SLC22A14

Summary

SLC22A14 (solute carrier family 22 member 14, HGNC:8495) is a protein-coding gene on chromosome 3p22.2, encoding Solute carrier family 22 member 14 (Q9Y267). Riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa midpiece, which is required for male fertility.

This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 3. The encoded protein is a transmembrane protein which is thought to transport small molecules and since this protein is conserved among several species, it is suggested to have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9389 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 105 total
• Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
• MANE Select transcript: NM_001320033

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8495
Approved symbol	SLC22A14
Name	solute carrier family 22 member 14
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	OCTL2
Ensembl gene	ENSG00000144671
Ensembl biotype	protein_coding
OMIM	604048
Entrez	9389

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000273173, ENST00000448498, ENST00000466887, ENST00000496724

RefSeq mRNA: 2 — MANE Select: NM_001320033 NM_001320033, NM_004803

CCDS: CCDS2677

Canonical transcript exons

ENST00000448498 — 11 exons

Exon	Start	End
ENSE00000966400	38307254	38307357
ENSE00000966401	38307566	38307720
ENSE00000966402	38308954	38309122
ENSE00000966403	38312999	38313119
ENSE00000966404	38313388	38313485
ENSE00000966405	38313727	38313941
ENSE00000966406	38315558	38315711
ENSE00000966407	38316324	38316524
ENSE00001612786	38318198	38318575
ENSE00001680318	38306027	38306542
ENSE00001893959	38282294	38282339

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 91.85.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	91.85	gold quality
olfactory bulb	UBERON:0002264	91.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.61	gold quality
diaphragm	UBERON:0001103	83.49	gold quality
nasal cavity epithelium	UBERON:0005384	81.84	gold quality
pancreatic ductal cell	CL:0002079	81.33	silver quality
triceps brachii	UBERON:0001509	79.87	gold quality
gluteal muscle	UBERON:0002000	79.28	gold quality
lateral nuclear group of thalamus	UBERON:0002736	78.64	silver quality
thymus	UBERON:0002370	78.51	gold quality
left testis	UBERON:0004533	78.09	gold quality
right testis	UBERON:0004534	77.95	gold quality
tibialis anterior	UBERON:0001385	77.53	gold quality
heart right ventricle	UBERON:0002080	76.85	gold quality
cervix squamous epithelium	UBERON:0006922	76.71	gold quality
substantia nigra pars reticulata	UBERON:0001966	76.59	silver quality
male germ cell	CL:0000015	76.19	silver quality
upper arm skin	UBERON:0004263	76.05	gold quality
deltoid	UBERON:0001476	75.83	silver quality
hair follicle	UBERON:0002073	75.68	gold quality
testis	UBERON:0000473	75.66	gold quality
substantia nigra pars compacta	UBERON:0001965	74.96	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	74.70	gold quality
sperm	CL:0000019	74.40	silver quality
cardia of stomach	UBERON:0001162	73.82	gold quality
vena cava	UBERON:0004087	73.70	gold quality
trachea	UBERON:0003126	73.38	gold quality
tongue	UBERON:0001723	72.83	gold quality
body of tongue	UBERON:0011876	72.83	gold quality
biceps brachii	UBERON:0001507	72.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting SLC22A14, 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-1207-5P	99.49	69.11	2983
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-513B-3P	98.76	68.12	1577
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-1285-3P	97.72	67.02	1932
HSA-MIR-5189-5P	97.72	66.96	1814
HSA-MIR-219B-3P	97.31	66.96	672
HSA-MIR-612	97.26	65.95	1597
HSA-MIR-6860	97.21	66.31	1656
HSA-MIR-3116	97.07	65.78	1324

