SEC61B

Summary

SEC61B (SEC61 translocon subunit beta, HGNC:16993) is a protein-coding gene on chromosome 9q22.33, encoding Protein transport protein Sec61 subunit beta (P60468). Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). It is a selective cancer dependency (DepMap: 47.5% of cell lines).

The Sec61 complex is the central component of the protein translocation apparatus of the endoplasmic reticulum (ER) membrane. Oligomers of the Sec61 complex form a transmembrane channel where proteins are translocated across and integrated into the ER membrane. This complex consists of three membrane proteins- alpha, beta, and gamma. This gene encodes the beta-subunit protein. The Sec61 subunits are also observed in the post-ER compartment, suggesting that these proteins can escape the ER and recycle back. There is evidence for multiple polyadenylated sites for this transcript.

Source: NCBI Gene 10952 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polycystic liver disease 1 (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 47.5% of screened cell lines
• MANE Select transcript: NM_006808

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16993
Approved symbol	SEC61B
Name	SEC61 translocon subunit beta
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106803
Ensembl biotype	protein_coding
OMIM	609214
Entrez	10952

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000223641, ENST00000481573, ENST00000498603, ENST00000926713

RefSeq mRNA: 1 — MANE Select: NM_006808 NM_006808

CCDS: CCDS6741

Canonical transcript exons

ENST00000223641 — 4 exons

Exon	Start	End
ENSE00001367372	99222282	99222366
ENSE00003526871	99227899	99228000
ENSE00003585059	99222546	99222643
ENSE00003632788	99230337	99230615

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 184.9262 / max 1619.1182, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97655	116.6730	1825
97656	67.6348	1822
97657	0.6184	191

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.61	gold quality
body of pancreas	UBERON:0001150	99.43	gold quality
oocyte	CL:0000023	99.19	gold quality
pylorus	UBERON:0001166	99.09	gold quality
adenohypophysis	UBERON:0002196	99.09	gold quality
corpus epididymis	UBERON:0004359	99.09	gold quality
pituitary gland	UBERON:0000007	99.04	gold quality
trachea	UBERON:0003126	98.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.96	gold quality
type B pancreatic cell	CL:0000169	98.90	gold quality
right lobe of liver	UBERON:0001114	98.89	gold quality
cardia of stomach	UBERON:0001162	98.89	gold quality
endocervix	UBERON:0000458	98.85	gold quality
left adrenal gland cortex	UBERON:0035825	98.83	gold quality
left adrenal gland	UBERON:0001234	98.82	gold quality
adrenal cortex	UBERON:0001235	98.81	gold quality
right adrenal gland	UBERON:0001233	98.78	gold quality
gingival epithelium	UBERON:0001949	98.72	gold quality
pericardium	UBERON:0002407	98.71	gold quality
lymph node	UBERON:0000029	98.67	gold quality
right adrenal gland cortex	UBERON:0035827	98.66	gold quality
secondary oocyte	CL:0000655	98.65	gold quality
caecum	UBERON:0001153	98.64	gold quality
vermiform appendix	UBERON:0001154	98.64	gold quality
germinal epithelium of ovary	UBERON:0001304	98.64	gold quality
saliva-secreting gland	UBERON:0001044	98.63	gold quality
body of stomach	UBERON:0001161	98.63	gold quality
seminal vesicle	UBERON:0000998	98.62	gold quality
gall bladder	UBERON:0002110	98.62	gold quality
left uterine tube	UBERON:0001303	98.59	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	3580.69
E-HCAD-36	yes	2417.52
E-MTAB-10662	yes	2097.46
E-MTAB-8322	yes	1862.70
E-MTAB-10553	yes	1794.95
E-GEOD-139324	yes	1750.67
E-MTAB-6653	yes	1710.78
E-MTAB-9467	yes	1665.09
E-CURD-46	yes	1594.94
E-HCAD-4	yes	1544.88
E-MTAB-10432	yes	1511.21
E-CURD-88	yes	1195.17
E-HCAD-1	yes	58.23
E-HCAD-6	yes	48.78
E-CURD-122	yes	44.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

28 targeting SEC61B, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-1248	98.47	67.54	1314
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-600	97.07	66.73	1259

