SFXN5

Summary

SFXN5 (sideroflexin 5, HGNC:16073) is a protein-coding gene on chromosome 2p13.2, encoding Sideroflexin-5 (Q8TD22). Mitochondrial amino-acid transporter.

Predicted to enable citrate transmembrane transporter activity. Predicted to be involved in citrate transport and mitochondrial transmembrane transport. Located in mitochondrion.

Source: NCBI Gene 94097 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 88 total
• MANE Select transcript: NM_144579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16073
Approved symbol	SFXN5
Name	sideroflexin 5
Location	2p13.2
Locus type	gene with protein product
Status	Approved
Aliases	BBG-TCC, SLC56A5
Ensembl gene	ENSG00000144040
Ensembl biotype	protein_coding
OMIM	615572
Entrez	94097

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 16 protein_coding_CDS_not_defined, 12 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000272433, ENST00000410065, ENST00000411783, ENST00000416579, ENST00000442582, ENST00000450185, ENST00000461352, ENST00000463277, ENST00000464825, ENST00000472259, ENST00000474528, ENST00000475630, ENST00000479293, ENST00000482289, ENST00000482542, ENST00000484123, ENST00000485057, ENST00000487508, ENST00000488839, ENST00000490056, ENST00000495208, ENST00000497144, ENST00000868595, ENST00000868596, ENST00000868597, ENST00000868598, ENST00000938187, ENST00000938188, ENST00000938189, ENST00000938190

RefSeq mRNA: 20 — MANE Select: NM_144579 NM_001330400, NM_001330401, NM_001330402, NM_001330403, NM_001330404, NM_001330405, NM_001330406, NM_001330407, NM_001330408, NM_001330410, NM_001330411, NM_001330412, NM_001371737, NM_001371738, NM_001371739, NM_001371740, NM_001371741, NM_001371742, NM_001371743, NM_144579

CCDS: CCDS1922, CCDS82469

Canonical transcript exons

ENST00000272433 — 14 exons

Exon	Start	End
ENSE00002304141	73071604	73071712
ENSE00003458390	73000431	73000487
ENSE00003483292	73022522	73022576
ENSE00003529291	72971570	72971685
ENSE00003537306	73020239	73020264
ENSE00003551203	72998949	72999014
ENSE00003552525	73001525	73001578
ENSE00003561008	72942036	72945099
ENSE00003594383	72988258	72988348
ENSE00003605043	73023188	73023214
ENSE00003617952	73040854	73040931
ENSE00003652282	72968448	72968533
ENSE00003661947	72961131	72961248
ENSE00003663237	73058528	73058596

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.3652 / max 248.1854, expressed in 1786 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29111	12.5853	1749
29109	2.6050	1122
29106	0.7284	92
29110	0.6600	345
29107	0.3216	68
29113	0.2858	130
29108	0.0947	51
29112	0.0399	7
29105	0.0345	24
29104	0.0097	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amygdala	UBERON:0001876	97.51	gold quality
putamen	UBERON:0001874	97.44	gold quality
right frontal lobe	UBERON:0002810	97.31	gold quality
caudate nucleus	UBERON:0001873	97.24	gold quality
nucleus accumbens	UBERON:0001882	97.23	gold quality
anterior cingulate cortex	UBERON:0009835	97.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.75	gold quality
ventricular zone	UBERON:0003053	95.29	gold quality
prefrontal cortex	UBERON:0000451	94.98	gold quality
hypothalamus	UBERON:0001898	94.93	gold quality
right lobe of liver	UBERON:0001114	94.80	gold quality
neocortex	UBERON:0001950	94.62	gold quality
frontal cortex	UBERON:0001870	94.49	gold quality
temporal lobe	UBERON:0001871	94.49	gold quality
cerebral cortex	UBERON:0000956	94.18	gold quality
Ammon’s horn	UBERON:0001954	93.77	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.56	gold quality
substantia nigra	UBERON:0002038	93.55	gold quality
forebrain	UBERON:0001890	93.53	gold quality
primary visual cortex	UBERON:0002436	93.46	gold quality
medial globus pallidus	UBERON:0002477	93.42	gold quality
brain	UBERON:0000955	93.22	gold quality
midbrain	UBERON:0001891	93.16	gold quality
occipital lobe	UBERON:0002021	93.01	gold quality
globus pallidus	UBERON:0001875	92.60	gold quality
cerebellar cortex	UBERON:0002129	92.41	gold quality
cerebellar hemisphere	UBERON:0002245	92.40	gold quality
liver	UBERON:0002107	92.39	gold quality
cerebellum	UBERON:0002037	92.04	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	67.05
E-HCAD-25	yes	21.54
E-CURD-46	yes	6.54
E-MTAB-7606	no	39.15
E-ANND-3	no	5.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting SFXN5, 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-5193	100.00	67.26	1744
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sfxn5b	ENSDARG00000026137
danio_rerio	sfxn5a	ENSDARG00000103595
mus_musculus	Sfxn5	ENSMUSG00000033720
rattus_norvegicus	Sfxn5	ENSRNOG00000037871
caenorhabditis_elegans		WBGENE00044049

