SLC35A4

Summary

SLC35A4 (solute carrier family 35 member A4, HGNC:20753) is a protein-coding gene on chromosome 5q31.3, encoding SLC35A4 upstream open reading frame protein (L0R6Q1). Required to maintain cellular respiration.

Predicted to enable transmembrane transporter activity. Involved in positive regulation of cellular respiration and positive regulation of translation in response to stress. Located in Golgi membrane and mitochondrial inner membrane.

Source: NCBI Gene 113829 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_080670

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20753
Approved symbol	SLC35A4
Name	solute carrier family 35 member A4
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000176087
Ensembl biotype	protein_coding
OMIM	620297
Entrez	113829

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000323146, ENST00000514199, ENST00000612662

RefSeq mRNA: 1 — MANE Select: NM_080670 NM_080670

CCDS: CCDS4231

Canonical transcript exons

ENST00000323146 — 3 exons

Exon	Start	End
ENSE00001225564	140565873	140565971
ENSE00001409798	140564828	140564858
ENSE00002026720	140566565	140569100

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.8923 / max 155.1186, expressed in 1813 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58915	15.4697	1805
58911	3.1000	1540
58912	1.6019	1076
58913	0.2467	70
58914	0.2462	81
58916	0.2278	95

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	97.72	gold quality
gastrocnemius	UBERON:0001388	96.67	gold quality
rectum	UBERON:0001052	96.22	gold quality
upper arm skin	UBERON:0004263	95.98	gold quality
muscle of leg	UBERON:0001383	95.87	gold quality
vermiform appendix	UBERON:0001154	95.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.56	gold quality
smooth muscle tissue	UBERON:0001135	95.55	gold quality
apex of heart	UBERON:0002098	95.38	gold quality
mucosa of transverse colon	UBERON:0004991	95.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.15	silver quality
ileal mucosa	UBERON:0000331	95.08	gold quality
heart left ventricle	UBERON:0002084	94.79	gold quality
left adrenal gland	UBERON:0001234	94.73	gold quality
left ventricle myocardium	UBERON:0006566	94.66	silver quality
gall bladder	UBERON:0002110	94.65	gold quality
left adrenal gland cortex	UBERON:0035825	94.59	gold quality
cardiac ventricle	UBERON:0002082	94.57	gold quality
adult mammalian kidney	UBERON:0000082	94.56	gold quality
lower esophagus mucosa	UBERON:0035834	94.50	gold quality
leukocyte	CL:0000738	94.49	gold quality
kidney epithelium	UBERON:0004819	94.48	silver quality
right adrenal gland	UBERON:0001233	94.45	gold quality
monocyte	CL:0000576	94.43	gold quality
skin of leg	UBERON:0001511	94.25	gold quality
right adrenal gland cortex	UBERON:0035827	94.25	gold quality
esophagus mucosa	UBERON:0002469	94.16	gold quality
metanephros cortex	UBERON:0010533	94.13	gold quality
minor salivary gland	UBERON:0001830	93.99	gold quality
adrenal cortex	UBERON:0001235	93.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

70 targeting SLC35A4, 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-4481	100.00	66.42	1669
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4472	99.56	66.08	1478

Literature-anchored findings (GeneRIF, showing 1)

• A modulatory role for SLC35A4 in intracellular trafficking of SLC35A2/SLC35A3 complexes. (PMID:28167211)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc35a4	ENSMUSG00000033272
rattus_norvegicus	Slc35a4	ENSRNOG00000002908
drosophila_melanogaster	senju	FBGN0031676

Paralogs (4): SLC35A2 (ENSG00000102100), SLC35A3 (ENSG00000117620), SLC35A5 (ENSG00000138459), SLC35A1 (ENSG00000164414)

Protein

Protein identifiers

SLC35A4 upstream open reading frame protein — L0R6Q1 (reviewed: L0R6Q1, Q96G79)

Alternative names: SLC35A4 microprotein

All UniProt accessions (1): Q96G79

UniProt curated annotations — full annotation on UniProt →

Function. Required to maintain cellular respiration.

Subcellular location. Mitochondrion inner membrane.

Miscellaneous. Product of the upstream open reading frame of this bicistronic gene. This may be the major product of the gene under normal conditions.

Isoforms (2)

UniProt ID	Names	Canonical?
L0R6Q1-1	2, uORF	yes
Q96G79-1	1

RefSeq proteins (1): NP_542401* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027854	STMP1	Family
IPR007271	Nuc_sug_transpt	Family
IPR037185	EmrE-like	Homologous_superfamily

Pfam: PF04142, PF15054

Catalyzed reactions (Rhea), 1 shown:

• CDP-L-ribitol(in) + CDP(out) = CDP-L-ribitol(out) + CDP(in) (RHEA:71579)

UniProt features (23 total): transmembrane region 9, topological domain 9, sequence conflict 3, chain 2

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-L0R6Q1-F1	63.60	0.00
AF-Q96G79-F1	85.01	0.56

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9939291	Matriglycan biosynthesis on DAG1

MSigDB gene sets: 140 (showing top): CAGCTG_AP4_Q5, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GTGCCTT_MIR506, MODULE_205, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, CCAGGTT_MIR490, GOBP_CARBOHYDRATE_DERIVATIVE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_PROTEIN_O_LINKED_GLYCOSYLATION, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (5): positive regulation of translation in response to stress (GO:0032056), positive regulation of cellular respiration (GO:1901857), protein O-linked glycosylation (GO:0006493), transmembrane transport (GO:0055085), pyrimidine nucleotide-sugar transmembrane transport (GO:0090481)

