SAR1A

Summary

SAR1A (secretion associated Ras related GTPase 1A, HGNC:10534) is a protein-coding gene on chromosome 10q22.1, encoding Small COPII coat GTPase SAR1A (Q9NR31). Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport.

Enables G protein activity and amino acid sensor activity. Involved in COPII-coated vesicle budding; cellular response to leucine starvation; and negative regulation of TORC1 signaling. Is active in COPII vesicle coat; endoplasmic reticulum exit site; and lysosomal membrane.

Source: NCBI Gene 56681 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 24 total
• Druggable target: yes
• MANE Select transcript: NM_020150

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10534
Approved symbol	SAR1A
Name	secretion associated Ras related GTPase 1A
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	SAR1, Sara
Ensembl gene	ENSG00000079332
Ensembl biotype	protein_coding
OMIM	607691
Entrez	56681

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 26 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000373236, ENST00000373238, ENST00000373239, ENST00000373241, ENST00000373242, ENST00000452767, ENST00000477464, ENST00000870136, ENST00000870137, ENST00000870138, ENST00000870139, ENST00000870140, ENST00000870141, ENST00000870142, ENST00000870143, ENST00000870144, ENST00000870145, ENST00000912263, ENST00000912264, ENST00000912265, ENST00000912266, ENST00000912267, ENST00000912268, ENST00000912269, ENST00000948610, ENST00000948611, ENST00000948612

RefSeq mRNA: 2 — MANE Select: NM_020150 NM_001142648, NM_020150

CCDS: CCDS7298

Canonical transcript exons

ENST00000373241 — 7 exons

Exon	Start	End
ENSE00000501177	70153838	70153969
ENSE00002444343	70161004	70161069
ENSE00002482832	70157764	70157867
ENSE00002506810	70161619	70161738
ENSE00003633397	70161858	70161931
ENSE00003707369	70147289	70152592
ENSE00003845969	70170413	70170514

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 114.5830 / max 1839.2630, expressed in 1827 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109827	103.5686	1827
109820	8.9573	1505
109826	0.9961	368
109821	0.4723	231
109824	0.3736	20
109825	0.0996	14
109823	0.0904	16
109822	0.0251	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.48	gold quality
tendon	UBERON:0000043	98.02	gold quality
pericardium	UBERON:0002407	98.01	gold quality
stromal cell of endometrium	CL:0002255	97.83	gold quality
periodontal ligament	UBERON:0008266	97.81	gold quality
hair follicle	UBERON:0002073	97.75	gold quality
palpebral conjunctiva	UBERON:0001812	97.51	gold quality
synovial joint	UBERON:0002217	97.45	gold quality
epithelium of nasopharynx	UBERON:0001951	97.43	gold quality
germinal epithelium of ovary	UBERON:0001304	97.31	gold quality
mammary duct	UBERON:0001765	97.31	gold quality
epithelium of mammary gland	UBERON:0003244	97.31	gold quality
decidua	UBERON:0002450	97.22	gold quality
adrenal tissue	UBERON:0018303	97.18	gold quality
tibia	UBERON:0000979	97.11	gold quality
visceral pleura	UBERON:0002401	97.05	gold quality
tendon of biceps brachii	UBERON:0008188	97.04	gold quality
endothelial cell	CL:0000115	96.93	gold quality
saphenous vein	UBERON:0007318	96.93	gold quality
pleura	UBERON:0000977	96.92	gold quality
olfactory bulb	UBERON:0002264	96.92	gold quality
medial globus pallidus	UBERON:0002477	96.91	gold quality
parietal pleura	UBERON:0002400	96.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.90	gold quality
buccal mucosa cell	CL:0002336	96.89	gold quality
amniotic fluid	UBERON:0000173	96.87	gold quality
endometrium	UBERON:0001295	96.84	gold quality
mammary gland	UBERON:0001911	96.82	gold quality
thoracic mammary gland	UBERON:0005200	96.81	gold quality
urethra	UBERON:0000057	96.67	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	80.09
E-MTAB-6379	no	5668.39
E-MTAB-7606	no	489.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

168 targeting SAR1A, 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-3925-3P	100.00	69.95	1237
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486

