SAR1B

Summary

SAR1B (secretion associated Ras related GTPase 1B, HGNC:10535) is a protein-coding gene on chromosome 5q31.1, encoding Small COPII coat GTPase SAR1B (Q9Y6B6). 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 protein encoded by this gene is a small GTPase that acts as a homodimer. The encoded protein is activated by the guanine nucleotide exchange factor PREB and is involved in protein transport from the endoplasmic reticulum to the Golgi. This protein is part of the COPII coat complex. Defects in this gene are a cause of chylomicron retention disease (CMRD), also known as Anderson disease (ANDD). Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 51128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): chylomicron retention disease (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 204 total — 21 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_016103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10535
Approved symbol	SAR1B
Name	secretion associated Ras related GTPase 1B
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000152700
Ensembl biotype	protein_coding
OMIM	607690
Entrez	51128

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 26 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000402673, ENST00000439578, ENST00000502286, ENST00000502539, ENST00000503318, ENST00000504242, ENST00000505758, ENST00000507419, ENST00000508363, ENST00000509730, ENST00000509937, ENST00000903489, ENST00000903490, ENST00000903491, ENST00000903492, ENST00000903493, ENST00000903494, ENST00000903495, ENST00000903496, ENST00000903497, ENST00000903498, ENST00000903499, ENST00000903500, ENST00000950564, ENST00000950565, ENST00000950566, ENST00000950567, ENST00000950568, ENST00000950569

RefSeq mRNA: 2 — MANE Select: NM_016103 NM_001033503, NM_016103

CCDS: CCDS4177

Canonical transcript exons

ENST00000402673 — 7 exons

Exon	Start	End
ENSE00001194944	134623962	134624037
ENSE00001520244	134632728	134632828
ENSE00001821345	134601149	134607066
ENSE00002475303	134620933	134621052
ENSE00003535335	134612691	134612756
ENSE00003540061	134608372	134608503
ENSE00003587423	134609571	134609674

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.3846 / max 797.7526, expressed in 1812 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63469	37.0375	1812
63470	0.3472	143

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	98.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.30	gold quality
biceps brachii	UBERON:0001507	97.96	gold quality
vastus lateralis	UBERON:0001379	97.84	gold quality
skeletal muscle tissue	UBERON:0001134	97.66	gold quality
diaphragm	UBERON:0001103	97.47	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.38	gold quality
quadriceps femoris	UBERON:0001377	97.31	gold quality
gastrocnemius	UBERON:0001388	97.22	gold quality
sperm	CL:0000019	97.21	gold quality
muscle organ	UBERON:0001630	97.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.18	gold quality
muscle of leg	UBERON:0001383	97.07	gold quality
choroid plexus epithelium	UBERON:0003911	97.04	gold quality
deltoid	UBERON:0001476	96.97	gold quality
islet of Langerhans	UBERON:0000006	96.92	gold quality
liver	UBERON:0002107	96.73	gold quality
jejunum	UBERON:0002115	96.52	gold quality
duodenum	UBERON:0002114	96.51	gold quality
adrenal tissue	UBERON:0018303	96.51	gold quality
triceps brachii	UBERON:0001509	96.42	gold quality
muscle tissue	UBERON:0002385	96.16	gold quality
corpus callosum	UBERON:0002336	96.12	gold quality
heart right ventricle	UBERON:0002080	95.85	gold quality
right lobe of liver	UBERON:0001114	95.84	gold quality
body of tongue	UBERON:0011876	95.44	gold quality
tibialis anterior	UBERON:0001385	95.31	gold quality
male germ cell	CL:0000015	94.92	gold quality
calcaneal tendon	UBERON:0003701	94.84	gold quality
esophagus squamous epithelium	UBERON:0006920	94.80	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	21.77
E-CURD-122	yes	20.95
E-GEOD-99795	no	299.69

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, HES1, HNF4A, MYBL2, PAX6

miRNA regulators (miRDB)

244 targeting SAR1B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 21)