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 47.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• This indicates that EGF receptors are trafficked from the endoplasmic reticulum to the nucleus by a novel pathway that involves the Sec61 translocon. (PMID:17215517)
• Sec61beta function provides an alternative pathway for nuclear transport that can be utilized by membrane-embedded proteins such as full-length EGFR. (PMID:20937808)
• SEC61beta and its autoantibody as biomarkers for colorectal cancer (PMID:21255561)
• Sec61beta-KD cells also exhibited altered ATP7A cellular distribution. (PMID:22710939)
• These data confirm that the exocyst is preferentially involved in basolateral protein translation and translocation, and may well act through the phosphorylation of Sec61beta. (PMID:23037926)
• Sec61beta overexpression increased tight junction modulation rates, in conjunction with enhanced delivery of claudin-4 from and to plasma membranes. (PMID:24882410)
• used whole exome sequencing in a discovery cohort of 102 unrelated patients who were excluded for mutations in the 2 most common polycystic liver disease genes, PRKCSH and SEC63, to identify heterozygous loss-of-function mutations in 3 additional genes, ALG8, GANAB, and SEC61B. Similarly to PRKCSH and SEC63, these genes encode proteins that are integral to the protein biogenesis pathway in the endoplasmic reticulum. (PMID:28375157)
• Sec61beta may stabilize protein translocation by linking translocon complex to microtubule and provide insight into the physiological function of ER-microtubule interaction (PMID:29168059)
• Let-7b-5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress-associated endoplasmic reticulum protein 1. (PMID:32534478)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec61b	ENSDARG00000076568
mus_musculus	Sec61b	ENSMUSG00000053317
rattus_norvegicus	Sec61b	ENSRNOG00000086213
drosophila_melanogaster	Sec61beta	FBGN0010638
caenorhabditis_elegans		WBGENE00021427

Protein

Protein identifiers

Protein transport protein Sec61 subunit beta — P60468 (reviewed: P60468)

All UniProt accessions (2): P60468, S4R3B5

UniProt curated annotations — full annotation on UniProt →

Function. Component of SEC61 channel-forming translocon complex that mediates transport of signal peptide-containing precursor polypeptides across the endoplasmic reticulum (ER). Forms a ribosome receptor and a gated pore in the ER membrane, both functions required for cotranslational translocation of nascent polypeptides. The SEC61 channel is also involved in ER membrane insertion of transmembrane proteins: it mediates membrane insertion of the first few transmembrane segments of proteins, while insertion of subsequent transmembrane regions of multi-pass membrane proteins is mediated by the multi-pass translocon (MPT) complex. The SEC61 channel cooperates with the translocating protein TRAM1 to import nascent proteins into the ER.

Subunit / interactions. The SEC61 channel-forming translocon complex consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63. The SEC61 channel associates with the multi-pass translocon (MPT) complex. Interacts with TRAM1.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Loss-of-function SEC61B variations may cause autosomal dominant polycystic liver disease (PCLD) in patients that lack variations in known causative genes, such as PRKCSH and SEC63.

Similarity. Belongs to the SEC61-beta family.

RefSeq proteins (1): NP_006799* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016482	SecG/Sec61-beta/Sbh	Family
IPR030671	Sec61-beta/Sbh	Family

Pfam: PF03911

UniProt features (18 total): modified residue 6, topological domain 2, compositionally biased region 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, mutagenesis site 1, strand 1, helix 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8DNZ	ELECTRON MICROSCOPY	2.57
8DNY	ELECTRON MICROSCOPY	2.85
8DO0	ELECTRON MICROSCOPY	2.86
8DO2	ELECTRON MICROSCOPY	2.95
8DNX	ELECTRON MICROSCOPY	2.98
8DO1	ELECTRON MICROSCOPY	3.01
8DNV	ELECTRON MICROSCOPY	3.03
9D6L	ELECTRON MICROSCOPY	3.1
9N9J	ELECTRON MICROSCOPY	3.2
8DO3	ELECTRON MICROSCOPY	3.22
8OJ0	ELECTRON MICROSCOPY	3.3
8OJ8	ELECTRON MICROSCOPY	3.3
8DNW	ELECTRON MICROSCOPY	3.4
6W6L	ELECTRON MICROSCOPY	3.84
9YGY	ELECTRON MICROSCOPY	4.1
8B6L	ELECTRON MICROSCOPY	7.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P60468-F1	58.08	0.05