GO Molecular Function (4): pyrimidine nucleotide-sugar transmembrane transporter activity (GO:0015165), pyrimidine nucleotide transmembrane transporter activity (GO:0015218), transmembrane transporter activity (GO:0022857), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), Golgi membrane (GO:0000139), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
DAG1 glycosylations	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
intracellular membrane-bounded organelle	2
translation	1
cellular response to stress	1
regulation of translation in response to stress	1
positive regulation of translation	1
positive regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
glycoprotein biosynthetic process	1
transport	1
cellular process	1
nucleotide-sugar transmembrane transport	1
nucleotide-sugar transmembrane transporter activity	1
pyrimidine nucleotide-sugar transmembrane transport	1
pyrimidine nucleotide transport	1
nucleotide transmembrane transporter activity	1
transporter activity	1
transmembrane transport	1
binding	1
organelle inner membrane	1
mitochondrial membrane	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

5 interactions, top by confidence:

A	B	Type	Score
MFSD6L	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A11	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-29	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0B4J2F0, A0A1D8PLP3, A1XQS1, A5E7J0, A5Z2X5, A7TQM5, A8E7D3, B3DFP2, B7Z0X7, C0HK61, C0HK65, C0HLN0, C5DE77, C6Y4A3, E0CX11, E1BHC3, G2TRJ9, L0R6Q1, O13931, O22912, O74433, O94705, P07255, P0DJ07, P0DJE0, P0DKM0, P0DP99, P19173, P20610, P22289, P48505, P81449, P81450, Q02820, Q42841, Q54QR8, Q6BPV1, Q6CCF6, Q6CMH6, Q6CS34

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

422 predictions. Top by Δscore:

Variant	Effect	Δscore
5:140565967:GCCAG:G	donor_gain	1.0000
5:140565970:AGG:A	donor_loss	1.0000
5:140565971:GGTAA:G	donor_loss	1.0000
5:140565972:G:GG	donor_gain	1.0000
5:140565972:GTAA:G	donor_loss	1.0000
5:140565973:T:A	donor_loss	1.0000
5:140566561:GCAG:G	acceptor_loss	1.0000
5:140566562:CA:C	acceptor_loss	1.0000
5:140566563:A:AG	acceptor_gain	1.0000
5:140566563:AG:A	acceptor_gain	1.0000
5:140566563:AGG:A	acceptor_loss	1.0000
5:140566563:AGGAT:A	acceptor_gain	1.0000
5:140566564:G:GG	acceptor_gain	1.0000
5:140566564:GG:G	acceptor_gain	1.0000
5:140566564:GGAT:G	acceptor_gain	1.0000
5:140566564:GGATG:G	acceptor_gain	1.0000
5:140564855:CAAGG:C	donor_loss	0.9900
5:140564856:AAGGT:A	donor_loss	0.9900
5:140564857:AGG:A	donor_loss	0.9900
5:140564858:GGT:G	donor_loss	0.9900
5:140564859:GTG:G	donor_loss	0.9900
5:140566564:GGA:G	acceptor_gain	0.9900
5:140564859:G:GG	donor_gain	0.9800
5:140564860:T:A	donor_loss	0.9800
5:140565867:TCCTA:T	acceptor_loss	0.9800
5:140565868:CCTA:C	acceptor_loss	0.9800
5:140565869:CTA:C	acceptor_loss	0.9800
5:140565870:TA:T	acceptor_loss	0.9800
5:140565871:A:AC	acceptor_loss	0.9800
5:140565872:G:GT	acceptor_loss	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000116414 (5:140568890 A>T), RS1000183069 (5:140565698 T>C), RS1000786513 (5:140564451 T>C), RS1001071782 (5:140564687 C>T), RS1001139894 (5:140569530 TAAAA>T,TAAA,TAAAAA), RS1001493681 (5:140569039 A>G), RS1002782870 (5:140567037 C>A,T), RS1002905015 (5:140564054 C>A), RS1003498866 (5:140565459 G>T), RS1003773896 (5:140565824 G>A), RS1004272608 (5:140568039 C>A,T), RS1004582830 (5:140566989 A>C,G), RS1005182139 (5:140565634 T>C), RS1005709594 (5:140565258 A>G), RS1005843107 (5:140564432 A>C,T)

Disease associations

OMIM: gene MIM:620297 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010146_22	Serum immune biomarker levels	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
trichostatin A	affects expression, decreases reaction	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, decreases expression	1
Cisplatin	decreases expression	1
Diuron	decreases expression	1
Environmental Pollutants	affects expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Nickel	affects expression, decreases reaction	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Zidovudine	increases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3HE	Abcam HEK293T SLC35A4 KO	Transformed cell line	Female
CVCL_D4LX	HCT116-SLC35A4-KO-c20	Cancer cell line	Male
CVCL_D4LY	HCT116-SLC35A4-KO-c7	Cancer cell line	Male
CVCL_TN07	HAP1 SLC35A4 (-) 1	Cancer cell line	Male
CVCL_XT18	HAP1 SLC35A4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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