SERINC1

Summary

SERINC1 (serine incorporator 1, HGNC:13464) is a protein-coding gene on chromosome 6q22.31, encoding Serine incorporator 1 (Q9NRX5). Enhances the incorporation of serine into phosphatidylserine and sphingolipids.

Predicted to enable acetyltransferase activator activity; enzyme binding activity; and protein-macromolecule adaptor activity. Predicted to be involved in membrane biogenesis; phosphatidylserine metabolic process; and sphingolipid metabolic process. Predicted to be located in endoplasmic reticulum membrane and plasma membrane. Predicted to be active in membrane.

Source: NCBI Gene 57515 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_020755

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13464
Approved symbol	SERINC1
Name	serine incorporator 1
Location	6q22.31
Locus type	gene with protein product
Status	Approved
Aliases	TMS-2, TDE1L, KIAA1253
Ensembl gene	ENSG00000111897
Ensembl biotype	protein_coding
OMIM	614548
Entrez	57515

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000339697, ENST00000910725, ENST00000910726, ENST00000910727, ENST00000910728, ENST00000910729, ENST00000910730, ENST00000910731, ENST00000951452, ENST00000951453

RefSeq mRNA: 1 — MANE Select: NM_020755 NM_020755

CCDS: CCDS5125

Canonical transcript exons

ENST00000339697 — 10 exons

Exon	Start	End
ENSE00000762913	122446774	122447004
ENSE00000762914	122447121	122447265
ENSE00000762915	122451664	122451754
ENSE00000762916	122451888	122452057
ENSE00000762917	122453770	122453907
ENSE00000762918	122454151	122454230
ENSE00000762919	122456481	122456650
ENSE00000762920	122458520	122458681
ENSE00000798535	122471699	122471807
ENSE00001447161	122443351	122445179

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 120.5342 / max 6545.2481, expressed in 1815 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75359	120.5342	1815

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	99.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.66	gold quality
orbitofrontal cortex	UBERON:0004167	99.66	gold quality
postcentral gyrus	UBERON:0002581	99.65	gold quality
substantia nigra pars compacta	UBERON:0001965	99.61	gold quality
subthalamic nucleus	UBERON:0001906	99.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.58	gold quality
cortical plate	UBERON:0005343	99.55	gold quality
superior vestibular nucleus	UBERON:0007227	99.54	gold quality
parietal lobe	UBERON:0001872	99.51	gold quality
lateral globus pallidus	UBERON:0002476	99.49	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.48	gold quality
spinal cord	UBERON:0002240	99.46	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.45	gold quality
calcaneal tendon	UBERON:0003701	99.45	gold quality
cerebellar vermis	UBERON:0004720	99.43	gold quality
medulla oblongata	UBERON:0001896	99.42	gold quality
prefrontal cortex	UBERON:0000451	99.41	gold quality
superior frontal gyrus	UBERON:0002661	99.35	gold quality
blood vessel layer	UBERON:0004797	99.31	gold quality
corpus callosum	UBERON:0002336	99.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.29	gold quality
CA1 field of hippocampus	UBERON:0003881	99.28	gold quality
hypothalamus	UBERON:0001898	99.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.27	gold quality
frontal cortex	UBERON:0001870	99.23	gold quality
trigeminal ganglion	UBERON:0001675	99.22	gold quality
substantia nigra	UBERON:0002038	99.22	gold quality
midbrain	UBERON:0001891	99.20	gold quality
lower lobe of lung	UBERON:0008949	99.17	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	46.45
E-MTAB-5061	yes	16.93
E-HCAD-25	yes	9.63
E-GEOD-83139	yes	8.91
E-GEOD-93593	no	15.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

102 targeting SERINC1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
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-4760-3P	99.93	70.50	2385
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-30A-3P	99.87	69.74	2928

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	serinc1	ENSDARG00000009106
mus_musculus	Serinc1	ENSMUSG00000019877
drosophila_melanogaster	Serinc	FBGN0028399
caenorhabditis_elegans		WBGENE00011250
caenorhabditis_elegans		WBGENE00021956

Paralogs (4): SERINC3 (ENSG00000132824), SERINC5 (ENSG00000164300), SERINC2 (ENSG00000168528), SERINC4 (ENSG00000184716)

Protein

Protein identifiers

Serine incorporator 1 — Q9NRX5 (reviewed: Q9NRX5)

Alternative names: Tumor differentially expressed protein 1-like, Tumor differentially expressed protein 2

All UniProt accessions (1): Q9NRX5

UniProt curated annotations — full annotation on UniProt →

Function. Enhances the incorporation of serine into phosphatidylserine and sphingolipids.

