SFXN2

Summary

SFXN2 (sideroflexin 2, HGNC:16086) is a protein-coding gene on chromosome 10q24.32, encoding Sideroflexin-2 (Q96NB2). Mitochondrial amino-acid transporter that mediates transport of serine into mitochondria.

Predicted to enable transmembrane transporter activity. Involved in mitochondrial transmembrane transport. Located in mitochondrial outer membrane.

Source: NCBI Gene 118980 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_178858

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16086
Approved symbol	SFXN2
Name	sideroflexin 2
Location	10q24.32
Locus type	gene with protein product
Status	Approved
Aliases	SLC56A2
Ensembl gene	ENSG00000156398
Ensembl biotype	protein_coding
OMIM	615570
Entrez	118980

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 26 protein_coding, 4 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000369893, ENST00000459894, ENST00000480358, ENST00000602287, ENST00000602439, ENST00000602544, ENST00000602647, ENST00000602660, ENST00000602670, ENST00000602764, ENST00000602785, ENST00000602831, ENST00000602868, ENST00000893978, ENST00000893979, ENST00000893980, ENST00000893981, ENST00000893982, ENST00000893983, ENST00000893984, ENST00000893985, ENST00000893986, ENST00000893987, ENST00000893988, ENST00000893989, ENST00000893990, ENST00000928868, ENST00000928869, ENST00000928870, ENST00000954661, ENST00000954662, ENST00000954663, ENST00000954664

RefSeq mRNA: 2 — MANE Select: NM_178858 NM_001350989, NM_178858

CCDS: CCDS7539

Canonical transcript exons

ENST00000369893 — 12 exons

Exon	Start	End
ENSE00001135706	102731723	102731783
ENSE00001135719	102729319	102729394
ENSE00001848203	102714636	102714681
ENSE00001858331	102737663	102743492
ENSE00003429830	102732152	102732218
ENSE00003464078	102735862	102735909
ENSE00003480974	102726612	102726797
ENSE00003507787	102728431	102728529
ENSE00003524397	102732859	102732908
ENSE00003568483	102726987	102727157
ENSE00003572938	102729723	102729808
ENSE00003601839	102733554	102733603

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1303 / max 83.5503, expressed in 1523 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106753	6.9237	1441
106752	0.7284	272
106754	0.4263	120
106755	0.0520	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.07	gold quality
pancreatic ductal cell	CL:0002079	92.61	gold quality
adult mammalian kidney	UBERON:0000082	91.55	gold quality
ileal mucosa	UBERON:0000331	90.50	gold quality
oviduct epithelium	UBERON:0004804	90.44	gold quality
kidney	UBERON:0002113	89.84	gold quality
adult organism	UBERON:0007023	87.87	gold quality
right lobe of liver	UBERON:0001114	87.61	gold quality
liver	UBERON:0002107	86.94	gold quality
parotid gland	UBERON:0001831	86.13	gold quality
cortex of kidney	UBERON:0001225	85.21	gold quality
right ovary	UBERON:0002118	84.06	gold quality
left ovary	UBERON:0002119	84.02	gold quality
body of pancreas	UBERON:0001150	83.93	gold quality
fallopian tube	UBERON:0003889	83.65	gold quality
right lobe of thyroid gland	UBERON:0001119	83.15	gold quality
metanephros	UBERON:0000081	83.10	gold quality
ovary	UBERON:0000992	82.91	gold quality
rectum	UBERON:0001052	82.77	gold quality
metanephros cortex	UBERON:0010533	82.54	gold quality
thyroid gland	UBERON:0002046	81.70	gold quality
left lobe of thyroid gland	UBERON:0001120	81.69	gold quality
pancreas	UBERON:0001264	81.41	gold quality
nasal cavity epithelium	UBERON:0005384	81.06	gold quality
tendon of biceps brachii	UBERON:0008188	80.14	gold quality
right uterine tube	UBERON:0001302	80.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.98	gold quality
endometrium	UBERON:0001295	79.89	gold quality
pituitary gland	UBERON:0000007	79.77	gold quality
left uterine tube	UBERON:0001303	79.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.85

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• molecular cloning of SFXN2 (PMID:12670026)
• SFXN2 functions in mitochondrial iron metabolism by regulating heme biosynthesis. (PMID:30570704)
• Elevated SFXN2 limits mitochondrial autophagy and increases iron-mediated energy production to promote multiple myeloma cell proliferation. (PMID:36163342)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sfxn2	ENSDARG00000017960
mus_musculus	Sfxn2	ENSMUSG00000025036
rattus_norvegicus	Sfxn2	ENSRNOG00000066618
drosophila_melanogaster	Sfxn2	FBGN0036843
caenorhabditis_elegans		WBGENE00015777

Paralogs (4): SFXN3 (ENSG00000107819), SFXN5 (ENSG00000144040), SFXN1 (ENSG00000164466), SFXN4 (ENSG00000183605)

Protein

Protein identifiers

Sideroflexin-2 — Q96NB2 (reviewed: Q96NB2)

All UniProt accessions (10): Q96NB2, A0A0C4DGR6, A0A1B0GX61, R4GMR9, R4GMS6, R4GMW0, R4GMX4, R4GN63, R4GN74, R4GNC2

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial amino-acid transporter that mediates transport of serine into mitochondria. Involved in mitochondrial iron homeostasis by regulating heme biosynthesis.

