SERINC5

Summary

SERINC5 (serine incorporator 5, HGNC:18825) is a protein-coding gene on chromosome 5q14.1, encoding Serine incorporator 5 (Q86VE9). Restriction factor required to restrict infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early step of viral infection.

Enables phospholipid scramblase activity. Involved in antiviral innate immune response and plasma membrane phospholipid scrambling. Located in several cellular components, including centrosome; cytosol; and plasma membrane.

Source: NCBI Gene 256987 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001174072

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18825
Approved symbol	SERINC5
Name	serine incorporator 5
Location	5q14.1
Locus type	gene with protein product
Status	Approved
Aliases	TPO1
Ensembl gene	ENSG00000164300
Ensembl biotype	protein_coding
OMIM	614551
Entrez	256987

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000502747, ENST00000507668, ENST00000509193, ENST00000512972, ENST00000513907, ENST00000632581, ENST00000867105, ENST00000867106

RefSeq mRNA: 3 — MANE Select: NM_001174072 NM_001174071, NM_001174072, NM_178276

CCDS: CCDS54874, CCDS83009

Canonical transcript exons

ENST00000507668 — 12 exons

Exon	Start	End
ENSE00001083209	80150882	80150948
ENSE00001083210	80169335	80169546
ENSE00001083258	80158836	80158962
ENSE00001272548	80147245	80147284
ENSE00001325283	80146090	80146234
ENSE00001329077	80166383	80166478
ENSE00001330114	80174954	80175047
ENSE00001727410	80138727	80143810
ENSE00002070808	80255896	80256048
ENSE00003518585	80177886	80178064
ENSE00003645464	80177315	80177397
ENSE00003677490	80202886	80203053

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.0030 / max 597.0157, expressed in 1816 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62293	30.9548	1806
62285	4.4195	1216
62292	1.2185	652
62286	0.4103	210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.77	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.64	gold quality
corpus epididymis	UBERON:0004359	98.50	gold quality
germinal epithelium of ovary	UBERON:0001304	98.39	gold quality
gingival epithelium	UBERON:0001949	98.33	gold quality
colonic mucosa	UBERON:0000317	98.27	gold quality
gingiva	UBERON:0001828	98.19	gold quality
oral cavity	UBERON:0000167	97.86	gold quality
trigeminal ganglion	UBERON:0001675	97.41	gold quality
adult organism	UBERON:0007023	97.28	gold quality
esophagus squamous epithelium	UBERON:0006920	97.02	gold quality
inferior vagus X ganglion	UBERON:0005363	97.00	gold quality
upper leg skin	UBERON:0004262	96.84	gold quality
visceral pleura	UBERON:0002401	96.79	gold quality
oocyte	CL:0000023	96.59	gold quality
mammalian vulva	UBERON:0000997	96.44	gold quality
epithelium of esophagus	UBERON:0001976	96.42	gold quality
penis	UBERON:0000989	96.23	gold quality
corpus callosum	UBERON:0002336	96.14	gold quality
dorsal root ganglion	UBERON:0000044	96.12	gold quality
subthalamic nucleus	UBERON:0001906	95.98	gold quality
secondary oocyte	CL:0000655	95.74	gold quality
squamous epithelium	UBERON:0006914	95.65	gold quality
palpebral conjunctiva	UBERON:0001812	95.55	gold quality
skin of hip	UBERON:0001554	95.41	gold quality
renal glomerulus	UBERON:0000074	95.34	gold quality
parietal pleura	UBERON:0002400	95.22	gold quality
parotid gland	UBERON:0001831	95.13	gold quality
metanephric glomerulus	UBERON:0004736	95.10	gold quality
caput epididymis	UBERON:0004358	95.04	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	1410.03
E-GEOD-93593	yes	4.54
E-CURD-85	no	235.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting SERINC5, 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-6758-5P	100.00	66.21	1470
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-7151-5P	99.37	67.82	613
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4274	98.59	66.10	630
HSA-MIR-548AO-5P	98.55	69.57	1362
HSA-MIR-548AX	98.55	69.58	1362
HSA-MIR-550A-3P	98.37	69.61	632
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-4638-3P	97.90	65.75	905
HSA-MIR-200C-5P	97.71	67.73	596
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-4670-3P	97.37	68.35	1378