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Cross-species orthologs

51 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc22a4	ENSDARG00000005335
danio_rerio	oatx	ENSDARG00000019713
danio_rerio	si:dkey-166k12.1	ENSDARG00000054690
danio_rerio	si:dkey-119m7.4	ENSDARG00000071049
danio_rerio	si:dkey-119m7.8	ENSDARG00000096654
mus_musculus	Slc22a14	ENSMUSG00000070280
rattus_norvegicus	AABR07071731.1	ENSRNOG00000042259
drosophila_melanogaster	Orct	FBGN0019952
drosophila_melanogaster	CG15221	FBGN0030331
drosophila_melanogaster	Balat	FBGN0033778
drosophila_melanogaster	CG4630	FBGN0033809
drosophila_melanogaster	CG5592	FBGN0035645
drosophila_melanogaster	CG10486	FBGN0035647
drosophila_melanogaster	SLC22A	FBGN0037140
drosophila_melanogaster	CG7458	FBGN0037144
drosophila_melanogaster	CG14691	FBGN0037829
drosophila_melanogaster	CG14855	FBGN0038260
drosophila_melanogaster	CG14856	FBGN0038261
drosophila_melanogaster	CG14857	FBGN0038262
drosophila_melanogaster	CG12783	FBGN0038448
drosophila_melanogaster	CG7333	FBGN0038715
drosophila_melanogaster	CG7342	FBGN0038716
drosophila_melanogaster	CG17751	FBGN0038717
drosophila_melanogaster	CG17752	FBGN0038718
drosophila_melanogaster	CG16727	FBGN0038719
drosophila_melanogaster	CG6231	FBGN0038720
drosophila_melanogaster	CG4465	FBGN0038750
drosophila_melanogaster	CG4462	FBGN0038752
drosophila_melanogaster	CG4459	FBGN0038753
drosophila_melanogaster	CG6356	FBGN0039178
drosophila_melanogaster	CG3690	FBGN0040350
drosophila_melanogaster	CG31103	FBGN0051103
drosophila_melanogaster	CG31106	FBGN0051106
drosophila_melanogaster	CG31272	FBGN0051272
drosophila_melanogaster	CG33233	FBGN0053233
drosophila_melanogaster	CG33234	FBGN0053234
drosophila_melanogaster	Orct2	FBGN0086365
drosophila_melanogaster	CG42269	FBGN0259164
drosophila_melanogaster	CG44098	FBGN0264907
caenorhabditis_elegans		WBGENE00003837
caenorhabditis_elegans	oct-1	WBGENE00003842
caenorhabditis_elegans		WBGENE00003843
caenorhabditis_elegans		WBGENE00006220
caenorhabditis_elegans		WBGENE00008110
caenorhabditis_elegans		WBGENE00011456
caenorhabditis_elegans		WBGENE00014127
caenorhabditis_elegans		WBGENE00015088
caenorhabditis_elegans		WBGENE00017751
caenorhabditis_elegans		WBGENE00019408
caenorhabditis_elegans		WBGENE00020701
caenorhabditis_elegans		WBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A2 (ENSG00000112499), SLC22A7 (ENSG00000137204), SLC22A23 (ENSG00000137266), SLC22A3 (ENSG00000146477), SLC22A8 (ENSG00000149452), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Solute carrier family 22 member 14 — Q9Y267 (reviewed: Q9Y267)

Alternative names: Organic cation transporter-like 4

All UniProt accessions (2): Q9Y267, F5H7H1

UniProt curated annotations — full annotation on UniProt →

Function. Riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa midpiece, which is required for male fertility. SLC22A14-mediated riboflavin transport is essential for spermatozoa energy generation and motility: riboflavin is the precursor of FMN and FAD, which are coenzymes of many enzymes in the TCA cycle (the citric acid cycle) in mitochondria. Required for sperm motility and normal sperm flagellar structure.

Subcellular location. Mitochondrion inner membrane. Cell projection. Cilium. Flagellum membrane.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

RefSeq proteins (2): NP_001306962, NP_004794 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005828	MFS_sugar_transport-like	Family
IPR020846	MFS_dom	Domain
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 1 shown:

• riboflavin(in) = riboflavin(out) (RHEA:35015)

UniProt features (47 total): topological domain 13, transmembrane region 12, sequence variant 9, glycosylation site 4, mutagenesis site 3, compositionally biased region 2, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y267-F1	81.04	0.48

Functional residue map

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

Glycosylation sites (4): 99, 117, 125, 150

Mutagenesis-validated functional residues (3):

