SLC35D4

Summary

SLC35D4 (solute carrier family 35 member D4, HGNC:31723) is a protein-coding gene on chromosome 18q11.2, encoding UDP-N-acetylglucosamine transporter SLC35D4 (Q24JQ0). Golgi-localized UDP-N-acetylglucosamine (UDP-GlcNAc) transporter that transports UDP-N-acetylglucosamine into Golgi lumen.

Enables UDP-N-acetylglucosamine transmembrane transporter activity. Involved in UDP-N-acetylglucosamine transmembrane transport. Located in Golgi apparatus.

Source: NCBI Gene 85019 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_032933

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31723
Approved symbol	SLC35D4
Name	solute carrier family 35 member D4
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC11386, FLJ44259
Ensembl gene	ENSG00000134490
Ensembl biotype	protein_coding
OMIM	615430
Entrez	85019

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 protein_coding, 8 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000383233, ENST00000460322, ENST00000473688, ENST00000475185, ENST00000477053, ENST00000482411, ENST00000497608, ENST00000542162, ENST00000577448, ENST00000577531, ENST00000578520, ENST00000578790, ENST00000580025, ENST00000581444, ENST00000582336, ENST00000583048, ENST00000584625, ENST00000907352, ENST00000907353, ENST00000907354, ENST00000907355, ENST00000938582, ENST00000938583, ENST00000938584, ENST00000938585, ENST00000951849, ENST00000951850

RefSeq mRNA: 2 — MANE Select: NM_032933 NM_001318834, NM_032933

CCDS: CCDS11876

Canonical transcript exons

ENST00000383233 — 15 exons

Exon	Start	End
ENSE00002168027	23437781	23437961
ENSE00003460372	23370216	23370261
ENSE00003461713	23365634	23365668
ENSE00003467343	23356594	23356663
ENSE00003470822	23373712	23373763
ENSE00003548097	23384990	23385067
ENSE00003560190	23371422	23371470
ENSE00003560952	23421367	23421444
ENSE00003561927	23399566	23399647
ENSE00003569476	23352196	23352289
ENSE00003603005	23309680	23309744
ENSE00003623398	23296013	23298067
ENSE00003645626	23430631	23430677
ENSE00003683251	23368715	23368750
ENSE00003694704	23377646	23377671

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5568 / max 54.1666, expressed in 1704 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171350	5.4147	1691
171346	0.0671	39
171347	0.0406	23
171349	0.0279	12
171348	0.0064	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.77	gold quality
pancreatic ductal cell	CL:0002079	97.61	gold quality
tendon of biceps brachii	UBERON:0008188	97.58	gold quality
nasal cavity epithelium	UBERON:0005384	96.81	gold quality
upper arm skin	UBERON:0004263	96.55	gold quality
kidney epithelium	UBERON:0004819	96.13	gold quality
medial globus pallidus	UBERON:0002477	95.65	gold quality
tibialis anterior	UBERON:0001385	94.98	silver quality
cardiac muscle of right atrium	UBERON:0003379	94.57	silver quality
ileal mucosa	UBERON:0000331	94.24	gold quality
globus pallidus	UBERON:0001875	94.21	gold quality
left ventricle myocardium	UBERON:0006566	93.89	silver quality
upper leg skin	UBERON:0004262	93.73	gold quality
oviduct epithelium	UBERON:0004804	93.62	gold quality
trabecular bone tissue	UBERON:0002483	92.94	gold quality
myocardium	UBERON:0002349	92.83	gold quality
epithelium of mammary gland	UBERON:0003244	92.50	gold quality
mammary duct	UBERON:0001765	92.46	gold quality
cerebellar vermis	UBERON:0004720	92.24	gold quality
deltoid	UBERON:0001476	91.09	silver quality
epithelial cell of pancreas	CL:0000083	91.02	gold quality
vena cava	UBERON:0004087	90.89	gold quality
quadriceps femoris	UBERON:0001377	90.86	gold quality
pigmented layer of retina	UBERON:0001782	90.77	gold quality
cardia of stomach	UBERON:0001162	90.63	gold quality
biceps brachii	UBERON:0001507	90.49	gold quality
vastus lateralis	UBERON:0001379	90.40	gold quality
subthalamic nucleus	UBERON:0001906	90.35	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.35	gold quality
ventral tegmental area	UBERON:0002691	89.82	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.73
E-MTAB-7606	no	21.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting SLC35D4, 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-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524