Literature-anchored findings (GeneRIF, showing 40)

• the apparent occurrence of an unusual TG 3’ splice site in intron 11 is discussed (PMID:17672918)
• results from a first genome-wide association study of Borderline personality disorder, which shows a promising signal on chromosome 5 corresponding to SERINC5, a protein involved in myelination. (PMID:23979607)
• SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef (PMID:26416733)
• identification of the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef (PMID:26416734)
• results suggest that the antagonism of HIV-1 Nef to SERINC5 restriction of virion infectivity is mediated by a dual mechanism that is related to CD4 downregulation (PMID:27681140)
• The increased HIV-1 sensitivity to anti-gp41 antibodies and peptides suggests that SER5 also delays refolding of the remaining fusion-competent Env trimers. (PMID:28179429)
• Ser5-001 isoform transcripts are produced at least 10-fold more than the others; only Ser5-001 produces stable proteins that are targeted to the plasma membrane; only Ser5-001 shows strong anti-HIV-1 activity; the extra transmembrane domain is required for Ser5 stable expression and plasma membrane localization; results suggest plasma membrane localization is required for Ser5 antiviral activity (PMID:28275190)
• Data suggest that restriction of HIV-1 particle infectivity by host-cell SERINC5 (which is antagonized by viral Nef) does not depend on alterations in lipid composition and organization of HIV-1 particles and suggest that channeling serine into lipid biosynthesis may not be a cardinal cellular function of SERINC5. (SERINC5 = serine incorporator 5; Nef = nef gene product, HIV1gp9) (PMID:28659343)
• Experiments using SERINC5(S5) S5- SERINC2(S5) chimeric proteins revealed two functional domains for restriction: one necessary for S5 incorporation into virions, which does not seem to be necessary for restriction, and a second one necessary to change the HIV-1 envelope conformation, localize to DRMs, and block infection. (PMID:29268082)
• SERINC5 is a glycosylated protein and N-glycosylation is important for its steady-state expression. N-glycosylation per se is required neither for the ability of SERINC5 to inhibit HIV-1 infectivity nor for its sensitivity to antagonism by Nef. (PMID:30158294)
• CD4 expression increases the Env sensitivity to SERINC5 and allows SERINC5 to dissociate the Env complex, suggesting that SERINC5 restriction is dependent on Env conformation. (PMID:31043528)
• In MOLT-3 cells, Nef remained crucial for HIV-1 replication even in the absence of SERINC3 and SERINC5. (PMID:31186327)
• Cellular multipass transmembrane protein SERINC5 reduces the infectivity of HIV-1 particles and is counteracted by HIV-1 Nef. (PMID:31597782)
• Flow Cytometry Analysis of HIV-1 Env Conformations at the Surface of Infected Cells and Virions: Role of Nef, CD4, and SERINC5. (PMID:31852789)
• Using cryo-EM, this study determined the structure of human SERINC5. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. (PMID:31907454)
• SERINC5 Is an Unconventional HIV Restriction Factor That Is Upregulated during Myeloid Cell Differentiation. (PMID:31935717)