Position	Phenotype
388	strongly reduced riboflavin transport; when associated with a-395 and a-487.
395	strongly reduced riboflavin transport; when associated with a-388 and a-487.
487	strongly reduced riboflavin transport; when associated with a-388 and a-395.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CELL_MATURATION, GOBP_CILIUM_MOVEMENT, MODULE_99, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, chr3p22, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_VITAMIN_TRANSPORT, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION

GO Biological Process (4): flagellated sperm motility (GO:0030317), sperm capacitation (GO:0048240), riboflavin transport (GO:0032218), transmembrane transport (GO:0055085)

GO Molecular Function (3): riboflavin transmembrane transporter activity (GO:0032217), protein binding (GO:0005515), transmembrane transporter activity (GO:0022857)

GO Cellular Component (8): mitochondrial inner membrane (GO:0005743), sperm principal piece (GO:0097228), mitochondrion (GO:0005739), plasma membrane (GO:0005886), cilium (GO:0005929), membrane (GO:0016020), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
vitamin transport	1
nitrogen compound transport	1
transport	1
cellular process	1
riboflavin transport	1
vitamin transmembrane transporter activity	1
binding	1
transporter activity	1
transmembrane transport	1
organelle inner membrane	1
mitochondrial membrane	1
sperm flagellum	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC22A14	XYLB	O75191	962
SLC22A14	OXSR1	O95747	836
SLC22A14	ACVR2B	Q13705	657
SLC22A14	SLC67A1	Q96BI1	608
SLC22A14	VILL	O15195	527
SLC22A14	SLC22A23	A1A5C7	487
SLC22A14	SLC22A17	Q8WUG5	477
SLC22A14	TMEM225	Q6GV28	474
SLC22A14	CIMIP4	O43247	430
SLC22A14	SLC6A9	P48067	428
SLC22A14	SLC22A24	Q8N4F4	423
SLC22A14	SLC2A9	Q9NRM0	421
SLC22A14	CTDSPL	O15194	406
SLC22A14	SLC22A15	Q8IZD6	404
SLC22A14	DLEC1	Q9Y238	401

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MS4A3	SLC22A14	psi-mi:“MI:0915”(physical association)	0.600
SLC22A14	SSR3	psi-mi:“MI:0915”(physical association)	0.400
SLC22A14	PTH1R	psi-mi:“MI:0915”(physical association)	0.400
SLC22A14	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC22A14	MS4A3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (63): SLC22A14 (Positive Genetic), MS4A3 (Two-hybrid), SLC22A14 (Proximity Label-MS), PTH1R (Affinity Capture-MS), SLC22A14 (Cross-Linking-MS (XL-MS)), SLC22A14 (Cross-Linking-MS (XL-MS)), ABCA3 (Affinity Capture-MS), AMFR (Affinity Capture-MS), ATP13A1 (Affinity Capture-MS), ATP5J2 (Affinity Capture-MS), ATP5L (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), BCAP31 (Affinity Capture-MS), CANX (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2IDB4, A0A8B7HA97, A4ZYQ5, A6NK97, G1SZD9, O35956, O57379, O88909, P22732, P23945, P43427, Q0IHM1, Q2KIV1, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R9C4, Q5RC45, Q5RCH6, Q5RET7, Q63ZE4, Q66J52, Q6DFR1, Q6NUB3, Q6NYN7, Q6PXP3, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q863Y9, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48, Q8N4F4, Q8R0S9

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, A7MBE0, B2GV36, G1SZD9, O02713, O08966, O15244, O15245, O35956, O57379, O70577, O70594, O75751, O76082, O77504, O88446, O88909, Q17QN9, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q497L9, Q4U2R8, Q4W8A2, Q4W8A3, Q504N2, Q5R540, Q5R5H7, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63089, Q63ZE4, Q66J52