Paralogs (4): SFXN3 (ENSG00000107819), SFXN2 (ENSG00000156398), SFXN1 (ENSG00000164466), SFXN4 (ENSG00000183605)

Protein

Protein identifiers

Sideroflexin-5 — Q8TD22 (reviewed: Q8TD22)

All UniProt accessions (5): Q8TD22, B8ZZJ6, C9JIV5, F8WBH6, H7C1S9

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial amino-acid transporter. Transports citrate. Does not act as a serine transporter: not able to mediate transport of serine into mitochondria. In brown adipose tissue, plays a role in the regulation of UCP1-dependent thermogenesis probably by supporting mitochondrial glycerol-3-phosphate utilization.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Primarily expressed in the brain.

Similarity. Belongs to the sideroflexin family.

RefSeq proteins (20): NP_001317329, NP_001317330, NP_001317331, NP_001317332, NP_001317333, NP_001317334, NP_001317335, NP_001317336, NP_001317337, NP_001317339, NP_001317340, NP_001317341, NP_001358666, NP_001358667, NP_001358668, NP_001358669, NP_001358670, NP_001358671, NP_001358672, NP_653180* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004686	Mtc	Family

Pfam: PF03820

Catalyzed reactions (Rhea), 1 shown:

• citrate(in) = citrate(out) (RHEA:33183)

UniProt features (5 total): transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TD22-F1	89.16	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, GOBP_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, HP1SITEFACTOR_Q6, GOCC_MITOCHONDRIAL_ENVELOPE, NRF2_Q4, AACTTT_UNKNOWN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, WONG_MITOCHONDRIA_GENE_MODULE, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_16D_DN, XU_GH1_EXOGENOUS_TARGETS_UP

GO Biological Process (7): amino acid transport (GO:0006865), citrate transport (GO:0015746), positive regulation of cold-induced thermogenesis (GO:0120162), mitochondrial transmembrane transport (GO:1990542), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (3): monoatomic ion transmembrane transporter activity (GO:0015075), citrate transmembrane transporter activity (GO:0015137), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
transmembrane transport	2
tricarboxylic acid transport	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
mitochondrial transport	1
monoatomic ion transport	1
cellular process	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
tricarboxylic acid transmembrane transporter activity	1
citrate transport	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFXN5	TMEM237	Q96Q45	537
SFXN5	CNPY3	Q9BT09	428
SFXN5	ASCC3	Q8N3C0	412
SFXN5	GPANK1	O95872	406
SFXN5	CPOX	P36551	388
SFXN5	TIMM22	Q9Y584	377
SFXN5	GPR37L1	O60883	361
SFXN5	UMPS	P11172	359
SFXN5	ISCU	Q9H1K1	356
SFXN5	SLC25A37	Q9NYZ2	356
SFXN5	TMEM181	Q9P2C4	350
SFXN5	SLC25A38	Q96DW6	344
SFXN5	CDC5L	Q99459	338
SFXN5	TADA1	Q96BN2	334
SFXN5	DNAJC19	Q96DA6	329

IntAct

96 interactions, top by confidence:

A	B	Type	Score
SFXN5	ERGIC3	psi-mi:“MI:0915”(physical association)	0.670
VSIG1	TTI1	psi-mi:“MI:0914”(association)	0.640
SFXN5	CTSA	psi-mi:“MI:0914”(association)	0.640
MGME1	POLG	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
SFXN5	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
SFXN5	STOM	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	SFXN5	psi-mi:“MI:0915”(physical association)	0.560
SFXN5	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
EBP	SFXN5	psi-mi:“MI:0915”(physical association)	0.560
SFXN5	APOL2	psi-mi:“MI:0915”(physical association)	0.560
TMPPE	SFXN5	psi-mi:“MI:0915”(physical association)	0.560
STOM	SFXN5	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SFXN5	psi-mi:“MI:0915”(physical association)	0.560
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC39A9	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SLC5A5	SLC19A2	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530

BioGRID (81): SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), LAMP2 (Affinity Capture-MS), SLC6A15 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS), SFXN5 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A6NI61, A6QQ59, B0CM95, B0KWE9, B1MTH4, B2KI79, B2RZC9, D0Q0Y7, O35089, O35372, O95406, P22234, P51583, P86229, Q0X0A5, Q13888, Q2TBV5, Q2YDL1, Q3KNM2, Q3ZC24, Q3ZCD7, Q5BIN6, Q5BJU5, Q5R589, Q5RB59, Q5RDB5, Q5RL79, Q64232, Q6P1K8, Q6PI25, Q6ZWS4, Q86YN1, Q8CFD0, Q8IZV2, Q8N6L1, Q8NFT2, Q8NFX7, Q8R3T5, Q8TBE1

Diamond homologs: A5A761, A6QP55, B2LU20, O13793, Q09201, Q12029, Q54NQ9, Q5E9M8, Q5EA43, Q5FC79, Q5RD16, Q63965, Q8CFD0, Q8TD22, Q91V61, Q925N0, Q925N2, Q96NB2, Q99JR1, Q9BWM7, Q9H9B4, Q9JHY2, Q9VN13, Q9VVW3, A8E7G5, Q3T0M2, Q6P4A7, Q925N1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2321 predictions. Top by Δscore:

Variant	Effect	Δscore
2:72968446:A:AC	donor_gain	1.0000
2:72968447:C:CT	donor_gain	1.0000
2:72968447:CTT:C	donor_gain	1.0000
2:72968447:CTTCT:C	donor_gain	1.0000
2:72971568:A:AC	donor_gain	1.0000
2:72971569:C:CC	donor_gain	1.0000
2:72998941:GTACT:G	donor_loss	1.0000
2:72998943:ACTC:A	donor_loss	1.0000
2:72998946:CA:C	donor_loss	1.0000
2:72998947:A:AC	donor_gain	1.0000
2:72998947:ACAG:A	donor_gain	1.0000
2:72998948:C:CA	donor_gain	1.0000
2:72998948:CA:C	donor_gain	1.0000
2:72998948:CAG:C	donor_gain	1.0000
2:72998948:CAGC:C	donor_gain	1.0000
2:72998948:CAGCA:C	donor_gain	1.0000
2:72999010:GAAGG:G	acceptor_gain	1.0000
2:72999012:AGG:A	acceptor_gain	1.0000
2:72999012:AGGC:A	acceptor_loss	1.0000
2:72999013:GG:G	acceptor_gain	1.0000
2:72999014:GC:G	acceptor_loss	1.0000
2:72999015:C:CC	acceptor_gain	1.0000
2:72999016:T:A	acceptor_loss	1.0000
2:73000426:CTCA:C	donor_loss	1.0000
2:73000427:TCAC:T	donor_loss	1.0000
2:73000428:CA:C	donor_loss	1.0000
2:73000429:ACC:A	donor_loss	1.0000
2:73000430:C:T	donor_loss	1.0000
2:73000485:CCA:C	acceptor_gain	1.0000
2:73000486:CA:C	acceptor_gain	1.0000

AlphaMissense

2195 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:72945031:C:A	K338N	1.000
2:72945031:C:G	K338N	1.000
2:72971622:A:T	V230D	1.000
2:72998964:G:C	S173R	1.000
2:72998964:G:T	S173R	1.000
2:72998966:T:G	S173R	1.000
2:73000444:C:G	R152P	1.000
2:73000455:G:C	N148K	1.000
2:73000455:G:T	N148K	1.000
2:73000473:G:C	S142R	1.000
2:73000473:G:T	S142R	1.000
2:73000475:T:G	S142R	1.000
2:73022530:C:A	R108I	1.000
2:73022530:C:G	R108T	1.000
2:72945029:C:T	G339E	0.999
2:72945030:C:A	G339W	0.999
2:72945030:C:G	G339R	0.999
2:72945030:C:T	G339R	0.999
2:72945032:T:A	K338M	0.999
2:72945033:T:C	K338E	0.999
2:72945039:A:C	Y336D	0.999
2:72961146:G:C	F310L	0.999
2:72961146:G:T	F310L	0.999
2:72961148:A:G	F310L	0.999
2:72961152:G:C	S308R	0.999
2:72961152:G:T	S308R	0.999
2:72961154:T:G	S308R	0.999
2:72961165:G:C	P304R	0.999
2:72961165:G:T	P304Q	0.999
2:72968518:C:G	A253P	0.999

dbSNP variants (sampled 300 via entrez): RS1000034416 (2:72958998 C>T), RS1000048300 (2:72954066 G>A), RS1000054018 (2:72994035 C>A,T), RS1000066399 (2:72998739 C>T), RS1000069931 (2:72981733 C>T), RS1000076236 (2:72998580 C>G,T), RS1000089286 (2:73036462 G>A), RS1000095741 (2:73042078 A>G), RS1000151985 (2:72971234 C>T), RS1000169161 (2:72976666 T>TAG), RS1000179199 (2:73017805 C>T), RS1000202423 (2:73011735 C>G,T), RS1000202918 (2:73065904 T>C), RS1000226306 (2:73042705 T>C), RS1000241133 (2:72942304 C>A,T)

Disease associations

OMIM: gene MIM:615572 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005586_5	Breast milk fatty acid composition (maternal genotype effect)	4.000000e-09
GCST007201_295	Schizophrenia	2.000000e-07
GCST007478_2	Non-word reading	3.000000e-06
GCST010725_60	Malaria	7.000000e-06
GCST010725_79	Malaria	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005939	parental genotype effect measurement
EFO:0005299	non-word reading

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 — SLC56 Sideroflexins

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
sodium arsenite	increases abundance, increases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
Leflunomide	decreases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
VX-agent	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	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
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Manganese	increases expression	1
Mercuric Chloride	increases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4RL	HuH7-SFXN5-KO-c12	Cancer cell line	Male
CVCL_D4RM	HuH7-SFXN5-KO-c14	Cancer cell line	Male
CVCL_E1F7	Ubigene Y-79 SFXN5 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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