• identify eight mutations in SARA2 that are associated with three severe disorders of fat malabsorption (PMID:12692552)
• Sara2 is an important gene in processes involving erythroid cell proliferation and differentiation. (PMID:15943909)
• Five mutations in the SAR1B gene causing Anderson disease. (PMID:17945526)
• muscular as well as cardiac abnormalities that could be related to the reported expression of SARA2 in these tissues (PMID:18786134)
• Variable phenotypic expression of chylomicron retention disease in a kindred carrying a mutation of the Sara2 gene. (PMID:19846172)
• Sar1b expression may promote intestinal lipid transport with the involvement of the coat protein complex II network and the processing of SREBP-1c. (PMID:21836065)
• the behavior of the human of Sar1A and Sar1B, a key component of the COPII family of vesicle coat proteins, was examined. (PMID:22974979)
• 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)
• SAR1B polymorphisms were associated with Alzheimer’s disease (AD) risk; results were not significant after correction for multiple tests. Simultaneous screening using SAR1B rs11948613 and ApoE epsilon4 status offered a better sensitivity for AD screening. (PMID:25703997)
• Our data also suggest that Sar1B overexpression contributes to regulation of CHOL transport and metabolism by facilitating rapid uptake and transport of CHOL. (PMID:25826777)
• Report compensatory Sar1a elevation after Sar1b gene deletion in Caco-2/15 cells prevents chylomicron collapse. (PMID:28982670)
• Targeted next generation DNA sequencing revealed several rare heterozygous missense variants in both MTTP and APOB genes known or predicted to be deleterious, in addition to a novel heterozygous missense variant in SAR1B, which encodes the gene causing chylomicron retention disease (PMID:29540175)
• 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)
• Chylomicron retention disease is an autosomal recessive disorder, in which intestinal fat malabsorption is the main cause of diverse severe manifestations due to mutations in the SAR1B. (Review) (PMID:30640893)
• Twenty-three patients were genetically confirmed as affected by primary hypobetalipoproteinemia. In this group of patients, the most prevalent mutated genes were APOB (in 17 patients, with eight novel mutations identified), SAR1B (in 3 patients, with one novel mutation identified), ANGPTL3 (in 2 patients), and MTTP (in 1 patient). The other 21 patients could not be genetically diagnosed with hypobetalipoproteinemia despit (PMID:30782561)
• SAR1B GTPase is necessary to protect intestinal cells from disorders of lipid homeostasis, oxidative stress, and inflammation (PMID:31409740)
• Small sequence variations between two mammalian paralogs of the small GTPase SAR1 underlie functional differences in coat protein complex II assembly. (PMID:32358066)
• Receptor-Mediated ER Export of Lipoproteins Controls Lipid Homeostasis in Mice and Humans. (PMID:33186557)
• Sar1b mutant mice recapitulate gastrointestinal abnormalities associated with chylomicron retention disease. (PMID:33964306)
• SAR1B senses leucine levels to regulate mTORC1 signalling. (PMID:34290409)
• Functional overlap between the mammalian Sar1a and Sar1b paralogs in vivo. (PMID:38687799)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sar1b	ENSMUSG00000020386
rattus_norvegicus	Sar1b	ENSRNOG00000004820

Paralogs (30): ARF5 (ENSG00000004059), SAR1A (ENSG00000079332), ARFRP1 (ENSG00000101246), TRIM23 (ENSG00000113595), ARL6 (ENSG00000113966), ARL1 (ENSG00000120805), ARL4A (ENSG00000122644), ARL8B (ENSG00000134108), ARF3 (ENSG00000134287), ARL3 (ENSG00000138175), ARL5C (ENSG00000141748), ARF1 (ENSG00000143761), ARL8A (ENSG00000143862), ARL11 (ENSG00000152213), 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 SAR1B — Q9Y6B6 (reviewed: Q9Y6B6)

Alternative names: GTP-binding protein B, Secretion-associated Ras-related GTPase 1B