Literature-anchored findings (GeneRIF, showing 20)

• The Sec31 fragment stimulates GAP activity of Sec23/24, and a convergence of Sec31 and Sec23 residues at the Sar1 GTPase active site explains how GTP hydrolysis is triggered leading to COPII coat disassembly. (PMID:17981133)
• Sar 1 H79G mutants efficiently blocked the plasma membrane trafficking of the Kir3.1/Kir3.4 complex however they did not block the Gbeta1gamma2/Kir3.1 interaction. (PMID:19135528)
• Kir6.2 contains a di-acidic endoplasmic reticulum exit signal, which promotes endoplasmic reticulum exit via a process that requires Sar1. (PMID:19357197)
• the intracellular trafficking of hCaR from the endoplasmic reticulum is Sar1-dependent via coat protein complex-II vesicles. (PMID:20457124)
• lipid-directed and tether-assisted Sar1 organization controls membrane constriction to regulate ER export. (PMID:20624903)
• Sar1 mutant proteins added to metaphase-arrested Xenopus laevis egg extracts cause dramatic effects on membrane organization. (PMID:22605651)
• the behavior of the human of Sar1A and Sar1B, a key component of the COPII family of vesicle coat proteins, was examined. (PMID:22974979)
• Sedlin bound and promoted efficient cycling of Sar1, a guanosine triphosphatase that can constrict membranes, and thus allowed nascent carriers to grow and incorporate procollagen prefibrils. (PMID:23019651)
• although Sar1A antagonizes the lipoprotein secretion-promoting activity of Sar1B, both isoforms modulate the expression of genes encoding cholesterol biosynthetic enzymes and the synthesis of cholesterol de novo. (PMID:24338480)
• Data indicate that hydroxyurea (HU) induces SAR1 protein expression, which in turn activates gamma-globin expression, predominantly through the Gialpha/JNK/Jun pathway. (PMID:24914133)
• SAR1A gene silencing in hepatocytes mimics the effect of ethanol: dedimerization of giantin, arresting PDIA3 in the endoplasmic reticulum (ER) and large-scale alterations in Golgi architecture. (PMID:26607390)
• Sar1 is a novel regulator of endoplasmic reticulum-mitochondrial contact sites in the metazoans. (PMID:27101143)
• No associations were observed between any of the secretion associated Ras related GTPase 1A (SAR1a) promoter variants and baseline fetal hemoglobin HbF among sickle cell disease (SCD) patients. (PMID:28499394)
• Study shows that the bona fide nonglycoprotein Nox5, a transmembrane superoxide-producing NADPH oxidase, is transported to the cell surface in a manner resistant to co-expression of Sar1 (H79G), a GTP-fixed mutant of the small GTPase Sar1, which blocks COPII vesicle fission from the endoplasmic reticulum. (PMID:29718541)
• The Sar1 and PREB are upregulated following the induction of morphological differentiation, suggesting the potential role of signaling through Sar1a during morphological differentiation. (PMID:30078678)
• Study data suggest that SAR1A and SAR1B are the critical regulators of trafficking of Nav1.5. Moreover, SAR1A and SAR1B interact with MOG1, and are required for MOG1-mediated cell surface expression and function of Nav1.5. (PMID:30251687)
• FABP5 promotes the budding of particles approximately 150 nm in diameter and modulates the kinetics of the SAR1 GTPase cycle. (PMID:30485159)
• Small sequence variations between two mammalian paralogs of the small GTPase SAR1 underlie functional differences in coat protein complex II assembly. (PMID:32358066)
• SAR1A regulates the RhoA/YAP and autophagy signaling pathways to influence osteosarcoma invasion and metastasis. (PMID:36047971)
• Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo. (PMID:38687799)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sar1a	ENSMUSG00000020088
rattus_norvegicus	Ppa1	ENSRNOG00000000557

