SERINC2

Summary

SERINC2 (serine incorporator 2, HGNC:23231) is a protein-coding gene on chromosome 1p35.2, encoding Serine incorporator 2 (Q96SA4). Non-ATP-dependent, non-specific lipid transporter for phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine.

Enables phospholipid scramblase activity. Involved in plasma membrane phospholipid scrambling. Located in plasma membrane.

Source: NCBI Gene 347735 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_178865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23231
Approved symbol	SERINC2
Name	serine incorporator 2
Location	1p35.2
Locus type	gene with protein product
Status	Approved
Aliases	FKSG84, PRO0899, TDE2
Ensembl gene	ENSG00000168528
Ensembl biotype	protein_coding
OMIM	614549
Entrez	347735

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000373709, ENST00000373710, ENST00000487207, ENST00000491976, ENST00000536384, ENST00000536859, ENST00000851490, ENST00000851491, ENST00000851492, ENST00000851493, ENST00000851494, ENST00000851495, ENST00000851496, ENST00000922301, ENST00000922302, ENST00000922303, ENST00000969154, ENST00000969155

RefSeq mRNA: 5 — MANE Select: NM_178865 NM_001199037, NM_001199038, NM_001199039, NM_018565, NM_178865

CCDS: CCDS30662, CCDS55583, CCDS55584, CCDS55585

Canonical transcript exons

ENST00000373709 — 10 exons

Exon	Start	End
ENSE00001461347	31413213	31413304
ENSE00001946740	31434064	31434678
ENSE00003475719	31428978	31429068
ENSE00003535882	31432967	31433185
ENSE00003581428	31426654	31426823
ENSE00003606452	31425776	31425913
ENSE00003618497	31423693	31423854
ENSE00003622655	31425330	31425409
ENSE00003644553	31424683	31424873
ENSE00003650780	31429397	31429538

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.6272 / max 780.5714, expressed in 1619 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1892	35.2612	1614
1893	0.7010	338
1888	0.4319	108
1904	0.3987	207
1890	0.2130	85
1905	0.1996	98
1891	0.1546	83
1894	0.1008	41
1906	0.0871	27
1889	0.0792	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.03	gold quality
lower esophagus mucosa	UBERON:0035834	98.28	gold quality
minor salivary gland	UBERON:0001830	97.55	gold quality
right lobe of liver	UBERON:0001114	97.38	gold quality
nasal cavity epithelium	UBERON:0005384	97.25	gold quality
kidney epithelium	UBERON:0004819	96.84	silver quality
saliva-secreting gland	UBERON:0001044	96.76	gold quality
metanephros cortex	UBERON:0010533	96.72	gold quality
ileal mucosa	UBERON:0000331	96.65	gold quality
esophagus mucosa	UBERON:0002469	96.04	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.94	gold quality
mouth mucosa	UBERON:0003729	95.61	gold quality
gall bladder	UBERON:0002110	95.37	gold quality
right uterine tube	UBERON:0001302	94.54	gold quality
upper arm skin	UBERON:0004263	94.27	silver quality
parotid gland	UBERON:0001831	94.23	silver quality
gastrocnemius	UBERON:0001388	94.04	gold quality
stromal cell of endometrium	CL:0002255	93.75	gold quality
rectum	UBERON:0001052	93.46	gold quality
adult mammalian kidney	UBERON:0000082	93.41	gold quality
skin of leg	UBERON:0001511	93.37	gold quality
skin of abdomen	UBERON:0001416	92.86	gold quality
muscle of leg	UBERON:0001383	92.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.81	gold quality
transverse colon	UBERON:0001157	91.75	gold quality
liver	UBERON:0002107	91.55	gold quality
zone of skin	UBERON:0000014	90.56	gold quality
duodenum	UBERON:0002114	90.53	gold quality
body of stomach	UBERON:0001161	90.35	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.05	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	1883.59
E-MTAB-10855	yes	698.13
E-MTAB-6701	yes	482.39
E-GEOD-81547	yes	416.87
E-MTAB-10287	yes	49.78
E-MTAB-10553	yes	19.94
E-ANND-3	yes	18.55
E-HCAD-10	yes	18.04
E-HCAD-1	yes	8.03
E-ENAD-27	yes	6.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting SERINC2, 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-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-509-3P	98.12	67.25	612
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-6787-5P	97.54	63.85	457
HSA-MIR-3622A-5P	97.43	67.11	356
HSA-MIR-4286	97.20	64.37	1587

Literature-anchored findings (GeneRIF, showing 8)

