SERINC4

Summary

SERINC4 (serine incorporator 4, HGNC:32237) is a protein-coding gene on chromosome 15q15.3, encoding Serine incorporator 4 (A6NH21). Incorporates a polar amino acid serine into membranes and facilitates the synthesis of two serine-derived lipids, phosphatidylserine and sphingolipids.

Predicted to be involved in phospholipid biosynthetic process. Predicted to be active in membrane.

Source: NCBI Gene 619189 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001258031

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32237
Approved symbol	SERINC4
Name	serine incorporator 4
Location	15q15.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40363
Ensembl gene	ENSG00000184716
Ensembl biotype	protein_coding
OMIM	614550
Entrez	619189

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 nonsense_mediated_decay, 2 protein_coding, 1 retained_intron

ENST00000299969, ENST00000319327, ENST00000412697, ENST00000448553, ENST00000457418, ENST00000476490

RefSeq mRNA: 2 — MANE Select: NM_001258031 NM_001258031, NM_001258032

CCDS: CCDS58360

Canonical transcript exons

ENST00000319327 — 12 exons

Exon	Start	End
ENSE00001279267	43797145	43797356
ENSE00001311073	43799310	43799486
ENSE00001914192	43799885	43800220
ENSE00003475306	43794162	43795213
ENSE00003482579	43795688	43795736
ENSE00003485312	43797920	43798013
ENSE00003486940	43798959	43799137
ENSE00003564783	43796845	43796940
ENSE00003632092	43796616	43796742
ENSE00003645130	43795388	43795541
ENSE00003653978	43798425	43798504
ENSE00003689422	43796155	43796227

Expression profiles

Bgee: expression breadth broad, 69 present calls, max score 89.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0824 / max 18.5877, expressed in 31 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149625	0.0497	21
149624	0.0256	8
149623	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.55	gold quality
cerebellar vermis	UBERON:0004720	88.33	gold quality
quadriceps femoris	UBERON:0001377	85.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.64	gold quality
thymus	UBERON:0002370	77.74	silver quality
colonic epithelium	UBERON:0000397	63.89	gold quality
testis	UBERON:0000473	59.89	gold quality
right testis	UBERON:0004534	59.17	gold quality
left testis	UBERON:0004533	58.69	gold quality
bone marrow cell	CL:0002092	53.24	gold quality
cortical plate	UBERON:0005343	49.89	gold quality
ventricular zone	UBERON:0003053	48.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	47.41	gold quality
prefrontal cortex	UBERON:0000451	46.79	gold quality
spinal cord	UBERON:0002240	46.00	gold quality
ganglionic eminence	UBERON:0004023	45.90	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	45.88	gold quality
substantia nigra	UBERON:0002038	45.00	gold quality
superior frontal gyrus	UBERON:0002661	44.27	gold quality
bone marrow	UBERON:0002371	43.56	gold quality
skeletal muscle tissue	UBERON:0001134	43.46	silver quality
putamen	UBERON:0001874	43.46	gold quality
frontal cortex	UBERON:0001870	42.98	gold quality
gall bladder	UBERON:0002110	41.51	gold quality
liver	UBERON:0002107	41.01	gold quality
caudate nucleus	UBERON:0001873	40.94	gold quality
islet of Langerhans	UBERON:0000006	40.92	gold quality
tonsil	UBERON:0002372	40.31	gold quality
cerebral cortex	UBERON:0000956	40.15	gold quality
muscle tissue	UBERON:0002385	40.01	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting SERINC4, 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-4795-3P	100.00	74.62	4024
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-4780	98.57	64.75	611
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-93-3P	98.15	66.65	1309

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	serinc4	ENSDARG00000044815
mus_musculus	Serinc4	ENSMUSG00000046110
rattus_norvegicus	Serinc4	ENSRNOG00000015499
drosophila_melanogaster	Serinc	FBGN0028399
caenorhabditis_elegans		WBGENE00011250
caenorhabditis_elegans		WBGENE00021956

Paralogs (4): SERINC1 (ENSG00000111897), SERINC3 (ENSG00000132824), SERINC5 (ENSG00000164300), SERINC2 (ENSG00000168528)

Protein

Protein identifiers

Serine incorporator 4 — A6NH21 (reviewed: A6NH21)

All UniProt accessions (5): A6NH21, A6NM42, F8WBD8, H7C188, H7C303

UniProt curated annotations — full annotation on UniProt →

Function. Incorporates a polar amino acid serine into membranes and facilitates the synthesis of two serine-derived lipids, phosphatidylserine and sphingolipids.

Subcellular location. Membrane.

Similarity. Belongs to the TDE1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NH21-1	1	yes
A6NH21-2	2

RefSeq proteins (2): NP_001244960, NP_001244961 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005016	TDE1/TMS	Family

Pfam: PF03348

UniProt features (13 total): transmembrane region 10, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NH21-F1	71.91	0.29

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: 50 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, PKCA_DN.V1_DN, CRX_DN.V1_UP, REACTOME_SERINE_METABOLISM, CRX_NRL_DN.V1_UP, ATF6_TARGET_GENES, FOXG1_TARGET_GENES, HES4_TARGET_GENES

GO Biological Process (2): phospholipid biosynthetic process (GO:0008654), lipid metabolic process (GO:0006629)

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

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
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
primary metabolic process	1
cellular anatomical structure	1