All UniProt accessions (6): Q9Y6B6, D6R9R5, D6RAA2, D6RD69, D6RDB2, Q9H029

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. In contrast to SAR1A, SAR1B specifically interacts with the cargo receptor SURF4 to mediate the transport of lipid-carrying lipoproteins including APOB and APOA1 from the endoplasmic reticulum to the Golgi and thereby, indirectly regulates lipid homeostasis. 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 site. Interacts with PREB; PREB acts as a guanine nucleotide exchange factor facilitating the activation of SAR1B by loading it with GTP. Interacts with SURF4; recruits the cargo receptor SURF4 and its lipoprotein cargos to COPII-coated ER to Golgi transport vesicles. Interacts with MIOS; the interaction is direct, disrupted by the binding of leucine and mediates the interaction of SAR1B 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.

Tissue specificity. Expressed in many tissues including small intestine, liver, muscle and brain.

Disease relevance. Chylomicron retention disease (CMRD) [MIM:246700] An autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. The condition is characterized by deficiency of fat-soluble vitamins, low blood cholesterol levels, and a selective absence of chylomicrons from blood. Affected individuals accumulate chylomicron-like particles in membrane-bound compartments of enterocytes, which contain large cytosolic lipid droplets. The disease is caused by variants affecting the gene represented in this entry.

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. GTP hydrolysis is stimulated by SEC23/24.

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

RefSeq proteins (2): NP_001028675, NP_057187* (*=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 (61 total): binding site 24, strand 9, helix 8, mutagenesis site 7, sequence variant 5, turn 4, chain 1, region of interest 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8E0A	X-RAY DIFFRACTION	1.8
8E0D	X-RAY DIFFRACTION	1.98
8E0C	X-RAY DIFFRACTION	1.99
8E0B	X-RAY DIFFRACTION	2.21

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6B6-F1	86.57	0.66

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 (24): 38; 39; 39; 40; 40; 58; 75; 134; 134; 135; 135; 137 …

Post-translational modifications (1): 164

Mutagenesis-validated functional residues (7):

Position	Phenotype
58	loss of interaction with mios. loss of localization to lysosomal membrane. loss of function in negative regulation of to
79	loss of gtpase activity. constitutively restricted in gtp active state.
100	loss of leucine binding. constitutive negative regulation of torc1 signaling.
114	loss of interaction with mios. loss of localization to lysosomal membrane. loss of function in negative regulation of to
122	loss of interaction with mios. loss of localization to lysosomal membrane. loss of function in negative regulation of to
141	loss of leucine binding. constitutive negative regulation of torc1 signaling.
144	loss of leucine binding. constitutive negative regulation of torc1 signaling.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5694530	Cargo concentration in the ER
R-HSA-8963888	Chylomicron assembly
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-8957322	Metabolism of steroids
R-HSA-8963898	Plasma lipoprotein assembly
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 396 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_VESICLE_TARGETING, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN

GO Biological Process (17): antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), 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), regulation of lipid transport (GO:0032368), lipoprotein transport (GO:0042953), COPII vesicle coat assembly (GO:0048208), lipid homeostasis (GO:0055088), membrane organization (GO:0061024), COPII-coated vesicle cargo loading (GO:0090110), lipid export from cell (GO:0140353), 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 (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), GTP binding (GO:0005525), metal ion binding (GO:0046872), amino acid sensor activity (GO:0140785), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (12): lysosomal membrane (GO:0005765), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), 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)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Metabolism of steroids	1
Adaptive Immune System	1
Plasma lipoprotein assembly	1
SARS-CoV-2-host interactions	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Transport of small molecules	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism	1
Disease	1