Functional residue map

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

Post-translational modifications (7): 9, 13, 14, 17, 39, 2, 7

Mutagenesis-validated functional residues (1):

Position	Phenotype
39	abolishes s-acylation.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-1799339	SRP-dependent cotranslational protein targeting to membrane
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-392499	Metabolism of proteins
R-HSA-72766	Translation
R-HSA-9609507	Protein localization
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 248 (showing top): GOBP_ENDOPLASMIC_RETICULUM_TO_CYTOSOL_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GRUETZMANN_PANCREATIC_CANCER_DN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, MODULE_151, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, MODULE_522, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, GOBP_PROTEIN_TARGETING, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES

GO Biological Process (6): SRP-dependent cotranslational protein targeting to membrane, translocation (GO:0006616), retrograde protein transport, ER to cytosol (GO:0030970), post-translational protein targeting to membrane, translocation (GO:0031204), ERAD pathway (GO:0036503), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (5): RNA binding (GO:0003723), guanyl-nucleotide exchange factor activity (GO:0005085), ribosome binding (GO:0043022), epidermal growth factor binding (GO:0048408), protein binding (GO:0005515)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), Sec61 translocon complex (GO:0005784), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), endoplasmic reticulum Sec complex (GO:0031205), endoplasmic reticulum quality control compartment (GO:0044322)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Antigen processing-Cross presentation	1
Translation	1
Protein localization	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Metabolism of proteins	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular protein transmembrane transport	2
intracellular protein localization	2
cytoplasm	2
SRP-dependent cotranslational protein targeting to membrane	1
protein exit from endoplasmic reticulum	1
ERAD pathway	1
endoplasmic reticulum to cytosol transport	1
post-translational protein targeting to endoplasmic reticulum membrane	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
nucleic acid binding	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
ribonucleoprotein complex binding	1
growth factor binding	1
hormone binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
translocon complex	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Sec61 translocon complex	1
rough endoplasmic reticulum membrane	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

126 interactions, top by confidence:

A	B	Type	Score
COPG1	COPB2	psi-mi:“MI:0914”(association)	0.730
GET3	SEC61B	psi-mi:“MI:0407”(direct interaction)	0.680
SEC61B	GET3	psi-mi:“MI:0407”(direct interaction)	0.680
	DDX3X	psi-mi:“MI:0914”(association)	0.630
SEC61B		psi-mi:“MI:0915”(physical association)	0.620
SEC61B	BCAP31	psi-mi:“MI:0915”(physical association)	0.600
BCAP31	SEC61B	psi-mi:“MI:0915”(physical association)	0.600
BCAP31	SEC61B	psi-mi:“MI:0403”(colocalization)	0.600
SEC61A2	SEC61B	psi-mi:“MI:0915”(physical association)	0.560
SEC61B	SSR1	psi-mi:“MI:0915”(physical association)	0.560
	XPO1	psi-mi:“MI:0914”(association)	0.530
	SCD	psi-mi:“MI:0914”(association)	0.500
STING1	SSR2	psi-mi:“MI:0914”(association)	0.480
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460
	DENR	psi-mi:“MI:0915”(physical association)	0.400
	AGPS	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SEC61B	ATP13A2	psi-mi:“MI:0915”(physical association)	0.370
AURKA	SEC61B	psi-mi:“MI:0915”(physical association)	0.370
BMPR1A	SEC61B	psi-mi:“MI:0915”(physical association)	0.370
SEC61B	BUB1	psi-mi:“MI:0915”(physical association)	0.370
SEC61B	CDKN2A	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	SEC61B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1059): SEC61B (Co-fractionation), LOC100355886 (Affinity Capture-MS), BAG6 (Affinity Capture-Western), ASNA1 (Affinity Capture-Western), BAG6 (Affinity Capture-MS), ASNA1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJB1 (Affinity Capture-Western), HSPA4 (Affinity Capture-MS), HSPA4 (Affinity Capture-Western), HSPA8 (Affinity Capture-MS), HSPA8 (Affinity Capture-Western), SGTA (Affinity Capture-Western), SEC61B (Affinity Capture-MS), SEC61B (Affinity Capture-Western)