Protein interactions and networks

STRING

206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERINC4	TRIM5	Q9C035	469
SERINC4	APOBEC3F	Q8IUX4	455
SERINC4	ELL3	Q9HB65	451
SERINC4	SERF2	P84101	449
SERINC4	RYR3	Q15413	445
SERINC4	BST2	Q10589	443
SERINC4	MYO15B	Q96JP2	431
SERINC4	MFAP1	P55081	403
SERINC4	RDH16	O75452	391
SERINC4	MUC7	Q8TAX7	382
SERINC4	CNPY2	Q9Y2B0	346
SERINC4	HYPK	Q9NX55	323
SERINC4	ICE2	Q659A1	321
SERINC4	APOBEC3D	Q96AK3	308
SERINC4	APOBEC3B	Q9UH17	301

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A8C2M425, A1L1J9, A1L504, A6NH21, A8WCG0, B0BNG2, F1RMN2, O43292, O75908, O76062, O77759, O88496, O88908, O89109, P38435, Q07175, Q0P4Y8, Q49LS0, Q5KR61, Q5RF50, Q5XK03, Q5ZKZ9, Q643R3, Q658P3, Q6MG14, Q6NVG1, Q767L9, Q7TN60, Q7TPN3, Q7TQM4, Q7ZWN0, Q8BKF1, Q8C3X8, Q8IUH8, Q8IZY2, Q8N130, Q8VC65, Q8WMV1, Q91YD1, Q9BU23

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2412 predictions. Top by Δscore:

Variant	Effect	Δscore
15:43796656:G:C	donor_gain	1.0000
15:43798030:A:T	acceptor_gain	1.0000
15:43795734:CTT:C	acceptor_gain	0.9900
15:43795735:TT:T	acceptor_gain	0.9900
15:43795737:C:CC	acceptor_gain	0.9900
15:43796223:CATTG:C	acceptor_gain	0.9900
15:43796225:T:TC	acceptor_gain	0.9900
15:43796228:C:CC	acceptor_gain	0.9900
15:43796655:AG:A	donor_gain	0.9900
15:43796673:T:C	donor_gain	0.9900
15:43796941:C:CC	acceptor_gain	0.9900
15:43798029:C:CT	acceptor_gain	0.9900
15:43798954:CAAA:C	donor_gain	0.9900
15:43794373:GTTT:G	acceptor_gain	0.9800
15:43795682:ACTC:A	donor_loss	0.9800
15:43795683:CTCA:C	donor_loss	0.9800
15:43795684:TCAC:T	donor_loss	0.9800
15:43795685:CACC:C	donor_loss	0.9800
15:43795686:A:C	donor_loss	0.9800
15:43795687:C:A	donor_loss	0.9800
15:43796221:CTCAT:C	acceptor_gain	0.9800
15:43796222:TCATT:T	acceptor_gain	0.9800
15:43796936:TTGCT:T	acceptor_gain	0.9800
15:43796937:TGCT:T	acceptor_gain	0.9800
15:43796939:CT:C	acceptor_gain	0.9800
15:43798955:AAACC:A	donor_loss	0.9800
15:43798956:AAC:A	donor_loss	0.9800
15:43798958:C:A	donor_loss	0.9800
15:43799146:G:GC	acceptor_gain	0.9800
15:43794372:A:AG	acceptor_gain	0.9700

AlphaMissense

3355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:43796900:G:C	S295R	0.980
15:43796900:G:T	S295R	0.980
15:43796902:T:G	S295R	0.980
15:43797976:G:C	F192L	0.975
15:43797976:G:T	F192L	0.975
15:43797978:A:G	F192L	0.975
15:43795137:A:G	W474R	0.958
15:43795137:A:T	W474R	0.958
15:43795390:G:C	F447L	0.954
15:43795390:G:T	F447L	0.954
15:43795392:A:G	F447L	0.954
15:43795159:G:C	F466L	0.953
15:43795159:G:T	F466L	0.953
15:43795161:A:G	F466L	0.953
15:43796910:G:T	S292Y	0.951
15:43799030:G:C	F129L	0.950
15:43799030:G:T	F129L	0.950
15:43799032:A:G	F129L	0.950
15:43796871:G:T	A305E	0.946
15:43795395:A:G	W446R	0.945
15:43795395:A:T	W446R	0.945
15:43798489:C:A	K158N	0.941
15:43798489:C:G	K158N	0.941
15:43795447:G:C	F428L	0.940
15:43795447:G:T	F428L	0.940
15:43795449:A:G	F428L	0.940
15:43796883:A:G	L301P	0.940
15:43796197:A:C	F366L	0.938
15:43796197:A:T	F366L	0.938
15:43796199:A:G	F366L	0.938

dbSNP variants (sampled 300 via entrez): RS1000288190 (15:43802217 G>A,C), RS1000304083 (15:43796488 T>G), RS1001772451 (15:43798138 C>G,T), RS1002247456 (15:43798011 A>G), RS1002691442 (15:43794588 G>A,T), RS1002792741 (15:43795252 C>T), RS1003110455 (15:43795579 G>C), RS1003348928 (15:43794448 G>T), RS1003946517 (15:43795604 A>C,G,T), RS1005044930 (15:43794340 T>C), RS1005495380 (15:43795940 T>A,C,G), RS1005550886 (15:43794202 C>A), RS1005966945 (15:43798848 C>A), RS1006787693 (15:43794132 T>C,G), RS1006955573 (15:43796092 ATGTG>A,ATG,ATGTGTG)

Disease associations

OMIM: gene MIM:614550 | 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)

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	decreases expression	1
Aldehydes	increases expression	1
Arsenic	decreases methylation, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Folic Acid	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Metals, Heavy	increases abundance, decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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