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
protein transport	2
lipid transport	2
COPII-coated vesicle budding	2
TORC1 signaling	2
transport	2
organelle membrane	2
endomembrane system	2
intracellular membrane-bounded organelle	2
antigen processing and presentation of peptide antigen	1
intercellular transport	1
Golgi vesicle transport	1
organelle organization	1
regulation of transport	1
regulation of lipid localization	1
lipoprotein localization	1
vesicle coat assembly	1
protein-containing complex assembly	1
chemical homeostasis	1
cellular component organization	1
vesicle cargo loading	1
export from cell	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
cation binding	1
molecular sensor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAR1B	SEC13	P55735	976
SAR1B	SEC24A	O95486	951
SAR1B	SEC24B	O95487	923
SAR1B	PREB	Q9HCU5	917
SAR1B	SEC31A	O94979	882
SAR1B	SEC24D	O94855	881
SAR1B	SEC23A	Q15436	816
SAR1B	SIL1	Q9H173	808
SAR1B	SEC23B	Q15437	799
SAR1B	GOLPH3	Q9H4A6	767
SAR1B	APOB	P04114	716
SAR1B	SURF4	O15260	710
SAR1B	MTTP	P55157	699
SAR1B	SEC24C	P53992	667
SAR1B	HYOU1	Q9Y4L1	631

IntAct

72 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VPS28	VPS37A	psi-mi:“MI:0914”(association)	0.640
SAR1A	SAR1B	psi-mi:“MI:0915”(physical association)	0.590
CIDEB	SAR1B	psi-mi:“MI:0915”(physical association)	0.560
TMEM14B	SAR1B	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
NT5E	SCAMP1	psi-mi:“MI:0914”(association)	0.530
TCL1B	MED14	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
FAM171B	FAM171A2	psi-mi:“MI:0914”(association)	0.530
GATC	NME4	psi-mi:“MI:0914”(association)	0.530
CBLN4	C1QL1	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
FUOM	EEF1A2	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530
	MYL12B	psi-mi:“MI:0914”(association)	0.460
PRR25	SAR1B	psi-mi:“MI:0915”(physical association)	0.400
TMEM175	SAR1B	psi-mi:“MI:0915”(physical association)	0.400
PCNA	SAR1B	psi-mi:“MI:0915”(physical association)	0.370
SRPRB	GOSR1	psi-mi:“MI:0914”(association)	0.350
PLPPR2	SEC24D	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
SAR1B	UBA6	psi-mi:“MI:0914”(association)	0.350
MID1	TLDC2	psi-mi:“MI:0914”(association)	0.350

BioGRID (383): SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SAR1B (Affinity Capture-MS), HNRNPH1 (Co-fractionation), SAR1B (Co-fractionation), SAR1B (Two-hybrid)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	5
Uncertain significance	56
Likely benign	88
Benign	9

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1209895	NM_016103.4(SAR1B):c.83_84del (p.Leu28fs)	Pathogenic
1424248	NM_016103.4(SAR1B):c.257G>A (p.Trp86Ter)	Pathogenic
1522233	NM_016103.4(SAR1B):c.442C>T (p.Arg148Ter)	Pathogenic
1879631	NM_016103.4(SAR1B):c.80_81del (p.Lys27fs)	Pathogenic
2423510	NC_000005.9:g.(?133942640)(133948466_?)del	Pathogenic
2423511	NC_000005.9:g.(?133942640)(133945384_?)del	Pathogenic
2734786	NM_016103.4(SAR1B):c.499G>T (p.Glu167Ter)	Pathogenic
2922	NM_016103.4(SAR1B):c.109G>A (p.Gly37Arg)	Pathogenic
2924	NM_016103.4(SAR1B):c.75_76del (p.Thr25_Gly26insTer)	Pathogenic
2926	NM_016103.4(SAR1B):c.555_558dup (p.Gly187fs)	Pathogenic
2927	NM_016103.4(SAR1B):c.349-1G>C	Pathogenic
2928	NM_016103.4(SAR1B):c.364G>T (p.Glu122Ter)	Pathogenic
2929	NM_016103.4(SAR1B):c.554G>T (p.Gly185Val)	Pathogenic
3246455	NC_000005.9:g.(?133944042)(133948466_?)del	Pathogenic
3622541	NM_016103.4(SAR1B):c.511C>T (p.Arg171Ter)	Pathogenic
3654937	NM_016103.4(SAR1B):c.235_242del (p.His79fs)	Pathogenic
3675283	NM_016103.4(SAR1B):c.20G>A (p.Trp7Ter)	Pathogenic
3721594	NM_016103.4(SAR1B):c.203del (p.Gly68fs)	Pathogenic
4693534	NM_016103.4(SAR1B):c.193_202del (p.Thr65fs)	Pathogenic
817510	NM_016103.4(SAR1B):c.194_197dup (p.Ala67fs)	Pathogenic
985564	NM_016103.4(SAR1B):c.336del (p.Glu113fs)	Pathogenic
2506539	GRCh37/hg19 5q31.1(chr5:133956623-133959709)	Likely pathogenic
3254897	NM_016103.4(SAR1B):c.244+1_244+2del	Likely pathogenic
4535451	GRCh37/hg19 5q31.1(chr5:133959652-133959709)x0	Likely pathogenic
4535452	GRCh37/hg19 5q31.1(chr5:133959652-133959709)x1	Likely pathogenic
4767000	NM_016103.4(SAR1B):c.59-2A>G	Likely pathogenic