ESM2 similar proteins: A8I6P9, B2ICM8, E7A253, O13394, O18811, O43002, P01307, P03197, P03274, P0C717, P19407, P20290, P24937, P27335, P34310, P38389, P52870, P52871, P60467, P60468, Q0CGL5, Q24546, Q28GG3, Q32KU9, Q32L85, Q3KST5, Q3T073, Q3ZBR1, Q4P9Q7, Q5RB31, Q5REZ1, Q64152, Q67593, Q6AX78, Q6TAW2, Q76MS9, Q80XX4, Q8IVN3, Q8J2P4, Q8K190

Diamond homologs: A8I6P9, O43002, P38389, P60467, P60468, Q54YR4, Q5RB31, Q9CQS8, Q9HFC7, P52870, P52871, Q8J2P4, Q5JDK7, B6YW71, C5A4H9, A6UWW7, O28498, P60461, P60462, P60463, Q2NHI7, Q8TZH7, Q975W7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SEC61B	“form complex”	“SEC61 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
VEGFR2 mediated cell proliferation	5	31.7×	7e-05
SRP-dependent cotranslational protein targeting to membrane	6	6.7×	5e-03
SLC-mediated transmembrane transport	7	4.6×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of gene expression	9	5.8×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	0
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

311 predictions. Top by Δscore:

Variant	Effect	Δscore
9:99227894:TTCA:T	acceptor_loss	1.0000
9:99227895:TCA:T	acceptor_loss	1.0000
9:99227897:A:AG	acceptor_gain	1.0000
9:99227897:AG:A	acceptor_gain	1.0000
9:99227898:G:GT	acceptor_gain	1.0000
9:99227898:GG:G	acceptor_gain	1.0000
9:99227898:GGA:G	acceptor_gain	1.0000
9:99227898:GGAA:G	acceptor_gain	1.0000
9:99227898:GGAAA:G	acceptor_gain	1.0000
9:99227996:AAAGT:A	donor_gain	1.0000
9:99227997:AAGT:A	donor_gain	1.0000
9:99227998:AGTGT:A	donor_loss	1.0000
9:99227999:GT:G	donor_gain	1.0000
9:99227999:GTGTA:G	donor_loss	1.0000
9:99228000:TGTAA:T	donor_loss	1.0000
9:99228001:G:GA	donor_loss	1.0000
9:99228001:G:GG	donor_gain	1.0000
9:99228002:TAAG:T	donor_loss	1.0000
9:99230335:A:AG	acceptor_gain	1.0000
9:99230336:G:GG	acceptor_gain	1.0000
9:99222544:AGCCT:A	acceptor_gain	0.9900
9:99222545:GCCTG:G	acceptor_gain	0.9900
9:99222640:AGAGG:A	donor_loss	0.9900
9:99222641:GAG:G	donor_gain	0.9900
9:99222643:GGT:G	donor_loss	0.9900
9:99222644:GT:G	donor_loss	0.9900
9:99222645:T:A	donor_loss	0.9900
9:99230335:AGT:A	acceptor_gain	0.9900
9:99230336:GT:G	acceptor_gain	0.9900
9:99230336:GTG:G	acceptor_gain	0.9900

AlphaMissense

603 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:99230362:A:C	S77R	1.000
9:99230364:T:A	S77R	1.000
9:99230364:T:G	S77R	1.000
9:99230375:T:A	I81N	1.000
9:99227991:G:A	G65E	0.999
9:99230363:G:T	S77I	0.999
9:99230366:T:A	L78H	0.999
9:99230371:T:C	F80L	0.999
9:99230373:C:A	F80L	0.999
9:99230373:C:G	F80L	0.999
9:99230378:C:A	A82D	0.999
9:99230386:T:C	F85L	0.999
9:99230388:T:A	F85L	0.999
9:99230388:T:G	F85L	0.999
9:99230395:C:A	H88N	0.999
9:99230395:C:G	H88D	0.999
9:99227969:T:C	F58L	0.998
9:99227971:C:A	F58L	0.998
9:99227971:C:G	F58L	0.998
9:99227990:G:A	G65R	0.998
9:99227990:G:C	G65R	0.998
9:99230338:G:C	G69R	0.998
9:99230351:T:A	V73E	0.998
9:99230354:T:C	L74S	0.998
9:99230360:T:A	M76K	0.998
9:99230360:T:G	M76R	0.998
9:99230366:T:C	L78P	0.998
9:99230371:T:A	F80I	0.998
9:99230372:T:C	F80S	0.998
9:99230397:C:A	H88Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000334666 (9:99229309 G>A), RS1000532325 (9:99225059 G>A,T), RS1000636995 (9:99222741 A>C,G), RS1000787592 (9:99229960 GA>G,GAA), RS1000847576 (9:99228911 A>C,G), RS1001308109 (9:99225877 G>A), RS1001382426 (9:99220741 A>G), RS1001401332 (9:99228418 G>A), RS1001678985 (9:99226238 C>T), RS1002123093 (9:99230590 C>A,G,T), RS1002410220 (9:99230923 A>G), RS1002952989 (9:99227284 A>C), RS1003061250 (9:99221774 G>A,T), RS1003393345 (9:99227110 A>T), RS1004629340 (9:99225470 C>A,T)