Literature-anchored findings (GeneRIF, showing 1)

• The Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 alpha binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans. (PMID:27199446)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	tmem241	ENSDARG00000090685
		ENSDARG00000104905
mus_musculus	Tmem241	ENSMUSG00000049411
rattus_norvegicus	Tmem241	ENSRNOG00000023412
drosophila_melanogaster	frc	FBGN0042641
caenorhabditis_elegans		WBGENE00005025

Paralogs (9): SLC35C2 (ENSG00000080189), SLC35E4 (ENSG00000100036), SLC35D1 (ENSG00000116704), SLC35E1 (ENSG00000127526), SLC35D2 (ENSG00000130958), SLC35E3 (ENSG00000175782), SLC35C1 (ENSG00000181830), SLC35D3 (ENSG00000182747), SLC35E2B (ENSG00000189339)

Protein

Protein identifiers

UDP-N-acetylglucosamine transporter SLC35D4 — Q24JQ0 (reviewed: Q24JQ0)

Alternative names: Solute carrier family 35 member D4, Transmembrane protein 241

All UniProt accessions (8): E9PJC2, E9PLG4, Q24JQ0, F5GXY7, H0YDH1, J3QL29, J3QR22, J3QRE6

UniProt curated annotations — full annotation on UniProt →

Function. Golgi-localized UDP-N-acetylglucosamine (UDP-GlcNAc) transporter that transports UDP-N-acetylglucosamine into Golgi lumen. Contributes to lysosomal targeting of NPC2, a key protein required for lysosomal cholesterol exiting, and that utilizes the mannose-6-phosphate (M6P) modification pathway for its lysosomal targeting.

Subcellular location. Golgi apparatus. cis-Golgi network membrane.

Induction. Up-regulated by inducers of the unfolded protein response (UPR), including tunicamycin and thapsigargin.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the nucleotide-sugar transporter family. SLC35D subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q24JQ0-1	1	yes
Q24JQ0-2	2
Q24JQ0-3	3

RefSeq proteins (2): NP_001305763, NP_116322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR050186	TPT_transporter	Family

UniProt features (17 total): transmembrane region 10, splice variant 5, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q24JQ0-F1	94.11	0.86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 88 (showing top): GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_CARBOHYDRATE_DERIVATIVE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, chr18q11, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOERING_BLOOD_HDL_CHOLESTEROL_QTL_TRANS, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, LIU_COMMON_CANCER_GENES, GOMF_ORGANOPHOSPHATE_ESTER_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (2): UDP-N-acetylglucosamine transmembrane transport (GO:1990569), GDP-mannose transmembrane transport (GO:1990570)

GO Molecular Function (4): GDP-mannose transmembrane transporter activity (GO:0005458), UDP-N-acetylglucosamine transmembrane transporter activity (GO:0005462), 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
pyrimidine nucleotide-sugar transmembrane transport	1
purine nucleotide-sugar transmembrane transport	1
purine nucleotide-sugar transmembrane transporter activity	1
GDP-mannose transmembrane transport	1
pyrimidine nucleotide-sugar transmembrane transporter activity	1
UDP-N-acetylglucosamine transmembrane transport	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

658 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC35D4	ANKRD29	Q8N6D5	527
SLC35D4	CABLES1	Q8TDN4	480
SLC35D4	CDH22	Q9UJ99	460
SLC35D4	FAM53A	Q6NSI3	459
SLC35D4	GREB1L	Q9C091	456
SLC35D4	THOC1	Q96FV9	420
SLC35D4	ZNF587B	E7ETH6	417
SLC35D4	TMEM169	Q96HH4	403
SLC35D4	ZNF521	Q96K83	401
SLC35D4	CHST11	Q9NPF2	375
SLC35D4	MRPL21	Q7Z2W9	365
SLC35D4	TIGD6	Q17RP2	359
SLC35D4	MYSM1	Q5VVJ2	353
SLC35D4	PHTF2	Q8N3S3	347
SLC35D4	MINDY4	Q4G0A6	330