SpliceAI

1153 predictions. Top by Δscore:

Variant	Effect	Δscore
5:134608367:TTTA:T	donor_loss	1.0000
5:134608369:TACCT:T	donor_loss	1.0000
5:134608370:A:AG	donor_loss	1.0000
5:134608371:C:T	donor_loss	1.0000
5:134608375:T:A	donor_gain	1.0000
5:134608409:CGCA:C	donor_gain	1.0000
5:134608499:AGTGA:A	acceptor_gain	1.0000
5:134608500:GTGA:G	acceptor_gain	1.0000
5:134608501:TGA:T	acceptor_gain	1.0000
5:134608502:GA:G	acceptor_gain	1.0000
5:134608504:C:CC	acceptor_gain	1.0000
5:134608514:C:CT	acceptor_gain	1.0000
5:134608515:A:T	acceptor_gain	1.0000
5:134609565:A:C	donor_gain	1.0000
5:134609565:ACTTA:A	donor_loss	1.0000
5:134609566:CT:C	donor_loss	1.0000
5:134609567:TT:T	donor_loss	1.0000
5:134609568:TACA:T	donor_loss	1.0000
5:134609569:A:AC	donor_gain	1.0000
5:134609569:ACATC:A	donor_loss	1.0000
5:134609570:C:CC	donor_gain	1.0000
5:134609570:CAT:C	donor_gain	1.0000
5:134609672:GAGC:G	acceptor_loss	1.0000
5:134609673:AGC:A	acceptor_loss	1.0000
5:134609674:GCTAA:G	acceptor_loss	1.0000
5:134609675:C:CC	acceptor_gain	1.0000
5:134620925:ATACT:A	donor_loss	1.0000
5:134620926:TACTT:T	donor_loss	1.0000
5:134620927:ACTTA:A	donor_loss	1.0000
5:134620928:CT:C	donor_loss	1.0000

AlphaMissense

1293 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:134608447:C:A	K135N	1.000
5:134608447:C:G	K135N	1.000
5:134608449:T:C	K135E	1.000
5:134608450:A:C	N134K	1.000
5:134608450:A:T	N134K	1.000
5:134608454:C:T	G133E	1.000
5:134609661:C:A	W86C	1.000
5:134609661:C:G	W86C	1.000
5:134609663:A:G	W86R	1.000
5:134609663:A:T	W86R	1.000
5:134612702:C:T	G78E	1.000
5:134612703:C:G	G78R	1.000
5:134612703:C:T	G78R	1.000
5:134612711:T:A	D75V	1.000
5:134612711:T:C	D75G	1.000
5:134612744:A:G	L64P	1.000
5:134620995:G:A	T39I	1.000
5:134620997:T:A	K38N	1.000
5:134620997:T:G	K38N	1.000
5:134620998:T:A	K38I	1.000
5:134620999:T:G	K38Q	1.000
5:134621001:C:A	G37V	1.000
5:134621001:C:T	G37E	1.000
5:134621002:C:G	G37R	1.000
5:134621002:C:T	G37R	1.000
5:134621016:C:T	G32E	1.000
5:134621017:C:G	G32R	1.000
5:134621017:C:T	G32R	1.000
5:134606971:C:A	W192C	0.999
5:134606971:C:G	W192C	0.999