Disease associations

OMIM: gene MIM:609214 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
polycystic liver disease 1	Moderate	Autosomal dominant
autosomal dominant polycystic liver disease	Moderate	Autosomal dominant
SEC61B-related polycystic liver disease	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
SEC61B-related polycystic liver disease	Limited	AD

Mondo (3): SEC61B-related polycystic liver disease (MONDO:0550003), polycystic liver disease 1 (MONDO:0008265), autosomal dominant polycystic liver disease (MONDO:0000447)

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002092_1	Callous-unemotional behaviour	3.000000e-06
GCST004899_5	Gestational age at birth (maternal effect)	5.000000e-07
GCST007327_2	Smoking status (ever vs never smokers)	3.000000e-10
GCST009798_9	Asthma	2.000000e-10
GCST010242_396	HDL cholesterol levels	6.000000e-10
GCST010244_388	Triglyceride levels	2.000000e-10
GCST010988_400	Adult body size	4.000000e-08

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005322	callous-unemotional behaviour
EFO:0005112	gestational age
EFO:0005939	parental genotype effect measurement
EFO:0004318	smoking behavior
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067175 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	Kd	3001	nM	CHEMBL5653589
5.52	ED50	3001	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149368: Binding affinity to human SEC61B incubated for 45 mins by Kinobead based pull down assay	kd	3.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation, affects cotreatment	4
bisphenol A	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Cisplatin	decreases expression	2
Tunicamycin	increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	decreases expression, increases abundance	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
chloropicrin	increases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	increases expression	1
Benztropine	increases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Clozapine	increases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652410	Binding	Binding affinity to human SEC61B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3GP	Abcam HEK293T SEC61B KO	Transformed cell line	Female
CVCL_D8V0	Ubigene HCT 116 SEC61B KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01157858	PHASE2	COMPLETED	Everolimus and LongActing Octreotide Trial in Polycystic Livers
NCT01670110	PHASE2	COMPLETED	Pasireotide LAR in Severe Polycystic Liver Disease
NCT02021110	PHASE2	COMPLETED	Ursodeoxycholic Acid as Treatment for Polycystic Liver Disease
NCT05478083	PHASE2	RECRUITING	A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
NCT00426153	PHASE2/PHASE3	COMPLETED	Octreotide in Severe Polycystic Liver Disease
NCT00565097	PHASE2/PHASE3	COMPLETED	Lanreotide as Treatment of Polycystic Livers
NCT00771888	PHASE2/PHASE3	UNKNOWN	Open-Label Extension of LOCKCYST Trial
NCT01315795	PHASE2/PHASE3	COMPLETED	Lanreotide Autogel in the Treatment of Symptomatic Polycystic Liver Disease
NCT05281328	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients With PLD
NCT00934791	Not specified	TERMINATED	Polycystic Liver Disease in Kidney Transplant
NCT01354405	Not specified	COMPLETED	Somatostatin Analogues as a Volume Reducing Treatment of Polycystic Livers (RESOLVE)
NCT02173080	Not specified	COMPLETED	Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).
NCT03960710	Not specified	UNKNOWN	Automatic Segmentation of Polycystic Liver
NCT04645251	Not specified	RECRUITING	Polycystic Liver Disease Registry (UK)
NCT05215964	Not specified	UNKNOWN	The Association Between Skeletal Muscle Mass and Severity of Polycystic Liver Disease and Polycystic Kidney Disease
NCT05500157	Not specified	UNKNOWN	Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts
NCT04111692	Not specified	RECRUITING	A Prospective Observational Study of Foam Sclerotherapy .