Paralogs (30): ARF5 (ENSG00000004059), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), SAR1B (ENSG00000152700), ARL5A (ENSG00000162980), ARF6 (ENSG00000165527), ARL5B (ENSG00000165997), ARF4 (ENSG00000168374), ARL13B (ENSG00000169379), ARL13A (ENSG00000174225), ARL10 (ENSG00000175414), ARL4D (ENSG00000175906), ARL14 (ENSG00000179674), ARL15 (ENSG00000185305), ARL17A (ENSG00000185829), ARL4C (ENSG00000188042), ARL9 (ENSG00000196503), ARL2 (ENSG00000213465), ARL16 (ENSG00000214087), ARL17B (ENSG00000228696)

Protein

Protein identifiers

Small COPII coat GTPase SAR1A — Q9NR31 (reviewed: Q9NR31)

Alternative names: COPII-associated small GTPase, Secretion-associated Ras-related GTPase 1A

All UniProt accessions (5): Q9NR31, H0Y5E8, Q5SQT8, Q5SQT9, X1WI22

UniProt curated annotations — full annotation on UniProt →

Function. Small GTPase that cycles between an active GTP-bound and an inactive GDP-bound state and mainly functions in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. The active GTP-bound form inserts into the endoplasmic reticulum membrane where it recruits the remainder of the coat protein complex II/COPII. The coat protein complex II assembling and polymerizing on endoplasmic reticulum membrane is responsible for both the sorting of cargos and the deformation and budding of membranes into vesicles destined to the Golgi. The GTPase activity of SAR1 by controlling the timing of COPII budding regulates the size of the formed vesicles and is important for cargo selection depending on their size. Together with SEC16A, forms the organized scaffold defining endoplasmic reticulum exit sites (ERES), some specific domains of the endoplasmic reticulum where COPII vesicles form. In addition to its role in vesicle trafficking, can also function as a leucine sensor regulating TORC1 signaling and more indirectly cellular metabolism, growth and survival. In absence of leucine, interacts with the GATOR2 complex via MIOS and inhibits TORC1 signaling. The binding of leucine abrogates the interaction with GATOR2 and the inhibition of the TORC1 signaling. This function is completely independent of the GTPase activity of SAR1B.

Subunit / interactions. Homodimer; upon association with membrane. Part of the coat protein complex II/COPII, composed of SEC23/24 and SEC13/31 heterodimers, that it helps recruit and assemble on endoplasmic reticulum (ER) membranes at ER exit sites. Interacts with PREB; PREB acts as a guanine nucleotide exchange factor facilitating the activation of SAR1B by loading it with GTP. Interacts with B3GAT1. Interacts with MIOS; the interaction is direct, disrupted by the binding of leucine and mediates the interaction of SAR1A with the GATOR2 complex to negatively regulate the TORC1 signaling upon leucine deprivation.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus. Golgi stack membrane. Cytoplasm. Cytosol. Lysosome membrane.

Activity regulation. Small GTPases activation is mediated by guanine exchange factors (GEF), while inactivation through hydrolysis of the bound GTP is stimulated by GTPase activating proteins (GAP). Activated by the guanine nucleotide exchange factor PREB/SEC12 that facilitates the loading of SAR1B with GTP. Inhibited by the alarmone ppGpp.

Similarity. Belongs to the small GTPase superfamily. SAR1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR31-1	1	yes
Q9NR31-2	2

RefSeq proteins (2): NP_001136120, NP_064535* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR006687	Small_GTPase_SAR1	Family
IPR006689	Small_GTPase_ARF/SAR	Family
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00025

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (47 total): binding site 23, helix 9, strand 6, turn 3, chain 1, region of interest 1, short sequence motif 1, modified residue 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8DZM	X-RAY DIFFRACTION	1.65
8DZO	X-RAY DIFFRACTION	1.8
8DZT	X-RAY DIFFRACTION	1.8
2GAO	X-RAY DIFFRACTION	2
8E0H	X-RAY DIFFRACTION	2
8DZN	X-RAY DIFFRACTION	2.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR31-F1	85.64	0.60

Functional residue map

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

Ligand- & substrate-binding residues (23): 38; 39; 39; 40; 40; 75; 134; 134; 135; 135; 137; 137 …

Post-translational modifications (1): 139

Mutagenesis-validated functional residues (1):