Subcellular location. Mitochondrion inner membrane. Mitochondrion outer membrane.

Tissue specificity. Widely expressed, highest levels in kidney, liver, and pancreas.

Similarity. Belongs to the sideroflexin family.

RefSeq proteins (2): NP_001337918, NP_849189* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004686	Mtc	Family

Pfam: PF03820

Catalyzed reactions (Rhea), 1 shown:

• L-serine(in) = L-serine(out) (RHEA:35031)

UniProt features (8 total): transmembrane region 5, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NB2-F1	85.11	0.24

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): RNGTGGGC_UNKNOWN, TGCGCANK_UNKNOWN, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GCAAGGA_MIR502, AP2_Q3, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSPORT, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, MYCMAX_01, MODULE_206

GO Biological Process (6): serine import into mitochondrion (GO:0140300), mitochondrial transmembrane transport (GO:1990542), monoatomic ion transport (GO:0006811), amino acid transport (GO:0006865), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (3): monoatomic ion transmembrane transporter activity (GO:0015075), transmembrane transporter activity (GO:0022857), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), 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
transmembrane transport	3
transport	3
mitochondrial membrane	2
amino acid transmembrane transport	1
serine transport	1
import into the mitochondrion	1
carboxylic acid transmembrane transport	1
mitochondrial transport	1
monoatomic ion transport	1
cellular process	1
transmembrane transporter activity	1
monoatomic ion transmembrane transport	1
transporter activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle outer membrane	1
organelle inner membrane	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFXN2	A0A2R8YGN2	A0A2R8YGN2	475
SFXN2	SLC22A12	Q96S37	465
SFXN2	SLC68A1	Q14CX5	452
SFXN2	ATP5MK	Q96IX5	438
SFXN2	WBP1L	Q9NX94	426
SFXN2	UQCC6	Q69YU5	414
SFXN2	SOCS3	O14543	394
SFXN2	SFXN1	Q9H9B4	392
SFXN2	ACTR1A	P42024	391
SFXN2	ARL3	P36405	385
SFXN2	AKT1	P31749	370
SFXN2	TLR4	O00206	365
SFXN2	SIAH2	O43255	364
SFXN2	NDUFAF6	Q330K2	363
SFXN2	MAPT	P10636	359

IntAct

73 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
SFXN2	REEP4	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SFXN2	psi-mi:“MI:0915”(physical association)	0.560
PDZK1IP1	SFXN2	psi-mi:“MI:0915”(physical association)	0.560
HSD17B13	SFXN2	psi-mi:“MI:0915”(physical association)	0.560
SFXN2	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530
SFXN2	CDK18	psi-mi:“MI:0915”(physical association)	0.400
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
NS1	HAX1	psi-mi:“MI:0914”(association)	0.350
PB2	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
MGARP	BTAF1	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
GP9	ESYT2	psi-mi:“MI:0914”(association)	0.350
NRG1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPA2	POTEF	psi-mi:“MI:0914”(association)	0.350
ASPH	POTEF	psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
SLC1A1	UBXN8	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): SFXN2 (Affinity Capture-MS), CDK18 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), SFXN2 (Affinity Capture-MS), CDK18 (Affinity Capture-MS), SFXN2 (Affinity Capture-MS), SFXN2 (Affinity Capture-MS), SFXN2 (Proximity Label-MS), SFXN2 (Proximity Label-MS), SFXN2 (Affinity Capture-MS), SFXN2 (Two-hybrid), SFXN2 (Two-hybrid), PDZK1IP1 (Two-hybrid), REEP4 (Two-hybrid), HSD17B13 (Two-hybrid)

ESM2 similar proteins: A5A761, A6QP55, A8E7G5, B2LU20, B3M6C8, B4H6M2, B4HKS2, B4J252, B4LE89, B4QNU8, B6IJ52, O13793, P00425, P25710, P38857, P53311, P81928, Q09201, Q12029, Q16FT5, Q2LZH7, Q32L86, Q3T0M2, Q54NQ9, Q5E9M8, Q5EA43, Q5FC79, Q5HZA9, Q5RD16, Q63965, Q6BKZ1, Q6CFW6, Q6CXR8, Q6FJJ0, Q6P4A7, Q759E9, Q91V61, Q925N1, Q925N2, Q95QD1

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2921 predictions. Top by Δscore:

Variant	Effect	Δscore
10:102726610:A:AG	acceptor_gain	1.0000
10:102726610:AG:A	acceptor_gain	1.0000
10:102726611:G:GT	acceptor_gain	1.0000
10:102726611:GG:G	acceptor_gain	1.0000
10:102726611:GGT:G	acceptor_gain	1.0000
10:102726611:GGTCC:G	acceptor_gain	1.0000
10:102728412:T:TA	acceptor_gain	1.0000
10:102728413:G:A	acceptor_gain	1.0000
10:102728423:ACT:A	acceptor_gain	1.0000
10:102728425:T:A	acceptor_gain	1.0000
10:102728525:GTCAG:G	donor_gain	1.0000
10:102728526:TCAGG:T	donor_loss	1.0000
10:102728527:CAG:C	donor_loss	1.0000
10:102728528:AGG:A	donor_loss	1.0000
10:102728529:GG:G	donor_loss	1.0000
10:102728531:T:A	donor_loss	1.0000
10:102729721:A:AG	acceptor_gain	1.0000
10:102729722:G:GG	acceptor_gain	1.0000
10:102729722:GAAA:G	acceptor_gain	1.0000
10:102729806:GCA:G	donor_gain	1.0000
10:102729809:G:GG	donor_gain	1.0000
10:102732213:GGA:G	donor_gain	1.0000
10:102732219:G:GG	donor_gain	1.0000
10:102732857:A:AG	acceptor_gain	1.0000
10:102732858:G:GG	acceptor_gain	1.0000
10:102737818:C:G	donor_gain	1.0000
10:102724934:A:AG	acceptor_gain	0.9900
10:102724935:G:GG	acceptor_gain	0.9900
10:102724994:GGG:G	donor_gain	0.9900
10:102724995:GGG:G	donor_gain	0.9900

AlphaMissense

2132 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:102728491:C:A	N131K	0.997
10:102728491:C:G	N131K	0.997
10:102728459:T:A	W121R	0.996
10:102728459:T:C	W121R	0.996
10:102729357:C:A	A157D	0.995
10:102729788:T:A	N191K	0.995
10:102729788:T:G	N191K	0.995
10:102729345:C:A	A153D	0.994
10:102732192:G:C	R232P	0.994
10:102732207:C:A	A237D	0.994
10:102727097:G:C	R91P	0.993
10:102728467:C:A	N123K	0.993
10:102728467:C:G	N123K	0.993
10:102728479:T:A	N127K	0.993
10:102728479:T:G	N127K	0.993
10:102729368:G:C	A161P	0.993
10:102729369:C:A	A161D	0.993
10:102729763:C:A	A183D	0.993
10:102729769:C:A	A185D	0.993
10:102729775:C:A	A187D	0.993
10:102727096:C:A	R91S	0.992
10:102728453:T:A	W119R	0.992
10:102728453:T:C	W119R	0.992
10:102729356:G:C	A157P	0.992
10:102729774:G:C	A187P	0.992
10:102737753:G:C	K320N	0.992
10:102737753:G:T	K320N	0.992
10:102726705:A:C	R23S	0.991
10:102726705:A:T	R23S	0.991
10:102726715:T:C	F27L	0.991

dbSNP variants (sampled 300 via entrez): RS1000069791 (10:102726252 G>A), RS1000197128 (10:102719374 A>C,G), RS1000241208 (10:102726882 A>G), RS1000296649 (10:102713312 A>G), RS1000322523 (10:102713698 A>G), RS1000469054 (10:102733248 T>C), RS1000482336 (10:102738278 T>C), RS1000532558 (10:102738019 C>A,G), RS1000547618 (10:102719651 C>G,T), RS1000652673 (10:102718726 C>T), RS1000854007 (10:102719787 T>A), RS1000904735 (10:102732970 A>G), RS1001045339 (10:102714474 G>C,T), RS1001071380 (10:102724615 C>T), RS1001128078 (10:102731646 G>C,T)

Disease associations

OMIM: gene MIM:615570 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST000528_8	Parkinson’s disease	7.000000e-08
GCST001942_1	Prostate cancer	5.000000e-10
GCST002149_2	Schizophrenia	4.000000e-13
GCST002539_4	Schizophrenia	6.000000e-19
GCST002782_114	Waist-to-hip ratio adjusted for body mass index	6.000000e-09
GCST002782_115	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST004162_16	Carotid plaque burden	2.000000e-08
GCST004505_102	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	7.000000e-06
GCST004505_103	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	5.000000e-08
GCST004521_172	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_53	Autism spectrum disorder or schizophrenia	9.000000e-10
GCST004521_78	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST004610_115	White blood cell count	2.000000e-09
GCST005956_50	Waist-to-hip ratio adjusted for BMI	8.000000e-06
GCST005958_15	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-06
GCST005962_36	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-07
GCST006952_33	Feeling tense	2.000000e-09
GCST010703_271	Brain morphology (MOSTest)	5.000000e-13
GCST012227_620	Hip circumference adjusted for BMI	9.000000e-11
GCST90020025_565	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020025_566	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST90020027_1642	Waist-hip index	2.000000e-10
GCST90020027_1643	Waist-hip index	2.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0006501	carotid plaque build
EFO:0004318	smoking behavior
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009596	feeling tense measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	7
Estradiol	decreases expression, increases expression, affects cotreatment	4
bisphenol A	decreases expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Leflunomide	decreases expression	2
Acetaminophen	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, increases expression	1
trametinib	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4HA	HCT116-SFXN2-KO-c1	Cancer cell line	Male
CVCL_D4HB	HCT116-SFXN2-KO-c11	Cancer cell line	Male

Clinical trials (associated diseases)

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