• A Conserved Acidic-Cluster Motif in SERINC5 Confers Partial Resistance to Antagonism by HIV-1 Nef. (PMID:31941773)
• Super-Resolution Fluorescence Imaging Reveals That Serine Incorporator Protein 5 Inhibits Human Immunodeficiency Virus Fusion by Disrupting Envelope Glycoprotein Clusters. (PMID:32441921)
• Differential Pressures of SERINC5 and IFITM3 on HIV-1 Envelope Glycoprotein over the Course of HIV-1 Infection. (PMID:32493821)
• Patient-Derived HIV-1 Nef Alleles Reveal Uncoupling of CD4 Downregulation and SERINC5 Antagonism Functions of the Viral Pathogenesis Factor. (PMID:32541384)
• An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles. (PMID:32590431)
• HIV-cell membrane fusion intermediates are restricted by Serincs as revealed by cryo-electron and TIRF microscopy. (PMID:32788212)
• SERINC5 Inhibits HIV-1 Infectivity by Altering the Conformation of gp120 on HIV-1 Particles. (PMID:32796070)
• Novel monoclonal antibodies to the SERINC5 HIV-1 restriction factor detect endogenous andvirion-associated SERINC5. (PMID:32835602)
• Sensitivity to monoclonal antibody 447-52D and an open env trimer conformation correlate poorly with inhibition of HIV-1 infectivity by SERINC5. (PMID:32838948)
• Nef homodimers down-regulate SERINC5 by AP-2-mediated endocytosis to promote HIV-1 infectivity. (PMID:32873704)
• Impaired ability of Nef to counteract SERINC5 is associated with reduced plasma viremia in HIV-infected individuals. (PMID:33173092)
• SERINC5 Can Enhance Proinflammatory Cytokine Production by Primary Human Myeloid Cells in Response to Challenge with HIV-1 Particles. (PMID:33597208)
• HIV envelope tail truncation confers resistance to SERINC5 restriction. (PMID:34001619)
• Downregulation of SERINC5 expression in buffy coats of HIV-1-infected patients with detectable or undetectable viral load. (PMID:34097204)
• Influence of Different Glycoproteins and of the Virion Core on SERINC5 Antiviral Activity. (PMID:34209034)
• HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity. (PMID:34380030)
• SERINC5-Mediated Restriction of HIV-1 Infectivity Correlates with Resistance to Cholesterol Extraction but Not with Lipid Order of Viral Membrane. (PMID:35893701)
• Restriction of Influenza A Virus by SERINC5. (PMID:36409124)
• Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells. (PMID:36577173)
• AP-2 Adaptor Complex-Dependent Enhancement of HIV-1 Replication by Nef in the Absence of the Nef/AP-2 Targets SERINC5 and CD4. (PMID:36622146)
• SERINC5 Mediates a Postintegration Block to HIV-1 Gene Expression in Macrophages. (PMID:36976020)
• Relative resistance of patient-derived envelope sequences to SERINC5-mediated restriction of HIV-1 infectivity. (PMID:37768085)
• Beyond Impairment of Virion Infectivity: New Activities of the Anti-HIV Host Cell Factor SERINC5. (PMID:38400059)
• Disruption of Transmembrane Phosphatidylserine Asymmetry by HIV-1 Incorporated SERINC5 Is Not Responsible for Virus Restriction. (PMID:38785977)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	serinc5	ENSDARG00000008153
mus_musculus	Serinc5	ENSMUSG00000021703
rattus_norvegicus	Serinc5	ENSRNOG00000024039
drosophila_melanogaster	Serinc	FBGN0028399
caenorhabditis_elegans		WBGENE00011250
caenorhabditis_elegans		WBGENE00021956