IntAct

6 interactions, top by confidence:

A	B	Type	Score
STX7	TMEM241	psi-mi:“MI:0915”(physical association)	0.560
TMEM241	LZTFL1	psi-mi:“MI:0915”(physical association)	0.400
TMEM241	FAAH	psi-mi:“MI:0914”(association)	0.350
STX7	TMEM241	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (73): KRT40 (Two-hybrid), TMEM241 (Two-hybrid), TMEM241 (Affinity Capture-RNA), TMEM241 (Synthetic Lethality), TMEM241 (Two-hybrid), LZTFL1 (Affinity Capture-MS), AAAS (Affinity Capture-MS), ACBD5 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), ALG10 (Affinity Capture-MS), AMFR (Affinity Capture-MS), ANKLE2 (Affinity Capture-MS), ANO10 (Affinity Capture-MS), ANO8 (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A084AFH0, A1L3G4, A1Z7R6, A5WWC6, A7YW81, B0B8F4, B0K004, D3YVE8, O04508, O74750, O84584, P0C7Q5, P0C7Q6, P39542, P40004, P53403, Q00974, Q0Q7U7, Q0Q7U8, Q0Q7U9, Q0Q7V0, Q0V9U2, Q1PFJ4, Q23444, Q24JQ0, Q3UME2, Q5F297, Q5M7A3, Q5PT55, Q5ZJZ4, Q7RTP0, Q8BHK1, Q8MXJ9, Q8N808, Q94EI9, Q96KT7, Q9C508, Q9C654, Q9C8M1, Q9FG70

Diamond homologs: A1C9R4, A1CZJ3, A1DA52, A1L3G4, A2R9P4, A3LWX1, A4RM13, A5DIN8, A6RJQ8, A6ZQY8, A6ZTW6, A7E558, A7TES5, A7TR80, A8N9T6, A8PTV6, B0DI84, B0Y384, B3LHR7, B3LS51, B3LS52, B5VHH5, C7GSI5, C7GSI6, C7GUZ7, C8Z742, C8Z830, P0CD97, P0CE11, P0CS02, P0CS03, P0CS04, P0CS05, P40107, Q0CA27, Q0UG89, Q1DTI4, Q24JQ0, Q2AAF6, Q2HA88

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4431 predictions. Top by Δscore:

Variant	Effect	Δscore
18:23213976:GAATA:G	acceptor_gain	1.0000
18:23237130:T:G	acceptor_gain	1.0000
18:23252948:T:TA	acceptor_gain	1.0000
18:23252952:T:TA	acceptor_gain	1.0000
18:23252958:A:AG	acceptor_gain	1.0000
18:23252958:A:G	acceptor_loss	1.0000
18:23252959:G:GA	acceptor_gain	1.0000
18:23252959:GA:G	acceptor_gain	1.0000
18:23252959:GAC:G	acceptor_gain	1.0000
18:23252959:GACA:G	acceptor_gain	1.0000
18:23252959:GACAA:G	acceptor_gain	1.0000
18:23253025:G:GT	donor_gain	1.0000
18:23253063:GGAG:G	donor_gain	1.0000
18:23253064:GAG:G	donor_gain	1.0000
18:23253064:GAGG:G	donor_gain	1.0000
18:23253065:AGG:A	donor_loss	1.0000
18:23253067:GT:G	donor_loss	1.0000
18:23253068:T:G	donor_loss	1.0000
18:23253716:T:A	acceptor_gain	1.0000
18:23253727:A:AG	acceptor_gain	1.0000
18:23253727:AGTCT:A	acceptor_gain	1.0000
18:23253728:G:GA	acceptor_gain	1.0000
18:23253728:GT:G	acceptor_gain	1.0000
18:23253728:GTC:G	acceptor_gain	1.0000
18:23253728:GTCT:G	acceptor_gain	1.0000
18:23253728:GTCTG:G	acceptor_gain	1.0000
18:23253852:G:GT	donor_gain	1.0000
18:23253896:G:GT	donor_gain	1.0000
18:23253916:G:GT	donor_gain	1.0000
18:23253932:TTGAC:T	donor_gain	1.0000