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	19
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2203 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38313386:A:AG	acceptor_gain	1.0000
3:38313386:A:G	acceptor_loss	1.0000
3:38313387:G:GA	acceptor_gain	1.0000
3:38313387:GCT:G	acceptor_gain	1.0000
3:38313387:GCTGC:G	acceptor_gain	1.0000
3:38316322:AGGGC:A	acceptor_gain	1.0000
3:38316323:GGGCG:G	acceptor_gain	1.0000
3:38283241:C:G	donor_gain	0.9900
3:38306541:AGG:A	donor_loss	0.9900
3:38306542:GGTA:G	donor_loss	0.9900
3:38306543:G:GA	donor_loss	0.9900
3:38306544:T:A	donor_loss	0.9900
3:38307358:G:GG	donor_gain	0.9900
3:38313302:G:T	donor_gain	0.9900
3:38313383:T:TA	acceptor_gain	0.9900
3:38313386:AGCT:A	acceptor_gain	0.9900
3:38313387:GC:G	acceptor_gain	0.9900
3:38313387:GCTG:G	acceptor_gain	0.9900
3:38313481:GTGTG:G	donor_gain	0.9900
3:38313483:GTG:G	donor_gain	0.9900
3:38313486:G:GG	donor_gain	0.9900
3:38313488:GAGT:G	donor_loss	0.9900
3:38313489:AG:A	donor_loss	0.9900
3:38313753:C:CA	acceptor_gain	0.9900
3:38315556:AGG:A	acceptor_gain	0.9900
3:38315557:GGG:G	acceptor_gain	0.9900
3:38315708:TCAG:T	donor_loss	0.9900
3:38315709:CAG:C	donor_loss	0.9900
3:38315710:AG:A	donor_loss	0.9900
3:38315711:GG:G	donor_loss	0.9900

AlphaMissense

3895 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38306219:T:C	F65L	0.898
3:38306221:C:A	F65L	0.898
3:38306221:C:G	F65L	0.898
3:38307254:T:C	F173L	0.884
3:38307256:T:A	F173L	0.884
3:38307256:T:G	F173L	0.884
3:38306210:T:C	F62L	0.865
3:38306212:T:A	F62L	0.865
3:38306212:T:G	F62L	0.865
3:38313878:A:C	S439R	0.820
3:38313880:C:A	S439R	0.820
3:38313880:C:G	S439R	0.820
3:38306332:G:C	W102C	0.811
3:38306332:G:T	W102C	0.811
3:38306318:T:A	C98S	0.805
3:38306319:G:C	C98S	0.805
3:38306503:G:C	W159C	0.791
3:38306503:G:T	W159C	0.791
3:38313728:T:C	F389L	0.785
3:38313730:T:A	F389L	0.785
3:38313730:T:G	F389L	0.785
3:38315647:A:C	S490R	0.765
3:38315649:C:A	S490R	0.765
3:38315649:C:G	S490R	0.765
3:38306334:T:C	I103T	0.758
3:38306465:T:C	F147L	0.744
3:38306467:T:A	F147L	0.744
3:38306467:T:G	F147L	0.744
3:38307708:A:C	S255R	0.744
3:38307710:C:A	S255R	0.744

dbSNP variants (sampled 300 via entrez): RS1000014884 (3:38283361 C>A,G), RS1000074773 (3:38276836 G>A), RS1000120469 (3:38292214 T>A), RS1000195292 (3:38312053 C>T), RS1000223755 (3:38290641 T>A), RS1000237301 (3:38308698 G>C), RS1000471181 (3:38283062 C>G,T), RS1000502973 (3:38310323 A>T), RS1000600842 (3:38299470 T>G), RS1000651877 (3:38299047 G>A), RS1000670844 (3:38293706 A>G), RS1000799185 (3:38287932 T>G), RS1000851796 (3:38287583 A>G), RS1000886682 (3:38279796 C>T), RS1001140230 (3:38315925 G>A)

Disease associations

OMIM: gene MIM:604048 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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 — Orphan or poorly characterized SLC22 family members

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
lead acetate	increases expression	1
terbufos	increases methylation	1
Acetaminophen	decreases expression	1
Amphotericin B	increases expression	1
Cocaine	decreases expression	1
Fonofos	increases methylation	1
Parathion	increases methylation	1
Tobacco Smoke Pollution	increases expression	1
Vanadium	increases expression	1
Cyclosporine	increases methylation	1

Clinical trials (associated diseases)

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