV2, F4IHS9, Q8GUJ1, Q8RWW7, Q8RXL8, Q9FDZ5, Q9FG70, Q9FIH5, Q9LPU2, Q9LU76, Q9SRE4, Q9SZ96

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1198 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30637065:GCAAA:G	donor_gain	1.0000
22:30637068:AA:A	donor_gain	1.0000
22:30637068:AAG:A	donor_loss	1.0000
22:30637069:AGT:A	donor_loss	1.0000
22:30637070:G:GG	donor_gain	1.0000
22:30637070:G:T	donor_loss	1.0000
22:30646593:TGCA:T	acceptor_loss	1.0000
22:30646594:GCAG:G	acceptor_loss	1.0000
22:30646595:CA:C	acceptor_loss	1.0000
22:30646596:A:AG	acceptor_gain	1.0000
22:30646597:G:A	acceptor_loss	1.0000
22:30646597:G:GG	acceptor_gain	1.0000
22:30646597:GGT:G	acceptor_gain	1.0000
22:30637066:CAAA:C	donor_gain	0.9900
22:30637071:TAAG:T	donor_loss	0.9900
22:30646596:AG:A	acceptor_gain	0.9900
22:30646596:AGGT:A	acceptor_gain	0.9900
22:30646597:GG:G	acceptor_gain	0.9900
22:30646597:GGTG:G	acceptor_gain	0.9900
22:30646597:GGTGC:G	acceptor_gain	0.9900
22:30663462:T:TA	donor_gain	0.9900
22:30664081:C:CC	acceptor_gain	0.9900
22:30664947:C:A	donor_gain	0.9900
22:30637067:AAA:A	donor_gain	0.9800
22:30646593:T:A	acceptor_gain	0.9800
22:30667467:T:A	donor_gain	0.9800
22:30637857:A:T	donor_gain	0.9700
22:30646590:T:TA	acceptor_gain	0.9700
22:30654646:T:C	acceptor_gain	0.9700
22:30664076:GAAAA:G	acceptor_gain	0.9700

AlphaMissense

2183 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30636790:A:C	S114R	0.995
22:30636792:T:A	S114R	0.995
22:30636792:T:G	S114R	0.995
22:30646660:A:C	S228R	0.995
22:30646662:C:A	S228R	0.995
22:30646662:C:G	S228R	0.995
22:30646759:A:C	S261R	0.995
22:30646761:C:A	S261R	0.995
22:30646761:C:G	S261R	0.995
22:30636643:A:C	S65R	0.991
22:30636645:C:A	S65R	0.991
22:30636645:C:G	S65R	0.991
22:30637056:G:C	K202N	0.987
22:30637056:G:T	K202N	0.987
22:30646762:T:C	C262R	0.987
22:30646792:A:C	S272R	0.983
22:30646794:C:A	S272R	0.983
22:30646794:C:G	S272R	0.983
22:30636634:A:C	S62R	0.980
22:30636636:C:A	S62R	0.980
22:30636636:C:G	S62R	0.980
22:30636979:A:C	S177R	0.980
22:30636981:C:A	S177R	0.980
22:30636981:C:G	S177R	0.980
22:30636961:T:C	C171R	0.979
22:30637048:G:A	G200R	0.976
22:30637048:G:C	G200R	0.976
22:30636799:T:C	F117L	0.975
22:30636801:T:A	F117L	0.975
22:30636801:T:G	F117L	0.975

dbSNP variants (sampled 300 via entrez): RS1000095639 (22:30652366 T>C), RS1000148986 (22:30660115 T>C), RS1000354461 (22:30666697 A>G), RS1000356204 (22:30661694 G>A), RS1000447800 (22:30652679 G>A), RS1000545903 (22:30636421 C>A,T), RS1000548381 (22:30638717 T>G), RS1000598244 (22:30636774 C>T), RS1000599373 (22:30644904 T>A,C), RS1000636128 (22:30650186 G>C,T), RS1000818153 (22:30666451 G>A), RS1000878520 (22:30638592 A>T), RS1000961869 (22:30660476 G>GA), RS1001011504 (22:30654304 T>C), RS1001046748 (22:30654140 C>A,T)

Disease associations

OMIM: gene `` | 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
GCST010002_80	Refractive error	2.000000e-09
GCST90002396_85	Mean reticulocyte volume	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC35 family of nucleotide sugar transporters

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
Acetaminophen	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
bisphenol A	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Oxygen	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Triclosan	increases expression	1
Urethane	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Okadaic Acid	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4MH	HCT116-SLC35E4-KO-c4	Cancer cell line	Male
CVCL_D4MI	HCT116-SLC35E4-KO-c8	Cancer cell line	Male
CVCL_TN24	HAP1 SLC35E4 (-) 1	Cancer cell line	Male
CVCL_XT25	HAP1 SLC35E4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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