Paralogs (4): SERINC1 (ENSG00000111897), SERINC3 (ENSG00000132824), SERINC2 (ENSG00000168528), SERINC4 (ENSG00000184716)

Protein

Protein identifiers

Serine incorporator 5 — Q86VE9 (reviewed: Q86VE9)

All UniProt accessions (2): A0A0J9YYI4, Q86VE9

UniProt curated annotations — full annotation on UniProt →

Function. Restriction factor required to restrict infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early step of viral infection. Impairs the penetration of the viral particle into the cytoplasm. 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. Phospholipid scrambling results in HIV-1 surface exposure of phosphatidylserine and loss of membrane asymmetry, which leads to changes in HIV-1 Env conformation and loss of infectivity. Enhances the incorporation of serine into phosphatidylserine and sphingolipids. May play a role in providing serine molecules for the formation of myelin glycosphingolipids in oligodendrocytes.

Subcellular location. Cell membrane Cytoplasm. Perinuclear region.

Tissue specificity. Highly expressed in placenta, skeletal muscle, spleen, thymus, testis and peripheral leukocyte and is expressed weakly in the heart, liver and fetal brain.

Similarity. Belongs to the TDE1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86VE9-1	1	yes
Q86VE9-2	2
Q86VE9-3	3
Q86VE9-4	4

RefSeq proteins (3): NP_001167542, NP_001167543, NP_840060 (=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 (27 total): topological domain 10, transmembrane region 9, splice variant 3, glycosylation site 2, mutagenesis site 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VE9-F1	78.17	0.36

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 (2): 113, 183

Mutagenesis-validated functional residues (2):

Position	Phenotype
328	no effect on scrambalase activity. impaired antiviral activity.
397	no effect on scrambalase activity. impaired antiviral activity.

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: 302 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, PEREZ_TP63_TARGETS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP

GO Biological Process (12): L-serine metabolic process (GO:0006563), phosphatidylserine metabolic process (GO:0006658), phospholipid biosynthetic process (GO:0008654), plasma membrane phospholipid scrambling (GO:0017121), myelination (GO:0042552), antiviral innate immune response (GO:0140374), immune system process (GO:0002376), L-serine biosynthetic process (GO:0006564), lipid metabolic process (GO:0006629), L-serine transport (GO:0015825), innate immune response (GO:0045087), defense response to virus (GO:0051607)

GO Molecular Function (3): phospholipid scramblase activity (GO:0017128), molecular carrier activity (GO:0140104), L-serine transmembrane transporter activity (GO:0015194)

GO Cellular Component (9): Golgi apparatus (GO:0005794), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), myelin sheath (GO:0043209), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasm (GO:0005737)

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
cellular anatomical structure	5
cytoplasm	3
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
modified amino acid metabolic process	1
glycerophospholipid metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
plasma membrane organization	1
phospholipid translocation	1
axon ensheathment	1
innate immune response	1
defense response to virus	1
biological_process	1
L-serine metabolic process	1
serine family amino acid biosynthetic process	1
L-amino acid biosynthetic process	1
proteinogenic amino acid biosynthetic process	1
primary metabolic process	1
L-amino acid transport	1
serine transport	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1
molecular_function	1
binding	1
L-amino acid transmembrane transporter activity	1
L-serine transport	1
endomembrane system	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
membrane	1
cell periphery	1
extracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERINC5	SLC75A1	Q14728	968
SERINC5	SAMHD1	Q9Y3Z3	669
SERINC5	BST2	Q10589	652
SERINC5	TRIM5	Q9C035	585
SERINC5	DCAF1	Q9Y4B6	562
SERINC5	APOBEC3G	Q9HC16	557
SERINC5	GBP5	Q96PP8	552
SERINC5	CXCR4	P30991	517
SERINC5	MX2	P20592	477
SERINC5	CD28	P10747	473
SERINC5	CD4	P01730	431
SERINC5	IL2	P01585	423
SERINC5	CD1D	P15813	416
SERINC5	TSG101	Q99816	395
SERINC5	CCR5	P51681	393

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SERINC5	PTAFR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (45): SERINC5 (Affinity Capture-RNA), SERINC5 (Affinity Capture-RNA), SERINC5 (Affinity Capture-RNA), SERINC5 (Two-hybrid), MAVS (Affinity Capture-Western), TRAF6 (Affinity Capture-Western), AMFR (Affinity Capture-MS), RNF40 (Affinity Capture-MS), STUB1 (Affinity Capture-MS), CUL1 (Affinity Capture-MS), CUL3 (Affinity Capture-MS), CUL4B (Affinity Capture-MS), HUWE1 (Affinity Capture-MS), KCMF1 (Affinity Capture-MS), MIB1 (Affinity Capture-MS)

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

1 interactions.