Position	Phenotype
79	decreases transport of sting1 from the endoplasmic reticulum to the golgi.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 284 (showing top): GCACCTT_MIR18A_MIR18B, YAGI_AML_WITH_INV_16_TRANSLOCATION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_TARGETING, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN

GO Biological Process (12): obsolete regulation of COPII vesicle coating (GO:0003400), intracellular protein transport (GO:0006886), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), vesicle organization (GO:0016050), COPII vesicle coat assembly (GO:0048208), membrane organization (GO:0061024), COPII-coated vesicle cargo loading (GO:0090110), regulation of TORC1 signaling (GO:1903432), negative regulation of TORC1 signaling (GO:1904262), cellular response to leucine starvation (GO:1990253), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192)

GO Molecular Function (7): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), amino acid sensor activity (GO:0140785), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (11): lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), COPII vesicle coat (GO:0030127), Golgi cisterna membrane (GO:0032580), endoplasmic reticulum exit site (GO:0070971), cytoplasm (GO:0005737), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
intracellular transport	3
intracellular protein localization	2
COPII-coated vesicle budding	2
TORC1 signaling	2
transport	2
organelle membrane	2
endomembrane system	2
intracellular membrane-bounded organelle	2
protein transport	1
intercellular transport	1
Golgi vesicle transport	1
organelle organization	1
vesicle coat assembly	1
protein-containing complex assembly	1
cellular component organization	1
vesicle cargo loading	1
regulation of TOR signaling	1
negative regulation of TOR signaling	1
regulation of TORC1 signaling	1
cellular response to amino acid starvation	1
establishment of protein localization	1
cellular process	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
molecular sensor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
lysosome	1
lytic vacuole membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
ER to Golgi transport vesicle membrane	1
vesicle coat	1

Protein interactions and networks

STRING

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAR1A	PREB	Q9HCU5	961
SAR1A	SEC13	P55735	959
SAR1A	SEC31A	O94979	929
SAR1A	SEC24B	O95487	928
SAR1A	SEC24C	P53992	920
SAR1A	SEC16A	O15027	908
SAR1A	SEC23A	Q15436	903
SAR1A	SEC24A	O95486	895
SAR1A	SEC24D	O94855	875
SAR1A	SEC23B	Q15437	844
SAR1A	GOLPH3	Q9H4A6	843
SAR1A	SEC16B	Q96JE7	807
SAR1A	LMAN1	P49257	759
SAR1A	SURF4	O15260	722
SAR1A	SEC22B	O75396	676

IntAct

288 interactions, top by confidence:

A	B	Type	Score
SAR1A	SAR1B	psi-mi:“MI:0915”(physical association)	0.590
VKORC1	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
TMEM60	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
SLC38A7	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
GIMAP1	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
PLPP4	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
LHFPL5	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
VAMP3	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
AQP10	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
CLDND2	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
MIP	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
SAR1A	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
FAM3C	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
GYPA	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
SAR1A	ORMDL1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (391): SAR1A (Affinity Capture-RNA), SAR1A (Affinity Capture-RNA), SAR1A (Affinity Capture-MS), SAR1A (Affinity Capture-MS), SAR1A (Affinity Capture-RNA), HMBS (Co-fractionation), SAR1A (Co-fractionation), SAR1A (Co-fractionation), SAR1A (Co-fractionation), SAR1A (Co-fractionation), SEC31A (Co-fractionation), SAR1A (Proximity Label-MS), SAR1B (Affinity Capture-MS), SAR1A (Affinity Capture-MS), SAR1A (Affinity Capture-MS)

ESM2 similar proteins: A1CRG9, A1D4D1, A3LTA2, A5DR82, A5E5G3, O04266, O04267, O04834, P0C583, P0C950, P0C951, P0CR30, P0CR31, P0CT16, P0CT17, P20606, P36536, P52884, P78976, Q01474, Q01475, Q02804, Q0CUN7, Q0UKC0, Q13795, Q23445, Q2HA55, Q3T0D7, Q3T0T7, Q4P0I7, Q4WJS7, Q52NJ3, Q559R0, Q59S78, Q5BGB9, Q5HZY2, Q5PYH3, Q5R548, Q5R579, Q6BVA7