dbSNP variants (sampled 300 via entrez): RS1000241586 (5:134615380 T>C,G), RS1000384691 (5:134609779 C>T), RS1000565922 (5:134611606 C>A,T), RS1000584730 (5:134633043 A>C,G), RS1000625925 (5:134618019 TA>T,TAA), RS1000776145 (5:134601447 A>G), RS1000946993 (5:134614741 A>G), RS1001032655 (5:134632774 C>A,T), RS1001136659 (5:134621605 G>T), RS1001224059 (5:134626571 C>A,G,T), RS1001385981 (5:134611456 C>T), RS1001521736 (5:134611098 A>G), RS1001549108 (5:134617346 T>C,G), RS1001639033 (5:134618362 A>C,T), RS1001685761 (5:134603148 G>A)

Disease associations

OMIM: gene MIM:607690 | disease phenotypes: MIM:167800, MIM:246700

GenCC curated gene-disease

Disease	Classification	Inheritance
chylomicron retention disease	Strong	Autosomal recessive

Mondo (2): hereditary chronic pancreatitis (MONDO:0008185), chylomicron retention disease (MONDO:0009528)

Orphanet (2): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676), Chylomicron retention disease (Orphanet:71)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000488	Retinopathy
HP:0000505	Visual impairment
HP:0001249	Intellectual disability
HP:0001284	Areflexia
HP:0001315	Reduced tendon reflexes
HP:0001397	Hepatic steatosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001927	Acanthocytosis
HP:0002013	Vomiting
HP:0002014	Diarrhea
HP:0002155	Hypertriglyceridemia
HP:0002495	Impaired vibratory sensation
HP:0002570	Steatorrhea
HP:0002630	Fat malabsorption
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003073	Hypoalbuminemia
HP:0003146	Hypocholesterolemia
HP:0003198	Myopathy
HP:0003270	Abdominal distention
HP:0003458	EMG: myopathic abnormalities
HP:0003563	Decreased LDL cholesterol concentration
HP:0003593	Infantile onset
HP:0004395	Malnutrition
HP:0006565	Increased hepatocellular lipid droplets
HP:0010831	Impaired proprioception
HP:0012153	Hypotriglyceridemia
HP:0034787	Accumulation of lipid droplets in small-bowel enterocytes
HP:0100508	Abnormality of vitamin metabolism

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_44	Bipolar disorder	2.000000e-07
GCST012227_188	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535460	Chylomicron retention disease (supp.)
C537262	Hereditary pancreatitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	7
trichostatin A	increases expression, affects cotreatment	3
mercuric bromide	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
bisphenol F	affects cotreatment, increases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects 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, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Disulfiram	affects binding, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05208879	Not specified	COMPLETED	CArotenoid in hypoChOlesterolemia
NCT00830557	Not specified	RECRUITING	Collecting Medical Information and Tissue Samples From Patients With Pancreatic Cancer or Other Pancreatic Disorders
NCT02078245	Not specified	UNKNOWN	Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.
NCT02206360	Not specified	ACTIVE_NOT_RECRUITING	Pancreatic Cancer Early Detection Program
NCT02309632	Not specified	WITHDRAWN	Pancreatic Cancer Screening of High-Risk Individuals in Arkansas
NCT04095195	Not specified	RECRUITING	Registry of Subjects at Risk of Pancreatic Cancer
NCT04743479	Not specified	RECRUITING	Artificial Intelligence-based Early Screening of Pancreatic Cancer and High Risk Tracing (ESPRIT-AI)
NCT07413029	Not specified	RECRUITING	French National Cohort of Patients With PRSS1 Mutations