Subunit / interactions. Interacts with SPTLC1.

Subcellular location. Endoplasmic reticulum membrane.

Similarity. Belongs to the TDE1 family.

RefSeq proteins (1): NP_065806* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005016	TDE1/TMS	Family

Pfam: PF03348

UniProt features (35 total): topological domain 11, transmembrane region 10, modified residue 4, sequence variant 3, sequence conflict 3, initiator methionine 1, chain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRX5-F1	78.12	0.37

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 (5): 351, 352, 361, 364, 2

Glycosylation sites (1): 298

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-977347	Serine metabolism
R-HSA-1430728	Metabolism
R-HSA-71291	Metabolism of amino acids and derivatives

MSigDB gene sets: 195 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, DORSAM_HOXA9_TARGETS_UP, TGCGCANK_UNKNOWN, GOBP_MEMBRANE_BIOGENESIS, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, SCHLOSSER_SERUM_RESPONSE_DN, DOUGLAS_BMI1_TARGETS_DN

GO Biological Process (5): phosphatidylserine metabolic process (GO:0006658), sphingolipid metabolic process (GO:0006665), phospholipid biosynthetic process (GO:0008654), membrane biogenesis (GO:0044091), lipid metabolic process (GO:0006629)

GO Molecular Function (3): acetyltransferase activator activity (GO:0010698), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
modified amino acid metabolic process	1
glycerophospholipid metabolic process	1
lipid metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
cellular component biogenesis	1
primary metabolic process	1
enzyme activator activity	1
acetyltransferase activity	1
protein binding	1
molecular adaptor activity	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1038 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERINC1	CNOT6L	Q96LI5	663
SERINC1	RUSC1	Q9BVN2	594
SERINC1	RUSC2	Q8N2Y8	591
SERINC1	VAPA	Q9P0L0	564
SERINC1	AP4E1	Q9UPM8	558
SERINC1	ZNF460	Q14592	543
SERINC1	AP4B1	Q9Y6B7	500
SERINC1	ATG9A	Q7Z3C6	483
SERINC1	RHO	P08100	420
SERINC1	TEPSIN	Q96N21	418
SERINC1	ICE2	Q659A1	417
SERINC1	DTWD2	Q8NBA8	411
SERINC1	ZZEF1	O43149	379
SERINC1	GLUD1	P00367	374
SERINC1	F5GXR3	F5GXR3	369

IntAct

114 interactions, top by confidence:

A	B	Type	Score
SERINC1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
GPX8	SERINC1	psi-mi:“MI:0915”(physical association)	0.560
GPR42	SERINC1	psi-mi:“MI:0915”(physical association)	0.560
AQP9	SERINC1	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	SERINC1	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3B1	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
ASGR2	MT-CO1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SLC9A8	ZNF432	psi-mi:“MI:0914”(association)	0.530
SLC22A16	APBA3	psi-mi:“MI:0914”(association)	0.530
SERINC1	LGALS3	psi-mi:“MI:0914”(association)	0.530
PAX8	SERINC1	psi-mi:“MI:0915”(physical association)	0.520
PCNA	SERINC1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (92): SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-RNA), SERINC1 (Two-hybrid), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), SERINC1 (Affinity Capture-MS)

ESM2 similar proteins: A2XSY1, A9CAZ8, B3Y064, B9TRX0, O13113, O15243, O22622, O24060, O65085, O81214, O89013, O95214, O95807, P46967, P52872, P61803, P61804, P61805, P61806, Q0JDK9, Q29036, Q32PD8, Q39080, Q3MHV9, Q3SYT0, Q3ZBX1, Q561T9, Q5E9C2, Q5PQQ4, Q5PSV5, Q5R419, Q5RBB4, Q5RDE9, Q5ZJD9, Q6PDU4, Q7TNK0, Q8I7Z2, Q92535, Q9CQ74, Q9CXL1

Diamond homologs: A4FUZ5, A6NH21, A7S4N4, A8WCG0, A9UY97, Q12116, Q13530, Q3MHV9, Q4R6L9, Q54UF8, Q58CW5, Q5R419, Q5R533, Q5XK03, Q63175, Q7TNK0, Q803X0, Q86VE9, Q8BHJ6, Q8K0E7, Q96SA4, Q9HDY3, Q9NRX5, Q9QZI8, Q9QZI9

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	48
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1065 predictions. Top by Δscore:

Variant	Effect	Δscore
6:122446862:C:A	donor_gain	1.0000
6:122451752:TTC:T	acceptor_gain	1.0000
6:122451753:TC:T	acceptor_gain	1.0000
6:122451754:CC:C	acceptor_gain	1.0000
6:122451755:C:CC	acceptor_gain	1.0000
6:122451755:C:CG	acceptor_loss	1.0000
6:122451756:T:A	acceptor_loss	1.0000
6:122451886:A:AC	donor_gain	1.0000
6:122451887:C:CC	donor_gain	1.0000
6:122452053:CAAGG:C	acceptor_gain	1.0000
6:122452054:AAGG:A	acceptor_gain	1.0000
6:122452055:AGG:A	acceptor_gain	1.0000
6:122452056:GG:G	acceptor_gain	1.0000
6:122452058:C:CC	acceptor_gain	1.0000
6:122452060:G:C	acceptor_gain	1.0000
6:122453764:GCTTA:G	donor_loss	1.0000
6:122453765:CTTA:C	donor_loss	1.0000
6:122453767:TA:T	donor_loss	1.0000
6:122453768:A:C	donor_loss	1.0000
6:122453903:CCACA:C	acceptor_gain	1.0000
6:122453904:CACA:C	acceptor_gain	1.0000
6:122453904:CACAC:C	acceptor_gain	1.0000
6:122453906:CA:C	acceptor_gain	1.0000
6:122453908:C:CC	acceptor_gain	1.0000
6:122454145:TCTTA:T	donor_loss	1.0000
6:122454146:CTTA:C	donor_loss	1.0000
6:122454147:TTAC:T	donor_loss	1.0000
6:122454148:TACC:T	donor_loss	1.0000
6:122454149:A:AC	donor_gain	1.0000
6:122454149:A:AT	donor_loss	1.0000

AlphaMissense

2968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:122445116:A:C	S430R	0.999
6:122445116:A:T	S430R	0.999
6:122445118:T:G	S430R	0.999
6:122454226:A:G	W126R	0.999
6:122454226:A:T	W126R	0.999
6:122445050:A:C	F452L	0.998
6:122445050:A:T	F452L	0.998
6:122445052:A:G	F452L	0.998
6:122445091:A:G	W439R	0.998
6:122445091:A:T	W439R	0.998
6:122445115:A:G	W431R	0.998
6:122445115:A:T	W431R	0.998
6:122446867:T:A	E378V	0.998
6:122451681:G:T	A278D	0.998
6:122451682:C:G	A278P	0.998
6:122445051:A:C	F452C	0.997
6:122445078:G:T	A443E	0.997
6:122446999:C:G	R334P	0.997
6:122451688:A:G	W276R	0.997
6:122451688:A:T	W276R	0.997
6:122451732:A:G	L261S	0.997
6:122451929:A:G	C240R	0.997
6:122453815:A:G	W182R	0.997
6:122453815:A:T	W182R	0.997
6:122453830:A:G	S177P	0.997
6:122454215:T:A	K129N	0.997
6:122454215:T:G	K129N	0.997
6:122456498:T:A	R118S	0.997
6:122456498:T:G	R118S	0.997
6:122456577:C:G	R92P	0.997

dbSNP variants (sampled 300 via entrez): RS1000075403 (6:122455066 T>C), RS1000111374 (6:122472984 C>T), RS1000409605 (6:122447776 A>G,T), RS1000460401 (6:122448085 C>G,T), RS1000548140 (6:122466424 C>T), RS1000601106 (6:122471952 C>A,G,T), RS1000653276 (6:122472216 A>G), RS1000852744 (6:122462474 G>A,C), RS1000862084 (6:122453673 T>C,G), RS1000898298 (6:122466245 G>A), RS1000921490 (6:122462245 A>C), RS1001033549 (6:122468375 C>T), RS1001458615 (6:122448631 G>A), RS1001463260 (6:122467992 C>A), RS1001504788 (6:122464859 G>A)

Disease associations

OMIM: gene MIM:614548 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004607_145	Plateletcrit	3.000000e-10
GCST90002400_590	Plateletcrit	5.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Valproic Acid	affects expression, decreases methylation, increases expression	4
Air Pollutants	affects expression, increases abundance, decreases expression	3
bisphenol A	decreases expression, affects cotreatment, increases expression	2
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
zinc chromate	increases abundance, increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1
Clozapine	increases expression	1
Coumestrol	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1

Clinical trials (associated diseases)

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