SEC63

SEC63 homolog, protein translocation regulator, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 6:107867756-107958208

Links

ENSG00000025796 ∙ NCBI:11231 ∙ OMIM:608648 ∙ HGNC:21082 ∙ Uniprot:Q9UGP8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic liver disease 2 (Strong), mode of inheritance: AD
• polycystic liver disease 1 (Supportive), mode of inheritance: AD
• polycystic liver disease 2 (Definitive), mode of inheritance: AD
• polycystic liver disease 2 (Strong), mode of inheritance: AD
• polycystic liver disease 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polycystic liver disease 2 with or without kidney cysts	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Gastrointestinal	15133510; 22099398; 23209713
Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEC63 gene.

• Polycystic liver disease 2 (7 variants)
• not provided (6 variants)
• Autosomal dominant polycystic liver disease (3 variants)
• SEC63-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEC63 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	29	6	37
missense			67	5	2	74
nonsense	5	3	1			9
start loss			1			1
frameshift	5	4	2			11
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)	1	2				3
splice region			9	24	8	41
non coding			86	59	68	213
Total	11	9	162	94	76

Highest pathogenic variant AF is 0.0000207

Variants in SEC63

This is a list of pathogenic ClinVar variants found in the SEC63 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-107867809-A-G		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107867885-T-C		Polycystic liver disease 2	Uncertain significance (Jan 12, 2018)
6-107867904-T-C		Polycystic liver disease 2	Uncertain significance (Jan 13, 2018)
6-107867932-C-T		Polycystic liver disease 2	Uncertain significance (Jan 13, 2018)
6-107867999-A-C		Polycystic liver disease 1	Uncertain significance (Jun 14, 2016)
6-107868000-G-C		Polycystic liver disease 2	Uncertain significance (Jan 13, 2018)
6-107868124-C-T		Polycystic liver disease 2	Benign (Jan 12, 2018)
6-107868129-T-TGTC		Polycystic liver disease 1	Benign (Jun 14, 2016)
6-107868194-A-T		Polycystic liver disease 2	Uncertain significance (Jan 13, 2018)
6-107868202-G-A		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107868203-T-C		Polycystic liver disease 2	Benign (Jan 12, 2018)
6-107868205-T-G		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107868206-G-A		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107868207-T-C		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107868215-T-C		Polycystic liver disease 2	Uncertain significance (Apr 27, 2017)
6-107868223-TA-T		Polycystic liver disease 1	Benign (Jun 14, 2016)
6-107868223-T-TA		Polycystic liver disease 1	Uncertain significance (Jun 14, 2016)
6-107868235-A-C		Polycystic liver disease 2	Likely benign (Jan 13, 2018)
6-107868248-A-G		Polycystic liver disease 2	Uncertain significance (Jan 12, 2018)
6-107868270-T-C		Polycystic liver disease 2	Uncertain significance (Jan 13, 2018)
6-107868271-T-TG		Polycystic liver disease 1	Uncertain significance (Jun 14, 2016)
6-107868273-T-G		Polycystic liver disease 2	Benign (Jan 13, 2018)
6-107868274-T-C		Polycystic liver disease 2	Uncertain significance (Jan 12, 2018)
6-107868311-G-A		Polycystic liver disease 2	Benign (Jan 12, 2018)
6-107868314-C-T		Polycystic liver disease 2	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEC63	protein_coding	protein_coding	ENST00000369002	21	90434

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.08e-7	1.00	125710	0	37	125747	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.20	275	399	0.690	0.0000201	5006
Missense in Polyphen		52	106.92	0.48634		1288
Synonymous	-0.0590	134	133	1.01	0.00000625	1323
Loss of Function	4.07	21	53.0	0.396	0.00000278	610

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000157	0.000157
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000109	0.000109
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000197	0.000185
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000691	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates cotranslational and post-translational transport of certain precursor polypeptides across endoplasmic reticulum (ER) (PubMed:22375059, PubMed:29719251). Proposed to play an auxiliary role in recognition of precursors with short and apolar signal peptides. May cooperate with SEC62 and HSPA5/BiP to facilitate targeting of small presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen (PubMed:29719251). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:Q8VHE0, ECO:0000269|PubMed:22375059, ECO:0000269|PubMed:29719251}.
• Pathway: Protein export - Homo sapiens (human);Protein processing in endoplasmic reticulum - Homo sapiens (human);XBP1(S) activates chaperone genes;IRE1alpha activates chaperones;Unfolded Protein Response (UPR);Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.731
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.268
• hipred: Y
• hipred_score: 0.706
• ghis: 0.626

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.643

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sec63
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; renal/urinary system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: sec63
• Affected structure: myelinating Schwann cell
• Phenotype tag: abnormal
• Phenotype quality: swollen

Gene ontology

• Biological process: liver development;protein targeting to membrane;SRP-dependent cotranslational protein targeting to membrane;posttranslational protein targeting to endoplasmic reticulum membrane;nitrogen compound metabolic process;multicellular organism aging;posttranslational protein targeting to membrane, translocation;renal system development
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;integral component of endoplasmic reticulum membrane;Sec62/Sec63 complex
• Molecular function: RNA binding;protein binding;protein transporter activity;signaling receptor activity