AlphaMissense

1914 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:23430654:A:C	F32L	0.993
18:23430654:A:T	F32L	0.993
18:23430656:A:G	F32L	0.993
18:23365668:A:C	S189R	0.990
18:23365668:A:T	S189R	0.990
18:23368716:T:G	S189R	0.990
18:23352289:A:C	S224R	0.989
18:23352289:A:T	S224R	0.989
18:23356595:T:G	S224R	0.989
18:23356614:G:C	F217L	0.989
18:23356614:G:T	F217L	0.989
18:23356616:A:G	F217L	0.989
18:23421443:A:G	W41R	0.989
18:23421443:A:T	W41R	0.989
18:23430655:A:G	F32S	0.989
18:23430655:A:C	F32C	0.974
18:23356615:A:G	F217S	0.973
18:23385053:A:C	F98L	0.973
18:23385053:A:T	F98L	0.973
18:23385055:A:G	F98L	0.973
18:23356638:G:C	F209L	0.970
18:23356638:G:T	F209L	0.970
18:23356640:A:G	F209L	0.970
18:23430632:C:G	G40R	0.969
18:23430632:C:T	G40R	0.969
18:23356605:G:C	S220R	0.966
18:23356605:G:T	S220R	0.966
18:23356607:T:G	S220R	0.966
18:23437781:C:A	K24N	0.965
18:23437781:C:G	K24N	0.965

dbSNP variants (sampled 300 via entrez): RS1000002065 (18:23342644 C>A,T), RS1000034644 (18:23387598 T>C), RS1000057030 (18:23302151 C>T), RS1000069960 (18:23289606 C>A), RS1000070076 (18:23432558 G>A), RS1000103356 (18:23395941 G>A,C), RS1000124583 (18:23292927 G>A), RS1000127176 (18:23375413 G>A), RS1000133014 (18:23434759 A>C,G), RS1000149043 (18:23317548 C>T), RS1000202976 (18:23382164 C>T), RS1000203448 (18:23344209 G>A), RS1000205672 (18:23322536 T>G), RS1000223493 (18:23336991 A>G), RS1000225182 (18:23414612 G>A)

Disease associations

OMIM: gene MIM:615430 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000175_6	Height	4.000000e-09
GCST001905_6	Hypertriglyceridemia	2.000000e-08
GCST003474_9	Scalp hair shape	6.000000e-06
GCST006946_17	Worry too long after an embarrassing experience	2.000000e-08
GCST008152_177	Weight	8.000000e-06
GCST008163_417	Height	2.000000e-06
GCST008163_493	Height	1.000000e-06
GCST008181_19	Spontaneous preterm birth without premature rupture of membranes	1.000000e-06
GCST010139_1	Poultry consumption	1.000000e-09
GCST012226_134	Waist circumference adjusted for body mass index	9.000000e-09
GCST012226_135	Waist circumference adjusted for body mass index	3.000000e-10
GCST012226_136	Waist circumference adjusted for body mass index	2.000000e-12
GCST012227_710	Hip circumference adjusted for BMI	6.000000e-11
GCST90020028_1302	Hip circumference adjusted for BMI	7.000000e-11
GCST90020028_1303	Hip circumference adjusted for BMI	2.000000e-16
GCST90020028_1304	Hip circumference adjusted for BMI	3.000000e-10
GCST90020029_6	Waist circumference adjusted for body mass index	2.000000e-08
GCST90020029_7	Waist circumference adjusted for body mass index	6.000000e-18
GCST90020029_8	Waist circumference adjusted for body mass index	6.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0009589	worry measurement
EFO:0004338	body weight
EFO:0006917	spontaneous preterm birth
EFO:0008111	diet measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
Air Pollutants	increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	increases abundance, increases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Benzo(a)pyrene	affects methylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Estradiol	increases expression	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Urethane	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4RA	HCT116-TMEM241-KO-c3	Cancer cell line	Male
CVCL_D4RB	HCT116-TMEM241-KO-c4	Cancer cell line	Male

Clinical trials (associated diseases)

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