Diamond homologs: A1CRG9, A1D4D1, A3LTA2, A5DR82, A5E5G3, A8ISN6, O04266, O04267, O04834, O45379, O48649, O48920, P0C583, P0C950, P0C951, P0CM16, P0CM17, P0CR30, P0CR31, P0CT16, P0CT17, P0DH91, P11076, P18085, P19146, P20606, P22274, P34727, P36397, P36536, P36579, P38116, P40940, P40945, P40994, P49702, P51643, P51821, P51823, P51824

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
SIRT7	“up-regulates activity”	SAR1A	deacetylation
SAR1A	“up-regulates quantity”	SEC23B	binding
SAR1A	“up-regulates quantity”	SEC23A	binding
SAR1A	“up-regulates quantity”	SEC24B	binding
SAR1A	“up-regulates quantity”	SEC24D	binding
SAR1A	“up-regulates quantity”	SEC24C	binding
SAR1A	“up-regulates quantity”	SEC24A	binding
SAR1A	“up-regulates quantity”	“COPII vesicle”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1412 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70152588:TTCCC:T	acceptor_gain	1.0000
10:70152590:CCC:C	acceptor_gain	1.0000
10:70152591:CCC:C	acceptor_gain	1.0000
10:70153832:TCTTA:T	donor_loss	1.0000
10:70153833:CTTAC:C	donor_loss	1.0000
10:70153834:TTACC:T	donor_loss	1.0000
10:70153835:TACCT:T	donor_loss	1.0000
10:70153836:A:AC	donor_gain	1.0000
10:70153837:C:CG	donor_gain	1.0000
10:70153837:CCTTT:C	donor_gain	1.0000
10:70153841:T:A	donor_gain	1.0000
10:70153965:AAAGC:A	acceptor_gain	1.0000
10:70153966:AAGC:A	acceptor_gain	1.0000
10:70153967:AGC:A	acceptor_gain	1.0000
10:70153967:AGCCT:A	acceptor_loss	1.0000
10:70153968:GC:G	acceptor_gain	1.0000
10:70153968:GCC:G	acceptor_loss	1.0000
10:70153969:CC:C	acceptor_gain	1.0000
10:70153969:CCT:C	acceptor_loss	1.0000
10:70153970:C:A	acceptor_loss	1.0000
10:70153970:C:CC	acceptor_gain	1.0000
10:70153970:C:T	acceptor_gain	1.0000
10:70153971:T:A	acceptor_loss	1.0000
10:70153976:A:AC	acceptor_gain	1.0000
10:70153976:A:C	acceptor_gain	1.0000
10:70153977:T:C	acceptor_gain	1.0000
10:70153977:T:TC	acceptor_gain	1.0000
10:70157762:A:AC	donor_gain	1.0000
10:70157763:C:CC	donor_gain	1.0000
10:70157774:A:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000293945 (10:70158406 G>A), RS1000438846 (10:70149185 C>A), RS1000469895 (10:70149397 G>A), RS1000602365 (10:70160572 A>G), RS1000647144 (10:70164976 G>A,T), RS1000658992 (10:70157959 G>A,T), RS1000678383 (10:70165133 C>A,T), RS1001036723 (10:70160310 A>C), RS1001182398 (10:70167608 A>G), RS1001265575 (10:70155240 T>A,C), RS1001695515 (10:70154926 G>T), RS1001769412 (10:70161933 T>C), RS1001910849 (10:70156866 T>C), RS1002101705 (10:70148001 C>T), RS1002132808 (10:70159881 T>G)

Disease associations

OMIM: gene MIM:607691 | 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: yes

ChEMBL targets (1): CHEMBL4295960 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	4
bisphenol A	increases expression, affects cotreatment	3
Tobacco Smoke Pollution	increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	affects binding	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
ochratoxin B	affects binding	1
dimethylarsinous acid	increases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	increases expression, affects cotreatment	1
Indomethacin	increases expression, affects cotreatment	1
Isoniazid	increases expression	1
Ivermectin	decreases expression	1
Nickel	increases expression	1
Phthalic Acids	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118667	Binding	Binding affinity to SAR1A in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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