• SERINC2 protein localizes in lysosomes in HeLa cells (PMID:21752829)
• In subjects of European descent, SERINC2-NKAIN1 expression of genes is associated with alcohol dependence. (PMID:23455491)
• study concluded that SERINC2 was a replicable and significant risk gene specific for alcohol dependence in individuals of European descent (PMID:23778322)
• TDE2 may have an effect on tumor cell growth by influencing the expression of SREBP and p21. (PMID:24424505)
• Results suggest that the serine incorporator 2 (SERINC2) gene is a novel autism spectrum disorder (ASD) candidate gene. (PMID:28935972)
• In contrast to human SERINC5(S5), we observed that human SERINC2(S2) did not restrict HIV-1, and was inefficiently incorporated into HIV-1 virions when compared to S5. (PMID:29268082)
• SERINC2 increases the risk of bipolar disorder in the Chinese population. (PMID:34288243)
• Serinc2 Drives the Progression of Cervical Cancer Through Regulating Myc Pathway. (PMID:39417376)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	serinc2l	ENSDARG00000053425
danio_rerio	serinc2	ENSDARG00000056532
mus_musculus	Serinc2	ENSMUSG00000023232
rattus_norvegicus	Serinc2	ENSRNOG00000012989
drosophila_melanogaster	Serinc	FBGN0028399
caenorhabditis_elegans		WBGENE00011250
caenorhabditis_elegans		WBGENE00021956

Paralogs (4): SERINC1 (ENSG00000111897), SERINC3 (ENSG00000132824), SERINC5 (ENSG00000164300), SERINC4 (ENSG00000184716)

Protein

Protein identifiers

Serine incorporator 2 — Q96SA4 (reviewed: Q96SA4)

Alternative names: Tumor differentially expressed protein 2-like

All UniProt accessions (1): Q96SA4

UniProt curated annotations — full annotation on UniProt →

Function. Non-ATP-dependent, non-specific lipid transporter for phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine. Functions as a scramblase that flips lipids in both directions across the membrane. In contrast to SERINC3 and SERINC5, has no effect on HIV-1 particles infectivity.

Subcellular location. Cell membrane.

Similarity. Belongs to the TDE1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96SA4-1	1	yes
Q96SA4-2	2
Q96SA4-3	3
Q96SA4-4	4

RefSeq proteins (5): NP_001185966, NP_001185967, NP_001185968, NP_061035, NP_849196* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005016	TDE1/TMS	Family

Pfam: PF03348

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) (RHEA:38663)
• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out) (RHEA:38895)

UniProt features (23 total): transmembrane region 11, sequence conflict 7, splice variant 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96SA4-F1	79.46	0.44

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: 110 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MAZ_Q6, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, HASEGAWA_TUMORIGENESIS_BY_RET_C634R, LIAO_METASTASIS, TGANTCA_AP1_C, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (2): phosphatidylserine metabolic process (GO:0006658), plasma membrane phospholipid scrambling (GO:0017121)

GO Molecular Function (2): acetyltransferase activator activity (GO:0010698), phospholipid scramblase activity (GO:0017128)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

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
plasma membrane organization	1
phospholipid translocation	1
enzyme activator activity	1
acetyltransferase activity	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERINC2	KIAA0040	Q15053	581
SERINC2	NKAIN1	Q4KMZ8	514
SERINC2	TTC14	Q96N46	481
SERINC2	LRRC14	Q15048	462
SERINC2	GPN3	Q9UHW5	449
SERINC2	ZCCHC17	Q9NP64	439
SERINC2	PHF3	Q92576	420
SERINC2	MPZL2	O60487	418
SERINC2	GLB1L	Q6UWU2	407
SERINC2	SNRNP40	Q96DI7	404
SERINC2	PLAAT3	P53816	404
SERINC2	IPO11	Q9UI26	389
SERINC2	ALDH4A1	P30038	382
SERINC2	MOSPD2	Q8NHP6	377
SERINC2	ICE2	Q659A1	360
SERINC2	LAPTM5	Q13571	360

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SERINC2	STOM	psi-mi:“MI:0914”(association)	0.530
SERINC2	PGRMC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): ATP6V0A2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), GHITM (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), STOM (Affinity Capture-MS), TMBIM6 (Affinity Capture-MS), LGALS3 (Affinity Capture-MS), GPR89B (Affinity Capture-MS), STOM (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), GHITM (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), TMBIM6 (Affinity Capture-MS), SERINC2 (Two-hybrid), SERINC2 (Two-hybrid)

ESM2 similar proteins: A3KMY4, A4FUZ5, A5PF08, A5PMW0, A8XKF2, B0S5A7, B5X3W7, O88407, O97704, P55019, P59158, Q06496, Q13530, Q14AT5, Q17JQ7, Q1LZ71, Q20026, Q28620, Q4R6L9, Q53GD3, Q58CW5, Q5R4I4, Q5R533, Q5R5L9, Q5RJI2, Q60825, Q63175, Q6GN42, Q6IFT6, Q6MG71, Q6T3U3, Q6T3U4, Q7PRJ0, Q7Q5R7, Q7SYC9, Q7T2B0, Q803X0, Q86VE9, Q8BHJ6, Q8K097

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2104 predictions. Top by Δscore:

Variant	Effect	Δscore
1:31423852:AAGGT:A	donor_loss	1.0000
1:31423853:AG:A	donor_gain	1.0000
1:31423854:GG:G	donor_gain	1.0000
1:31423854:GGT:G	donor_loss	1.0000
1:31423855:G:GG	donor_gain	1.0000
1:31423855:GTG:G	donor_loss	1.0000
1:31424678:CACA:C	acceptor_loss	1.0000
1:31424679:ACAGC:A	acceptor_loss	1.0000
1:31424680:C:G	acceptor_gain	1.0000
1:31424680:CAGCT:C	acceptor_loss	1.0000
1:31424681:A:AG	acceptor_gain	1.0000
1:31424681:AGCT:A	acceptor_gain	1.0000
1:31424682:G:GT	acceptor_gain	1.0000
1:31424682:GC:G	acceptor_gain	1.0000
1:31424682:GCT:G	acceptor_gain	1.0000
1:31424682:GCTG:G	acceptor_gain	1.0000
1:31424682:GCTGC:G	acceptor_gain	1.0000
1:31424872:GG:G	donor_gain	1.0000
1:31424873:GG:G	donor_gain	1.0000
1:31424873:GGTGA:G	donor_loss	1.0000
1:31424874:G:GG	donor_gain	1.0000
1:31424874:G:T	donor_loss	1.0000
1:31424875:T:A	donor_loss	1.0000
1:31425410:G:GG	donor_gain	1.0000
1:31425427:G:GT	donor_gain	1.0000
1:31425771:CCCA:C	acceptor_loss	1.0000
1:31425772:CCA:C	acceptor_loss	1.0000
1:31425773:CAGT:C	acceptor_loss	1.0000
1:31425774:A:AG	acceptor_gain	1.0000
1:31425774:AGTC:A	acceptor_loss	1.0000

AlphaMissense

2985 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:31434125:A:C	S432R	0.993
1:31434127:C:A	S432R	0.993
1:31434127:C:G	S432R	0.993
1:31425334:T:A	W133R	0.990
1:31425334:T:C	W133R	0.990
1:31425791:G:A	G163D	0.989
1:31434128:T:A	W433R	0.988
1:31434128:T:C	W433R	0.988
1:31429051:C:A	A285D	0.986
1:31425345:G:C	K136N	0.985
1:31425345:G:T	K136N	0.985
1:31425799:G:C	G166R	0.985
1:31429044:T:A	W283R	0.985
1:31429044:T:C	W283R	0.985
1:31429050:G:C	A285P	0.985
1:31425790:G:C	G163R	0.984
1:31425800:G:A	G166D	0.984
1:31429012:C:G	S272W	0.984
1:31425856:T:A	W185R	0.982
1:31425856:T:C	W185R	0.982
1:31424777:G:C	R99P	0.980
1:31425361:G:C	G142R	0.980
1:31425868:T:A	W189R	0.980
1:31425868:T:C	W189R	0.980
1:31426772:C:A	N243K	0.978
1:31426772:C:G	N243K	0.978
1:31433127:C:G	H392D	0.978
1:31433162:G:A	M403I	0.978
1:31433162:G:C	M403I	0.978
1:31433162:G:T	M403I	0.978

dbSNP variants (sampled 300 via entrez): RS1000205693 (1:31420099 C>T), RS1000791489 (1:31410185 G>A), RS1000867736 (1:31427662 G>A,C), RS1000920091 (1:31427331 A>G), RS1001032151 (1:31432735 T>C), RS1001200398 (1:31429222 G>C), RS1001251280 (1:31428814 G>A), RS1001485946 (1:31432599 T>C), RS1001498427 (1:31433220 G>A,C), RS1001616664 (1:31416156 G>T), RS1001903614 (1:31411373 G>A,C), RS1001974242 (1:31418023 A>T), RS1002407119 (1:31417725 A>G), RS1002872974 (1:31430738 A>G), RS1003163724 (1:31434372 C>G,T)

Disease associations

OMIM: gene MIM:614549 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001874_1	Alcohol dependence	3.000000e-08
GCST005848_8	Heart rate response to recovery post exercise (50 sec)	7.000000e-09
GCST005951_36	Body mass index	9.000000e-10
GCST006186_9	Systolic blood pressure x smoking status (current vs non-current) interaction (1df test)	2.000000e-07
GCST006193_8	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	8.000000e-06
GCST006195_95	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	8.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009185	heart rate response to recovery post exercise
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Calcitriol	increases expression, affects cotreatment	3
bisphenol A	affects cotreatment, increases methylation, affects expression	2
chloropicrin	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
titanium dioxide	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric chloride	decreases expression	1
glycidamide	increases expression	1
ICG 001	increases expression	1
jinfukang	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Rosiglitazone	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Azathioprine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Folic Acid	decreases expression	1

Clinical trials (associated diseases)

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