A	Effect	B	Mechanism
CDK13	“down-regulates quantity by destabilization”	SERINC5	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2651 predictions. Top by Δscore:

Variant	Effect	Δscore
5:80143620:T:A	donor_gain	1.0000
5:80143677:C:CA	donor_gain	1.0000
5:80146084:ACTCA:A	donor_loss	1.0000
5:80146085:CTCAC:C	donor_loss	1.0000
5:80146086:TCACT:T	donor_loss	1.0000
5:80146087:CACT:C	donor_loss	1.0000
5:80146088:A:AC	donor_gain	1.0000
5:80146088:A:T	donor_loss	1.0000
5:80146089:C:CC	donor_gain	1.0000
5:80146091:TGA:T	donor_gain	1.0000
5:80146231:GTGT:G	acceptor_gain	1.0000
5:80146232:TGT:T	acceptor_gain	1.0000
5:80146232:TGTC:T	acceptor_loss	1.0000
5:80146233:GT:G	acceptor_gain	1.0000
5:80146235:C:CC	acceptor_gain	1.0000
5:80146235:CT:C	acceptor_loss	1.0000
5:80150877:CTTA:C	donor_loss	1.0000
5:80150878:TTACC:T	donor_loss	1.0000
5:80150879:TACCT:T	donor_loss	1.0000
5:80150880:ACCT:A	donor_gain	1.0000
5:80150881:CCTC:C	donor_gain	1.0000
5:80150944:TCAAA:T	acceptor_gain	1.0000
5:80150945:CAAA:C	acceptor_gain	1.0000
5:80150945:CAAAC:C	acceptor_gain	1.0000
5:80150946:AAA:A	acceptor_gain	1.0000
5:80150947:AA:A	acceptor_gain	1.0000
5:80150949:C:A	acceptor_loss	1.0000
5:80150949:C:CC	acceptor_gain	1.0000
5:80158829:GACTT:G	donor_loss	1.0000
5:80158830:ACTTA:A	donor_loss	1.0000

AlphaMissense

3018 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003844 (5:80242038 G>C), RS1000009145 (5:80124582 G>C), RS1000020881 (5:80207118 C>T), RS1000024968 (5:80200120 T>C), RS1000026121 (5:80191509 G>A), RS1000027701 (5:80162417 A>G), RS1000037619 (5:80163153 C>A,G,T), RS1000041826 (5:80168628 C>T), RS1000063090 (5:80124860 G>T), RS1000081950 (5:80200680 C>T), RS1000084572 (5:80248657 T>C), RS1000127022 (5:80237806 C>G), RS1000153784 (5:80222003 T>C), RS1000194520 (5:80238943 C>T), RS1000211092 (5:80146463 A>T)

Disease associations

OMIM: gene MIM:614551 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002150_1	Borderline personality disorder features	4.000000e-07
GCST002817_4	Alzheimer’s disease in APOE e4- carriers	9.000000e-06
GCST004240_1	Fasting blood glucose	7.000000e-06
GCST004781_3	Sulfasalazine-induced agranulocytosis	3.000000e-08
GCST004781_30	Sulfasalazine-induced agranulocytosis	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005429	borderline personality disorder symptom

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs185462714	Toxicity	3	meperidine	adverse events

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs185462714	SERINC5	3	0.00	1	meperidine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	4
bisphenol A	affects methylation, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
GSK-J4	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation	1
tamibarotene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	increases methylation	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Coumestrol	decreases expression, affects cotreatment	1
Demecolcine	increases expression	1
Diethylstilbestrol	increases expression	1

Clinical trials (associated diseases)

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